Surgical resection to the point of no residual macroscopic disease significantly improved survival among patients with low-grade serous ovarian carcinoma, based on the findings of a large multicenter retrospective cohort study.
Adjuvant platinum-based therapy, however, did not appear to boost survival in the analysis, Tamayaa May, MD, MSc, said at the annual meeting of the Society of Gynecologic Oncology. “Genotyping and targeted sequencing of low-grade serous ovarian carcinoma often identifies actionable mutations, and treatment with MEK-based combination therapy might be a viable therapeutic strategy in patients with KRAS or NRAS mutations,” added Dr. May of Princess Margaret Cancer Center at the University of Toronto. She and her associates plan to examine more subgroups to determine if genomic alterations predict systemic response, she said.
Low-grade (Silverberg grade 1) serous ovarian tumors are slow growing but tend to resist chemotherapy, making optimal debulking a crucial part of treatment. In past studies, debulking that eliminated macroscopic evidence of disease was associated with a median survival time of about 115 months, compared with about 43 months if patients had residual disease, Dr. May noted.
To further explore outcomes after surgical resection, and to help clarify the role of systemic platinum-based therapy in low-grade serous ovarian carcinoma, she and her associates analyzed clinical data from 714 patients with low-grade serous ovarian carcinomas, including 40 from her institution and 674 from the Ovarian Cancer Association Consortium Registry. Most (60%) patients had stage III disease at diagnosis.
Complete data on surgical outcomes were available for 382 patients, of whom 202 (53%) had residual macroscopic disease and 43% did not. Among 439 patients with complete treatment data, 170 (39%) received first-line platinum-based chemotherapy. For the 391 patients with complete data on progression-free survival (PFS), the median follow-up was 4.9 years and median PFS was 3.1 years (95% confidence interval, 2.6-4.5 years). Residual macroscopic disease correlated with shorter PFS (P less than .001), as did higher tumor stage and baseline CA125 (P less than .001), but platinum-based therapy did not (P = .1).
A multivariable analysis of 333 patients confirmed these findings, Dr. May said. Independent correlates of death or disease progression included residual macroscopic disease (hazard ratio, 2.38; 95% CI, 1.68-3.37; P less than .001), older age (HR, 1.15; 95% CI, 1.02-1.30; P = .02), and stage III (HR, 3.28; 95% CI, 1.87-5.76; P less than .001) or stage IV disease (HR, 5.68; 95% CI, 2.73-11.83; P less than .001), compared with stage I disease. In contrast, platinum-based therapy did not correlate with survival (HR, 0.94; 95% CI, 0.69-1.28; P = .69).
The overall survival analysis also linked mortality with higher tumor stage, increased baseline CA125, and residual disease (P less than .001 for each association), but not with platinum-based therapy (P = .2). The multivariable analysis independently tied mortality to older age (HR, 1.25; P less than .001), stage III (HR, 2.31; P = .006) or IV disease (HR, 3.86; P less than .001), and residual disease (HR, 2.53; P less than .001), but not to platinum-based therapy (HR, 1.05; P = .77).
Data consistency and completeness were issues in this study: most notably, 45% of patients had no PFS data, Dr. May commented. Nonetheless, this type of large retrospective multicenter analysis is one of the best ways to study rare tumors, including low-grade serous ovarian carcinoma, she said.
The Ovarian Cancer Research Fund provides financial support for OCAC. Dr. May reported having no conflicts of interest.
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