Survival outcome of adjuvant chemotherapy in deficient mismatch repair stage III colon cancer

Abstract

Background The prognostic impact of DNA mismatch repair (MMR) status remains controversial in patients with stage III colon cancer who are treated with adjuvant chemotherapy (AC). The aim of this study was to evaluate the survival outcome of AC in deficient mismatch repair (dMMR)/microsatellite instable (MSI) stage III CC. Methods Patients with pathological stage III CC between 2010 and 2013 were identified from the National Cancer Database using International Classification of Diseases for Oncology (3rd Edition) morphology and topography codes 8140, 8480, and C18.0‐18.8. Patients with pathologic stage T3N2, T4N1, or T4N were considered high risk; patients with stage T3N1 were considered low risk. Univariate and multivariable analyses were conducted, and Kaplan‐Meier analysis and Cox proportional hazards models were used to identify the association between AC and overall survival (OS). Results A total of 9226 patients with pathological stage III CC were identified, of which 2384 (25.8%) were MSI‐high (MSI‐H) and met the inclusion criteria of the final analysis. MSI‐low (MSI‐L) patients (n = 6842) were excluded. There was a preponderance of women (55.0% [n = 1311]), and 76.6% (n = 1825) of patients were non‐Hispanic white. The median age was 65 years (range, 19‐90 years). The primary sites were the cecum (29.7% [n = 707]), ascending colon (26.0% [n = 620]), sigmoid colon (17.2% [n = 410]), and transverse colon (10.8% [n = 257]). The most common tumor grade was moderately differentiated (n = 50.4% [1202]), followed by poorly differentiated (34.1% [n = 813]) and well differentiated (5.1% [n = 121]). High‐risk pathologic stage III CC (T4N1, TxN2) constituted 51.0% (n = 1215) of the study population. High‐risk stage III was associated with worse OS compared with low‐risk stage III on univariate (P < .001) analysis and displayed a similar trend on multivariable analysis, without a statistically significant difference. Multiagent AC was associated with improved OS compared with no treatment on univariate (P < .001) and multivariable (P < .001) analysis. When stratified by risk status, multiagent AC was associated with improved OS compared with no treatment for high‐risk (P < .001) and low‐risk (P < .001) stage III disease. Conclusion Adjuvant chemotherapy is associated with better OS in stage III dMMR/MSI‐H CC. An enhanced benefit was shown for high‐risk stage III disease.

Poorer Survival in Patients with Cecum Cancer Compared with Sigmoid Colon Cancer

“…The present study showed that the survival difference between cecum cancers and sigmoid colon cancers is the largest among the six colon sites, which is akin to the results of Shaib et al [ 21 ]. By analyzing the data of patients with non-metastatic, invasive right-sided adenocarcinoma of the colon from 1988 to 2014 who underwent partial colectomy in SEER, Nasseri at al found that cecum cancers were prone to poorer disease-specific survival (median 86.0, 93.0, and 89.0 months, respectively, p < 0.001) and OS (median not reached, p < 0.001) compared with cancers in other sites of the right colon [ 19 ].…”

“…Therefore, the conflicting results may be partly due to the inconsistency of location grouping criteria, and the dichotomy model (right-sided vs. left-sided colon) may be inappropriate for the study of colon cancer [ 16 , 17 , 18 , 19 ]. Moreover, the prognostic differences between specific subsites (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon) have also been reported in a few studies [ 19 , 20 , 21 ]. In order to further explore the effects of tumor locations on prognosis, it is essential to find two parts with the greatest survival differences by comparing different primary tumor locations.…”

Number of negative lymph nodes with a positive impact on survival of stage III colon cancer; a retrospective observation study for right side and left side colon

“…Although MSI/dMMR is a positive prognostic factor for stage II colon cancer after curative resection, the prognostic impact of MSI/dMMR status remains controversial in patients with stage III colon cancer who have received postoperative adjuvant chemotherapy [ 30 – 32 ]. In some conditions, for example, proximal colon cancer or adjuvant chemotherapy with multiple regimens, patients with stage III colon cancer and MSI/dMMR tumors who received oxaliplatin-based adjuvant chemotherapy had better survival outcomes [ 33 , 34 ]. Moreover, the presence of BRAF status, which occurs in approximately 10% of colorectal cancer, has been considered a predictive marker in the survival of patients with metastatic colorectal cancer because the mutation status correlates with lower therapeutic response to chemotherapy with or without target agents [ 35 ].…”