Assessing platinum response in first-line advanced ovarian cancer: clinical implications and future directions

Ovarian cancer is one of the gynecologic malignancies with the highest mortality, largely due to diagnosis at advanced stages and high recurrence rates. Standard first-line treatment consists of platinum-based chemotherapy followed by maintenance with poly (adenosine diphosphate-ribose) polymerase inhibitors and/or bevacizumab. Approximately 70% to 80% of patients with high-grade serous ovarian cancer respond to first-line platinum-based chemotherapy, while only a small proportion exhibit de novo platinum-resistant disease, a clinical scenario associated with poorer outcomes. Assessing platinum response during chemotherapy provides both prognostic and predictive information, functioning as a surrogate marker of genomic instability and informing subsequent therapeutic decisions. Although BRCA mutations and homologous recombination deficiency help identify tumors with increased vulnerability to platinum-induced DNA damage, these biomarkers only partially capture the underlying biological heterogeneity and do not fully guide therapeutic decision-making. Notably, a subset of homologous recombination-proficient tumors still achieves meaningful responses to platinum and poly (adenosine diphosphate-ribose) polymerase inhibitors, underscoring the need for complementary approaches to better characterize platinum sensitivity and refine therapeutic decision-making. This review summarizes the current evidence on methods used to assess response to platinum-based chemotherapy in first-line advanced ovarian cancer and discusses their clinical relevance. Radiological evaluation using Response Evaluation Criteria in Solid Tumors 1.1 remains the standard approach, while emerging imaging techniques aimed at quantifying changes in tumor volume and density may improve response assessment. Biochemical markers, including CA125 kinetics and the modeled CA125 ELIMination rate constant K, provide prognostic information and help identify platinum sensitivity. Pathologic assessment through the chemotherapy response score offers standardized evaluation of response to neoadjuvant chemotherapy. In addition, emerging molecular tools such as circulating tumor DNA and circulating tumor cells show promising results for improving response evaluation and detecting resistance mechanisms. A multi-factorial approach combining these molecular, radiological, biochemical, and pathologic parameters is critical to improve patient stratification and optimize individualized treatment strategies in clinical practice.