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Original Article
Characteristics of patients with cervical cancer during pregnancy: a multicenter matched cohort study. An initiative from the International Network on Cancer, Infertility and Pregnancy
  1. Michael J Halaska1,
  2. Catherine Uzan2,3,
  3. Sileny N Han4,
  4. Robert Fruscio5,
  5. Karina Dahl Steffensen6,
  6. Ben Van Calster7,
  7. Hana Stankusova8,
  8. Martina Delle Marchette5,
  9. Astrid Mephon9,
  10. Roman Rouzier10,
  11. Petronella O Witteveen11,
  12. Patrizia Vergani5,
  13. Kristina Van Calsteren7,12,
  14. Lukas Rob1 and
  15. Frederic Amant4,13,14
  1. 1 Department of Obstetrics and Gynaecology, Faculty Hospital Kralovske Vinohrady, 3rd Medical Faculty, Charles University, Prague, Czech Republic
  2. 2 Department of Gynaecological Surgery, Institut Gustave Roussy, Villejuif, France
  3. 3 Department of Gynecology and Breast surgery, Pitié Salpêtrière Hospital, Institut Universitaire de Cancérologie, Sorbonne University, INSERM U938, Paris, France
  4. 4 Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University Hospitals Leuven, Leuven, Belgium
  5. 5 Clinic of Obstetrics and Gynecology, University of Milan-Bicocca, San Gerardo Hospital, Monza, Italy
  6. 6 Department of Oncology, Vejle Hospital, Vejle, Denmark
  7. 7 Department of Development and Regeneration, KU Leuven, Leuven, Belgium
  8. 8 Department of Medical Oncology, Faculty Hospital Motol, 2nd Medical Faculty, Charles University, Prague, Czech Republic
  9. 9 Hospital Tenon, Paris, France
  10. 10 Institut Curie, Paris, France
  11. 11 Department of Medical Oncology, Cancer Center University Medical Center, Utrecht, The Netherlands
  12. 12 Department of Obstetrics & Gynecology, University Hospitals Leuven, Leuven, Belgium
  13. 13 Department of Oncology, KU Leuven, Leuven, Belgium
  14. 14 Centre for Gynecologic Oncology Amsterdam, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
  1. Correspondence to Frederic Amant, Gynecologic Oncology, University Hospitals Leuven, Leuven 3000, Belgium; frederic.amant{at}uzleuven.be

https://doi.org/10.1136/ijgc-2018-000103

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    HIGHLIGHTS

    • Cervical cancer found during pregnancy is usually diagnosed at an early stage.

    • Treatment options for cervical cancer during pregnancy may include conization, pelvic lymphadenectomy, and/or neoadjuvant chemotherapy.

    • Pregnancy does not adversely impact the prognosis of pregnant patients with cervical cancer.

    Introduction

    Cervical cancer is the fourth most common cancer in women worldwide.1 Generally, large differences between developed and low and middle income countries have been reported. For example, in developed countries the incidence of cervical cancer is decreasing, whereas in low and middle income countries the incidence is on the rise.1 In developed countries, more women are delaying childbirth and thus cervical cancer is more often diagnosed during pregnancy.2 Still, cervical cancer in pregnancy is a rare event and therefore current knowledge is limited to a small series and institutional experience.

    Standard treatment for early cervical cancer (2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA-IB) in non-pregnant patients without metastatic disease is radical hysterectomy with pelvic lymphadenectomy. However, in pregnancy this is not an ideal option as it would lead to pregnancy termination and eliminate the possibility of future fertility. Furthermore, in advanced stage or metastatic disease standard treatment with chemoradiotherapy interferes with pregnancy preservation. In recent years, fertility-preserving options that include radical or simple trachelectomy with or without neoadjuvant chemotherapy have been successfully applied in cervical cancer patients.3 Such procedures may be offered during pregnancy when the primary aim is to save the life of the fetus (level III evidence). Moreover, chemotherapy might postpone local definitive treatment until term or until after delivery. It is unknown whether pregnancy-preserving approaches have a negative impact on the maternal prognosis.

    There are limited data on current approaches in the management of cervical cancer during pregnancy. The aim of our study was to design a matched cohort study to investigate characteristics and treatment decisions during pregnancy and evaluate the oncologic outcomes of such therapy.

    Methods

    Design and Setting

    Using an international database of pregnant cancer patients (International Network on Cancer Infertility and Pregnancy study (INCIP), a task force of the European Society of Gynecological Oncology (ESGO), www.cancerinpregnancy.org registered at www.ClinicalTrials.gov under the number NCT00330447), we retrieved consecutive patients diagnosed with cervical cancer during pregnancy at six European centers (Charles University in Prague, Czech Republic; Institut Gustave Roussy, Paris, France; University Hospital Gasthuisberg, Leuven, Belgium; University of Milan-Bicocca, Milano, Italy; Vejle Hospital, Vejle, Denmark; University Medical Center, Utrecht, The Netherlands). Patients were included from January 1990 to December 2012. The study was approved by the respective institutional ethics committees.

    Data Collection

    Diagnosis of cancer was by biopsy or conization and was reviewed by a pathologist at each institution. Staging and treatment were performed at the discretion of the treating physician, usually on the decision of a multidisciplinary team. Each center randomly matched one pregnant patient with two non-pregnant patients for age (±5 years) and 2009 FIGO stage (IB1 tumors were additionally divided into <2 cm and >2 cm). Information was recorded for age at diagnosis, histopathological type (squamous, adenocarcinoma, adenosquamous, other), grade, lymphovascular space invasion, 2009 FIGO stage, size of tumor, symptom or method that led to a diagnosis (bleeding, Pap smear, colposcopy/conization, other), mode of delivery, date and location of recurrence, and date of death.

    For the decision-making analysis, treatment options during pregnancy were divided into five groups: (1) Surgery: surgical treatment including conization/simple trachelectomy, lymphadenectomy, or both; (2) Neoadjuvant chemotherapy: chemotherapy administered during pregnancy; (3) Delay: delaying the definitive treatment until delivery with regular follow-up of the tumor only; (4) Preterm delivery: medical induction of pre-term delivery; (5) Termination of pregnancy (TOP): performance of TOP during the first or second trimester, including treatment sacrificing the fetus (hysterectomy or chemoradiotherapy with fetus in utero or after previous evacuation). For analysis of progression-free survival, data on disease recurrence or death from any cause were recorded until February 2015. Patients who did not experience recurrence or who were alive at the end of their follow-up were censored at the last known date before or at the end of follow-up.

    Statistical Analysis

    As this was a retrospective descriptive study, no sample size calculation was performed and no α level was used to determine statistical significance. Clinical and tumor characteristics were compared between pregnant and non-pregnant patients using 95% confidence intervals (95% CI) for differences in means or proportions, as appropriate. For a comparison of stage distribution, which was a matching variable in this study, a 26th FIGO database derived from a reference group of women from the age cohort of 30–40 years was used.4 Progression-free survival was calculated from the date of cervical cancer diagnosis to the date of recurrence (any invasive locoregional recurrence of disease, any distant recurrence of disease or any secondary malignancy, whichever occurred first). One patient did not die from disease and was censored at the date of death. Overall survival was calculated from the time of cervical cancer diagnosis to death from any cause. Survival was visualized by Kaplan-Meier curves. We used multivariable Cox regression analysis to assess the relationship between pregnancy and prognosis. The following covariates were included: pregnancy (yes/no), age, 2009 FIGO stage (IA, IB1, IB2, II-IV), tumor size, high grade (2/3 vs 1), and treatment (surgery, chemotherapy, other). Analyses were done with SAS version 9.4 and R version 3.4.1. Information on the handling of missing values is described in the online supplementary appendix 1.

    Supplemental material

    Results

    There were 137 pregnant patients identified, of whom five were excluded because of incomplete records at follow-up, leaving 132 pregnant patients and 256 matched non-pregnant patients for evaluation (eight control patients had to be used twice). Distribution of patients between centers was 37 (28%) from the Institut Gustave Roussy, Paris, 30 (23%) from Charles University in Prague, 20 (15%) from the University of Milan-Bicocca, Monza, 20 (15%) from the University Medical Center Utrecht, 18 (14%) from the University Hospitals Gasthuisberg, Leuven, and seven (5%) from the Vejle Hospital, Denmark.

    Disease Characteristics

    Both the pregnant and non-pregnant groups were similar in most of the demographic and tumor characteristics (table 1). The method/symptoms of diagnosis were also similar in the two groups. Staging was done according to local policy using clinical examination and magnetic resonance imaging or ultrasonography. The median age at diagnosis was 34 years (range 21–43) for pregnant patients and 35 years (range 16–45) for non-pregnant patients. Median gestational age at diagnosis was 18.4 weeks (range −7–39). Two patients were diagnosed before pregnancy but were first treated during pregnancy. Concerning the trimester of pregnancy, 33% of the patients were diagnosed in the first trimester, 49% in the second, and 18% in the third.

    View this table:
    Table 1

    Descriptive statistics of demographic and tumor characteristics

    Using a 26th FIGO database derived from the reference group, we observed that cervical cancer was diagnosed more often at early stage (IA1-IB2) disease in pregnant patients. Stages IA1-IB2 were found in 106/132 (80.3%) pregnant patients and in 1594/2596 (61.4%) in the FIGO reference group (difference 18.9, 95% CI 11.1 to 25.1).

    Management During Pregnancy

    Antenatal treatment (surgical or systemic) was initiated in 45 (34.1%) patients.

    Surgery of the cervix was performed in 23 (17.4%) women. In 17 women only conization was performed: on three occasions conization was combined with pelvic lymphadenectomy, and pelvic lymphadenectomy was combined with simple vaginal trachelectomy three times. In three patients lymphadenectomy was performed without a surgical procedure on the cervix (these patients belong to the Delay group). No sentinel lymph node mapping was performed because of contraindication of technetium and patent blue application during pregnancy. Conization was performed in IA1 tumors, except for two cases of IB1 tumors. In four cases a reconization or simple hysterectomy was performed after delivery. One patient (IB1 tumor) experienced a recurrence but all patients were alive at follow-up with no evidence of disease.

    Pelvic lymphadenectomy was performed in nine (6.8%) patients at a median gestational age of 13 weeks (range 10–19) without any reported complications. The median number of lymph nodes harvested was 21 (range 9–71) in pregnant patients versus 18 (range 11–50) in non-pregnant patients. No positive nodes were found in either the pregnant or the non-pregnant group.

    Neoadjuvant chemotherapy was administered to 22 (16.7%) pregnant women. Single agent chemotherapy using cisplatin was administered to 59.1% of the patients, while combination chemotherapy was used in 40.9% (cisplatin with paclitaxel, cisplatin with vinorelbine, cisplatin with ifosfamide and paclitaxel or carboplatin with paclitaxel). On average, 3.6 cycles of chemotherapy were administered during pregnancy. Dosages were calculated according to guidelines for non-pregnant patients based on actual weight, height and glomerular function.

    Treatment delay until after delivery was performed in 35 (26.5%) patients. Most patients in this group (65.2%) had stage IB1 tumors; in addition, 13.1% had stage IB2 tumors and 21.7% had stage II tumors. Delivery was postponed by a median of 8 weeks (range 3–28). In three patients a staging lymphadenectomy was performed before follow-up. A radical procedure was performed after delivery in 17 patients and 18 underwent chemoradiotherapy.

    Pre-term delivery was performed by cesarean section in 17 (12.9%) patients, delivering at a median gestational age of 36 weeks (range 28–39). Eight patients had cesarean section combined with radical hysterectomy while nine underwent only cesarean section, with postponement of radical surgery in five patients and chemoradiotherapy in four patients.

    Termination of pregnancy was performed in 35 (26.5%) patients. In four patients chemoradiotherapy was administered with the fetus in utero and in 19 patients termination was performed during radical surgery.

    Delivery was performed by cesarean section in 84 patients (87.5%) and vaginally in 12 (12.5%). All vaginal deliveries were performed in patients after conization, except for four patients (twice planned spontaneous delivery after trachelectomy and twice accidentally in IB1 and IIB patients). In a subgroup of 17 patients who underwent conization during pregnancy, nine underwent cesarean section and eight delivered vaginally. Characteristics of pregnant patients, stratified by treatment, are depicted in table 2.

    View this table:
    Table 2

    Clinical, demographic and tumor characteristics of pregnant patients with cervical cancer stratified by major treatment modality

    Patient Outcome

    Median follow-up was 67 months (range 2–269) for pregnant patients and 95 months (range 2–260) for non-pregnant patients. Overall, median follow-up was 84 months (range 2–269). We observed 27 recurrences with 19 deaths in the pregnant patients and 51 recurrences with 47 deaths in the non-pregnant patients. The unadjusted hazard ratio (HR) for pregnancy was 1.18 for progression-free survival (95% CI 0.74 to 1.88). Figure 1 shows Kaplan-Meier curves for stages IB1 and IB2 separately (note the limited number of patients with IB2 tumors). The outcome based on treatment modality is presented in figure 2. Based on multivariable analysis, the adjusted HR for pregnancy was 1.17 for progression-free survival (95% CI 0.64 to 2.13, p=0.62) (table 3).

    Figure 1
    Figure 1

    Subanalysis of progression-free survival in IB stages. PFS, progression-free survival; NP, non-pregnant; P, pregnant.

    Figure 2
    Figure 2

    Subanalysis of progression-free survival based on treatment during pregnancy. PFS, progression-free survival; TOP, termination of pregnancy; NAC, neoadjuvant chemotherapy.

    View this table:
    Table 3

    Multivariable analysis of prognostic factors for progression-free survival

    Discussion

    Our study showed that there is a trend towards an increased use of surgery and chemotherapy in the management of patients with cervical cancer diagnosed during pregnancy. Although guidelines for treatment options in pregnant women have recently been published,5–7 these are expert-based recommendations only and were developed with minimal data on the efficacy of cancer treatment during pregnancy. Comparing variables that influenced the choice of treatment, it is evident that gestational age at diagnosis was one of the main determinants. Chosen therapeutic modalities (termination of pregnancy, surgery, neoadjuvant chemotherapy, delay and induction of pre-term delivery) are arrayed in ascending order based on the gestational age at diagnosis. Patients diagnosed during the first trimester more often underwent surgery or termination of pregnancy. Stage or tumor volume was the second most important determinant. Early stage/microscopic tumors were more likely treated by surgery, which, in most cases, was conization. The largest tumors, on the other hand, were preferably treated by neoadjuvant chemotherapy or induction of pre-term delivery.

    Neoadjuvant chemotherapy is more commonly administered during pregnancy today.5 The critical issue is transplacental transfer of chemotherapy agents. Therefore, it is of interest to examine the impact on prognosis. An analysis of cytostatic use during pregnancy in a neoadjuvant setting showed an advantage of combination therapy over single agent platinum-based treatment.5 Platinum-based chemotherapy seems to be the most active8; outside of pregnancy, it is the most applied therapy in cervical cancer patients.9 10 It has been reported that 11–42% of cisplatin crosses the placental barrier.11 Ototoxicity of cisplatin was reported in one case.12 However, two reviews of the literature on platinum derivatives did not report any ototoxicity in 47 cases.8 13 As it pertains to carboplatin, no such adverse events have been reported; however, only a few cases have been followed. Thus, the ideal agent still needs to be determined.

    Pelvic lymphadenectomy has been shown to be feasible during pregnancy until the 22nd–25th gestational week.5 Most cases reported were performed using a transperitoneal laparoscopic approach. In our series, the median number of lymph nodes harvested was 21. Similar to other reports,14 15 a comparable number of positive lymph nodes between pregnant and non-pregnant groups were found. As it pertains to surgery of the cervix, radical trachelectomy is an alternative surgical procedure for non-pregnant patients with negative lymph nodes and tumors ˂2 cm, but during pregnancy major complications may occur (eg, fetal loss, excessive bleeding, and prolonged surgery).5 In the past decades, more data have become available on the negligible risk of parametrial involvement, suggesting that simple trachelectomy might be a safe option.3 16 17 In our series, large conization or simple trachelectomy was performed without complications in six cases in tumors with a mean size of 17.2 mm (range 7–27). The subsequent mean gestational week of delivery was 37 (range 34–39). Similar findings have recently been reported in five patients after laparoscopic pelvic lymphadenectomy and simple vaginal trachelectomy with median gestational age of delivery at 39 weeks (range 28–40.6).18

    In our series 26.5% of the patients underwent termination of pregnancy during the first or second trimester. When we divided our set of patients into 5-year periods from 1990, there was a trend towards reduction of termination of pregnancy and an increase in active treatment (eg, surgery or neoadjuvant chemotherapy) (see Supplemental Data Online). This reflects increasing knowledge about active management using surgery and neoadjuvant chemotherapy and generally pregnancy-preserving options in the past few decades. Given that cervical carcinoma does not generally demonstrate rapid growth, one should consider more pregnancy-preserving procedures, including postponing the treatment until the second trimester when diagnosed during early pregnancy. An evaluation of prognosis within pregnant patients based on the chosen treatment modality is relevant in relation to the overall characteristics of tumors in each treatment group (table 2 and figure 2), something that is especially seen in patients with larger volume tumors receiving neoadjuvant chemotherapy.

    Recent publications have shown that the most important factor predicting psychomotor development of a child is gestational age at delivery.19 20 For the development of the child, it is of greater benefit to undergo more cycles of chemotherapy during pregnancy to prevent prematurity than to receive fewer cycles and premature delivery. In our series, we showed that patients undergoing surgical treatment delivered near term, indicating that this subgroup of patients was considered low risk because of the smallest tumor size. One particularly noteworthy finding was that, despite an active therapy (neoadjuvant chemotherapy), the mean age at delivery in this group was lower than in a group of patients undergoing follow-up delaying the treatment to post-partum.

    Mode of delivery depends on the presence of the tumor in the cervix. If no residual tumor is present in the cervix, spontaneous delivery is a feasible option. However, in the presence of tumor in the cervix, this may be an obstacle for cervical ripening and delivery and could be accompanied by severe hemorrhaging. Moreover, there could be an elevated risk of a metastatic disease in the vagina or episiotomy, which was previously reported in a summary of 15 patients.5 Demographic characteristics showed a higher prevalence of multigravida patients when compared with the control group. For stage, pregnancy is accompanied by frequent gynecological examinations and we were able to demonstrate that cervical cancer is more often diagnosed at an early stage during pregnancy compared with non-pregnant women.

    Several older and smaller datasets have been used to evaluate the prognosis of pregnancy-associated cervical cancer.20 21 In most of these series a termination of pregnancy or a delay of the treatment until after delivery has been recommended. Additionally, the treatment procedures have evolved throughout the years, with some manuscripts dating back to the 1950s. Nisker et al reported worse 5-year disease-free survival in 43 stage IB pregnant patients compared with 118 non-pregnant patients (69.8% vs 87.3%, p<0.001).22 A recently published Danish registry-based study found a hazard ratio for death of 1.77 (95% CI 1.21 to 2.60) in 126 patients with cervical cancer observed during pregnancy.23 Contrary to that finding, Lee et al reported no difference in 5-year overall survival for 40 stage IB pregnant patients compared with non-pregnant patients (75.0% vs 89.4%, p=0.41).14 Another matched cohort study of 28 pregnant patients with cervical cancer found a similar prognosis (89.3% vs 98.1%, p=0.09) at a median follow-up of 3.4 and 3.7 years.24

    In the largest series to date, we provide data regarding the oncological outcome of cervical cancer treatment during pregnancy. In a matched cohort setting we observed that the prognosis of 132 patients with cervical cancer during pregnancy was similar to non-pregnant patients. This observation is especially important because patients receiving chemotherapy during pregnancy and patients undergoing watchful waiting were both included. From other studies, it appears that fetal safety is not compromised by the administration of chemotherapy.19 These maternal safety data support the argument that cervical cancer can be actively treated during pregnancy.

    Strengths and Weaknesses

    Our study, involving six centers across Europe, represents the largest series of patients with cervical cancer diagnosed during pregnancy. Differences in the treatment of the disease between each center correspond to ‘real-world’ practice in the sense that there still exists no consensus on the treatment of these patients despite published guidelines. Moreover, the present study evaluates cases from the past two decades representing recent advances in treatment. The risk of bias from differences in treatment has been minimized by matching patients with controls from each center. A weakness of our study is the difference in follow-up between the patient and control group. The use of a retrospective design was inevitable because the aim was to collect enough data and to present the outcome analysis. The number of patients per subgroup is not large enough to provide robust prognostic evidence and therefore at this stage we restricted our evaluation to progression-free survival analysis.

    Cervical cancer found during pregnancy is usually present at an early stage. Treatment options include conization, pelvic lymphadenectomy and neoadjuvant chemotherapy. In neoadjuvant chemotherapy treatment a platinum-based combination regimen is preferred. The prognosis of cervical cancer is not impacted by the pregnancy and this is important when counseling patients on the treatment modalities available during pregnancy. Patients should be referred to specialized centers with a dedicated multidisciplinary team in close cooperation with a perinatology center. We continue to collect data to obtain more robust evidence and to refine the results. We welcome clinicians to collaborate and register patients at www.cancerinpregnancy.org

    Appendix

    For the survival analysis, missing data were handled as follows. Twelve patients (3%) had missing relapse status. Eight of these died of disease shortly after the diagnosis without knowledge of the date of recurrence. For these patients, we used time to death for the analysis of relapse-free survival. The other four patients were omitted from the analysis. In one patient (pregnant, stage IV cancer) the tumor size was missing. In five other pregnant patients with stage IV cancer the average size was 70 mm. This value was used to replace the missing value. Forty-nine (13%) patients had a missing value for grade. We imputed these missing values using stochastic imputation based on logistic regression. The logistic regression model to predict high grade (2/3 vs 1) used size, stage, age, treatment, and relapse information (relapse indicator, follow-up time and their interaction) as predictors.

    References

    1. 1.↵
      2. Bray F ,
      3. Ferlay J ,
      4. Soerjomataram I , et al
      . Global Cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin2018;68:394–424.doi:10.3322/caac.21492
      OpenUrlCrossRefPubMed
    2. 2.↵
      2. Stensheim H ,
      3. Møller B ,
      4. van Dijk T , et al
      . Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: a registry-based cohort study. JCO2009;27:45–51.doi:10.1200/JCO.2008.17.4110
      OpenUrlAbstract/FREE Full Text
    3. 3.↵
      2. Rob L ,
      3. Skapa P ,
      4. Robova H
      . Fertility-sparing surgery in patients with cervical cancer. Lancet Oncol2011;12:192–200.doi:10.1016/S1470-2045(10)70084-X
      OpenUrlCrossRefPubMedWeb of Science
    4. 4.↵
      2. Quinn MA ,
      3. Benedet JL ,
      4. Odicino F , et al
      . Carcinoma of the cervix uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet2006;95(Suppl 1):S43–103.
      OpenUrlCrossRefPubMed
    5. 5.↵
      2. Amant F ,
      3. Halaska MJ ,
      4. Fumagalli M , et al
      . Gynecologic cancers in pregnancy: guidelines of a second international consensus meeting. Int J Gynecol Cancer2014;24:394–403.doi:10.1097/IGC.0000000000000062
      OpenUrlAbstract/FREE Full Text
    6. 6.↵
      2. Hunter MI ,
      3. Tewari K ,
      4. Monk BJ
      . Cervical neoplasia in pregnancy. Part 2: current treatment of invasive disease. Am J Obstet Gynecol2008;199:10–18.doi:10.1016/j.ajog.2007.12.011
      OpenUrlCrossRefPubMed
    7. 7.↵
      2. Morice P ,
      3. Narducci F ,
      4. Mathevet P , et al
      . French recommendations on the management of invasive cervical cancer during pregnancy. Int J Gynecol Cancer2009;19:1638–41.doi:10.1111/IGC.0b013e3181a83017
      OpenUrlAbstract/FREE Full Text
    8. 8.↵
      2. Zagouri F ,
      3. Sergentanis TN ,
      4. Chrysikos D , et al
      . Platinum derivatives during pregnancy in cervical cancer: a systematic review and meta-analysis. Obstet Gynecol2013;121:337–43.doi:http://10.1097/AOG.0b013e31827c5822
      OpenUrlPubMed
    9. 9.↵
      2. Friedlander M ,
      3. Kaye SB ,
      4. Sullivan A , et al
      . Cervical carcinoma: a drug-responsive tumor--experience with combined cisplatin, vinblastine, and bleomycin therapy. Gynecol Oncol1983;16:275–81.doi:10.1016/0090-8258(83)90102-6
      OpenUrlCrossRefPubMed
    10. 10.↵
      2. Rydzewska L ,
      3. Tierney J ,
      4. Vale CL , et al
      . Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer. Cochrane Database Syst Rev2012;32.doi:10.1002/14651858.CD007406.pub3
    11. 11.↵
      2. Köhler C ,
      3. Oppelt P ,
      4. Favero G , et al
      . How much platinum passes the placental barrier? Analysis of platinum applications in 21 patients with cervical cancer during pregnancy. Am J Obstet Gynecol2015;213:206.e1–206.e5.doi:10.1016/j.ajog.2015.02.022
      OpenUrl
    12. 12.↵
      2. Geijteman ECT ,
      3. Wensveen CWM ,
      4. Duvekot JJ , et al
      . A child with severe hearing loss associated with maternal cisplatin treatment during pregnancy. Obstet Gynecol2014;124(2 Pt 2 Suppl 1):454–6.doi:10.1097/AOG.0000000000000389
      OpenUrl
    13. 13.↵
      2. Mir O ,
      3. Berveiller P ,
      4. Ropert S , et al
      . Use of platinum derivatives during pregnancy. Cancer2008;113:3069–74.doi:10.1002/cncr.23935
      OpenUrlCrossRefPubMed
    14. 14.↵
      2. Lee J-M ,
      3. Lee K-B ,
      4. Kim Y-T , et al
      . Cervical cancer associated with pregnancy: results of a multicenter retrospective Korean study (KGOG-1006). Am J Obstet Gynecol2008;198:92.e1–92.e6.doi:10.1016/j.ajog.2007.06.077
      OpenUrlPubMed
    15. 15.↵
      2. Vercellino GF ,
      3. Koehler C ,
      4. Erdemoglu E , et al
      . Laparoscopic pelvic lymphadenectomy in 32 pregnant patients with cervical cancer: rationale, description of the technique, and outcome. Int J Gynecol Cancer2014;24:364–71.doi:10.1097/IGC.0000000000000064
      OpenUrlAbstract/FREE Full Text
    16. 16.↵
      2. Gemer O ,
      3. Eitan R ,
      4. Gdalevich M , et al
      . Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement. Eur J Surg Oncol2013;39:76–80.doi:10.1016/j.ejso.2012.10.013
      OpenUrlCrossRefPubMed
    17. 17.↵
      2. Strnad P ,
      3. Robova H ,
      4. Skapa P , et al
      . A prospective study of sentinel lymph node status and parametrial involvement in patients with small tumour volume cervical cancer. Gynecol Oncol2008;109:280–4.doi:10.1016/j.ygyno.2008.02.004
      OpenUrlPubMed
    18. 18.↵
      2. Salvo G ,
      3. Frumovitz M ,
      4. Pareja R , et al
      . Simple trachelectomy with pelvic lymphadenectomy as a viable treatment option in pregnant patients with stage IB1 (≥2 cm) cervical cancer: Bridging the gap to fetal viability. Gynecol Oncol2018;150:50–5.doi:10.1016/j.ygyno.2018.05.021
      OpenUrl
    19. 19.↵
      2. Amant F ,
      3. Vandenbroucke T ,
      4. Verheecke M , et al
      . Pediatric outcome after maternal cancer diagnosed during pregnancy. N Engl J Med2015;373:1824–34.doi:10.1056/NEJMoa1508913
      OpenUrlCrossRefPubMed
    20. 20.↵
      2. van der Vange N ,
      3. Weverling GJ ,
      4. Ketting BW , et al
      . The prognosis of cervical cancer associated with pregnancy: a matched cohort study. Obstet Gynecol1995;85:1022–6.doi:10.1016/0029-7844(95)00059-Z
      OpenUrlCrossRefPubMedWeb of Science
    21. 21.↵
      2. Manuel-Limson GA ,
      3. Ladines-Llave CA ,
      4. Sotto LS , et al
      . Cancer of the cervix in pregnancy: a 31-year experience at the Philippine General Hospital. J Obstet Gynaecol Res1997;23:503–9.doi:10.1111/j.1447-0756.1997.tb00879.x
      OpenUrlPubMed
    22. 22.↵
      2. Nisker JA ,
      3. Shubat M
      . Stage IB cervical carcinoma and pregnancy: report of 49 cases. Am J Obstet Gynecol1983;145:203–6.doi:10.1016/0002-9378(83)90492-1
      OpenUrlPubMedWeb of Science
    23. 23.↵
      2. Eibye S ,
      3. Krüger Kjær S ,
      4. Nielsen TSS , et al
      . Mortality among women with cervical cancer during or shortly after a pregnancy in Denmark 1968 to 2006. Int J Gynecol Cancer2016;26:951–8.doi:10.1097/IGC.0000000000000708
      OpenUrlAbstract/FREE Full Text
    24. 24.↵
      2. Bigelow CA ,
      3. Horowitz NS ,
      4. Goodman A , et al
      . Management and outcome of cervical cancer diagnosed in pregnancy. Am J Obstet Gynecol2017;216:276.e1–276.e6.doi:10.1016/j.ajog.2016.10.034
      OpenUrl

    Footnotes

    • Funding FA is senior researcher for the Research Fund Flanders (FWO). FA was supported by CRADLE, European Research Council (consolidator grant no. ZKD0230). MJH was supported by Charles University research project Progres Q28-Oncology and Q34.

    • Competing interests None declared.

    • Patient consent for publication Not required.

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