2192 - Does Regimen Selection Matter? Pathologic Complete Response across Four Contemporary Neoadjuvant Strategies in Rectal Cancer
Presenter(s)
A. Rommal1, H. Rahman1, C. E. Devoe1, J. Ricci1, M. Greenwald1, R. Sharma2, and B. Parashar2; 1Northwell Health, New Hyde Park, NY, 2Northwell, New Hyde Park, NY
Purpose/Objective(s): Total neoadjuvant therapy (TNT) is now a standard approach for locally advanced rectal cancer; however, comparative effectiveness of contemporary TNT regimens in routine clinical practice remains unclear. We evaluated differences in pathologic complete response (pCR) rates across four commonly used neoadjuvant strategies at a large US tertiary care center.
Materials/Methods: We conducted a retrospective single-institution study of patients with rectal adenocarcinoma treated with neoadjuvant chemotherapy and radiation followed by surgical resection between 2016 and 2025. Eligible patients had locally advanced disease (cT3–4). Patients were grouped by regimen: OPRA-like (long-course chemoradiation followed by consolidation FOLFOX/CAPOX; n=20), PRODIGE23-like (induction FOLFIRINOX followed by long-course chemoradiation; n=13), PROSPECT-like (induction FOLFOX followed by long-course chemoradiation; n=51), and RAPIDO-like (short-course radiotherapy with induction or consolidation FOLFOX/CAPOX; n=16). The primary endpoint was pCR. Comparisons were performed using chi-square testing, and multivariable logistic regression estimated odds ratios (OR).
Results: A total of 100 patients met inclusion criteria. Median age was 59 years (IQR, 49–69), and 38% were female. Most patients had cT3 disease (80%) and stage III disease (75%). Overall, 24 patients (24%) achieved pCR. pCR rates differed significantly across regimens (p=0.026): OPRA 45.0% (9/20), RAPIDO 37.5% (6/16), PROSPECT 15.7% (8/51), and PRODIGE23 7.7% (1/13). Using OPRA as reference, odds of pCR were significantly lower with PRODIGE23 (OR 0.10; 95% CI, 0.01–0.94; p=0.044) and PROSPECT (OR 0.23; 95% CI, 0.07–0.73; p=0.012), while RAPIDO was not significantly different (OR 0.73; 95% CI, 0.19–2.81; p=0.651). No significant associations were observed between pCR and age, sex, T stage, or overall stage.
Conclusion: In this real-world cohort, pCR rates varied significantly across contemporary TNT regimens, with OPRA-like therapy demonstrating the highest response. These findings complement randomized data and suggest that regimen selection may meaningfully influence pathologic response.