Diagnosis and Treatment of Gestational Non-Epithelial Ovarian Cancer: A Systematic Review

Discussion

Ultrasonography for diagnosis of gestational NEOC. A key theme emerging from the analyzed studies is the crucial role of routine ultrasonography in the initial detection of gestational NEOC. Luh LCPN et al. highlighted ultrasonography findings in three cases of GCT diagnosed during pregnancy, each showing a hypo-hyperechoic mass with solid and cystic features characteristic of NEOC (29). These cases, which included an immature teratoma, dysgerminoma, and yolk sac tumor, underscore the value of ultrasonography as a key tool for preliminary identification, aiding clinicians in recognizing abnormal ovarian masses during routine scans. Importantly, most NEOC cases were detected at FIGO stage I, emphasizing ultrasonography’s effectiveness in early-stage identification. Early detection is essential for timely intervention, potentially preventing disease progression that could complicate pregnancy and management. In England, standard prenatal care includes at least two ultrasound scans, with the first performed between 11-14 weeks of gestation (30). This routine scan not only evaluates the fetus and placenta but also allows for the observation of maternal ovaries, facilitating the incidental detection of ovarian abnormalities in asymptomatic patients. Thus, ultrasonography proves to be an essential tool for routine pregnancy assessments and for the early detection of NEOC.

Tumor markers and MRI. Tumor markers, including CA-125, were not primarily used for diagnosing gestational NEOC but were more effective as indicators for monitoring treatment response, particularly following chemotherapy. This is likely because certain tumor markers can naturally increase during pregnancy, leading to potentially misleading results if relied upon solely for diagnosis. MRI, meanwhile, was not a primary diagnostic tool but played an essential role in staging NEOC. Staging through MRI aids in evaluating the extent of tumor growth, helping clinicians make informed treatment decisions. Therefore, while ultrasonography remains the first-line tool for early detection, MRI provides valuable detailed assessment when abnormalities are detected.

Fertility-sparing surgical management. The management of NEOC during pregnancy varied across cases, underscoring the need for an individualized approach that considers factors such as gestational age, FIGO stage, and patient preferences. Despite these variations, a common practice was the use of fertility-sparing surgery for early-stage NEOC, particularly in FIGO stage I cases. This typically involves USO with subsequent staging when only one ovary is affected, allowing the preservation of fertility for future pregnancies. This method aligns with patients’ wishes to maintain fertility while effectively managing the cancer during pregnancy. However, for gestational NEOC at stage IC or higher, fertility-sparing surgery is generally not the recommended first-line option due to the increased risk of recurrence beyond the ovary. Studies indicate that delaying future pregnancies for at least two years post-treatment is advisable, as the risk of recurrence is higher during this period (31). The optimal timing for surgery during pregnancy remains debated, though adjuvant chemotherapy is usually initiated in the second trimester to avoid disruption of fetal organogenesis. This strategy seeks to balance effective cancer treatment with minimizing risks to fetal development.

Platinum-based chemotherapy. Platinum-based chemotherapy, particularly the BEP regimen (bleomycin, etoposide, and cisplatin), emerged as an essential adjunctive therapy for managing advanced NEOC during pregnancy. While BEP therapy has demonstrated therapeutic efficacy in treating NEOC, cisplatin, a core component, is associated with systemic side effects, including nephrotoxicity and myelosuppression. Luh LCPN et al. reported using a docetaxel-carboplatin regimen as an alternative, which resulted in no complications for either the mother or fetus (29). Carboplatin is considered safer than cisplatin, with a reduced profile of toxic effects on both the mother and fetus, making it a viable option when cisplatin’s side effects present significant concerns. Chemotherapy administration during pregnancy is generally limited to the second trimester and beyond, as fetal risks – such as congenital malformations, preterm labor, and the need for neonatal intensive care – are significantly higher if given during the first trimester. This timing ensures safer fetal development while facilitating necessary maternal cancer treatment.

Maternal/fetal outcomes. The impact of NEOC on pregnancy outcomes is multifactorial, influenced by factors such as tumor stage, histological subtype, and gestational age at diagnosis. Wang L, et al. reported six cases where pregnancy was terminated, including five involving GCT and one case of small-cell ovarian cancer (32). Although the specific GCT subtypes were not detailed, these cases illustrate the complex decision-making required when balancing cancer treatment with pregnancy continuation. In contrast, successful treatment in most FIGO stage I GCT cases allowed pregnancies to proceed without significant risk, highlighting the critical role of early detection in safeguarding maternal and fetal health. Some studies lacked detailed reporting on maternal and fetal outcomes, limiting comprehensive understanding of the long-term effects of NEOC management during pregnancy. Nonetheless, the existing data underscore the importance of early staging and diagnosis, as early-stage NEOC often correlates with better pregnancy outcomes. Additionally, discontinuing chemotherapy three weeks before delivery, as noted by Luh LCPN et al., facilitated bone marrow recovery for both the mother and fetus, reducing hematologic risks and underscoring the importance of precise treatment timing (29).

Study limitations. This systematic review encountered several limitations that impacted the generalizability and comprehensiveness of its findings. Firstly, the rarity of the gestational NEOC led to a limited pool of eligible studies, complicating the ability to draw robust conclusions across all NEOC subtypes. The small sample size and geographical diversity of the included studies introduced heterogeneity, as variations in healthcare settings, diagnostic protocols, and treatment standards could influence the applicability of the findings across different regions and patient populations. Additionally, most studies were retrospective case reports or case series, limiting the capacity to assess causative relationships and definitively evaluate treatment effectiveness. The absence of randomized controlled trials or prospective cohort studies hindered the ability to make strong recommendations for optimal diagnostic and management approaches for NEOC during pregnancy. Moreover, inconsistencies in standardized outcome measures across studies made direct comparisons of maternal/fetal outcomes challenging.

A notable limitation was the incomplete data reporting in the included studies. Some articles lacked detailed information on tumor markers, specific gestational ages at treatment, and long-term maternal and fetal outcomes. These gaps hinder a comprehensive understanding of the full impact of NEOC management, particularly regarding post-treatment recovery and the risk of recurrence. Additionally, this systematic review only included articles published in English and limited to the past five years to maintain methodological relevance. This language restriction may have excluded valuable studies published in other languages, potentially limiting the diversity of the evidence base. Furthermore, while the five-year publication window ensured contemporary relevance, it may have omitted studies with long-term outcome data, which are essential for understanding the extended impact of fertility-sparing treatments and chemotherapy on maternal and fetal health. Future reviews should aim to include a broader timeframe and consider studies in multiple languages to mitigate these limitations.