Abstract
Clinical observations have demonstrated that microsatellite instability-high (MSI-H) and/or deficient MMR (dMMR) status are associated with favorable prognosis and no benefit from 5-Fluorouracil (5-FU)-based adjuvant chemotherapy in patients with resected stage II colorectal cancer (CRC). This study represents a systematic review and meta-analysis exploring the predictive role of MSI-H status in stage III CRC undergoing or not adjuvant chemotherapy. Published articles that evaluated the role of adjuvant chemotherapy in resected stage III CRC from inception to September 2020 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. The random-effects model was conducted to estimate the pooled effect size of OS and DFS. The primary outcome of interest was OS. 21,590 patients with MSI-H/dMMR stage III CRC, from n = 17 retrospective studies, were analyzed. Overall, OS was improved with any adjuvant chemotherapy vs. any control arm (single-agent 5-FU or surgery alone): HR 0.42, 95% CI 0.26–0.66; P < 0.01. Conversely, DFS was not significantly improved (HR 0.7, 95% CI 0.45–1.09; P = 0.11). In patients with stage III MSI-H/dMMR CRC, adjuvant chemotherapy is associated with a significant OS improvement. Thus, MSI-H/dMMR status does represent a predictive factor for postoperative chemotherapy benefit in stage III CRC beyond its prognostic role.
Highlights
A large amount of evidence is currently available on the less beneficial, or even potentially detrimental effect of adjuvant, single-agent, fluoropyrimidine-based chemotherapy in patients with microsatellite high (MSI-H) or deficient mismatch repair stage II colorectal cancer (CRC)[1]
Inclusion criteria were: (1) original articles, with outcome data available, that compared the survival among adjuvant and no adjuvant chemotherapy arms in stage III microsatellite instability-high (MSI-H) CRC, (2) comparison of single-agent 5-FU/capecitabine or combination chemotherapy with observation, (3) available hazard ratio (HR) for overall survival (OS), disease-free survival (DFS), that compared experimental and control arms, or that may be calculated from survival curves
While the negative impact of adjuvant chemotherapy in stage II has been established, less clear is the role of postoperative treatments for MSI-H/deficient MMR (dMMR) stage III CRC
Summary
A large amount of evidence is currently available on the less beneficial, or even potentially detrimental effect of adjuvant, single-agent, fluoropyrimidine-based chemotherapy in patients with microsatellite high (MSI-H) or deficient mismatch repair (dMMR) stage II colorectal cancer (CRC)[1]. Much less clear is the impact of MSI-H/ dMMR status in radically resected, node-positive CRCs. Updated results of the "MOSAIC" trial with 10-year median follow up, showed important disease-free (DFS) and overall survival (OS) improvements (hazard ratios [HRs] 0.48 [95% CI 0.20 to 1.12] and 0.41 [95% CI 0.16 to 1.07], respectively), in 9.4% of patients with stage II to III dMMR by the addition of oxaliplatin to 5-FU chemotherapy b ackbone[2]. We performed a systematic review and meta-analysis to explore the predictive role of MSI-H/dMMR status in stage III CRC patients undergoing or not adjuvant chemotherapy
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