Chemoradiotherapy may be safely omitted in some patients with locally advanced rectal cancer: PROSPECT trial

The findings were presented at the 2023 ASCO Annual Meeting (Abstract LBA2) and subsequently published in the Journal of Clinical Oncology (patient-reported outcomes data) and The New England Journal of Medicine (efficacy data). The findings imply that omitting radiation therapy can decrease short- and long-term side effects impacting the quality of life and provides similar outcomes in overall and disease-free survival.

Pelvic radiation combined with sensitizing chemotherapy with fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. There is no knowledge on whether neoadjuvant chemotherapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) can be used instead of chemoradiotherapy.

To fill this knowledge gap, Deborah Schrag, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, and colleagues conducted an unblinded, multicenter, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumour reduced in size by <20% or if FOLFOX was discontinued due to side effects) as compared with chemoradiotherapy.

The phase III PROSPECT trial enrolled 1,194 patients with rectal cancer that had spread to nearby tissue or lymph nodes but had not spread to distant organs and who were candidates for sphincter-sparing surgery. Patients were randomly assigned to the chemoradiation therapy group (control) or the modified FOLFOX6 chemotherapy with selective use of the chemoradiation therapy group (intervention), and 1,128 patients went on to receive treatment through the study.

In the control group, 543 patients were given chemoradiation with 28 radiation treatments over 5.5 weeks before a low anterior resection with total mesorectal excision. Chemoradiation comprised a drug combination called 5FUCRT, a combination of radiation therapy and a sensitizing fluoropyrimidine. In the intervention group, 585 patients received six cycles of modified FOLFOX6 followed by tumour restaging.

The primary endpoint was to determine disease-free survival. Secondary endpoints were local recurrence, overall survival, complete response, complete pathological resection, and toxic effects.

The study revealed the following findings:

• At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92).
• Five-year disease-free survival was 80.8% in the FOLFOX group and 78.6% in the chemoradiotherapy group.
• The groups were similar concerning overall survival (hazard ratio for death, 1.04) and local recurrence (hazard ratio, 1.18).
• In the FOLFOX group, 9.1% received preoperative chemoradiotherapy, and 1.4% received postoperative chemoradiotherapy.

"Patients with locally advanced rectal cancer with tumours that respond to chemotherapy may safely forgo radiation therapy before surgery," the authors concluded.

Reference:

The study "Preoperative Treatment of Locally Advanced Rectal Cancer" was published in The New England Journal of Medicine.

DOI: 10.1056/NEJMoa2303269