Risk of Distant Metastasis and Oncologic Outcomes of Clinical Near-Complete Responders After Neoadjuvant Therapy in Rectal Cancer: A Meta-Analysis

BACKGROUND: Watch-and-wait has allowed organ preservation in patients with locally advanced rectal cancer who have a clinical complete response to neoadjuvant therapy. The expansion of non-operative management to patients with a near-complete response raises the question of oncological safety in a nonoperative approach in this subset of patients. OBJECTIVE: We aimed to assess the prognostic impact of clinical response after neoadjuvant therapy and to assess the oncologic safety of nonoperative management in patients with near-complete or complete clinical responses. DATA SOURCES: We systematically reviewed PubMed, Embase and Web of Science in October 2025 to identify studies comparing oncological outcomes of patients with clinical or near-complete response. STUDY SELECTION: Studies comparing clinical response after neoadjuvant therapy in patients with locally advanced rectal cancer were included. We excluded conference abstracts. MAIN OUTCOME MEASURES: Primary outcome was overall survival. Secondary outcomes included distant metastasis, local regrowth, local regrowth-free survival, and organ preservation rate. RESULTS: We included 10 studies and 1,763 patients. Near-complete response after neoadjuvant therapy for rectal cancer is associated with higher risk of distant metastasis (16.8 vs 7.3%; RR 2.31; 95% CI: 1.63-3.26; p < 0.001; I² = 0%), and local regrowth (32.8 vs 19.7%; RR 1.75; 95% CI: 1.31-2.34; p < 0.001; I² = 42%), as well as reduced organ preservation (73.5 vs 80.7%; RR 0.84; 95% CI: 0.74-0.95; p = 0.007; I² = 69%) compared with clinical complete response. No statistical differences were seen in overall survival (HR 1.43; 95% CI: 0.94-2.16; p = 0.076; I² = 0%). LIMITATIONS: Heterogeneous definitions of near-complete response and lack of standardized reassessment timing and management. CONCLUSION: In contrast to individual studies, we found that near-complete response after neoadjuvant therapy may have an increased risk of distant metastasis compared to patients with a complete clinical response.