Selective Benefit of Adjuvant Chemotherapy in Stage II dMMR Colon Cancer with High-Risk Features or Poorly Differentiated Histology: A Retrospective Study

TL;DR

This study finds that adjuvant chemotherapy improves survival in high-risk stage II dMMR colon cancer patients, especially those with poorly differentiated tumors.

Contribution

The study identifies a selective benefit of adjuvant chemotherapy in specific high-risk dMMR colon cancer subgroups.

Findings

Adjuvant chemotherapy improved survival in high-risk stage II dMMR colon cancer patients.

Poorly differentiated histology was associated with better outcomes with chemotherapy.

Low-risk or well-differentiated subgroups did not benefit significantly from chemotherapy.

Abstract

Deficient mismatch repair (dMMR) stage II colon cancer generally has a favorable prognosis, yet the prognostic value of conventional high-risk features and the benefit of adjuvant chemotherapy (ACT) remain controversial. We retrospectively analyzed 273 patients with stage II dMMR colon cancer who underwent curative resection at Peking University Cancer Hospital between August 2010 and October 2023. Overall, 31.9% received ACT (predominantly CAPOX or capecitabine). With a median follow-up of 62.6 months, 5-year overall survival (OS) and disease-free survival (DFS) were 94.7% and 89.8%. Age ≥ 65 years and examination of fewer than 12 lymph nodes were independent adverse factors for OS, while age ≥ 65 years, fewer than 12 lymph nodes, and ACT status were independently associated with DFS. Subgroup and propensity score–matched analyses suggested that ACT was associated with improved survival in selected patients, particularly those with high-risk features and those with poorly differentiated histology, whereas no clear benefit was observed in low-risk or well/moderately differentiated subgroups.

Background: The prognostic value of conventional high-risk factors and the benefits of adjuvant chemotherapy (ACT) in stage II colon cancer with deficient mismatch repair (dMMR) remain controversial. The function of ACT in stage II dMMR colon cancer and survival results were assessed in this research. Methods: 273 patients with stage II dMMR colon cancer who had curative resection between August 2010 and October 2023 underwent a retrospective analysis. Clinicopathologic variables, postoperative treatment strategies, and survival endpoints were systematically assessed. Independent prognostic factors were identified using a multivariable Cox proportional hazards regression model. For subgroup analyses, a propensity score–matched (PSM) approach was used to minimize intergroup imbalances. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan–Meier approach. Results: 177 (64.8%) patients had at least one high-risk factor. With a median follow-up of 62.6 months, the estimated 5-year OS and DFS rates were 94.7% and 89.8%. Age ≥ 65 years and examination of fewer than 12 lymph nodes were independently associated with OS. For DFS, age ≥ 65 years, LNs < 12, and receipt of ACT were identified as independent prognostic factors. According to subgroup analyses, ACT was linked to better OS and DFS in patients with high-risk features or poorly differentiated histology. Results were similar after propensity score matching. Conclusion: Traditional high-risk features also exert prognostic impact on this population. ACT appeared to be associated with improved survival in selected high-risk patients, particularly those with poorly differentiated histology.

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