Controversies in the management of serous borderline tumors and low-grade serous ovarian cancer.

Low-grade serous ovarian cancer has been recognized as a distinct oncologic entity for the last 20 years. Over the last 10 years, treatment strategies tailored to the biological and clinical characteristics of the disease have been tested and implemented. However, several key controversies remain. Here, we articulate the uncertainties surrounding the identification of the tissues of origin of low-grade serous ovarian cancer and its precursor lesion, the serous borderline tumor, the challenges in identifying molecular drivers of low-grade serous ovarian cancer, where a driver mutation in the mitogen-activated protein kinase pathway has not been identified, and discuss the phenomenon of co-existent low- and high-grade components in a tumor. In the clinical arena, we discuss the challenges surrounding fertility preservation in young patients, difficulties encountered in patients with unresectable disease, and the controversy surrounding the recommendation of adjuvant chemotherapy. We also discuss the role of secondary debulking surgery, how to order the administration of biological therapies, and the key issues in accelerating the discovery and development of new therapies. For many of these issues, the solution lies in improved international collaboration and cooperation. For each, we allude to how this might best be achieved.