Metastatic colorectal signet ring cell carcinoma (mSRCRC) is a rare entity and data are limited, concerning small number of patients. Chemosensitivity for metastatic disease has never been assessed. This study analyzes their chemosensitivity and investigates their clinicopathological, molecular and prognostic characteristics.
This nationwide retrospective study included patients with mSRCRC from 2003 to 2017 in 31 french centers. They were divided into three groups: curative care (group 1), palliative chemotherapy (group 2) and best supportive care (group 3).
Data on 204 patients were collected. Median age was 63 years. Tumors were more frequent in proximal colon (46%) and rectum (29%), were T4 (71%) and poorly differenciated (86%). Sites for metastases were mainly peritoneum (69%), lymph nodes (28%) and liver (23%). Microsatellite instability (MSI) and BRAF V600E mutation were found in 19% (21/108) and 9% (9/103) of patients, and were mainly right sided (respectively 27% and 12% respectively). BRAF mutation was found in 19% of MSI tumors. RAS mutation was found in 23% (29/127) and did not vary with side. Median overall survival (mOS) was 10,1 months (95%CI = [7.9;12.8]). mOS for group 1 (n = 38), group 2 (n = 112) and group 3 (n = 54) were 45,1 months, 10,9 months and 1,8 months. No difference in mOS was found between tumor location, signet ring cell's percentage and MSI status (p = 0,13; p = 0,40 and p = 0,82). In group 2, first-line treatment (1L) was antiVEGF-based in 28,4% and antiEGFr-based in 22% of cases. Response and control rates were 13,2% and 50% respectively in 1L. Progression-free survival (PFS) was 5 months with biotherapy and 3,9 months with cytotoxics alone (p = 0,016). There was no difference in PFS between antiVEGF and antiEGFr (p = 0,8) in 1L, and between right-sided (p = 0,275) and left-sided (p = 0,265) tumors.
This large cohort of mSRCRC shows poor prognosis, specific location and molecular alterations which provides low chemosensitivity. Microsatellite analysis should be done regarding promising results of immunotherapy in MSI-high tumors.
Clinical trial identification
Legal entity responsible for the study
AGEO (Association des Gastroentérologues Oncologues).
Has not received any funding.
All authors have declared no conflicts of interest.