The Increasing Prognostic and Predictive Roles of the Tumor Primary Chemosensitivity Assessed by CA-125 Elimination Rate Constant K (KELIM) in Ovarian Cancer: A Narrative Review

Simple Summary In patients with advanced ovarian cancers, the standard first-line treatment includes debulking surgery and platinum-based chemotherapy, followed by a maintenance treatment. Contrary to the completeness of the debulking surgery, the prognostic impact of the tumor chemosensitivity in the success of the first-line treatment has been insufficiently addressed due to the lack of a reliable indicator of the primary chemosensitivity, as acknowledged by European consensus conferences. The objective of this narrative review is to present an overview of the modeled CA-125 ELIMination rate constant K (KELIM) calculation based on the longitudinal CA-125 kinetics during the first chemotherapy cycles and its utility as an early marker of tumor primary chemosensitivity. Easily calculable online, KELIM was shown to be a consistent and reproducible early prognostic marker that could be useful for understanding the prognosis of patients and adjusting the medical-surgical treatments. Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate because 75% of patients are diagnosed with advanced stage III-IV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery (IDS). In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent IDS. Across seven studies with more than 12,000 patients, including six large randomized clinical trials and a national cancer registry, along with a mega-analysis database with 5842 patients, the modeled CA-125 ELIMination rate constant K (KELIM), the calculation of which is based on the longitudinal kinetics during the first three cycles of platinum-based chemotherapy, was shown to be a reproducible indicator of tumor intrinsic chemosensitivity. Indeed, KELIM is strongly associated with the likelihood of complete IDS, subsequent platinum-free interval, progression-free survival, and overall survival, along with the efficacy of maintenance treatment with bevacizumab or veliparib. As a consequence, KELIM might be used to guide more subtly the medical and surgical treatments in a first-line setting. Moreover, it could be used to identify the patients with poorly chemosensitive disease, who will be the best candidates for innovative treatments meant to reverse the chemoresistance, such as cell cycle inhibitors or immunotherapy.