PROSPECT
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
66.0% male
N = 1128
1128 patients (389 female, 739 male).
Inclusion criteria: adult patients 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).
N=543 chemoradiotherapy (pelvic radiotherapy with 50.4 Gy delivered in 28 fractions plus chemotherapy with 5-FU or capecitabine).
Primary outcome
Disease-free survival at 5 years
80.8%
78.6%
80.8 %
60.6 %
40.4 %
20.2 %
0.0 %
FOLFOX
Chemoradiotherapy
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority 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 adult patients 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 Jul 27;389(4):322-334.
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