We sought to evaluate the oncologic outcomes of simple hysterectomy in patients with low-risk early-stage cervical cancer (tumors ≤2 cm with limited stromal invasion).
This study was registered in PROSPERO (registration number CRD42023433840) following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) checklist. MEDLINE (through Ovid), EmMBASEbase, and Cochrane Central Register of Controlled Trials were searched from inception until June 2023. Randomized controlled trials and observational studies with two arms of comparison (simple hysterectomy with lymph node assessment vs radical hysterectomy with lymph node assessment) in patients with low-risk early-stage cervical cancer were considered.
The search identified 1270 articles; eighteen studies were considered potentially eligible after removing duplicates, and four met the selection criteria. Three studies were randomized controlled trials, and the other was a retrospective cohort study. In total, 981 patients were included. There were 485 (49.4%) and 496 (50.6%) patients in the simple hysterectomy and radical hysterectomy groups, respectively. Simple hysterectomy with lymph node assessment was not associated with a higher risk of death at 5 years (RR 0.98, 95% CI: 0.31 to 3.10; I2=0%, two randomized controlled trials, 141 patients, for an absolute risk reduction of zero percentage points [95% CI –9.0 to 9.0]), pelvic recurrence at 3 years (97.5% and 97.8% for simple hysterectomy and radical hysterectomy, respectively, p=0.79), and overall recurrence at 3 years (95 %% and 100% for simple hysterectomy and radical hysterectomy, respectively, p=0.30).
Simple hysterectomy with lymph node evaluation for low-risk early-stage cervical cancer is not associated with a detrimental effect on oncologic outcomes and has a better morbidity profile.
To review rates of uterine preservation and gonadal function, surgical outcomes, and pregnancy outcomes in patients undergoing surgical uterine transposition.
A structured search and analysis of the published literature on uterine transposition was conducted. Information on study type, sample size, patient characteristics, clinical indications, details of the surgical technique, trans-operative and post-operative results, success rates in preserving reproductive organ function and fertility were extracted.
A total of 18 cases were reported to date. Patients’ median age was 29 (range 3–38) years. Rectal cancers accounted for 9 (50%) cases of published cases of uterine transposition, followed by 6 (33%) cervical squamous cell carcinomas, 1 (6%) vaginal squamous cell carcinoma, 1 (6%) sacral yolk sac tumor, and 1 (6%) pelvic liposarcoma. The median time for uterine transposition to the upper abdomen was 150 (range 80–360) min, and 90 (range 80–310) min for organ reimplantation in the pelvis. Cervical ischemia occurred in 5 (27.8%) cases, being the most commonly reported complication. The median follow-up time was 25 months, and three patients achieved spontaneous pregnancies resulting in successful gestations, out of five patients who were reported as having tried. One patient experienced recurrence and succumbed to the tumor during treatment.
Uterine transposition is a feasible and safe surgical approach that offers patients undergoing pelvic radiotherapy an option to preserve gonadal and uterine function, with the potential for spontaneous pregnancy.
In the era of ‘less is more’, pelvic exenteration in gynecologic oncology is still indicated when there are no other curative-intent alternatives in persistent or recurrent gynecological malignancies confined to the pelvis or with otherwise unmanageable symptoms from fistula or radiation necrosis. Pelvic exenteration is one of the most destructive procedures performed on an elective basis, which inevitably carries a significant psychologic, sexual, physical, and emotional burden for the patient and caregivers. Such complex ultraradical surgery, which requires removal of the vagina, vulva, urinary tract, and/or gastrointestinal tract, subsequently needs creative and complex reconstructive procedures. The additional removal of sidewall or perineal structures, like pelvic floor muscles/vulva, or portions of the musculoskeletal pelvis, and the inclusion of intra-operative radiation further complicates reconstruction. This review paper will focus on the reconstruction aspects following pelvic exenteration, including options for urinary tract restoration, reconstruction of the vulva and vagina, as well as how to fill large empty spaces in the pelvis. While the predominant gastrointestinal outcome after exenteration in gynecologic oncology is an end colostomy, we also present some novel new options for gastrointestinal tract reconstruction at the end.
]]>The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients.
Patients with SLNs–isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan–Meier methods.
494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs–isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1–3.0) and 2.6 years (IQR 0.6–4.2) in the SLN–isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN–isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion.
Patients with SLNs–isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs–isolated tumor cells was not associated with worse overall survival.
Vaginal carcinoma is a rare malignancy accounting for 1–2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy–chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy–chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy.
Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy–chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities.
14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/β10, to the high risk clinical target volume, and 60 Gy EQD2α/β10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10–56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity.
In this study, definitive radiotherapy–chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.
The aim of this study was to compare the incidence of intra-operative and post-operative complications in open and minimally invasive radical hysterectomy for patients with early-stage cervical cancer.
Data were collected from the SUCCOR database of 1272 patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO), 2009) who underwent radical hysterectomy in Europe between January 2013 and December 2014. We reviewed the duration of the surgeries, estimated blood loss, length of hospital stay, intra-operative and post-operative complications. The inclusion criteria were age ≥18 years and histologic type (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma). Pelvic MRI confirming a tumor diameter ≤4 cm with no parametrial invasion and a pre-operative CT scan, MRI, or positron emission tomography CT demonstrating no extra-cervical metastatic disease were mandatory. Outcomes of interest were any grade >3 adverse events, intra-operative adverse events, post-operative adverse events, length of hospital stay, length of operation, and blood loss.
The study included 1156 patients, 633 (54%) in the open surgery group and 523 (46%) in the minimally invasive surgery group. Median age was 46 years (range 18–82), median body mass index 25 kg/m2 (range 15–68), and 1022 (88.3%) patients were considered to have an optimal performance status (ECOG Performance Status 0). The most common histologic tumor type was squamous carcinoma (n=794, 68.7%) and the most frequent FIGO staging was IB1 (n=510, 44.1%). In the minimally invasive surgery group the median duration of surgery was longer (240 vs 187 min, p<0.01), median estimated blood loss was lower (100 vs 300 mL, p<0.01), and median length of hospital stay was shorter (4 vs 7 days, p<0.01) compared with the abdominal surgery group. There was no difference in the overall incidence of intra-operative and post-operative complications between the two groups. Regarding grade I complications, the incidence of vaginal bleeding (2.9% vs 0.6%, p<0.01) and vaginal cuff dehiscence was higher in the minimally invasive surgery group than in the open group (3.3% vs 0.5%, p<0.01). Regarding grade III post-operative complications, bladder dysfunction (1.3% vs 0.2%, p=0.046) and abdominal wall infection (1.1% vs 0%, p=0.018) were more common in the open surgery group than in the minimally invasive surgery group. Ureteral fistula was more frequent in the minimally invasive group than in the open surgery group (1.7% vs 0.5%, p=0.037).
Our study showed that there was no significant difference in the overall incidence of intra-operative and post-operative complications between minimally invasive radical hysterectomy and the open approach.
The impact of adjuvant pelvic radiation therapy on the rate and location of recurrences was evaluated in patients with early-stage (IA1–IB2) neuroendocrine cervical carcinoma who underwent prior conization or polypectomy with no residual disease and negative nodes in the subsequent upfront radical hysterectomy specimen. As a secondary objective, disease-free and overall survival were analyzed.
We searched the Neuroendocrine Cervical Tumor Registry (NeCTuR) to identify patients with clinical early-stage neuroendocrine cervical carcinoma with no residual disease in the specimen from upfront radical surgery and negative nodes. Patients who received pelvic radiation therapy were compared with those who did not, regardless of whether they received adjuvant chemotherapy.
Twenty-seven patients met the inclusion criteria, representing 17% of all patients with clinical early-stage disease who underwent upfront radical hysterectomy included in the NeCTuR registry. The median age was 36.0 years (range 26.0–51.0). Six (22%) patients had stage IA, 20 (74%) had stage IB1, and one (4%) had stage IB2 disease. Seven (26%) patients received adjuvant radiation therapy and 20 (74%) did not. All seven patients in the radiation group and 14 (70%) in the no-radiation group received adjuvant chemotherapy (p=0.16). Fifteen percent (4/27) of patients had a recurrence, 14% (1/7) in the radiation group and 15% (3/20) in the no-radiation group (p=0.99). In the radiation group the recurrence was outside the pelvis, and in the no-radiation group, 67% (2/3) recurred outside the pelvis and 33% (1/3) recurred both inside and outside the pelvis (p=0.99). In the radiation group the 5-year disease-free and overall survival rates were 100% while, in the no-radiation group, the 5-year disease-free and overall survival rates were 81% (95% CI 61% to 100%) (p=0.99) and 80% (95% CI 58% to 100%) (p=0.95), respectively.
For patients with no residual disease and negative nodes in the upfront radical hysterectomy specimen, our study did not find that pelvic radiation therapy improves survival.
The management and surveillance of glandular pre-cancerous lesions of the uterine cervix present distinct challenges compared with squamous lesions, primarily attributed to the lower effectiveness of diagnostic methods such as cytology or colposcopy. This study aimed to investigate the long-term safety of fertility-sparing treatment for adenocarcinoma in situ and microinvasive adenocarcinoma of the cervix, while identifying factors associated with recurrence, with a particular emphasis on the role of human papillomavirus (HPV) testing.
We retrospectively reviewed data from all patients with histopathologically confirmed adenocarcinoma in situ or microinvasive cervical adenocarcinoma who received treatment at a single center between 2002 and 2023. The study involved the examination of consecutive surgical specimens and the follow-up details. Factors associated with recurrence were assessed in a subgroup of patients with available long-term follow-up data (at least 6 months).
In total, 143 patients (112 with adenocarcinoma in situ and 31 with adenocarcinoma) were included in the analysis. Among the 86 patients who underwent fertility-sparing treatment, the recurrence rate was 9% (12% for adenocarcinoma in situ and 4% for adenocarcinoma) during a median follow-up period of 56.6 months (range 7–179). No patients who were HPV negative experienced recurrence during the follow-up period. In contrast, among patients who were HPV positive, the recurrence rate was 38%. Additionally, HPV 16/18 positivity displayed a notable association with a higher risk of recurrence compared with the other high-risk genotypes, although this difference did not reach statistical significance (83% vs 10%; p=0.083, log-rank).
Our retrospective study demonstrated a significant association between the risk of recurrence and HPV status during the follow-up period. Consequently, long-term follow-up utilizing HPV testing and genotyping appears to be a secure alternative to a hysterectomy.
The COVID-19 pandemic had significant effects on healthcare systems worldwide, including the disruption of routine screening programs for cervical cancer. This study aimed to compare the incidence of cervical intra-epithelial neoplasia (CIN)2 and CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix before and after the COVID-19 pandemic.
A retrospective analysis was performed using archive data from the Policlinico di Bari, Unit of Gynecology and Obstetrics. The study included patients who tested positive for high-risk human papillomavirus (HPV) at the level I screening test (HPV test) and were subsequently referred to level II screening, which involves the Papanicolaou (Pap) test and colposcopic examination. We excluded individuals who did not comply with the recommended follow-up, patients with low-risk HPV infection, those with autoimmune diseases, oncologic diseases, or those undergoing immunosuppressive therapies. The time period spanned from January 2020 to December 2022. The incidence of CIN2/CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix was compared between the pre-screening period (2017–2019) and the post-screening period (2020–2022).
The study comprised a cohort of 1558 consecutive European sexually active women with a median age of 34 years (range 25–65) who underwent colposcopic evaluation of the uterine cervix as a level II screening program. The comparison between the pre-screening and post-screening periods showed an increase in the incidence of CIN2/CIN3 lesions, rising from 23.9 to 63.3 per 100 000 (HR 2.62, 95% CI 1.64 to 4.20; p<0.001). Additionally, although there was an absolute increase in the incidence of cervical carcinoma and adenocarcinoma, the comparison did not reach statistical significance (squamous carcinoma: 2017–2019, 2.5 per 100 000; 2020–2022 3.4 per 100 000, p=0.72; adenocarcinoma: 2017–2019, 3.5 per 100 000; 2020–2022 7.6 per 100 000, p=0.24).
This study showed a significant increase in the incidence rate of CIN2/CIN3 lesions after the COVID-19 pandemic. Our findings may be attributed to the temporary suspension of follow-up programs during the pandemic, although the study does not rule out direct effects of SARS-CoV-2 on the risk of pre-neoplastic and neoplastic conditions of the cervix.
Endometrial cancers with more than one molecular feature—POLE mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)—are called ‘multiple classifiers’.
To describe our cohort of multiple classifiers and to report the results of a review on their incidence and the techniques used to identify them.
Multiple classifiers identified at the European Institute of Oncology, Milan, between April 2019 and Decmber 2022, were included. Clinicopathological, molecular characteristics, and oncologic outcomes were summarized and compared between single and multiple classifiers sharing common features. Studies on molecular classification of endometrial cancer were searched in the PubMed Database to collect data on the incidence of multiple classifiers and the techniques used for classification.
Among 422 patients, 48 (11.4%) were multiple classifiers: 15 (3.6%) POLEmut-p53abn, 2 (0.5%) POLEmut-MMRd, 28 (6.6%) MMRd-p53abn, and 3 (0.7%) POLEmut-MMRd-p53abn. MMRd-p53abn and MMRd differed in histotype (non-endometrioid: 14.8% vs 2.0%, p=0.006), grade (high-grade: 55.6% vs 22.2%, p=0.001), and MMR proteins expression, whereas they differed from p53abn in histotype (non-endometrioid: 14.8% vs 50.0%, p=0.006). POLEmut-p53abn and POLEmut differed only in grade (high-grade: 66.7% vs 22.7%, p=0.008), while they differed from p53abn in age (56.1 vs 66.7 years, p=0.003), stage (advanced: 6.7% vs 53.4%, p=0.001), and histotype (non-endometrioid: 6.7% vs 50.0%, p=0.002). Two (7.1%) patients with MMRd-p53abn, 4 (4.0%) with MMRd, and 25 (34.3%) with p53abn had a recurrence. No recurrences were observed in POLEmut-p53abn and POLEmut. TP53 sequencing allowed the detection of additional 7 (18.9%) multiple classifiers with normal p53 immunostaining. The incidence of multiple classifiers ranged from 1.8% to 9.8% in 10 published studies including >100 patients. When only p53 immunohistochemistry was performed, the highest incidence was 3.9%.
The characteristics of POLEmut-p53abn resembled those of POLEmut, whereas MMRd-p53abn appeared to be intermediate between MMRd and p53abn. The high proportion of multiple classifiers may be related to the methods used for molecular classification, which included both p53 immunohistochemistry and TP53 sequencing.
There is a continued need for improvement of second-line systemic treatment for metastatic and/or recurrent endometrial cancer.
In this phase II, open-label study, eligible patients had histologically or cytologically confirmed endometrial cancer, documented progressive disease, and a WHO performance status of ≤2. All participants received treatment with pazopanib 800 mg once daily until progression, unacceptable toxicity, or patient refusal. The primary endpoint was progression-free survival at 3 months, with secondary outcomes of overall response rate, progression-free survival, overall survival, and toxicity. The study was powered to demonstrate 50% progression-free survival at 3 months with α=0.05 and β=80%.
Between January 2011 and February 2016, 60 eligible patients were included (intention-to-treat population). Median age was 68 (range, 53–85) years. Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%), and hormonal therapy (43%). Three-month progression-free survival was 63.3% in the intention-to-treat population, with median progression-free survival and overall survival of 3.4 and 7.5 months, respectively. Overall response rate was 8.3%, and median follow-up 7.6 months. The most common grade 3 or higher adverse events were gastrointestinal toxicity in 21% of participants, including two patients with a gut perforation, one fatal gastrointestinal hemorrhage, one enterocutaneous fistula, and one fatal enterovaginal fistula. Extensive peritoneal disease existed in 80% of the patients with severe gastrointestinal toxicity. A definite correlation with previous radiotherapy could not be established.
Pazopanib met its primary endpoint of 3 months’ progression-free survival in advanced endometrial cancer (63.3%), but response rates were modest. There may be a correlation for rare but severe gastrointestinal toxicity with previous treatments and/or disease site that has yet to be elucidated.
To evaluate a wide range of clinical and ultrasound characteristics of different uterine smooth muscle tumors to identify features capable of discriminating between these types.
This was a retrospective, multicenter study that included 285 patients diagnosed with uterine smooth muscle tumors (50 leiomyosarcomas, 35 smooth muscle tumors of uncertain malignant potential, and 200 leiomyomas). The patients were divided into three groups based on the histological type of their tumors, and the groups were compared according to the variables collected.
Leiomyosarcomas were more common in older and post-menopausal women. Compared with leiomyomas, smooth muscle tumors of uncertain malignant potential and leiomyosarcomas had similar ultrasound features such as absence of normal myometrium, multilocular appearance, hyper-echogenicity in case of uniform echogenicity, absence of posterior shadows, echogenic areas, and hyperechoic rim. Leiomyosarcomas were larger, had more cystic areas, and were associated with a higher prevalence of pelvic free fluid. Smooth muscle tumors of uncertain malignant potential were characterized by a higher frequency of International Federation of Gynecology and Obstetrics (FIGO) type 6–7, the absence of internal shadows, and, in the case of cystic area, the presence of a regular internal wall. Tumor outline varied among the three histological types. A color score of 1 was typical of leiomyoma, a color score 2 was mainly observed in leiomyomas and smooth muscle tumors of uncertain malignant potential, a color score 3 did not differ among the tumors, while a color of score 4 was related to leiomyosarcomas. When combining color scores 3 and 4, leiomyosarcomas and smooth muscle tumors of uncertain malignant potential showed a high percentage of both circumferential and intra-lesional vascularization. A cooked appearance was not statistically different among the tumors.
Based on our findings, specific ultrasonographic features as well as age and menopausal status are associated with different uterine smooth muscle tumor types. Integration of these data can help the pre-operative assessment of these lesions for proper management.
Opioid over-prescription is wasteful and contributes to the opioid crisis. We implemented a personalized tiered discharge opioid protocol and education on opioid disposal to minimize over-prescription.
To evaluate the intervention by investigating opioid use post-discharge for women undergoing abdomino-pelvic surgery, and patient adherence to opioid disposal education.
We analyzed post-discharge opioid consumption among 558 patients. Eligible patients included those who underwent elective gynecologic surgery, were not taking scheduled opioids pre-operatively, and received discharge opioids according to a tiered prescribing algorithm. A survey assessing discharge opioid consumption and disposal safety knowledge was distributed on post-discharge day 21. Over-prescription was defined as >20% of the original prescription left over. Descriptive statistics were used for analysis.
The survey response rate was 61% and 59% in the minimally invasive surgery and open surgery cohorts, respectively. Overall, 42.8% of patients reported using no opioids after hospital discharge, 45.2% in the minimally invasive surgery and 38.6% in the open surgery cohort. Furthermore, 74.9% of respondents were over-prescribed, with median age being statistically significant for this group (p=0.004). Finally, 46.4% of respondents expressed no knowledge regarding safe disposal practices, with no statistically significant difference between groups (p>0.99).
Despite implementation of the tiered discharge opioid algorithm aimed to personalize opioid prescriptions to estimated need, we still over-prescribed opioids. Additionally, despite targeted education, nearly half of all patients who completed the survey did not know how to dispose of their opioid tablets. Additional efforts are needed to further refine the algorithm to reduce over-prescription of opioids and improve disposal education.
To study and quantify the attitude of BRCA1/2 mutation carriers towards surgical risk reduction procedures.
This cross-sectional national study was conducted by distribution of an anonymous questionnaire on social media platforms and to BRCA1/2 carriers’ medical clinic.
530 BRCA1/2 mutation carriers answered the survey. Risk reduction bilateral salpingo-oophorectomy was discussed with 447/489 (91%) of patients and performed in 260/489 (53%). Hormonal replacement therapy was discussed in 280/474 (59%) of patients. Addition of hysterectomy to risk reduction bilateral salpingo-oophorectomy was discussed in 129/481 (27%) of patients and performed in 44/443(10%). Age over 35 years at time of mutation detection was found to be significant in raising risk reduction bilateral salpingo-oophorectomy and hysterectomy performance rates. Risk reduction mastectomy was discussed in 390/471 (83%) of patients and performed in 156/471 (33%). In a multivariate analysis, BRCA1 mutation carriers (OR=1.66 (95% CI 1.07 to 2.57), p=0.024) and a personal cancer history leading to the mutation detection (OR=4.75 (95% CI 1.82 to 12.4), p=0.001) were found to be significant in increasing the likelihood of opting for risk reduction mastectomy. Additionally, highest risk reduction mastectomy performance rates were observed in the group of patients with a first-degree family history of breast cancer under the age of 50 years (OR=1.58 (95% CI 1.07 to 2.32), p=0.01).
This study highlights the high performance rates of risk reduction bilateral salpingo-oophorectomy, while hysterectomy was added in 10%, and that despite high awareness and acceptance rates for risk reduction mastectomy, only 33% had the procedure. The data presented provides insights for the clinician counseling BRCA1/2 mutation carriers, with regards to adherence to recommendations, understanding their concerns towards treatment and management alternatives; and finally, to construct a personalized management medical plan.
Abnormalities in mismatch repair have been described in ovarian cancer, but few studies have examined the causes of mismatch repair deficiency (MMRd). To address this, we completed targeted mutational and methylation sequencing on MMRd ovarian cancer cases. The objective of this study was to explore the molecular mechanism of MMRd using our targeted next generation sequencing panel.
Newly diagnosed non-serous/mucinous ovarian cancers (n=215) were prospectively recruited from three cancer centers in Ontario, Canada, between 2015 and 2018. Tumors were reflexively assessed for mismatch repair protein by immunohistochemistry. Matched tumor–normal MMRd cases were analyzed on a custom next generation sequencing panel to identify germline and somatic mutations, copy number variants, rearrangements, and promoter methylation in mismatch repair and associated genes.
Of 215 cases, 28 (13%) were MMRd. The MMRd cohort had a median age of 52.3 years (range 33.6–62.2), with mostly stage I (50%) and grade 1 or 2 endometrioid histotype (57%). Of the 28 cases, 22 were available for molecular analysis, and Lynch syndrome was detected in 50% of MMRd cases (11/22; seven ovarian cancer and four synchronous ovarian and endometrial cancer: seven MSH6, two MLH1, one PMS2, and one MSH2). An explanation for the observed mismatch repair phenotype was available for 22/22 deficient cases, including 12 MLH1/PMS2 deficient (nine somatic methylation, one bi-allelic somatic deletion, and two pathogenic germline variant), one PMS2 deficient (one pathogenic germline variant), seven MSH6 deficient (seven pathogenic germline variant), and two MSH2/MSH6 deficient (one pathogenic germline variant and one bi-allelic somatic mutation). Concordance between clinical germline testing and panel sequencing results was 100%.
Use of our custom next generation sequencing panel allowed for the streamlined assessment of hereditary and somatic causes of MMRd in ovarian cancers.
The PAOLA-1 trial confirmed that adding olaparib to bevacizumab significantly increased clinical benefit following response to platinum-based chemotherapy in homologous recombination deficiency-positive ovarian cancer. The objective of this analysis was to determine the cost-effectiveness of olaparib plus bevacizumab compared with bevacizumab alone as maintenance treatment for patients with homologous recombination deficiency-positive advanced ovarian cancer from the Spanish National Health System perspective.
A lifetime partitioned survival model with four health states (progression-free, post-progression 1, post-progression 2, and death) and monthly cycles was developed. Long-term survival, defined as 60 months, was included as a landmark to extrapolate progression-free survival from PAOLA-1. Weibull distribution was selected as the most accurate survival model for progression-free survival extrapolation. Time to second progression and overall survival were extrapolated using parametric survival models. Mortality was obtained from the overall survival and adjusted by Spanish women mortality rates. Health state utilities and utility decrements for adverse events were included. An expert panel validated data and assumptions. Direct costs (in 2021 euros ()) were obtained from local sources and included drug acquisition and administration, subsequent therapies, monitoring costs, adverse events, and palliative care. A 3% annual discount rate was applied to costs and outcomes. The incremental cost-effectiveness ratio was calculated as cost per quality-adjusted life-years (QALYs) gained. Deterministic and probabilistic sensitivity analyses were performed.
Compared with bevacizumab alone, olaparib plus bevacizumab increased QALYs and life-years by 2.39 and 2.77, respectively, at an incremental cost of 58 295.31, resulting in an incremental cost-effectiveness ratio of 24 371/QALY. Probabilistic sensitivity analysis demonstrated that olaparib plus bevacizumab had a 49.5% and 90.3% probability of being cost-effective versus bevacizumab alone at a willingness-to-pay threshold of 25 000 and 60 000 per QALY gained, respectively.
For patients with homologous recombination deficiency-positive advanced ovarian cancer, olaparib plus bevacizumab is a cost-effective maintenance therapy compared with bevacizumab alone in Spain.
To determine oncological outcomes and to identify prognostic factors in women aged <45 years with epithelial ovarian cancer.
A multicenter retrospective study was performed of patients treated for epithelial ovarian cancer aged <45 years between January 2010 and December 2019.
A total of 998 patients with epithelial ovarian cancer from 55 different institutions in Spain were collected. The median age of the study population was 40.8 years (range 35.6–43.4). The grouped International Federation of Gynecology and Obstetrics (FIGO) stage distribution was 508 (50.9%) patients in initial stages (I and II) and 490 (49.1%) with advanced stages (III and IV). Three hundred and twenty-five (32.6%) patients presented with recurrent disease after a median follow-up of 33.1 months (range 16.1–66.4). The type of staging surgery (incomplete vs complete), type of initial treatment modality (primary cytoreduction vs interval surgery), and amount of residual disease were all significantly associated with overall survival. Tumor rupture was noted in 288 (27.9%) cases, but it was not associated with oncologic outcomes (p=0.11 for overall survival). In the multivariate analysis, the response based on radiological findings (HR 3.24, 95% CI 2.14 to 4.91 for partial response; HR 6.93, 95% CI 4.79 to 10.04 for progression), neoadjuvant chemotherapy (HR 1.42, 95% CI 1.04 to 1.94), and FIGO stage (HR 1.68, 95% CI 1.40 to 2.02) were identified as independent prognostic factors associated with worse oncologic outcomes (p<0.001).
The partial and progression radiology-based response after chemotherapy, neoadjuvant chemotherapy, and advanced FIGO stage are independent prognostic factors associated with worse oncological outcomes in women aged <45 years with epithelial ovarian cancer.
Retrospective series have shown secondary cytoreductive surgery improves oncological outcomes in recurrent low-grade serous ovarian cancer. We aim to compare surgical procedures and complications between patients with low-grade and high-grade recurrent serous ovarian cancer.
This retrospective single-institution study includes patients with recurrent low-grade and high-grade serous ovarian cancer undergoing surgery between January 2012 to December 2021. Patients were propensity matched 1:3 for residual tumor at first surgery, presence of ascites and performance status. Complexity of surgery and postoperative complications were analyzed.
A total of 116 patients undergoing secondary cytoreductive surgery were included with 29 patients (25%) having low-grade ovarian cancer. The median age of the patients was 54 years (range: 19–85) and 57 years (range: 29–78) in low-grade and high-grade ovarian cancer, respectively (p=0.13). Stages III/IV at diagnosis were more frequent in patients with high-grade ovarian cancers (p<0.001). Peritoneal involvement was higher in low-grade compared with high-grade ovarian cancer as shown by the higher rate of diaphragmatic (41.4% vs 21.8%, p=0.05), abdominal wall (41.4% vs 18.4%, p=0.02) and pelvic (51.7% vs 21.8%, p=0.01) peritonectomy. Multiple bowel resections were higher in low-grade ovarian cancer (24.1% vs 8.0%, p=0.04), while high-grade ovarian cancer had a higher rate of nodal recurrences (73.2%% vs 37.9%, p=0.03). Overall, surgical complexity was higher in low-grade ovarian cancer (58.6% vs 36.8%; p=0.05), with higher median estimated blood loss (400 vs 200 mL; p=0.01) compared with high-grade. Complete cytoreduction was achieved in 26 patients (89.7%) with low-grade and 84 (96.6%) with high-grade (p=0.16) ovarian cancer, with no significant differences in postoperative complications.
Secondary cytoreductive surgery in low-grade serous ovarian cancer patients was associated with higher complexity, multiple bowel resections, and higher median estimated blood loss than in high-grade serous ovarian cancer. The comparable rate of postoperative complications suggests that secondary cytoreductive surgery in this group of patients is feasible in expert centers.
Frailty is more reliable than chronological age in predicting the effectiveness and tolerability of treatments in cancer patients. An increasing number of screening tools have been proposed, however none have received unanimous consent or been specifically designed for women with gynecological malignancies.
This study’s aim was to develop a clinical application of a screening tool to identify frail patients >70 years old diagnosed with either ovarian or endometrial cancers.
A 20 item questionnaire was developed and administered to the cohort before surgery or neoadjuvant chemotherapy. A cut-off for frailty definition was determined by analyzing the correlation of questionnaire scores with the completion of treatments. The association between frailty and treatment related complications was assessed using a Chi-squared test for categorical variables and a t-test for continuous variables.
Our study included 100 patients, 50% diagnosed with endometrial cancer and 50% with ovarian cancer. A questionnaire score of 4 was the best cut-off for frailty definition (sensitivity 77%, specificity 100%). Surgical grade III and grade IV complications were observed only in frail patients (p=0.01) and hospitalization was significantly longer in frail women affected by ovarian cancer (p=0.01). Frail patients were more exposed to chemotherapy administration delay (p=0.0005), treatment discontinuation (p=0.001) and hematological toxicities, especially anemia ≥grade 2 (p=0.009) and thrombocytopenia any grade (p=0.0001).
With a cut-off score of 4, our tool can identify frail patients with significantly higher incidence of grade III-IV postoperative complications, length of stay, medical treatment discontinuation rates and hematological toxicities.
In recent years, the microbiota of the gut and female reproductive tracts have been linked to many diseases, including gynecologic cancers. Numerous pre-clinical and clinical studies have demonstrated that specific bacteria or microbial communities may contribute to the development of gynecologic cancers. Further, the microbiota may also impact the toxicity and efficacy of cancer therapies, including chemotherapy, immunotherapy, and radiation therapy in women with gynecologic malignancies. The microbiota is highly dynamic and may be altered through various mechanisms, including diet, exercise, medications, and fecal microbiota transplantation. This review provides an overview of the current literature detailing the relationship between gynecologic cancers and the microbiota of the female reproductive and gastrointestinal tracts, focusing on mechanisms of carcinogenesis and strategies for modulating the microbiota for cancer prevention and treatment. Advancing our understanding of the complex relationship between the microbiota and gynecologic cancer will provide a novel approach for prevention and therapeutic modulation in the future.
]]>Poly ADP-ribose polymerase inhibitors (PARPi) treatment has radically changed the treatment strategy for epithelial ovarian cancer. Cancer progression with PARPi maintenance is a new problem that has arisen in clinical practice, and the value of secondary cytoreduction surgery remains unknown.
To evaluate the benefits of secondary cytoreductive surgery and to clarify the sensitivity to platinum in patients with firstline or secondline recurrent epithelial ovarian cancer who have completed ≥6 months of PARPi maintenance.
Carefully selected patients who progress on PARPi maintenance will benefit from secondary cytoreductive surgery.
This is a multicenter phase III trial. Eligible patients will be randomly assigned at a ratio of 1:1 to either the experimental or standard arm. Patients in the experimental arm will receive secondary cytoreductive surgery followed by platinum based chemotherapy, while patients in the standard arm will be provided with chemotherapy alone.
Patients diagnosed with firstline or secondline recurrent epithelial ovarian cancer who had previously received ≥4 cycles of platinum based chemotherapy in initial treatment followed by PARPi maintenance therapy for ≥6 months prior to recurrence.
Progression free survival.
400 patients.
Accrual completion is expected in December 2024 with results mature after 2 years of follow-up in 2026.
ClinicalTrials.gov NCT05607329
Cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) is being explored in the upfront, interval, and recurrent setting in patients with ovarian cancer. The objective of this systematic review was to assess the rate of complications associated with HIPEC in epithelial ovarian cancer surgery over two time periods.
This study was registered in PROSPERO (CRD42022328928). A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Ovid/Medline, Ovid/Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials were searched from January 2004 to April 2022. We included studies reporting on patients with advanced primary or recurrent epithelial ovarian cancer who underwent cytoreductive surgery and HIPEC. We evaluated two different time periods: 2004–2013 and 2014–2022. A random-effects meta-analysis was used to produce an overall summary. Subgroup analyses were planned according to recruited period for each specific complication type. Heterogeneity was assessed using the I2 statistic.
A total of 4928 patients were included from 69 studies for this systematic review; 19 published from 2004–2013, and 50 published from 2014–2022. No significant differences were found between the two time periods in terms of blood transfusions (33% vs 51%; p=0.46; I2=95%) overall gastrointestinal complications (15% vs 21%; p=0.36; I2=98%), infectious diseases (16% vs 13%; p=0.62; I2=93%), overall respiratory complications (12% vs 12%; p=0.88; I2=91%), overall urinary complications (6% vs 12%; p=0.06; I2=94%), or thromboembolic events (5% vs 3%; p=0.25; I2=63%). Also, no differences were found in intensive care unit (ICU) admissions (89% vs 28%; p=0.06; I2=99%), reoperations (8% vs 7%; p=0.50; I2=37%), or deaths (3% vs 3%; p=0.77; I2=57%).
Our review showed that overall complications have not changed over time for patients undergoing HIPEC in the setting of primary or recurrent ovarian cancer. There was no decrease in the rates of ICU admissions, reoperations, or deaths.
Our study used human papillomavirus (HPV) genotyping to assess the disease occurrence probability in women with a low-grade squamous intraepithelial lesion (LSIL) without histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+).
This study investigated CIN2+ incidence in 1986 women from January 2005 to August 2016, including 1123 with LSIL who were histology-proven negative and 863 with LSIL who were histology-proven CIN1. Baseline high-risk HPV (HR-HPV) status was determined using the hybrid capture II assay (HC2), and HR-HPV genotype was determined using the HPV DNA chip test (HDC).
Among 1986 women, the HC2 yielded positive results in 1529 (77.0%), while the HDC identified 1624 (81.8%). Thus, the overall HDC and HC2 agreement was 93.2%. Overall, 169 (8.5%) patients developed CIN2+. The 5-year cumulative CIN2+ incidence rates for HPV-16, HPV-18, HPV-31, and HPV-33 were 11.8%, 9.9%, 16.3%, and 16.1%, respectively. Multivariate analysis revealed that HPV-16 (HR 1.637, 95% CI 1.064 to 2.520, p=0.025), HPV-31 (HR 1.845, 95% CI 1.051 to 3.238, p=0.033), and HPV-33 (HR 2.272, 95% CI 1.235 to 4.183, p=0.008) were significantly associated with CIN2+ development.
Among women with LSIL, those who test positive for HPV-16, HPV-31, or HPV-33 may require more rigorous follow-up because of a higher CIN2+ risk.
We investigated the utility of telehealth instruction versus mail-based written instruction in facilitating high-risk human papillomavirus (hrHPV) self-collection among post-menopausal patients compared with pre-menopausal patients, as well as the impact on acceptability and feasibility.
We conducted a prospective, randomized study of people eligible for cervical cancer screening, stratified by menopausal status, to undergo standard written or telehealth-based instructions for hrHPV self-collection. English speaking individuals residing in Oregon, with a cervix, eligible for primary hrHPV testing, and with access to a video-capable device were included. Patients with prior hysterectomy, trachelectomy, diagnosis of cervical cancer, or pelvic radiation for gynecologic cancer were excluded. We compared preference for and opinions about self-collection and hrHPV test results, by randomization group and stratified by menopausal status using descriptive statistics.
Among 123 patients enrolled, 61 identified as post-menopausal with a median age of 57 years. While the majority of post-menopausal participants who received telehealth instructions found it helpful, only 6.1% considered telehealth instructions necessary to complete self-testing. There was no difference in opinion of telehealth by menopausal status. Overall, 88.5% of post-menopausal participants preferred self-collection to provider-collection. There were no significant differences between pre- and post-menopausal participants in terms of test preference, discomfort, ease of use, or perceptions of self-collection.
Telehealth instruction did not add significant value to patients participating in hrHPV self-collection, nor did it alter the acceptability of hrHPV-self collection among an English-speaking cohort. Compared with prior experiences with provider-collected screening, hrHPV self-collection was preferred by both pre- and post-menopausal participants. There were no significant differences in preference for provider- versus self-collection when stratified by menopausal status.
To evaluate the detection rate of at least one sentinel lymph node (SLN) in patients with early cervical cancer who underwent open radical hysterectomy or trachelectomy using indocyanine green (ICG) with the SPY Portable Handler Imager (SPY-PHI) system.
We retrospectively reviewed patients with cervical cancer FIGO 2018 stage IA1 with lymphovascular invasion up to stage IIIC1p who underwent SLN mapping and open radical hysterectomy or trachelectomy from March 2018 through August 2022 at The University of Texas MD Anderson Cancer Center. ICG was the only tracer used with the SPY-PHI system. Patient demographics, surgical approach, and tumor factors were analyzed. Overall detection, bilateral detection, and empty lymph node packet rates were determined.
A total of 106 patients were included. Ninety-four (88.7%) patients underwent open radical hysterectomy and 12 (11.3%) open radical trachelectomy. Median age was 40 years (range, 23–71). Median body mass index was 28.8 kg/m2 (range, 17.6–48.4). The most common FIGO 2018 stages were IB1 (35%) and IB2 (30%). The most common histologic subtypes were squamous cell carcinoma (45%) and adenocarcinoma (45%). Most patients had grade 2 disease (61%) and no lymphovascular invasion (58%). Median tumor size was 1.8 cm (range, 0.3–4). Median number of detected SLN was 4 (range, 0–12). An SLN was identified during surgery in 104 patients (98%), with bilateral mapping in 94 (89%) and unilateral mapping in 10 (9%). The empty lymph node packet rate was 4 (3.8%). The external iliac (73%) was the most common site of SLN detection. Fourteen patients had positive lymph nodes (13.5%); 3 (21.4%) had macrometastases, 9 (64.3%) had micrometastases, and 2 (14.3%) had isolated tumor cells.
SLN mapping using ICG with the SPY-PHI system in open radical hysterectomy or trachelectomy is reliable and results in high overall and bilateral detection rates in patients with early cervical cancer.
The objective of this systematic review was to evaluate the effect of different types of neoadjuvant chemotherapy regimens, in terms of optimal pathological response and oncological outcomes, in patients with locally advanced cervical cancer.
A systematic search of the literature was performed. MEDLINE through PubMed and Embase databases were searched from inception to June 2023. The study was registered in PROSPERO (ID number CRD42023389806). All women with a pathological diagnosis of locally advanced cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009 classification stages IB2-IVA), any age or histology, who underwent intravenous neoadjuvant chemotherapy before radical surgery, and articles only in English language, were included. We conducted a meta-analysis for optimal pathological response after surgery and survival outcomes. The risk of bias was assessed using the Newcastle-Ottawa scale and the Risk of Bias 2 (RoB) tools. The review methods and results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
25 studies with a total number of 1984 patients fulfilled the eligibility criteria of our review and were included for data extraction and efficacy analysis. When compared with a two-drug regimen, the three-drug combination including cisplatin, paclitaxel, and ifosfamide or anthracyclines showed superior efficacy in terms of optimal pathological response with an odds ratio of 0.38 (95% CI 0.24 to 0.61, p<0.0001), with no difference in disease-free survival (hazard ratio (HR) 0.72, 95% CI 0.50 to 1.03, I2=0%, p=0.07) and higher overall survival (HR 0.63, 95% CI 0.41 to 0.97, I2=0%, p=0.03).
The three-drug combination of cisplatin, paclitaxel, and ifosfamide or anthracyclines showed a higher rate of complete or optimal partial response, with the triple regimens having an advantage over the platinum-based schedules in terms of overall survival. Neoadjuvant chemotherapy followed by radical surgery should not be considered a standard of care in locally advanced cervical cancer.
To evaluate the role of dose-dense neoadjuvant chemotherapy followed by radical hysterectomy in reducing adjuvant radiotherapy in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB1-IB2/IIA1 cervical cancer with disrupted stromal ring and as an alternative to concurrent chemoradiotherapy in FIGO 2018 stages IB3/IIA2.
This was a retrospective cohort study including patients with FIGO 2018 stage IB1-IIA2 cervical cancer undergoing dose-dense neoadjuvant chemotherapy at the European Institute of Oncology in Milan, Italy between July 2014 and December 2022. Weekly carboplatin (AUC2 or AUC2.7) plus paclitaxel (80 or 60 mg/m2, respectively) was administered for six to nine cycles. Radiological response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria. The optimal pathological response was defined as residual tumor ≤3 mm. Kaplan–Meier curves were used to estimate survival rates. A systematic literature review on dose-dense neoadjuvant chemotherapy before surgery for cervical cancer was also performed.
A total of 63 patients with a median age of 42.8 years (IQR 35.3–47.9) were included: 39.7% stage IB-IB2/IIA1 and 60.3% stage IB3/IIA2. The radiological response was as follows: 81% objective response rate (17.5% complete and 63.5% partial), 17.5% stable disease, and 1.6% progressive disease. The operability rate was 92.1%. The optimal pathological response rate was 27.6%. Adjuvant radiotherapy was administered in 25.8% of cases. The median follow-up for patients who underwent radical hysterectomy was 49.7 months (IQR 16.8–67.7). The 5-year progression-free survival and overall survival were 79% (95% CI 0.63 to 0.88) and 92% (95% CI 0.80 to 0.97), respectively. Fifteen studies including 697 patients met the eligibility criteria for the systematic review. The objective response rate, operability rate, and adjuvant radiotherapy rate across studies ranged between 52.6% and 100%, 64% and 100%, and 4% and 70.6%, respectively.
Dose-dense neoadjuvant chemotherapy before radical surgery could be a valid strategy to avoid radiotherapy in stage IB1-IIA2 cervical cancer, especially in young patients desiring to preserve overall quality of life. Prospective research is warranted to provide robust, high-quality evidence.
This study aimed to examine the correlation between malignant peritoneal cytology and overall survival among patients with uterine leiomyosarcoma and endometrial stromal sarcoma.
Patients with uterine leiomyosarcoma and endometrial stromal sarcoma between January 2010 and December 2016 were identified from the Surveillance, Epidemiology, and End Results database. The multiple imputation method was used to address missing values. Propensity score matching was conducted to balance baseline data between the malignant and negative peritoneal cytology groups. The prognostic significance of malignant peritoneal cytology was evaluated using Cox regression, random survival forest, and subgroup analyses.
Among 733 eligible patients, 8% (59/733) had malignant peritoneal cytology, increasing to 20% (42/209) in advanced cases. Before and after propensity score matching, patients with malignant peritoneal cytology had significantly lower 5-year overall survival rates and shorter median survival time than patients with negative peritoneal cytology. Multivariate Cox regression revealed that malignant peritoneal cytology (hazard ratio 2.03, 95% confidence interval 1.29 to 3.20, p=0.002) was an independent prognostic factor for uterine leiomyosarcoma and endometrial stromal sarcoma. Random survival forest further indicated that, among the factors analyzed, peritoneal cytology status was second only to the International Federation of Gynecology and Obstetrics (FIGO) stage in terms of prognostic prediction. Finally, subgroup analyses substantiated the correlation between malignant peritoneal cytology and unfavorable overall survival in most subgroups.
Malignant peritoneal cytology status was an important prognostic factor complementing FIGO stage and was associated with a reduction in overall survival. Peritoneal cytology evaluation during hysterectomy may be recommended for prognosis estimation for uterine leiomyosarcoma and endometrial stromal sarcoma.
This systematic review and meta-analysis aimed to assess the rate of sentinel lymph node (SLN) metastases in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia and endometrial cancer in hysterectomy specimens.
A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and the protocol was registered in PROSPERO (CRD42023416769). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2023. The inclusion criteria were patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia undergoing hysterectomy who did or did not undergo SLN assessment.
Four studies met the inclusion criteria. All studies were non-randomized studies with a total of 10 217 patients, 1044 in the SLN group and 9173 in the non-nodal assessment group. The unilateral and bilateral detection rate was 89% (I2=27.6%, 2 studies, 342 participants, 304 events) and 79% (I2=89.2%, 2 studies, 342 participants, 271 events), respectively. The rate of involved SLNs was 1.6% (I2=0%, 3 studies, 424 participants, 7 involved SLN) and 3.5% (I2=0%, 3 studies, 197 participants, 7 involved SLN) in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia as the denominator and in those with endometrial cancer in the hysterectomy specimen, respectively. The cancer rate in the hysterectomy specimen was 45% (I2=72.8%, 3 studies, 503 participants, 224 events) and the most frequent endometrial cancer International Federation of Gynecology and Obstetrics 2009 stage was IA in 199 (89.2%) patients. The complication rate was similar between the groups.
The rate of SLN metastases in patients with pre-operative atypical hyperplasia/endometrial intra-epithelial neoplasia is less than 2%, suggesting that routine SLN evaluation may not be necessary in this population.
To develop and test a novel instrument to assess public awareness of endometrial cancer symptoms and risk factors in a UK population.
A 36-item questionnaire was developed through literature review and extraction from cancer awareness materials. The Womb Cancer Awareness Measure (WCAM) was tested for content validity in 65 self-identified female research participants and 10 endometrial cancer experts prior to UK-wide field testing using social media. Test-retest reliability was assessed over 2 weeks, construct validity was assessed by comparing womb cancer experts and non-medical academics, and sensitivity to change was assessed by comparing scores of participants who read an endometrial cancer leaflet with those given a control leaflet.
Fifty-two percent of the items in the test-retest reliability showed >80% agreement. Construct validity was demonstrated; endometrial cancer experts achieved higher scores (median 79 (IQR 18)) than non-medical academics (median 50 (IQR 18)) (p<0.001). The WCAM was sensitive to change; volunteers who read an endometrial cancer leaflet showed greater awareness (median 73 (IQR 9)) than those who read the control leaflet (median 59 (IQR 9)) (p<0.001). Knowledge of endometrial cancer red flag symptoms and risk factors was poor in the 847 UK-based participants.
Our findings support the validity and reliability of the Womb Cancer Awareness Measure in assessing public awareness of endometrial cancer. In a UK population sample, knowledge of warning symptoms and risk factors was low, highlighting the need for public awareness campaigns.
Sentinel lymph node mapping by intracervical indocyanine green injection is the preferred method for surgical staging in endometrial cancer. Adverse reactions to indocyanine green are extremely rare, and information about the safety of this tracer in patients with a history of other allergies, asthma, or comorbidities is limited. We aim to evaluate the rate of adverse reactions to indocyanine green injected during sentinel lymph node mapping in patients with endometrial cancer and review the etiology of such reactions.
All patients with endometrial cancer undergoing sentinel lymph node mapping with indocyanine green cervical stroma injection at the Mayo Clinic in Rochester, Minnesota between June 2014 and December 2018 were retrospectively evaluated. Any adverse reaction occurring intra-operatively or within 7 days after surgery was identified. A thorough chart review was performed by an allergy specialist physician for any patient with an allergic-type reaction.
We included 923 patients of which 565 (61.2%) had a history of allergy to antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), other medications, and/or environmental exposures. Of 490 patients who had previously received contrast media, 25 (5.1%) had a history of an adverse reaction. No immediate anaphylaxis or other allergic reactions were observed after indocyanine green injection. 10 (1.1%) patients developed a transient skin reaction within 7 days after surgery. None of these patients had a history of contrast media reaction. Based on timing and clinical/peri-operative history of affected patients, it was determined that skin reactions were likely induced by other newly prescribed medications or contact sensitivity, not administration of indocyanine green.
Indocyanine green injection for sentinel lymph node mapping in patients with endometrial cancer caused no immediate/delayed anaphylactic or other severe allergic reactions. This included patients with a history of other allergies, asthma, and comorbidities. The myth of iodine’s relationship to allergic reactions must be refuted to allow indocyanine green use in patients with a history of contrast media or shellfish allergy.
To evaluate disease characteristics and survival according to BRCA status, administration of poly-(ADP-ribose) polymerase inhibitors (PARPi), and surgery in patients with ovarian cancer and brain metastases.
This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) BRCA mutation; (2) PARPi before and after brain metastases; (3) surgery for brain metastases.
Eighty-five patients with ovarian cancer and brain metastasis and known BRCA status (31 BRCA mutated (BRCAm), 54 BRCA wild-type (BRCAwt)) were analyzed. Twenty-two patients had received PARPi before brain metastases diagnosis (11 BRCAm, 11 BRCAwt) and 12 after (8 BRCAm, 4 BRCAwt). Brain metastases occurred >1 year later in patients who had received previous PARPi. Survival was longer in the BRCAm group (median post-brain metastasis survival: BRCAm 23 months vs BRCAwt 8 months, p=0.0015). No differences were found based on BRCA status analyzing the population who did not receive PARPi after brain metastasis (median post-brain metastasis survival: BRCAm 8 months vs BRCAwt 8 months, p=0.31). In the BRCAm group, survival was worse in patients who had received previous PARPi (median post-brain metastasis survival: PARPi before, 7 months vs no-PARPi before, 24 months, p=0.003). If PARPi was administered after brain metastases, survival of the overall population improved (median post-brain metastasis survival: PARPi after, 46 months vs no-PARPi after, 8 months, p=0.00038).
In cases of surgery for brain metastases, the prognosis seemed better (median post-brain metastasis survival: surgery 13 months vs no-surgery 8 months, p=0.036). Three variables were significantly associated with prolonged survival at multivariate analysis: BRCA mutation, multimodal treatment, and ≤1 previous chemotherapy line.
BRCA mutations might impact brain metastasis occurrence and lead to better outcomes. In a multimodal treatment, surgery seems to affect survival even in cases of extracranial disease. PARPi use should be considered as it seems to prolong survival if administered after brain metastasis.
To compare surgery and survival outcomes between neoadjuvant chemotherapy and primary debulking surgery in patients with advanced ovarian yolk sac tumor.
In this retrospective cohort analysis, patients with stage III to IV ovarian yolk sac tumor or mixed germ cell tumors containing yolk sac tumor elements, and who underwent surgery at Peking Union Medical College Hospital between January 2011 and December 2021, were identified. Patient characteristics, treatment, and survival data were analyzed between the two groups.
A total of 40 patients were enrolled: 19 patients received neoadjuvant chemotherapy followed by interval surgery, and 21 patients were treated with primary debulking surgery. After neoadjuvant chemotherapy, the surgical conditions of patients were improved. All patients achieved cytoreduction to R0 or R1 at interval surgery. No statistical difference was found in 3-year disease-free survival and overall survival between the neoadjuvant chemotherapy group and the primary debulking surgery group (log rank p=0.4 and 0.94). Patients had less blood loss (328.4 vs 1285.7 mL, p=0.029), lower transfusion volume (1044.4 vs 3066.7 mL, p=0.011), and fewer peri-operative complications (15.8% vs 47.6%, p=0.032) at the interval debulking surgery after neoadjuvant chemotherapy compared with patients who underwent primary debulking surgery.
For patients with advanced-stage ovarian yolk sac tumor, neoadjuvant chemotherapy followed by interval surgery is an alternative option, especially for those who cannot tolerate the primary debulking surgery because of high tumor burden and vulnerable status.
In Belgium there is no centralization of surgery for ovarian cancer, with more than 100 centers treating around 800 cases per year. In 2017 a network with several collaborating hospitals was established to centralize surgery for ovarian cancer (UCLouvain Network of Gynecological Oncology; UNGO) following publication of the European Society of Gynecological Oncology (ESGO) recommendations and quality criteria for surgery of advanced ovarian cancer. We obtained ESGO accreditation in 2019.
We retrospectively collected data associated with patients undergoing surgery in our institution from 2007 to 2016, before the creation of the network (cohort 1) and, following the establishment of UNGO (2017–2021), patients undergoing surgery were prospectively registered in a REDCap database (cohort 2). The outcomes of the two cohorts were compared.
A total of 314 patients underwent surgery in our institution from 2007 and 2021: 7.5 patients/year in cohort 1 (retrospective, 2007–2016) and 40.8 patients/year in cohort 2 (after network creation, 2017–2021). Median disease-free survival was increased from 16.5 months (range 13.2–20.4) in cohort 1 to 27.1 months (range 21.5–33.2) in cohort 2 (p=0.0004). In cohort 2, the rate of patients with residual disease at the end of the surgery was significantly less (18.7% vs 8.8%, p=0.023), although more patients in cohort 1 received neoadjuvant chemotherapy (89% vs 54%, p<0.001). However, there was a higher rate of complications in the patients in cohort 2 (18.8% vs 30%, p=0.041).
Our study shows that, with the help of ESGO and its recommendations, we have been able to create an efficient advanced ovarian cancer centralized network and this may provide an improvement in the quality of care.
We sought to investigate the safety and feasibility of therapeutic anticoagulation for newly diagnosed venous thromboembolism among women who undergo neoadjuvant chemotherapy for the treatment of advanced ovarian cancer.
A retrospective study using data extrapolated from a prospectively maintained institutional database was used to identify all patients with ovarian cancer who underwent neoadjuvant chemotherapy from April 2015 through September 2018 at our institution. All patients who received therapeutic anticoagulation for newly diagnosed venous thromboembolism at initial diagnosis or during neoadjuvant chemotherapy were included.
Of 290 patients who underwent neoadjuvant chemotherapy for advanced ovarian cancer during the study period, 67 (23%) had newly diagnosed venous thromboembolism at the time of initial diagnosis or developed venous thromboembolism during neoadjuvant chemotherapy. Of these 67 patients, 64 (96%) received therapeutic anticoagulation. A total of 13 (20%) of 64 patients who underwent therapeutic anticoagulation experienced a bleeding episode while on anticoagulation; 4 (31%) of the 13 events were of major severity. Three patients developed major internal bleeding in the peritoneal cavity, and one patient suffered from a major vaginal bleeding episode. All four patients were hospitalized (range, 5–11 days) and received ≥2 units of red blood cells for anemia. None of these patients died from fatal bleeding or had to delay starting chemotherapy. Of note, all four patients received low-molecular-weight heparin via subcutaneous injection. Overall, 13 (20%) of 64 patients required an anticoagulant dose reduction, mostly due to weight loss or new bleeding episodes.
Therapeutic anticoagulation in this setting appeared safe, with a low risk of major bleeding complications. Furthermore, anticoagulation did not result in delay of chemotherapy or cytoreductive surgery.
Primary debulking surgery has been the preferred surgical route and is still considered a quality indicator for advanced ovarian cancer surgery. However, a significant number of patients are not amenable to upfront surgery. Neoadjuvant chemotherapy and interval debulking surgery may be the most suitable approach for this group. This study aimed to evaluate a novel score for prediction of the cytoreduction results at primary debulking surgery for ovarian cancer patients.
This observational prospective study was conducted at a tertiary gynecologic oncology center between December 2020 and August 2022. Presumed primary stage III-IV epithelial ovarian carcinoma cases were included. Borderline tumors, and metastatic or non-epithelial ovarian malignancies, were excluded. Based on imaging findings, points were assigned to each anticipated surgical procedure required for complete cytoreduction. The sum of these points was multiplied by the patient’s Eastern Cooperative Oncology Group (ECOG) score, and thus, the Cukurova-clinic score was established. Furthermore, the required surgical procedures based on laparoscopic evaluation were recorded, and the score was readjusted and calculated to obtain the Cukurova score.
One hundred and fourteen patients were included in the study. Primary debulking surgery was performed in 70% of cases. Among them, complete cytoreduction (Cukurova score ≤12) was obtained in 97.3% of cases. Complete cytoreduction was not achieved in cases with Cukurova score >12. The odds ratio of 90-day mortality was 13.4 for patients with Cukurova score >12, compared with those with Cukurova score ≤12.
The Cukurova score is a model for classifying advanced ovarian cancer patients who may be candidates for primary debulking surgery.
Our objective was to use real-world data to investigate the impact of delayed interval cytoreductive surgery on the survival of patients with advanced stage high-grade ovarian carcinoma.
We accessed the National Cancer Database and identified patients diagnosed between 2004–2015 with advanced stage high-grade ovarian carcinoma who received neoadjuvant chemotherapy and underwent interval cytoreductive surgery. Based on timing between surgery and chemotherapy administration patients were categorized into standard (9–13.0 weeks) and delayed (13.01–26 weeks) interval cytoreductive surgery groups. Overall survival was compared with the log-rank test and a Cox model was constructed to control for a priori selected confounders.
We identified a total of 5051 patients; 2389 (47.3%) and 2662 (52.7%) in the standard and delayed interval cytoreductive surgery groups respectively. There was no difference in complete gross resection rates (53.2% vs 54.5%, p=0.51). Patients in the delayed interval cytoreductive surgery group were less likely to undergo complex surgery (39.3% vs 45.6%, p<0.001) and had lower rates of unplanned re-admission (4.1% vs 2.6%, p=0.003). There was no difference in overall survival between the standard and delayed interval cytoreductive surgery groups, p=0.13 (median 34.3 vs 33.9 months) even after controlling for confounders (hazard ratio (HR) 1.04, 95% confidence intervals (CIs): 0.97, 1.12). There was no difference in overall survival between the two groups for patients with no gross residual (p=0.95; median overall survival 40.08 vs 39.8 months) or gross residual disease (p=0.16; median overall survival 32.89 and 32.16 months).
For patients with advanced stage ovarian cancer delayed interval cytoreductive surgery may not be associated with worse overall survival.
The objective of this review is to discuss the burden of pelvic floor disorders in the gynecologic population and to contextualize these needs within broader survivorship needs. The review will then discuss current strategies of survivorship care, including a discussion of whether these methods meet survivorship pelvic floor disorder needs. This review addresses several gaps in the literature by contextualizing pelvic floor disorder needs within other survivorship needs and providing a critical discussion of current survivorship care strategies with a focus on pelvic floor disorders.
]]>To evaluate the feasibility of uterine transposition as a method of preserving fertility and ovarian function after pelvic radiation.
This prospective multicenter observational study included patients with non-gynecologic pelvic cancers who underwent pelvic radiation as part of their cancer treatment between June 2017 and June 2019. For inclusion in the study, patients were required to have normal menstrual cycles and hormone levels (follicle-stimulating hormone, luteinizing hormone, and estrogen) before treatment. Uterine transposition to the upper abdomen was performed prior to irradiation. Clinical examinations and Doppler ultrasonography were used to evaluate the gonadal vasculature post-surgery. The uterus was repositioned into the pelvis 2–4 weeks after radiation therapy or at the time of rectosigmoid resection in patients with rectal cancer who had undergone neoadjuvant treatment. Cancer treatment and follow-up were performed according to standard guidelines.
Eight patients (seven with rectal cancer and one with pelvic liposarcoma) underwent uterine transposition at a median age of 30.5 years (range 19–37). The uterus was successfully preserved in six patients, accompanied by normal menses, hormonal levels, and vaginal intercourse after treatment. One patient with rectal cancer died of carcinomatosis 4 months after uterine transposition. One patient presented with uterine necrosis 4 days after uterine transposition, and the uterus was removed; however, one ovary was preserved. Cervical ischemia was the most common post-surgical complication in three (37.5%) patients. Three patients attempted to conceive, and two (66%) were spontaneously successful and delivered healthy babies at 36 and 38 weeks by cesarean section without complications.
Uterine transposition is a feasible procedure for preserving gonadal and uterine function in patients requiring pelvic radiotherapy for non-gynecological cancer, with the potential for achieving spontaneous pregnancy and successful delivery.
To assess detection rates and negative predictive values of sentinel node biopsy in vulvar squamous cell carcinoma with tumors ≥4 cm, multifocal tumors, and in locally recurrent disease.
Between December 2019 and December 2022, patients with vulvar squamous cell carcinoma with tumors ≥4 cm (group 1), multifocal tumors (group 2), or a first local recurrence without or with previous groin treatment (groups 3 and 4, respectively) were included in a prospective, nationwide multicenter interventional pilot study. The participants underwent a sentinel node biopsy followed by inguinofemoral lymph node dissection. Detection rates, negative predictive values, the proportion of micrometastases, and isolated tumor cells were determined separately for each group.
In all, 64 women were included, 36 women in group 1 (56%), and 17 women in group 2 (27%). Due to the small number and heterogeneity of the 11 women in groups 3 and 4, they were excluded from further analyses. In groups 1 and 2, 25 women (47%) were diagnosed with node-positive disease, and in 16 women (64%) only in the sentinel nodes. The detection rates varied between 94.1–100% per patient and 84.1–85.3% per groin. No false-negative sentinel nodes were identified, giving a negative predictive value of 100% for group 1 (95% CI 91.2% to 100%) and for group 2 (95% CI 83.9% to 100%). Of the node-positive patients, 32% had micrometastasis or isolated tumor cells only. One third of the metastases were detected by ultrastaging. In 27% of the non-mapping groins, metastases were found in the lymphadenectomy specimen, and in 75% the metastases showed extranodal growth.
In this small cohort of patients, we provide further data that may widen the indication of the sentinel node technique to women with tumors ≥4 cm and multifocal tumors.
Sentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy alone versus pelvic lymphadenectomy is missing.
To investigate, with this meta-analysis, the impact of sentinel lymph node biopsy alone versus pelvic lymphadenectomy on survival for patients with early-stage cervical cancer.
A systematic literature review was performed. We excluded studies in which pelvic lymphadenectomy was systematically performed after every sentinel lymph node biopsy, including only articles where pelvic lymphadenectomy was performed because sentinel lymph node biopsy was not conclusive. A meta-analysis was carried out combining 5-year disease-free survival and overall survival rates with a random and fixed effect model. Heterogeneity was tested using the Cochran X2 test and quantified with Higgins information I2.
The search of databases and registers found 927 items and six articles (two retrospective and four prospective). The median time of follow-up was 34.8 months (range 13–53). Overall common effect disease-free survival was 98% while random effect disease-free survival was 94%. Overall heterogeneity was 77%. A subgroup analysis was applied, dividing studies into one group including sentinel lymph node biopsy negative data only (common effect disease-free survival 91%; random effect disease-free survival 90%), and one group with a negative and positive sentinel lymph node biopsy (common effect disease-free survival 98%; random effect disease-free survival 96%). In the analysis of overall survival, positive and negative sentinel lymph node biopsy cases were examined together (common and random effect overall survival 99%). Ultrastaging did not affect disease-free survival (common and random effect disease-free survival 92% in the ultrastaging group vs common effect disease-free survival 99% and random effect disease-free survival 96% in the non-ultrastaging group).
Both 5-year disease-free survival and overall survival rate after sentinel lymph node biopsy alone are higher than 90% and do not differ from pelvic lymphadenectomy survival data. Ultrastaging did not impact survival.
There is an unmet need to improve clinical outcomes for patients with recurrent/metastatic cervical cancer. Checkpoint inhibitors represent a promising treatment strategy. We evaluated the safety and anti-tumor activity of zimberelimab, an anti-programmed cell death protein-1 antibody, in patients with previously treated, recurrent, metastatic cervical cancer.
This phase II, single-arm, open-label study used a Simon two-stage minimax design. Eligible patients were women aged 18–75 years with programmed death ligand-1-positive recurrent or metastatic cervical cancer that had progressed after first- or subsequent-line chemotherapy (Eastern Cooperative Oncology Group (ECOG) performance status 0–1). Patients received intravenous zimberelimab (240 mg every 2 weeks) for 2 years until disease progression, intolerable adverse effects, or withdrawal from the study. The primary endpoint was objective response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, by an independent review committee.
A total of 105 patients were enrolled. Median age was 51 (range, 31–75) years; 63.8% had an ECOG performance status of 1. The median number of previous treatment lines was 1 (range, 1–4). Median follow-up was 16.9 (range, 16.3–18.4) months. The objective response rate was 27.6%, and the disease control rate was 55.2%. Median duration of response was not reached. Median overall survival was 16.8 months, and median progression-free survival was 3.7 months. The incidence of treatment-related adverse events of any grade was 78.1%, of which the most common were hypothyroidism (26.7%) and anemia (19.0%).
Zimberelimab monotherapy demonstrated durable anti-tumor activity and an acceptable safety profile in patients with cervical cancer.
To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally.
Women aged 30–49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected.
Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30–49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self-collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV-positive patients, 2588 (92.3%) returned for all steps of their diagnostic work-up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty-one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology.
It is feasible to perform cervical cancer screening with primary HPV testing and follow-up in low-resource settings. Participants preferred self-collection, and the majority of screen-positive patients completed all steps of their diagnostic work-up and treatment. Our findings provide important information for further implementation and scale-up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.
To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer.
All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained.
Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY.
In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.
Pregnancy loss, occurring after miscarriage or after gestational trophoblastic disease, has a psychological impact. Besides pregnancy loss, women diagnosed with gestational trophoblastic disease have to deal with a prolonged period of follow-up and potential advice to postpone a future pregnancy. We studied the severity and course of the psychological impact after gestational trophoblastic disease and miscarriage, to identify whether women with gestational trophoblastic disease need different psychological care.
A prospective multicenter study using online questionnaires was performed. Women diagnosed with gestational trophoblastic disease or miscarriage received the following questionnaires directly after diagnosis, and after 6, 6, and 12 months: a self-report questionnaire, the Hospital Anxiety and Depression Scale (HADS), the Impact of Event Scale, and the Reproductive Concerns Scale.
74 women with gestational trophoblastic disease and 76 women with miscarriage were included. At baseline, the proportion of women scoring above the cut-off level for the anxiety subscale of the HADS and for the Impact of Event Scale was significantly higher for women with gestational trophoblastic disease than for women after miscarriage (43.2% vs 28.9%, p=0.02 and 87.8% vs 78.9%, p=0.03, respectively). During follow-up, the differences between both groups vanished and only the Impact of Event Scale after 12 months remained significantly different between women with gestational trophoblastic disease and women after miscarriage (62.7% vs 37.3%, p=0.005). All outcomes, except the Reproductive Concerns Scale, showed a significant decline. However, in women who scored above the cut-off level on the HADS-total or Impact of Event Scale at baseline, and women with psychological or psychiatric history, significant higher scores persisted.
Although women with gestational trophoblastic disease at baseline had more anxiety and distress than women after miscarriage, no significant differences were seen using the HADS-total after 12 months. Using the HADS or Impact of Event Scale directly after pregnancy loss is helpful to identify women at risk of remaining psychological symptoms to provide them with extra psychological support.
To determine the diagnostic value of whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) to predict resectable disease at the time of secondary cytoreductive surgery for relapsed epithelial ovarian cancer with a platinum-free interval of at least 6 months.
A retrospective cohort study between January 2012 and December 2021 in a tertiary referral hospital. Inclusion criteria were: (a) first recurrence of epithelial ovarian cancer; (b) platinum-free interval of ≥6 months; (c) intent to perform secondary cytoreductive surgery with complete macroscopic resection; and (d) WB-DWI/MRI was performed.
Diagnostic tests of WB-DWI/MRI for predicting complete resection during secondary cytoreductive surgery are calculated as well as the progression-free and overall survival of the patients with a WB-DWI/MRI scan that showed resectable disease or not.
In total, 238 patients could be identified, of whom 123 (51.7%) underwent secondary cytoreductive surgery. WB-DWI/MRI predicted resectable disease with a sensitivity of 93.6% (95% confidence interval [CI] 87.3% to 96.9%), specificity of 93.0% (95% CI 87.3% to 96.3%), and an accuracy of 93.3% (95% CI 89.3% to 96.1%). The positive predictive value was 91.9% (95% CI 85.3% to 95.7%).
Prediction of resectable disease by WB-DWI/MRI correlated with improved progression-free survival (median 19 months vs 9 months; hazard ratio [HR] for progression 0.36; 95% CI 0.26 to 0.50) and overall survival (median 75 months vs 28 months; HR for death 0.33; 95% CI 0.23 to 0.47).
WB-DWI/MRI accurately predicts resectable disease in patients with a platinum-free interval of ≥6 months at the time of secondary cytoreductive surgery and could be of complementary value to the currently used models.
The aim of this study was to provide real-world efficacy and safety data on niraparib maintenance treatment in patients with non-germline (gBRCA)1/2 mutated platinum-sensitive recurrent ovarian cancer.
This retrospective multi-center cohort study included 94 platinum-sensitive recurrent ovarian cancer patients without known gBRCA1/2 mutation treated in an individual patient access program in Norway. The primary outcome was time from start of niraparib treatment to first subsequent treatment. Secondary endpoints included progression-free survival, safety, and tolerability.
After median follow-up of 13.4 months (95% confidence interval (CI) 10.0 to 16.8), 68.1% had progressed and 22.3% had died. Of the entire cohort, 61.7% had commenced a new line of treatment, and 24.5% were still receiving niraparib. The median duration of niraparib treatment was 5.0 months (range 0.4 to 27.3), and the median time to first subsequent treatment was 10.7 months (95% CI 8.4 to 13.0). Patients with elevated CA125 prior to start of niraparib had shorter time to first subsequent treatment (7.3 months, 95% CI 4.2 to 10.3) than patients with normalized CA125 (12.2 months, 95% CI 10.9 to 13.7 (p=0.002). Patients who started on individual dose based on weight and platelet counts had fewer dose reductions (p<0.001) and interruptions (p=0.02).
In a real-world setting, niraparib maintenance treatment in patients with non-gBRCA1/2 mutated recurrent platinum-sensitive ovarian cancer showed effectiveness comparable with published phase III studies and acceptable safety. Individualized dosing is essential to minimize adverse events. CA125 levels at start of niraparib treatment may help to estimate the individual prognosis.
To investigate the use and outcomes of adjuvant chemotherapy for patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery.
Patients diagnosed between 2010 and 2015 with International Federation of Gynecology and Obstetrics stage II–IV low-grade serous ovarian carcinoma who underwent primary debulking surgery with known residual disease status and had at least 1 month of follow-up were identified in the National Cancer Database. Adjuvant chemotherapy was defined as receipt of chemotherapy within 6 months of surgery. Overall survival was evaluated using the Kaplan-Meier method and compared with the log-rank test. A Cox model was constructed to control for a priori-selected confounders. A systematic review of the literature was also performed.
In total, 618 patients with stage II–IV low-grade serous ovarian carcinoma who underwent primary cytoreductive surgery were identified; 501 (81.1%) patients received adjuvant chemotherapy, while 117 (18.9%) patients did not. The median follow-up of the present cohort was 47.97 months. There was no difference in overall survival between patients who did and did not receive adjuvant chemotherapy (p=0.78; 4-year overall survival rates were 77.5% and 76.1%, respectively). After controlling for patient age, medical co-morbidities, disease stage, and residual disease status, administration of adjuvant chemotherapy was not associated with better overall survival (HR=0.87, 95% CI 0.55 to 1.38). Based on data from three retrospective studies, omission of adjuvant chemotherapy following cytoreductive surgery was not associated with worse progression-free survival benefit (HR=1.25, 95% CI 0.80 to 1.95) for patients with stage III–V low-grade serous ovarian carcinoma.
Adjuvant chemotherapy may not be associated with an overall survival benefit for patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery.
To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers.
A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics.
A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival.
Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer.
The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).
Sertoli–Leydig cell tumors are rare tumors of the ovary. Moderate and poorly differentiated tumors can metastasize and have a poor outcome. A pathogenic variant in DICER1 is associated with an increased risk of developing these tumors along with other clinical phenotypes. We aimed to describe a national cohort of all Sertoli–Leydig cell tumors with regard to clinicopathological characteristics and frequency of DICER1 pathogenic variants.
In May 2018, all patients registered from January 1997 to December 2017 with the Systematized Nomenclature of Medicine code M86310 (Sertoli–Leydig cell tumor) were obtained from the Danish National Pathology Registry. Validation of the diagnosis depended on comments in the reports that two pathologists validated the initial diagnosis or revision of the pathology at another facility. We performed descriptive statistics to describe baseline characteristics, and cancer related survival was calculated using Kaplan–Meier analysis followed by a log rank test for differences between variables
41 women with Sertoli–Leydig cell tumors were identified. Median age was 41 years (range 6–79). The stages according to the International Federation of Gynecology and Obstetrics (FIGO) were: stage I, 85% (n=35), stage II, 2% (n=1), stage III, 5% (n=2), and stage IV, 7% (n=3). The 5 year cancer related survival was 100% for patients with localized disease (stages I–II) and 0% in advanced tumor stages (stages III–IV). Histological differentiation grade of the tumors was well differentiated in 29% (n=12), moderately differentiated in 56% (n=23), and poorly differentiated in 15% (n=6), and the 5 year cancer related survival was 100%, 96%, and 33%, respectively, according to grade. All patients underwent surgery. Twenty-two patients had fertility sparing surgery and four of these had given birth at the time of follow-up. Analysis of DICER1 was performed in eight women. Four carried a pathogenic variant. Four patients received adjuvant chemotherapy, three because of advanced tumor stage, and one because of a poorly differentiated Sertoli–Leydig cell tumor.
The prognosis for women with Sertoli–Leydig cell tumors with localized disease is excellent. Women with advanced stages (III–IV) have a poor prognosis, regardless of adjuvant chemotherapy. Fertility sparing surgery seems to be a viable option for localized Sertoli–Leydig cell tumors. DICER1 screening was rarely performed in previous cohorts and concomitant organ screening programs are topics for discussion.
Lower extremity lymphedema secondary to cancer treatment impacts quality of life for gynecological cancer survivors. Complex decongestive physiotherapy is applied when lymphedema is diagnosed, but prophylactic physiotherapy is not yet a standard of care. The aim of this study is to evaluate prophylactic complex physiotherapy in patients with gynecological cancer and its effects on patient-reported symptoms based on the Gynecologic Cancer Lymphedema Questionnaire.
The data of patients diagnosed with gynecological cancers who underwent lymphadenectomy from July 2021 to June 2022 was evaluated. All patients were referred to the physiotherapy unit before adjuvant treatment. Patients who accepted prophylactic physiotherapy were informed and massage and exercise training were implemented, whereas patients who declined were solely informed. Bilateral lower extremity circumferences were measured at 1, 3, 6, and 12 months at the levels of 10 cm, 30 cm, and 50 cm above the heels. A translated form of the Gynecologic Cancer Lymphedema Questionnaire was administered to all patients at the last visit.
A total of 100 patients were included in the study. Patients were diagnosed with endometrial (50%), ovarian (32%), cervical (16%), and vulvar (2%) cancer. Overall, 70% underwent systematic pelvic±para-aortic lymphadenectomy whereas sentinel lymph node mapping was performed in 30%. Lymphedema was seen in 5% (n=3) of the prophylactic physiotherapy positive group and in 60% (n=24) of the physiotherapy negative group. The median score was 3 (range 1–5) in the physiotherapy positive group and 16 (range 9–20) in the physiotherapy negative group. In patients diagnosed with lymphedema in the physiotherapy negative group, systematic lymphadenectomy was performed in 91.7% (n=22) and a higher number of lymph nodes was extracted (median 45.5; p=0.002).
Prophylactic complex physiotherapy is associated with lower rates of lymphedema and better patient-reported symptom scores according to the Gynecologic Cancer Lymphedema Questionnaire.
Delivering bad news to patients is one of the most challenging tasks in medical practice. Despite its great relevance to patients, relatives, and medical staff, there is a paucity of data pertaining to training, experience, expectations, and preferences of physicians and medical students on breaking bad news.
We conducted an international survey in Germany, Switzerland, and Austria using an online questionnaire among physicians and medical students.
A total of 786 physicians and 303 medical students completed the survey. Physicians stated that 32.7% deliver bad news several times a week and 45.2% several times a month. Difficulties controlling their emotions (35.1%) and remaining professional (43.4%) were the greatest challenges for physicians. Delivering bad news is associated with feelings of anxiety, both among experienced physicians (median of 3.8 out of 10.0) and medical students (median of 5.3). Conveying bad news is a burden to physicians and consequently has a substantial impact on their job satisfaction. All participants reported the need for more communication training concerning this subject. Only 49.5% of medical students and 67.3% of physicians mentioned having learned adequate communication skills. Our data demonstrate that communication training decreases the level of anxiety and increases the feeling of self-confidence towards breaking bad news. Preferred educational tools were seminars with simulation (students: 71.4%, physicians: 49.5%), observing more senior faculty (students: 57.4%, physicians: 55.1%), and supervision and feedback sessions (students: 36.3%, physicians: 45.7%). The largest barriers regarding education on communication were limited time (students: 77.0%, physicians: 74.9%) and missing awareness of supervisors (students: 60.6%, physicians: 41.1%).
Our study showed a great need for systematic training and education in breaking bad news among physicians and medical students. Hospitals, medical schools, and postgraduate training programs are strongly encouraged to fill this gap, and improve sustainable doctor–patient communication to overcome the psychological burden for physicians.
Obesity is known to be both a major risk factor for endometrial cancer and associated with surgical complexity. Therefore, the management of patients with obesity is a challenge for surgeons and oncologists. The aim of this study is to assess the adherence to European Society of Gynaecological Oncology (ESGO) guidelines in morbidly obese patients (body mass index (BMI) >40 kg/m2). The secondary objectives were the impact on overall survival and recurrence-free survival.
All the patients who were treated for an endometrial cancer in the 11 cancer institutes of the FRANCOGYN group were included and classified into three weight groups: morbid (BMI >40 kg/m2), obese (BMI 30–40), and normal or overweight (BMI <30). Adherence to guidelines was evaluated for surgical management, lymph node staging, and adjuvant therapies.
In total, 2375 patients were included: 1330 in the normal or overweight group, 763 in the obese group, and 282 in the morbid group. The surgical management of the morbid group was in accordance with the guidelines in only 30% of cases, compared with 44% for the obese group and 48% for the normal or overweight group (p<0.001); this was largely because of a lack of lymph node staging. Morbid group patients were more likely to receive the recommended adjuvant therapy (61%) than the obese group (52%) or the normal or overweight group (46%) (p<0.001). Weight had no impact on overall survival (p=0.6) and morbid group patients had better recurrence-free survival (p=0.04).
Adherence to international guidelines for surgical management is significantly lower in morbid group patients, especially for lymph node staging. However, morbidly obese patients had more often the adequate adjuvant therapies. Morbid group patients had a better recurrence-free survival likely because of better prognosis tumors.
Phase III trial data have shown a significant benefit by the addition of a maintenance treatment with niraparib, irrespective of BRCA or HRD status, in patients with advanced high-grade ovarian cancers; and, a significant benefit of the combination of olaparib and bevacizumab compared with bevacizumab monotherapy in HRD positive patients. However, it is unclear whether a PARP inhibitor monotherapy is sufficient, or if the addition of bevacizumab is needed.
This trial will investigate if the treatment strategy of carboplatin/paclitaxel/bevacizumab/niraparib is superior to the treatment of carboplatin/paclitaxel/niraparib in an all-comer population.
Adding bevacizumab to chemotherapy followed by niraparib maintenance improves progression-free survival in patients with newly diagnosed advanced ovarian cancer.
AGO-OVAR 28/ENGOT-ov57 is an international, multicenter, randomized, prospective phase III trial within the the European Network for Gynecological Oncological Trial (ENGOT), led by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study group. All patients should have completed the first cycle of chemotherapy (carboplatin and paclitaxel) as part of the Study Run-In-Period. Prior to day 1 of cycle 2, patients with a valid central tumor BRCA (tBRCA) test result were randomized in a 1:1 ratio into either: Arm 1, to receive five additional cycles of carboplatin and paclitaxel q21d, followed by niraparib for up to 3 years; or Arm 2, to receive five additional cycles of carboplatin and paclitaxel plus bevacizumab q21d, followed by bevacizumab q21d (for up to 1 year), and niraparib for up to 3 years.
The trial population is composed of adult patients with newly diagnosed, advanced high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery are also eligible for the trial.
The primary endpoint is progression-free survival.
The study plans to recruit 970 patients (485 patients in each arm).
The Last-Patient-In is expected to be enrolled in September 2024, with presentation of the primary endpoint in 2028.
NCT05009082; EudraCT Number: 2021-001271-16