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Bladder and Urothelial Cancer Treatments / Colorectal Cancer Surgical Treatments / Colorectal and Anal Carcinomas · Review
Frontiers in Oncology · August 7, 2026
Encouraging direction, but not yet definitive.
This meta-analysis pooled 16 predominantly single-arm studies (540 rectal cancer patients) investigating neoadjuvant therapy combined with immunotherapy, reporting high pooled anal sphincter preservation (90%) and R0 resection (98%) rates, alongside moderate pathological complete response (34%) and notable grade ≥3 adverse events (17%). The evidence is of low-to-moderate certainty without direct RCT comparisons, and the authors explicitly call for confirmatory high-quality RCTs before clinical implementation can be considered established.
Systematic review and meta-analysis of RCTs, single-arm trials, and observational studies. Studies investigating neoadjuvant therapy combined with immunotherapy for rectal cancer; 16 eligible studies identified with 540 rectal cancer patients total.. Intervention: Neoadjuvant therapy combined with immunotherapy for rectal cancer. Compared with: None (single-arm pooling only; no direct comparative arms included in meta-analysis). n = 540.
Pooled anal sphincter preservation rate 0.90 (95% CI: 0.87–0.93) with I²=37.4% R0 resection rate 0.98 (95% CI: 0.96–1.00) with I²=51.4% Pathological complete response rate 0.34 (95% CI: 0.29–0.38) with I²=71.8%
High heterogeneity reported for grade ≥3 adverse events (I²=97.4%) and postoperative complications (I²=92.4%), suggesting potential heterogeneity in patient populations, definitions, or reporting Grade ≥3 adverse events incidence 0.17 (95% CI: 0.13–0.21) with I²=97.4%
While the pooled sphincter preservation (90%) and R0 resection (98%) rates appear favorable, clinicians should note that evidence derives predominantly from single-arm studies with no direct comparative control arms and low-to-moderate certainty by GRADE assessment. The authors emphasize that confirmatory high-quality RCTs are needed before this regimen can be recommended for routine clinical practice.
Meta-analysis of 16 predominantly single-arm studies (540 patients) reports favorable pooled proportions for sphincter preservation (90%) and R0 resection (98%), but evidence is low-to-moderate certainty without direct RCT comparisons; confirmatory trials needed.
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Quoted from the source exactly as published.
While the pooled sphincter preservation (90%) and R0 resection (98%) rates appear favorable, clinicians should note that evidence derives predominantly from single-arm studies with no direct comparative control arms and low-to-moderate certainty by GRADE assessment. The authors emphasize that confirmatory high-quality RCTs are needed before this regimen can be recommended for routine clinical practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background Neoadjuvant therapy combined with immunotherapy has emerged as a promising strategy for rectal cancer (RC), but its efficacy in anal sphincter preservation, clinical outcomes, and safety profile remains to be systematically validated. This meta-analysis aims to comprehensively evaluate the anal sphincter preservation rate, clinical efficacy, and safety of neoadjuvant therapy combined with immunotherapy in rectal cancer patients, providing evidence-based support for clinical decision-making. Objective To assess the anal sphincter preservation rate, key clinical efficacy indicators (including pathological complete response rate, R0 resection rate, and tumor regression grade), and safety indicators (adverse events and postoperative complications) of neoadjuvant therapy combined with immunotherapy in rectal cancer patients. We systematically synthesize the absolute sphincter-preservation, pathological-response, and safety proportions of neoadjuvant immunotherapy in rectal cancer patients, with any comparison to historical data of conventional regimens presented as indirect and exploratory only. Methods This study was prospectively registered in PROSPERO (registration number: CRD420251159170) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of this systematic review was evaluated using the AMSTAR 2 tool. A comprehensive electronic search was performed across eight databases (PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, WanFang, and VIP) up to February 2, 2026. Eligible studies included randomized controlled trials (RCTs), single-arm trials, and observational studies (cohort studies, case-control studies) investigating neoadjuvant therapy combined with immunotherapy for rectal cancer. Data extraction was independently performed by two authors, and risk of bias was assessed using the ROBINS-I tool (for non-randomized studies) and the Cochrane Collaboration risk of bias tool (for RCTs). The GRADE approach was used to evaluate the certainty of evidence. Statistical analysis was conducted with R Studio 4.3.2 software, employing random-effects or fixed-effects models based on heterogeneity (assessed by I² statistic and chi-squared test). This meta-analysis does not include controlled comparative trials and that all analyses are single-arm proportion pooling without direct between-group comparisons. Results A total of 16 studies involving 540 rectal cancer patients were included. The pooled anal sphincter preservation rate was 0.90 (95% CI: 0.87–0.93) with moderate heterogeneity (I²=37.4%, P = 0.0716). The R0 resection rate was 0.98 (95% CI: 0.96–1.00) (I²=51.4%, P = 0.0361), and the pathological complete response (pCR) rate was 0.34 (95% CI: 0.29–0.38) (I²=71.8%, P 0.0001). The overall complete response (CR) rate was 0.49 (95% CI: 0.44–0.54) (I²=66.0%, P = 0.0007), and the tumor regression grade (TRG) 0–1 rate was 0.55 (95% CI: 0.49–0.62) (I²=78.6%, P 0.0001). Regarding safety, the incidence of grade 1–2 adverse events was 0.80 (95% CI: 0.71–0.89) (I²=0.0%, P = 0.8159), grade ≥3 adverse events was 0.17 (95% CI: 0.13–0.21) (I²=97.4%, P 0.0001), and postoperative complications rate was 0.24 (95% CI: 0.18–0.30) (I²=92.4%, P 0.0001). Pooled estimates within clinically defined subgroups were generally consistent and are reported descriptively only. Conclusions Neoadjuvant therapy combined with immunotherapy was associated with favorable pooled proportions of sphincter preservation and R0 resection in the included studies, although these estimates are derived predominantly from single-arm studies. This regimen warrants further investigation for organ preservation strategies, but confirmatory evidence from high-quality RCTs is needed. Given that the current evidence is predominantly of low-to-moderate certainty, high-quality, large-scale RCTs with long-term follow-up are needed to further validate these findings and optimize treatment regimens. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=CRD420251159170, identifier CRD420251159170.
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