Survival rate and Toxicity (GI and Hematology) of Neoadjuvant Therapies for Locally Advanced Rectal Cancer Patients: A Systematic Review and Meta-analysis Comparing Long-course Chemoradiation versus Short-course Radiation with Consolidation Chemother

Background: Neoadjuvant long-course chemoradiation (LCCRT) has been the conventional approach for managing locally advanced rectal cancer (LARC). However, short-course radiation followed by consolidation chemotherapy (SCRT-CC) has gained attention as an alternative strategy that may improve oncologic outcomes while optimizing treatment duration and tolerance. Objective: To compare survival outcomes and treatment-related gastrointestinal and hematologic toxicities between SCRT-CC and LCCRT in adult patients with LARC through a systematic review and meta-analysis. Methods: Following PRISMA guidelines, a systematic search of PubMed, Scopus, and Web of Science (January 2020–December 2025) identified randomized controlled trials and prospective/retrospective cohort studies evaluating SCRT-CC versus LCCRT. The primary outcome was overall survival; secondary outcomes included gastrointestinal (nausea, vomiting, diarrhea) and hematologic toxicities. Risk of bias was assessed using ROB-1 for randomized trials and the Newcastle–Ottawa Scale for observational studies. Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated using random- or fixed-effects models based on heterogeneity (I²). Results: Nine studies (n = 2,869) met inclusion criteria, comprising 1,331 patients treated with SCRT-CC and 1,538 with LCCRT. SCRT-CC demonstrated a favorable trend in overall survival (HR: 0.91; 95% CI: 0.79–1.06), which became statistically significant following sensitivity analysis (HR: 0.78; 95% CI: 0.65–0.94). Hematologic toxicity did not differ significantly between groups (OR: 0.95; 95% CI: 0.34–2.65). Gastrointestinal toxicity rates were also comparable, although heterogeneity was considerable among studies. Conclusion: SCRT-CC provides survival outcomes comparable or superior to LCCRT without increasing hematologic or gastrointestinal toxicity, supporting its role as an effective neoadjuvant option for LARC. Treatment selection should still be individualized based on patient tolerance and institutional expertise. Larger, standardized clinical trials are warranted to further refine optimal sequencing strategies.