You are here
Clinical prognostic factors and genomic analysis of ovary metastases (mets) from colorectal cancer (CRC).
Background: Ovary mets constitute 5-10% of CRC mets, are associated with poor prognosis, cause morbidity due to disproportionately rapid growth compared with other mets and are less responsive to chemotherapy. The optimal management of ovary mets and the molecular basis of their unique growth pattern is unknown. Methods: 505 MSKCC patients with CRC (ICD-9 153, 154) and ovary mets (ICD-9 198.6) were identified. Patients without available pathology, with appendix cancer or only serosal ovary mets were excluded. Regression models were used to identify predictors of progression-free survival (PFS) and overall survival (OS) after surgery. Targeted exome sequencing of 341 cancer-associated genes was performed on 34 CRC ovary mets, including 20 matched pairs or trios of primary tumors, ovary mets and other mets from the same patient. Results: 184 patients with surgically resected CRC ovary mets were evaluated (median age 50 (17-86); OS 40 months (0.8-218) from CRC diagnosis, 23 months (0.2-199) from oophorectomy). 93/116 (80.2%) evaluable patients had concurrent growth of ovary mets on chemotherapy but shrinkage of other mets. In multivariate analysis, optimal surgical debulking was associated with improved PFS (HR = 0.11 (0.04-0.36)) and OS (HR = 0.42 (0.28-0.63)). Discordant ovary therapy response was associated with early progression (HR = 20.8 (1.59-274), and post-oophorectomy chemotherapy with reduced mortality (HR = 0.53 (0.33-0.84)). Ovary mets had increased KRAS (61.7% vs. 45.2%, p= 0.05) and SMAD4 (29.4% vs. 15.5%, p= 0.04) mutations compared to a 453 CRC cohort without ovary mets. In matched trios, mutations were largely concordant across tumor sites and no recurrent ovary met-specific mutations were found. However, 3/14 cases had identical mutations in the ovary mets and primary tumors, but additional private mutations in other mets. Conclusions: CRC ovary mets have frequent KRAS and SMAD4 mutations. Matched trios show clonal similarities between primary tumors and ovary mets, and divergence from other mets. Complete surgical resection of ovary mets is associated with substantially improved PFS and OS, similar to outcomes for localized CRC.