Cervical cancer during pregnancy is a rare event. The guidelines for the management of cervical cancer during pregnancy are based on limited data from a small number of cases and expert opinion. Hence, the management of pregnancy complicated by a concomitant diagnosis of cervical cancer remains complex and challenging. Due to delays in childbearing to the third or fourth decade of life, the diagnosis of cervical cancer during pregnancy has risen over recent decades. In addition, the optimal treatment for cervical cancer diagnosed during pregnancy has not been fully clarified. Therefore, studies investigating continuation of pregnancy in patients diagnosed with cervical cancer, specifically detailing outcomes of both mother and fetus, are necessary. In this study, patients who continued the pregnancy showed similar survival compared with patients who terminated the pregnancy. Similarly, the patients who opted to continue the pregnancy showed few obstetric complications, the most common of which was iatrogenic preterm birth that was electively carried out to facilitate treatment. Newborns did not develop medical or surgical complications following NACT.
Whether continuing pregnancy accelerates the malignancy in the mother is controversial. A review of 76 patients diagnosed with stage IB1 or higher cervical cancer, reported that the survival rate of the patients, with an average delay in treatment of 16 weeks, was 95%. This was taken to indicate that continuation of the pregnancy did not adversely affect maternal oncologic treatment. In contrast, other studies have reported that delayed treatment did aggravate tumor progression, with higher mortality rates and disease recurrences[19, 20]. However, in these studies, the clinical features (such as clinical stage, tumor size, lymph node metastasis) were not compared between the continuation of pregnancy group and the termination of pregnancy group. Furthermore, most of the patients in the studies were stage III and IV, potentially leading to biased results. The staging of cervical cancer should be considered during the treatment of cervical cancer in pregnant women. The 2014 and 2019 International Gynecologic Cancer Society (IGCS) and European Society of Gynecological Oncology (ESGO) guidelines[3, 21], propose less radical surgery (deep cone and simple trachelectomy) for early cervical cancer whose tumor size is smaller than 2 cm. Further studies have confirmed the safety of less radical surgery in non-pregnant women[22, 23]. However, reports have concluded that 1 of 7 (14.3%) cases treated with vaginal radical trachelectomy during pregnancy have resulted in early abortions[24, 25]. Ideally, future prospective studies should be carried to validate these findings. For patients diagnosed after 22 weeks gestation, either NACT or postpartum treatment may be an option. For stage IIA tumors and above, NACT is the only approach to continue the pregnancy.
NACT is an innovative method for the treatment of cervical cancer in pregnant women. This method prevents cervical cancer progression and facilitates delay to delivery in patients whose fetus are not yet mature. The recommended type of NACT for pregnant patients is platinum-based chemotherapy. Teratogenicity of any drug depends on exposure time, the dose, and factors that affect placental transfer. High lipid solubility, low molecular weight, and loose binding to plasma proteins promote transfer of drugs from mother to fetus. Previous studies have reported that the type of fetal deformities is related to the gestational age of exposure to chemotherapeutic drugs. The use of chemotherapy in the first trimester of pregnancy increases the risk of spontaneous abortion, fetal death and severe malformations[27, 28]. Recent studies have shown that the concentrations of chemotherapeutic drugs in the amniotic fluid and umbilical cord blood are significantly lower than in maternal blood when chemotherapy is carried out in the second and third trimesters of pregnancy[10, 29]. In these studies, all 30 of the newborns were born alive without evidence of disease and all children developed normally. However, a systematic review reported that one of 14 neonates whose mother was diagnosed with cervical cancer and treated with NACT was diagnosed with embryonal rhabdomyosarcoma 60 months after delivery, probably due to paclitaxel. Further, another baby developed severe bilateral hearing loss in 6 months after delivery due to cisplatin administration. Overall, the incidence of complications of NACT are low and NACT appears to be a relatively safe method for cervical cancer patients to allow continuation of the pregnancy.
This study has limitations. We carried out a retrospective study which may be affected by confounding and reporting bias. In addition, the sample size was small due to the rarity of cervical cancer occurring during pregnancy. Further, because the study was carried out several years after cervical cancer diagnosis, we were unable to achieve follow-up of all participants.