Unlike rectal lesions, the reported prevalence of submucosal invasive cancer (SMIC) in large non-pedunculated colonic polyps (LNPcPs >20 mm) is discordant. We conducted a systematic review and meta-analysis to estimate the pooled prevalence of SMIC in LNPcPs, including rates of superficial SMIC (sSMIC) and low-risk SMIC (lrSMIC), and to provide stratified prevalence estimates by colonic location (right and left colon). 

Multiple databases were searched through October 2025 for studies on the endoscopic resection of LNPcPs (≥20 mm) reporting SMIC, including cohorts from both Eastern and Western countries. Data were extracted for overall SMIC and, when available, for sSMIC (defined as submucosal invasion <1000 μm) and lrSMIC (superficial invasion without high-risk histologic features). Pooled prevalence estimates with 95% confidence intervals (CI) were calculated using a random-effects model. Prevalence estimates were also generated stratified by colonic location. Between-study heterogeneity was assessed using the I² statistic.

A total of 80 studies including 17,927 lesions were analyzed. Across all LNPcPs, the pooled prevalence of SMIC was 6.2% (95% CI 5.2–7.5%). Among the 38 studies (n = 8,977) reporting depth of invasion, the pooled prevalence of superficial SMIC (sSMIC) was 3.7% (95% CI 2.6–5.2%), while low-risk SMIC (lrSMIC), reported in 25 studies (n = 7,009), had a pooled prevalence of 2.8% (95% CI 1.8–4.3%). All analyses showed substantial heterogeneity (overall SMIC I² = 83%; sSMIC I² = 80%; lrSMIC I² = 74%).

When stratified by colonic location, SMIC prevalence was 5.1% (95% CI 4.0–6.5%) in right-colon LNPcPs (12,926 lesions) and 13.5% (95% CI 11.7–15.6%) in left-colon lesions (3,314 lesions). Superficial SMIC prevalence was 3.3% (95% CI 2.1–5.1%) in the right colon and 6.0% (95% CI 4.4–8.3%) in the left colon. The prevalence of lrSMIC was 2.3% (95% CI 1.3–4.1%) in the right colon and 4.5% (95% CI 3.3–6.2%) in the left colon.

In this meta-analysis approximately 6% of LNPcPs harbored SMIC, with variation by colonic location. The prevalence of lrSMIC was uncommon overall and approximately 2% in the right colon. These estimates provide comprehensive benchmarks that may support the selection of appropriate resection strategies for LNPcPs, helping to balance risks and benefits and to determine the level of technical expertise required.