Primary versus interval cytoreductive surgery in patients with rare epithelial or non-epithelial ovarian cancer

Background: The standard treatment for advanced epithelial ovarian cancer is primary cytoreductive surgery, with the goal of achieving no residual disease. Neoadjuvant chemotherapy and interval cytoreductive surgery can be viable treatment options for patients with extensive disease that precludes complete tumor removal during initial surgery, or when significant comorbidities increase the surgical risk without adversely impacting overall survival rates. However, published studies mostly included patients with high-grade serous ovarian cancer, with an underrepresentation of non-high-grade serous epithelial and non-epithelial cancers. This review aimed to provide an overview of the available data on the outcomes of primary cytoreductive surgery versus interval cytoreduction in patients with rare ovarian cancer histotypes. Methods: Published literature on primary versus interval cytoreductive surgery in non-high-grade serous ovarian cancers from 2004 to 2024 was searched using PubMed, EMBASE, and Google Scholar and reported for each histological subtype. The outcomes of patients with low-grade serous, endometrioid, clear-cell, and mucinous carcinomas after neoadjuvant chemotherapy were reviewed. Furthermore, the results following neoadjuvant chemotherapy in non-epithelial ovarian cancers, such as ovarian germ cell tumors, sex cord-stromal tumors, and small-cell carcinoma of the ovary, have also been reported. Most data were derived from retrospective studies, with heterogeneity in design. Results & Conclusions: Several ovarian cancer histotypes, including low-grade serous and mucinous carcinomas, may be less responsive than high-grade serous carcinomas to neoadjuvant chemotherapy. Consequently, primary cytoreduction with maximal surgical effort may confer a survival advantage. Other tumors responded well to neoadjuvant chemotherapy, allowing for interval fertility-sparing surgeries. Additional evidence is required because no prospective studies are currently available. Given the low incidence of these diseases, randomized controlled trials may not be feasible. However, national or international registries could play a pivotal role in determining the optimal approach for managing patients with these rare histotypes.