Real-world clinicopathologic characteristics and outcomes of MSI-high colon cancer in community oncology practice from western India.

Abstract

e15585 Background: Microsatellite instability–high (MSI-H) colon cancer represents a distinct molecular subset with prognostic and therapeutic implications particularly in the era of immunotherapy. However, real-world data from community oncology settings in India remains limited. Methods: This retrospective study evaluated MSI-H colon cancer patients from March 2018 to May 2025 at Western India community oncology centers. PFS and OS were analyzed using Kaplan-Meier. Results: A total of 1100 colon cancer patients were evaluated out of which 358 underwent MSI testing & 66/358 (18.43%) were MSI-H. The median age of the MSI-H cohort was 66 years (IQR, 43.5–72), with M:F ratio of 1.7:1; most patients had an ECOG PS of 0–1 (87.8%)& stage distribution was: Stage I -3.0%, Stage II- 40.9%, Stage III -48.5%,Stage IV- 7.6%. MSI testing was performed at baseline in 80.3% & at progression in 19.7%, predominantly by IHC (86.3%), followed by NGS (10.6%) and PCR (3%). Loss of expression was most frequently observed for hMLH-1 (47%) followed by hPMS-2 (45.5%), hMSH-2 (18.2%) and hMSH-6 (16.7%). In 31.8% (n = 21), expression status was unknown, with variable instability detected across microsatellite markers NR-21 (n = 2), NR-24 (n = 2), BAT-25 (n = 2), BAT-26 (n = 2), and MONO-27 (n = 1). MSI-H incidence was most common in adenocarcinoma (95%) most commonly involved the ascending (n = 34) and descending colon (n = 11) with a predominance of right-sided over left-sided disease (54.5% vs 42.4%).PD-L1 status was available in 7.6% (n = 5), with positivity in 4/5 and TMB-high ( > 10muts) in n = 1. Common co-mutation included KRAS (n = 2). First line therapy was mainly surgery (n = 61), chemotherapy (n = 35) and targeted therapy (n = 4). Immunotherapy was administered in combination or as single agent to 9.3% (n = 6) with distribution: Pembrolizumab, nivolumab and dostarlimab in n = 2 each with 60% ORR. Among first line recipients, best responses included complete response in 39.1%, partial response in 14.1%, and stable disease in 10.9%. For MSI tested patients, the median follow-up was 19.9 months (95% CI 17.4-22.4) and Median OS (mOS) was not reached in either the MSI-stable or MSI-H groups with 23.9%(n = 70) and 6.1% (n = 4)events reported respectively (NA; 95% CI, NA–NA) (p = 0.001). Median PFS was 25.9 months (95% CI, 15.96–35.8) in MSI-stable cohort vs 71.9 months (95% CI, 0.0–168.02) in the MSI-H cohort (p = 0.006). Conclusions: This real-world analysis from Western India identifies MSI-H colon cancer as a biologically distinct entity with right-sided predominance and superior survival outcomes; however, underutilization of MSI testing and immunotherapy underscores the need for systematic MSI assessment to facilitate timely, biomarker-driven treatment in community oncology settings.