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Original research
Low-grade versus high-grade serous ovarian cancer: comparison of surgical outcomes after secondary cytoreductive surgery
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  1. Serena Cappuccio1,
  2. Claudia Marchetti1,2,
  3. Defne Alara Altıntaş2,
  4. Riccardo Oliva2,
  5. Silvio Andrea Russo2,
  6. Barbara Costantini1,3,
  7. Diana Giannarelli4,
  8. Lorena Quagliozzi1,
  9. Giovanni Scambia1,2 and
  10. Anna Fagotti1,2
  1. 1 Department of Women, Child and Public Health Sciences, Gynecologic Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  2. 2 Università Cattolica del Sacro Cuore, Rome, Italy
  3. 3 UniCamillus, Rome, Italy
  4. 4 Epidemiology and Biostatistics Facility, G-STeP Generator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  1. Correspondence to Dr Anna Fagotti, Department of Woman’s and Child Health and Public Health Sciences, Gynecologic Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Lazio, Italy; anna.fagotti{at}policlinicogemelli.it

Abstract

Objective 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.

Methods 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.

Results 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.

Conclusions 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.

  • ovarian cancer
  • cytoreduction surgical procedures
  • gynecologic surgical procedures
  • neoplasm recurrence, local
  • postoperative period

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/ijgc-2023-004854

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    WHAT IS ALREADY KNOWN ON THIS TOPIC

    • Retrospective studies and a meta-analysis showed that secondary cytoreductive surgery in recurrent low-grade serous ovarian cancer improves oncologic outcomes, with a greater benefit when optimal cytoreduction is achieved. Data regarding surgical characteristics and postoperative outcomes is lacking for this subset of patients.

    WHAT THIS STUDY ADDS

    • High-grade and low-grade serous ovarian cancers each have a different presentation at time of recurrence. Therefore, secondary cytoreductive surgery in low-grade ovarian cancer is significantly more complex than its high-grade counterpart, while maintaining a similar rate of postoperative complications.

    HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

    • This study emphasizes the value of centralization of secondary cytoreductive surgery for recurrent low-grade serous ovarian cancer patients in referral centers, to maintain a tolerable adverse event profile.

    Introduction

    Ovarian cancer is a complex disease, with various subtypes showing different biological behaviors and different clinical presentations. High-grade serous tubo-ovarian cancer is the most common and well-studied entity, accounting for around 70% of all cases.1 By contrast, low-grade serous ovarian cancer is a less common histology, representing only 2–5% of all ovarian cancers and 5–10% of serous ovarian cancers.1 2 Low-grade serous ovarian cancer tumors have a younger mean age at diagnosis with a longer overall survival compared with high-grade serous ovarian cancer,3 4 which is mainly attributed to different biological characteristics and a more indolent clinical behavior.5 Numerous clinical studies have demonstrated the lower chemosensitivity of low-grade serous ovarian cancer in various settings, including first-line and neoadjuvant chemotherapy.6 7 This reduced chemosensitivity has also been observed in cases of disease recurrence with similar results.8 9

    For all the reasons above when it comes to recurrent disease, patients with low-grade serous ovarian cancer may benefit from complete cytoreduction.8 10 Retrospective studies and a meta-analysis on secondary cytoreductive surgery showed that surgery improves oncological outcomes in recurrent low-grade serous ovarian cancer, and the benefit is greater when optimal cytoreduction is achieved.9 11–14 However, evidence on secondary cytoreductive surgery feasibility and safety in low-grade serous ovarian cancer are scarce; also, due to the distinct clinical presentations between high-grade serous ovarian cancer and low-grade serous ovarian cancer, the distribution of the disease at recurrence may differ between the two subtypes and, consequently, the surgery that follows may vary significantly, about approach and complication rates.

    As such, our hypothesis is that surgery could have different characteristics in recurrent low-grade serous ovarian cancer compared with high-grade serous ovarian cancer. In this study, we aim to report our 10-year single center experience on the surgical treatment of recurrent low-grade serous ovarian cancer by comparing surgical presentation, procedures, and postoperative outcomes to a matched population of platinum sensitive high-grade serous ovarian cancer counterpart.

    Methods

    This is a single-center, institutional review board approved retrospective study performed at Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, in Rome, Italy (ID 5767; n.0015726/23). Patients’ consent was obtained for the collection and use of their data for scientific purposes.

    Patients who were diagnosed with recurrent platinum sensitive low-grade serous ovarian cancer or high-grade serous ovarian cancer and had secondary cytoreductive surgery in the period of interest (January 2012 - December 2021) were included in the study. Patients were eligible for the analysis if they met the predefined criteria: available surgical, postoperative complications and follow-up data. The exclusion criteria included: secondary cytoreductive surgery performed at other institutions and/or surgery performed for palliative reasons. All high-grade serous ovarian cancer had a platinum-sensitive recurrence, whereas some low-grade serous ovarian cancer had no adjuvant chemotherapy after primary surgery. In every case secondary cytoreductive surgery was performed at least 6 months after primary diagnosis.

    Patients were either followed up at our institution or referred from other centers once clinical or radiological recurrence was diagnosed. Treatment was decided at a multidisciplinary tumor board, according to the platinum-free interval, disease spread, general health condition, physician’s, and patient’s choice. Patients deemed suitable for secondary cytoreductive surgery after radiological evaluation underwent staging laparoscopy to assess the chance of complete/optimal secondary cytoreductive surgery.

    Medical and surgical data were extracted from the https://redcap-irccs.policlinicogemelli.it/redcap/ (Research Electronic Data Capture) platform which is a database that is prospectively completed and regularly updated for all ovarian cancer patients undergoing treatment. Cases were defined as low-grade serous ovarian cancer patients who underwent secondary cytoreductive surgery; controls were high-grade serous ovarian cancer patients who underwent secondary cytoreductive surgery. To avoid an imbalance between the two groups, cases were matched with controls according to the residual tumor at first surgery, presence of ascites and Eastern Cooperative Oncology Group performance status at recurrence in a 1:3 ratio.15

    Associations between categorical and continuous variables were assessed using a Chi-squared test, Fisher’s exact, Welch t-test and analysis of variance when appropriate. Individual Aletti’s surgical complexity scores16 were computed for each patient, and the Clavien–Dindo Classification17 was utilized to evaluate postoperative complications. Standard univariate analyses were performed. The Kaplan–Meier method was used to estimate post-recurrence survival. Post-recurrence survival was calculated from the date of secondary cytoreductive surgery to date of death or last follow-up.

    A two tailed p-value of 0.05 was considered statistically significant. SPSS (Statistical Package for the Social Sciences) was used for the statistical analyses.

    Results

    A total of 611 women with recurrent serous ovarian cancer were considered suitable for secondary cytoreductive surgery. However, 244 (39.9%) were then excluded by diagnostic laparoscopy due to the disease distribution: 10 of 39 (25.6%) patients had low-grade serous ovarian cancer and 234 of 572 (40.9%) patients had high-grade serous ovarian cancer (p=0.06). Of the 367 patients who underwent secondary cytoreductive surgery, 338 patients had high-grade serous ovarian cancer and 29 patients had low-grade serous ovarian cancer (Figure 1). The latter is our cohort of interest.

    Figure 1
    Figure 1

    Flow chart of the study population. Over the study period, a total of 611 ROC women were considered suitable for SCS at our Institution. We excluded 244 of them (39.9%) by diagnostic laparoscopy due to the disease distribution: 10 of 39 (25.6%) were LGSOC and 234 of 572 (40.9%) were HGSOC (p, 0.06). Of the 367 patients who received SCS, 338 of them were HGSOC and 29 LGSOC.Key: HGSOC, high-grade serous ovarian cancer; LGSOC, low-grade serous ovarian cancer; LPS, laparoscopy; ROC, recurrent ovarian cancer; SCS, secondary cytoreductive surgery.

    After 1:3 propensity matching, we obtained a total of 116 patients included in the study; age, body mass index (BMI), and the Arbeitsgemeinschaft Gynaekologische Onkologie score18 variables resulted comparable between the two cohorts, while advanced stage and systemic therapy at diagnosis were significantly higher in high-grade serous ovarian cancer compared with low-grade serous ovarian cancer (Table 1). All surgical procedures are shown in Table 1 according to histological subtype. Aletti’s surgical complexity score was >1 in 17 (58.6) low-grade serous ovarian cancer compared with 32 (36.8%) high-grade serous ovarian cancer patients (p=0.05). Specifically, patients with low-grade serous ovarian cancer recurrence had significantly higher rates of diaphragmatic peritonectomy (12, 41.4% vs 19, 21.8%, p=0.05), peritonectomy of the abdominal wall and of the pelvis (18, 62.1% vs 25, 28.7 %, p=0.02) compared with high-grade serous ovarian cancer patients. In addition, 13 (44.8%) patients received bowel resection in the low-grade serous ovarian cancer cohort vs 24 (27.6%) in the high-grade serous ovarian cancer group (p=0.07).

    View this table:
    Table 1

    Characteristics of patients and surgical procedures analysis

    A total of 16 (13.8%) patients underwent small bowel resection, with eight of these being low-grade (27.6%) and eight (9.2%) being high-grade serous ovarian cancer (p=0.03). No differences were seen as regards of colon resection (41.4% vs 25.3% in low-grade and high-grade ovarian cancer, respectively; p=0.11). When accounting for multiple bowel resections in the same patient, low-grade serous ovarian cancer patients had significantly higher rates compared with high-grade serous ovarian cancer (24.1% vs 8%, p=0.04). Also, in patients who received a bowel resection a higher rate of ostomy placement was found in the low-grade serous ovarian cancer group compared with the high-grade serous ovarian cancer group (9 of 13 [69.2%] vs 7 of 24 patients [29.2%], p=0.04). On the contrary, among the 66 (56.9%) patients undergoing lymphadenectomy, 55 patients had high-grade serous ovarian cancer (63.2%) and 11 (37.9%) patients had low-grade serous ovarian cancer (p=0.029).

    There was no difference in operative time in the low-grade vs high-grade serous ovarian cancer group (308 vs 278 min, p=0.35) while median estimated blood loss was higher in the low-grade vs high-grade serous ovarian cancer patients (400 vs 200 mL, p=0.01). The rate of complete cytoreduction was 89.7% in low-grade vs 96.6% in high-grade serous ovarian cancer patients (p=0.16). Median length of stay was similar between the two groups, with 6 days (range; 2–27) for low-grade and 7 days (range, 2–32) for high-grade serous ovarian cancer patients (p=0.48). Intraoperative and postoperative complications are shown in Table 2. The overall rate of intra-operative complications was 36%, recorded for 10 (43.5%) patients affected by low-grade serous ovarian cancer and for 17 (32.7%) high-grade serous ovarian cancer patients with no statistically significant differences observed between the two groups (p=0.44). All were managed intraoperatively without sequelae, except for one patient who required a subsequent surgery (perihepatic packing was performed at secondary cytoreductive surgery).

    View this table:
    Table 2

    Complications

    All grade 30-day postoperative complications were observed in 28 patients (24.1%), with no differences between the two groups (8, 27.6% low-grade vs 20, 23.0% high-grade serous ovarian cancer). Overall, nine patients (7.8%) had a Clavien-Dindo score exceeding 2 and no differences were observed between the groups. Similarly, the rate of readmission to the hospital (4.3%) and of reoperation (4.3%) was not different between the groups, with only five patients requiring surgery due to a complication (one occurred during the secondary cytoreductive surgery as previously mentioned, two for postoperative adhesions, one for bowel perforation and one for abdominal collection). No perioperative deaths occurred. Both groups showed a high rate of systemic therapy after secondary cytoreductive surgery with high-grade serous ovarian cancer being more likely to receive adjuvant treatment compared with low-grade (89.7% vs 82.8% respectively; p=0.02). With a median follow-up of 37 months (range 1–119), and 10 patients lost to follow-up, we did not reach the median of post-recurrence survival, but 4 year post-recurrence survival was 78% and 70% for low-grade serous ovarian cancer and high-grade serous ovarian cancer, respectively (Figure 2).

    Figure 2
    Figure 2

    Post-recurrence survival (PRS) with a median follow-up of 37 months (range 1–119), and with 10 patients lost to follow-up, we did not reach the median of PRS, but 4 year PRS was 78% and 70% for LGSOC and HGSOC, respectively.HGSOC, high-grade serous ovarian cancer; LGSOC, low-grade serous ovarian cancer; NR, not reached.

    Discussion

    Summary of the Results

    Our study showed that patients with recurrent low-grade serous ovarian cancer undergoing secondary cytoreductive surgery, undergo more complex surgery than high-grade serous ovarian cancer patients, including higher rates of extensive peritonectomies and multiple bowel resections followed by ostomy. Conversely, recurrent high-grade serous ovarian cancer patients undergo lymphadenectomy more frequently than those with low-grade serous ovarian cancer. In addition, the study revealed higher rates of estimated blood loss and intraoperative hemorrhage in low-grade patients undergoing secondary cytoreductive surgery compared with those with high-grade serous ovarian cancer. Both groups achieved a complete gross resection in ≥90%. Despite the increased complexity of the surgical procedure in low-grade serous ovarian cancer patients, the comparable rate of postoperative complications and similar length of hospital stay, support the use of secondary cytoreductive surgery as a viable treatment option for this group of patients.

    Results in the Context of Published Literature

    In case of recurrent platinum-sensitive epithelial ovarian cancer, the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) consensus conference recommends complete cytoreductive surgery followed by systemic treatment for selected patients, regardless of histotype.19 Additionally, for low-grade serous ovarian cancer, National Comprehensive Cancer Network (NCCN) Guidelines for Ovarian Cancer (Version 1.2023) suggest that secondary cytoreductive surgery should be considered in patients with long-disease free interval, isolated masses rather than diffuse carcinomatosis on imaging, and/or bowel obstruction.20

    Despite the beneficial role of secondary cytoreductive surgery in ovarian cancer as demonstrated by two important randomized trials,15 21 it should be noted that in these trials, low-grade serous ovarian cancer patients were underrepresented. Overall, in the DESKTOP III trial, only 10 patients were low-grade serous ovarian cancer patients, distributed as four in the secondary cytoreductive surgery arm, and six in the chemotherapy only arm. In the SOC-1 trial, most patients, (87% in the surgery group and 83% in the no surgery group), belonged to the serous grade 2–3 category, while the remaining subtypes were grouped together. A meta-analysis including 57 studies on patients with platinum-sensitive relapsed ovarian cancer has recently shown there is a statistically significant positive relationship between the proportion of complete or optimal cytoreduction and the median overall survival. The authors concluded that the maximal surgical effort must be balanced and combined to the best medical treatment option to increase survival.22

    Only a few studies have investigated the issue of secondary cytoreductive surgery specifically in recurrent low- grade serous ovarian cancer11 20 23 and most have been included in a recently published meta-analysis.14 Goldberg et al included nine studies, evaluating clinical outcomes in patients who underwent optimal or complete vs suboptimal secondary cytoreductive surgery. Overall, results suggest that complete secondary cytoreductive surgery, and to a lesser extent optimal secondary cytoreductive surgery, are associated with improved progression-free survival and overall survival in patients with recurrent low-grade serous ovarian cancer. However, none of the studies was focused on the complexity and feasibility of surgical procedures.

    No prospective randomized studies have compared the role of chemotherapy after secondary cytoreductive surgery with secondary cytoreductive surgery alone in this subset of patients. Usually, systemic chemotherapy is a standard approach at recurrence, and previous secondary cytoreductive surgery should enhance its effectiveness, eliminating resistant clones. This may be even more relevant in low-grade serous ovarian cancer, which is notably chemoresistant. Furthermore, studies agree in establishing that the more radical (complete) the secondary cytoreductive surgery, the greater the effectiveness of the subsequent chemotherapy.15

    Recent data on medical options for recurrent low-grade serous ovarian cancer reveal the opportunity of tailored therapy due to the introduction of mitogen-activated protein kinase kinase-inhibitors, such as trametinib, which has been proven to be highly effective for this disease.24 In particular, in a phase II randomized trial, the median progression-free survival for patients treated with trametinib was 13 months compared to 7.2 months for women receiving standard of care (including paclitaxel, pegylated liposomal doxorubicin, topotecan; oral letrozole or oral tamoxifen), and in a post-hoc analysis the benefit was maintained also when comparing trametinib to letrozole arm (15 months VS 10.6 months). Also, median overall survival was longer in the trametinib group compared with the standard-of-care group (37.6 months vs 29.2 months). However, in this study,24 no data on secondary cytoreductive surgery are available, whereas retrospective data on secondary cytoreductive surgery in low-grade serous ovarian cancer show a median post-recurrence survival of 60 months or more when an optimal/complete debulking is achieved.9 11 14

    Strengths and Weaknesses

    To the best of our knowledge, this is the first study to analyze in detail the surgical characteristics of secondary cytoreductive surgery in low-grade serous ovarian cancer and is the first to highlight its complexity and feasibility. Finally, a strength of this study is that we used propensity matching to mitigate selection bias given the small numbers of low-grade serous ovarian cancer patients compared with high-grade serous ovarian cancer patients. This is a single-center study with a small sample size and requires larger multi-center studies to support and generalize the results obtained. In addition, possible changes in the evaluation of histological samples may occur since the retrospective design of this clinical study covering a large time frame. Lastly, this is a study with notable selection bias encompassing patients who were selected for secondary cytoreductive surgery as per the criteria of the surgeons.

    Implications for Practice and Further Research

    Our results are representative of our single center clinical experience, and should be validated in other centers to determine if similar results can be obtained at other centers. To further evaluate the effectiveness of secondary cytoreductive surgery in treating low-grade serous ovarian cancer, a case-control study involving patients with recurrent low-grade serous ovarian cancer who did not receive secondary cytoreductive surgery would be an interesting next step. Indeed, new target therapies might offer better results. Another study with ribociclib and letrozole in the same group of patients (GOG3026, NCT03673124) reported a median progression-free survival of 19.1 months, while median overall survival was still not reached.

    Although it is unlikely that patients with complete resection and therefore without measurable disease could be included in the trials, we could hypothesize that tumor removal might enhance the efficacy of targeted therapies.

    Conclusions

    In this study secondary cytoreductive surgery in patients with recurrent low-grade serous ovarian cancer was associated with higher complexity, multiple bowel resections, and higher median estimated blood loss compared with high-grade serous ovarian cancer. However, we observed a comparable rate of postoperative complications. Because low-grade serous ovarian cancer is a rare disease that is relatively chemoresistant, patients should be managed by referral centers with appropriate expertise, and efforts in surgical training and scientific research should be promoted.

    Data availability statement

    Data are available upon reasonable request.

    Ethics statements

    Patient consent for publication

    Ethics approval

    This study involves human participants and was approved by Comitato Etico Fondazione Policlinico Universitario A. Gemelli IRCCS - Università Cattolica del Sacro Cuore ID 5767; n.0015726/23. Participants gave informed consent to participate in the study before taking part.

    References

    1. ↵
      2. Devouassoux-Shisheboran M ,
      3. Genestie C
      . Pathobiology of ovarian carcinomas. Chin J Cancer 2015;34:50–5. doi:10.5732/cjc.014.10273
      OpenUrl
    2. ↵
      2. Babaier A ,
      3. Mal H ,
      4. Alselwi W , et al
      . Low-grade serous carcinoma of the ovary: the current status. Diagnostics (Basel) 2022;12:458. doi:10.3390/diagnostics12020458
    3. ↵
      2. Plaxe SC
      . Epidemiology of low-grade serous ovarian cancer. Am J Obstet Gynecol 2008;198:459. doi:10.1016/j.ajog.2008.01.035
      OpenUrlPubMed
    4. ↵
      2. Gockley A ,
      3. Melamed A ,
      4. Bregar AJ , et al
      . Outcomes of women with high-grade and low-grade advanced-stage serous epithelial ovarian cancer. Obstet Gynecol 2017;129:439–47. doi:10.1097/AOG.0000000000001867
      OpenUrlCrossRefPubMed
    5. ↵
      2. Gershenson DM ,
      3. Sun CC ,
      4. Lu KH , et al
      . Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary. Obstet Gynecol 2006;108:361–8. doi:10.1097/01.AOG.0000227787.24587.d1
      OpenUrlCrossRefPubMedWeb of Science
    6. ↵
      2. Gershenson DM ,
      3. Sun CC ,
      4. Bodurka D , et al
      . Recurrent low-grade serous ovarian carcinoma is relatively chemoresistant. Gynecol Oncol 2009;114:48–52. doi:10.1016/j.ygyno.2009.03.001
      OpenUrlCrossRefPubMed
    7. ↵
      2. Schmeler KM ,
      3. Sun CC ,
      4. Bodurka DC , et al
      . Neoadjuvant chemotherapy for low-grade Serous carcinoma of the ovary or peritoneum. Gynecologic Oncology 2008;108:510–4. doi:10.1016/j.ygyno.2007.11.013
      OpenUrlCrossRefPubMed
    8. ↵
      2. Grabowski JP ,
      3. Harter P ,
      4. Heitz F , et al
      . Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO study group metadatabase. Gynecol Oncol 2016;140:457–62. doi:10.1016/j.ygyno.2016.01.022
      OpenUrlCrossRefPubMed
    9. ↵
      2. Bristow RE ,
      3. Gossett DR ,
      4. Shook DR , et al
      . Recurrent micropapillary serous ovarian carcinoma. Cancer 2002;95:791–800. doi:10.1002/cncr.10789
      OpenUrlCrossRefPubMed
    10. ↵
      2. Johnson RL ,
      3. Laios A ,
      4. Jackson D , et al
      . The uncertain benefit of adjuvant chemotherapy in advanced low-grade Serous ovarian cancer and the pivotal role of surgical cytoreduction. J Clin Med 2021;10:5927. doi:10.3390/jcm10245927
    11. ↵
      2. Crane EK ,
      3. Sun CC ,
      4. Ramirez PT , et al
      . The role of secondary cytoreduction in low-grade serous ovarian cancer or peritoneal cancer. Gynecol Oncol 2015;136:25–9. doi:10.1016/j.ygyno.2014.11.005
      OpenUrlCrossRefPubMed
    12. ↵
      2. Crispens MA ,
      3. Bodurka D ,
      4. Deavers M , et al
      . Response and survival in patients with progressive or recurrent serous ovarian tumors of low malignant potential. Obstet Gynecol 2002;99:3–10. doi:10.1016/s0029-7844(01)01649-0
      OpenUrlCrossRefPubMedWeb of Science
    13. ↵
      2. Bristow RE ,
      3. Puri I ,
      4. Chi DS
      . Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 2009;112:265–74. doi:10.1016/j.ygyno.2008.08.033
      OpenUrlCrossRefPubMedWeb of Science
    14. ↵
      2. Goldberg RM ,
      3. Kim SR ,
      4. Fazelzad R , et al
      . Secondary cytoreductive surgery for recurrent low-grade serous ovarian carcinoma: a systematic review and meta-analysis. Gynecol Oncol 2022;164:212–20. doi:10.1016/j.ygyno.2021.10.080
      OpenUrlPubMed
    15. ↵
      2. Harter P ,
      3. Sehouli J ,
      4. Vergote I , et al
      . Randomized trial of cytoreductive surgery for relapsed ovarian cancer. N Engl J Med 2021;385:2123–31. doi:10.1056/NEJMoa2103294
      OpenUrlCrossRefPubMed
    16. ↵
      2. Aletti GD ,
      3. Santillan A ,
      4. Eisenhauer EL , et al
      . A new frontier for quality of care in gynecologic oncology surgery: multi-institutional assessment of short-term outcomes for ovarian cancer using a risk-adjusted model. Gynecol Oncol 2007;107:99–106. doi:10.1016/j.ygyno.2007.05.032
      OpenUrlCrossRefPubMedWeb of Science
    17. ↵
      2. Katayama H ,
      3. Kurokawa Y ,
      4. Nakamura K , et al
      . Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today 2016;46:668–85. doi:10.1007/s00595-015-1236-x
      OpenUrlCrossRefPubMed
    18. ↵
      2. Harter P ,
      3. Sehouli J ,
      4. Reuss A , et al
      . Prospective validation study of a predictive score for Operability of recurrent ovarian cancer: the multicenter Intergroup study DESKTOP II. A project of the AGO Kommission OVAR, AGO study group, NOGGO, AGO-Austria, and MITO. Int J Gynecol Cancer 2011;21:289–95. doi:10.1097/IGC.0b013e31820aaafd
      OpenUrlAbstract/FREE Full Text
    19. ↵
    20. ↵
      1. National Comprehensive Cancer Network
      . NCCN clinical practice guidelines in oncology: ovarian cancer, including Fallopian tube cancer and primary peritoneal cancer (version 1.2023). 2022. Available: https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf [Accessed 13 Jul 2023].
    21. ↵
      2. Shi T ,
      3. Zhu J ,
      4. Feng Y , et al
      . Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2021;22:439–49. doi:10.1016/S1470-2045(21)00006-1
      OpenUrlPubMed
    22. ↵
      2. Baek M-H ,
      3. Park EY ,
      4. Ha HI , et al
      . Secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer: a meta-analysis. J Clin Oncol 2022;40:1659–70. doi:10.1200/JCO.21.02085
      OpenUrl
    23. ↵
      2. Yazigi A ,
      3. Ray-Coquard IL ,
      4. Pujade-Lauraine E , et al
      . Survival outcomes for patients with recurrent low-grade serous ovarian carcinoma. Gynecologic Oncology 2020;159:93–4. doi:10.1016/j.ygyno.2020.05.080
      OpenUrl
    24. ↵
      2. Gershenson DM ,
      3. Miller A ,
      4. Brady WE , et al
      . Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet 2022;399:541–53. doi:10.1016/S0140-6736(21)02175-9
      OpenUrlCrossRefPubMed

    Footnotes

    • Twitter @annafagottimd

    • Contributors Conception of study: AF and GS. Guarantor: AF and GS. Design and development: SC, CM and AF. Data collection: SC, RO, SAR, DAA, BC, LQ, CM Data analysis: SC, CM, DG. Preparation of tables: SC and CM. Initial draft of manuscript: SC, CM, DAA, RO. Manuscript writing, review, and approval: all authors.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.