Some patients with locally advanced rectal cancer can be spared pelvic radiation
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Key takeaways:
- The PROSPECT trial showed FOLFOX to be noninferior to pelvic chemoradiation before surgery with regard to DFS.
- Only 9% of patients assigned to the FOLFOX group required pelvic chemoradiation.
CHICAGO — Most patients with intermediate-risk rectal cancer can undergo curative-intent treatment without the need for pelvic radiation, according to study results presented during a press conference at ASCO Annual Meeting.
“Why is this a big deal? It’s a big deal because we have been radiating pelvises to treat this type of rectal cancer for the past 30 years,” Deborah Schrag, MD, MPH, gastrointestinal oncologist, chair of the department of medicine and George J. Bosl chair at Memorial Sloan Kettering Cancer Center, said during a presentation.
Background, methodology
Standard treatment for locally advanced rectal cancer consists of 5.5 weeks of pelvic chemoradiation daily with a dollop of chemotherapy administered at the same time. About 8 weeks after chemoradiation, patients undergo total mesorectal resection followed by approximately 4 months of CAPOX or FOLFOX chemotherapy.
The regimen reduces the risk for local pelvic recurrence and produces very good outcomes, “but it’s long and it’s hard,” Schrag said.
Patients experience a host of long-term toxic effects from pelvic chemoradiation, including impairments in bowel, bladder and sexual function, higher risk for pelvic fracture and second malignancy, and infertility and premature menopause.
Improvements in chemotherapy, surgical techniques, screening and imaging prompted researchers to question whether radiation could be used more selectively and only for people who fail to respond to chemotherapy, Schrag said.
The randomized phase 3 PROSPECT trial tested the current standard of care against a regimen that included six cycles of FOLFOX first, followed by surgery for those who responded and pelvic chemoradiation for those whose primary tumor decreased by less than 20% in size or who had to discontinue chemotherapy due to adverse events.
The study included 1,128 patients (mean age, 57 years) with T2 node-positive, T3 node-negative and T3 node-positive disease who qualified for sphincter-sparing surgery.
DFS served as the primary endpoint. Secondary endpoints included OS, local recurrence, complete surgical resection, complete response, toxicity and quality of life.
Median follow-up was 58 months.
Results, implications
The results, published simultaneously in The New England Journal of Medicine, showed FOLFOX with selective pelvic chemoradiation to be noninferior to pelvic chemoradiation in terms of DFS (HR = 0.92; 90.2% CI, 0.74-1.14). Schrag reported 5-year DFS rates of 80.8% in the FOLFOX group (n = 585) and 78.6% in the chemoradiation group (n = 543).
The groups also had similar rates of 5-year OS (89.5% FOLFOX vs. 90.2% chemoradiation; HR = 1.04; 95% CI, 0.74-1.44), and freedom from local recurrence at 5 years (98.2% vs. 98.4%; HR = 1.18; 95% CI, 0.44-3.16). Moreover, only 9% of patients assigned to the FOLFOX group required pelvic chemoradiation, Schrag said.
The FOLFOX group had a higher rate of grade 3 or greater adverse events during neoadjuvant therapy than the chemoradiation group (41% vs. 22.8%), but treatment lasted about twice as long (minimum 12 weeks, vs. 5.5 weeks). The FOLFOX group had a lower rate of grade 3 or greater postoperative adverse events (25.6% vs. 32.6%) and improved bowel and sexual function.
“We think that we can successfully de-escalate treatment of rectal cancer and achieve the same high cure rates, [and] keep patients disease-free with less long-term toxicity,” Schrag said.
References:
Schrag D, et al. Abstract LBA2. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
Schrag D, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2303269.
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Schrag D, et al. Abstract LBA2. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
Schrag D, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2303269.
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