Abstract
BACKGROUND: The neoadjuvant chemotherapy (nCT) could achieve outcomes comparable to neoadjuvant chemoradiotherapy (nCRT) and reduced radiation toxicity, radiotherapy is questioned. Comparing nCRT and nCT in locally advanced rectal cancer (LARC) in the real world to identify patient subgroups that may benefit most from each approach. METHODS: This retrospective study included patients with rectal cancer located within 10 cm from the anal verge and clinical staging of T2N + M0 or T3-4NanyM0. Patients were stratified into the nCRT group, which received radiotherapy (45.0 to 50.4 Gy/25 or 28 fractions) with concurrent Capecitabine chemotherapy, or the nCT group which received chemotherapy alone. RESULTS: In total, 380 patients (nCRT, n = 196, nCT, n = 184) were recruited. The rate of pathologic complete response (pCR) in the nCRT and nCT group was 22.4% and 9.2%, T downstaging was 69.4% and 47.8%, and tumor regression grade (TRG) 1–2 was 59.7% and 24.5%, respectively. Similarly, The nCRT group also had a favorable pCR, T downstaging, and TRG 1–2 rate than the nCT group in the bad-risk, advanced-risk, and subgroup A (tumors located at < 8 cm from the anal verge). In contrast, outcomes were comparable for subgroup B (tumors located at ≥ 8 cm) between the two groups. Moreover, the nCRT had a better rate of 3-year locoregional relapse-free survival (LRFS) (98.1% vs. 88.0%, P = 0.031) in the bad-risk category compared with the nCT group. Conversely, the disease-free survival (DFS) and overall survival (OS) were similar. The nCRT was associated with a higher rate of grade 1–2 myelosuppression (69.9% vs. 37.0%), diarrhea (54.1% vs. 10.3%), preventive stoma (62.8% vs. 44.6%), postoperative bowel obstruction (9.2% vs. 1.1%), and postoperative anastomotic stenosis (4.1% vs. 0.5%) (all P < 0.05). CONCLUSION: Tumor location and risk category may serve as a practical index for clinical decision-making on neoadjuvant therapy strategies in LARC. Patients with bad-risk or tumors located at < 8 cm from the anal verge may be benefited from nCRT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-025-14616-9.