6/29/23, 1:44 AM PROSPECT Pathway Feedback Search Clinical Topics Home Studies PROSPECT PROSPECT Disease Rectal cancer Trial question Is preoperative neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin noninferior to chemoradiotherapy in patients with locally advanced rectal cancer? Study design Multi-center Open label RCT Population Characteristics of study participants 34.0% female N = 1128 66.0% male 1128 patients (389 female, 739 male) Inclusion criteria: adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery Key exclusion criteria: T4 tumors; 4 pelvic lymph nodes with a short axis > 10 mm or tumor visible within 3 mm of the radial margin seen on baseline pelvic imaging; previous pelvic radiation therapy; chemotherapy within the previous 5 years; abnormal laboratory measures Interventions N=585 FOLFOX (neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin every 2 weeks for 6 cycles) https://web.pathway.md/studies/recMAVMwJT2DJsSRv 1/2 6/29/23, 1:45 AM PROSPECT Pathway N=543 chemoradiotherapy (pelvic radiotherapy with 50.4 Gy delivered in 28 fractions plus chemotherapy with 5-fluorouracil or capecitabine) Primary outcome Disease-free survival at 5 years 80.8 % 80.8 78.6 60.6 % 40.4 % Difference not exceeding nonferiority margin 20.2 % 0.0 % FOLFOX Chemoradiotherapy Difference not exceeding nonferiority margin in disease-free survival at 5 years (80.8% vs. 78.6%; AD 2.2%, 95% CI 0.67 to 3.73) Secondary outcomes No significant difference in overall survival at 5 years (89.5% vs. 90.2%; HR 0.96, 96% CI 0.69 to 1.35) No significant difference in local recurrence at 5 years (1.8% vs. 1.6%; HR 1.18, 95% CI 0.44 to 3.16) Safety outcomes No significant difference in hypertension. Significant difference in severe grade 3 adverse events (41.0% vs. 22.8%). Conclusion In adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery, FOLFOX was noninferior to chemoradiotherapy with respect to a disease-free survival at 5 years. Reference Deborah Schrag, Qian Shi, Martin R Weiser et al. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jun 4. Online ahead of print. Open reference URL https://web.pathway.md/studies/recMAVMwJT2DJsSRv 2/2