Many patients with locally advanced rectal cancer may be able to receive curative-intent treatment without pelvic radiation, according to research presented at the ASCO Annual Meeting 2023.1
Results from the PROSPECT trial showed that patients with locally advanced rectal cancer had similar outcomes if they received pelvic chemoradiation or if they received fluorouracil, leucovorin, and oxaliplatin (FOLFOX) with chemoradiation added only in select cases.
The phase 3 PROSPECT trial (ClinicalTrials.gov Identifier: NCT01515787) included 1128 patients with clinical T2 node-positive, T3 node-negative, or T3 node-positive rectal cancer who were candidates for sphincter-sparing surgery and chemoradiation.
The patients were randomly assigned to receive chemoradiation (n=543) or FOLFOX with selective chemoradiation if necessary (n=585). Patients in the chemoradiation arm received pelvic radiation (5040 cGy for 5.5 weeks) plus capecitabine or fluorouracil, followed by surgery and adjuvant FOLFOX or capecitabine plus oxaliplatin (CAPOX).
Patients in the FOLFOX arm received 6 cycles of this regimen, followed by surgery and adjuvant FOLFOX or CAPOX. Patients in this arm were given neoadjuvant chemoradiation before surgery if they had a poor response or were intolerant to FOLFOX, and 9% of patients met these criteria.
The median follow-up was 58 months. The 5-year disease-free survival rate in the FOLFOX arm was noninferior to that in the chemoradiation arm — 80.8% and 78.6%, respectively (hazard ratio [HR], 0.92; 90.2% CI, 0.74-1.14).
Local recurrence-free survival, overall survival, complete resection, and pathologic complete response rates were all similar between the treatment arms.
The 5-year local recurrence-free survival rate was 98.2% in the FOLFOX arm and 98.4% in the chemoradiation arm (HR, 1.18; 95% CI, 0.44-3.16). The 5-year overall survival rate was 89.5% and 90.2%, respectively (HR, 1.04; 95% CI, 0.74-1.44).
The complete resection rate was 99% in the FOLFOX arm and 97% in the chemoradiation arm. The pathologic complete response rate was 22% and 24%, respectively. The proportion of patients who received adjuvant therapy was 82% and 83%, respectively.
Grade 3 or higher adverse events during neoadjuvant treatment occurred in 41% of patients in the FOLFOX arm over 12 weeks and 23% of the chemoradiation arm over 6 weeks. Fatigue, constipation, appetite loss, nausea, and neuropathy were more common in the FOLFOX arm. Diarrhea was more common in the chemoradiation arm.
“Neoadjuvant FOLFOX, with only selective use of pelvic chemoradiation, is a safe and effective treatment option for patients with clinical T2 node-positive, clinical T3 node-negative, or clinical T3 node-positive rectal cancer,” said study presenter Deborah Schrag, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
“PROSPECT found that most intermediate-risk rectal cancer patients can receive curative-intent treatment without the need for pelvic radiation,” she noted.
Results from PROSPECT were also published in The New England Journal of Medicine.2
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.
1. Schrag D, Shi Q, Weiser MR, et al. PROSPECT: A randomized phase III trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC) (Alliance N1048). ASCO 2023. June 2-6, 2023. Abstract LBA2.
2. Schrag D, Shi Q, Weiser MR, et al. Preoperative treatment of locally advanced rectal cancer. N Engl J Med. Published online June 4, 2023. doi:10.1056/NEJMoa2303269