Some patients with locally advanced rectal cancer may avoid chemoradiotherapy before surgery.

As you know, the standard treatment for locally advanced rectal cancer consists of 5.5 weeks of chemoradiotherapy with the simultaneous use of fluoropyrimidine. And about 8 weeks after chemoradiotherapy, patients undergo a total mesorectal resection followed by a course of CAPOX or FOLFOX chemotherapy.

In this study, the authors asked whether radiation could be used more selectively and only for patients who did not respond to preoperative chemotherapy?

The Phase 3 PROSPECT randomized trial compared the current standard of care with a regimen that initially included six cycles of FOLFOX followed by surgery for those who responded to treatment and chemoradiotherapy for those whose primary tumor was reduced by less than 20% or who should was to discontinue chemotherapy due to adverse events.

The study included 1128 patients (mean age 57 years) with T2N+, T3N- and T3N+ disease. Patients with distal T4 tumors, or > 4 enlarged lymph nodes were not included in the study. DFS (progression-free/progression-free survival) served as the primary endpoint. Secondary endpoints included overall survival, local recurrence, complete surgical resection, complete response, toxicity, and quality of life. The median follow-up was 58 months.

The results, published concurrently in The New England Journal of Medicine, showed that FOLFOX with selective chemoradiotherapy is not inferior to pelvic chemoradiotherapy in terms of DFS. Schrag reported a 5-year DFS of 80.8% in the FOLFOX group (n = 585) and 78.6% in the chemoradiotherapy group (n = 543).

The groups also had similar 5-year overall survival rates of 89.5 for FOLFOX versus 90.2% for chemoradiotherapy and no local recurrence at 5 years (98.2% versus 98.4%. Moreover, only 9 % of patients included in the FOLFOX group required pelvic chemoradiation The FOLFOX group had a greater incidence of grade 3 or higher adverse events than the chemoradiotherapy group (41% vs 22.8%), but treatment lasted approximately two times longer (at least 12 weeks vs. 5.5 weeks) The FOLFOX group had a lower rate of grade 3 or higher postoperative adverse events (25.6% vs. 32.6%).

Output:

FOLFOX preoperative chemotherapy with selective use of chemoradiotherapy is not inferior to chemoradiotherapy in neoadjuvant treatment of rectal cancer. Findings expand treatment options for rectal cancer.