Secondary and tertiary ovarian cancer recurrence: What is the best management?

Ovarian cancer with complete clinical response recurs with a high rate. Recurrence is observed in almost 25% of cases with early-stage diseases and in more than 80% with more advance stages. Based on a platinum-free interval cut-off of 6 months, the first recurrence is usually classified in platinum-sensitive versus platinum-resistant, reflecting the biological characteristics underlying the clinical behavior. After this first recurrence, the patients are rarely cured, but second-line therapy can provide significant clinical responses, particularly in first platinum-sensitive recurrence. The approach to secondary and tertiary recurrence follows the same general principles applied in the first recurrence. Platinum-sensitivity based on the treatment-free interval defines the available chemotherapeutic regimens, whit less therapeutic options and a generally worse prognosis in platinum-resistant recurrent disease. Nevertheless, in this scenario, the introduction of new targeted therapies changed the prognosis of patients with both platinum-sensitive and platinum-resistant recurrence. The first introduced antiangiogenic therapy resulted able to improve prognosis in recurrent disease both as a single-agent and combined therapy, although the growing adoption in the first line therapy requires further investigation to prove their efficacy after repeated use. More recently, the approach to secondary, tertiary, and later recurrence has been changed by the introduction of PARP inhibitors, which resulted effective as maintenance monotherapy in both platinum-sensitive and platinumresistant recurrence when the genetic background of the tumor allows their application with a significant improvement of oncological outcomes. Overall, although the growing body of promising therapeutic options to approach recurrent ovarian cancer, all the available evidence suggests that the best unique management of secondary and tertiary recurrence does not exist but should be personalized based on the disease characteristics, previous treatments, patient characteristics, and patient preference. On that basis, in this review, we report a general and complete overview of the approach at the secondary and tertiary ovarian cancer recurrence with the aim to provide a wide vision on the multiple available therapeutic options.