Clinical outcomes of women with ovarian metastases of colorectal cancer treated with oophorectomy with respect to their somatic mutation profiles

Abstract

We clarified the clinical prevalence of ovarian metastases from colorectal cancers (CRCs) in 296 female patients with CRC and evaluated clinical outcomes with relation to their mutational profiles, such as BRAF/KRAS mutation and microsatellite instability (MSI) status. The female CRCs were categorised into three subsets: CRCs with ovarian metastases [6.4% (n = 19), 5-year overall survival (OS) = 24.7%], CRCs with extra-ovarian metastases only [32.4% (n = 96), 5-year OS = 34.5%] and CRCs without any recurrence or metastasis [61.2% (n = 181), 5-year OS = 91.3%]. All patients with ovarian metastases underwent oophorectomy; of these, 9 who received preoperative chemotherapy had measurable metastases to extra-ovarian sites and the ovaries. Although 5 of 9 (56%) achieved partial response or complete response at extra-ovarian sites, no patient archived objective response at ovarian sites. Regarding the mutation profiles, in CRCs with extra-ovarian metastases only, the median survival time (MST) after initial treatments to progression to stage IV or recurrence was 13 [95% confidence interval (CI): 7–16 months] in BRAF-mutant and 34 months (95% CI: 22–58 months) in BRAF wild-type (P = 0.0033). Although ovarian metastases demonstrated poor response to systemic chemotherapy in CRCs with ovarian metastases, the MST after initial treatments to progression to stage IV or recurrence was 22 (95% CI: 21–25 months) in BRAF-mutant and 38 months (95% CI: 24–42 months) in BRAF wild-type (P = 0.0398). The outcomes of patients with ovarian metastases could be improved by oophorectomy regardless of their mutation profiles.

Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

“…The level of methylation is targetable by drugs, 34 and discrepancies in methylation between primary and metastatic tumors have been reported. 35 Consistent with this assumption, we found no discrepancies in MSIhigh tumors caused by germline mutations of MMR genes, whereas one patient with a MLH1 promoter 36 and worse prognosis. 36,37 Specifically, 2 patients in this study with MSI-high primary tumors had metastasis to 2 sites, and only the peritoneal metastasis showed MSS, whereas other metastases remained MSI-high.…”

Ultrasound and Clinical Preoperative Characteristics for Discrimination Between Ovarian Metastatic Colorectal Cancer and Primary Ovarian Cancer: A Case-Control Study

“…Long-term survival can be attained in 20%-50% of patients who undergo complete resection [3]. The clinical prevalence of ovarian metastases among patients with CRC was 6.4%, and 5-year OS for those with ovarian and extra-ovarian metastases was 24.7% and 34.5%, respectively (difference not significant) [4]. OS was longer if surgical resection of ovarian metastases was performed, compared with chemotherapy alone (43.1 vs. 17.0 months) [5].…”

A novel in vivo Cerenkov luminescence image‐guided surgery on primary and metastatic colorectal cancer

“…On the swine models, the intraoperative CLI effectively guided the resection of the metastasis in the bladder and the ovary. Although the CRC metastasis in the bladder or ovary is not in the majority , the feasibility of the intraoperative CLI was proved by the experimental data. The in vivo results on the animals also showed that the intraoperative CLI provided an efficient approach to evaluate the tumor resection quality accurately (Figures , quantitative results).…”

“…The feasibility of the intraoperative CLI was also investigated with the metastatic CRC on the swine models. Pseudotumors were established in bladder and ovary, which are two adjacent organs that probably involved by CRC in the clinic . 18 F‐FDG of 0.37 MBq was used to simulate metastatic CRC in the bladder, and 0.29 MBq 18 F‐FDG was used in the ovary.…”