Radiation can be safely omitted in selected patients with locally advanced rectal cancer

By the staff of ASCO Post

Posted: 6/4/2023 11:46:00 AM

Last update: 6/4/2023 10:53:02

Locally advanced rectal cancer patients with chemotherapy-responsive tumors can safely forego radiation therapy before surgery, based on results from the PROSPECT trial. These data were presented by Deborah Schrag, MD, FASCO, MPHat the ASCO Annual Meeting 2023 (Abstract LBA2) and contextually published in The New England Journal of Medicine(effectiveness data) and theJournal of Clinical Oncology (data on patient-reported outcomes). Omitting radiotherapy can reduce short- and long-term side effects that affect quality of life, providing similar results in disease-free survival and overall survival.

Deborah Schrag, MD, FASCO, MPH

About the study

The phase III PROSPECT study enrolled 1,194 patients from June 2012 to December 2018 with rectal cancer that had spread to nearby tissues or lymph nodes but had not spread to distant organs. Patients were randomly assigned to the chemotherapy group (control) or modified FOLFOX6 chemotherapy (leucovorin, fluorouracil, oxaliplatin) with selective use of the chemotherapy group (intervention), and 1,128 patients continued to receive treatment throughout the study.

In the control group, 543 patients received chemoradiotherapy with 28 radiotherapy treatments for 5.5 weeks before low anterior resection with total mesorectal excision. Chemoradiation consisted of a combination drug called 5FUCRT, a combination of radiation therapy and a fluoropyrimidine sensitizer (intravenous fluorouracil or oral capecitabine).

In the intervention group, 585 patients received six cycles of modified FOLFOX6 followed by tumor restaging. If the tumor shrunk by 20% or more based on follow-up MRI of the pelvis, no radiation therapy was given before surgery. If the tumors did not shrink by 20% or more, radiation therapy with fluorouracil or capecitabine was given before surgery. In the intervention group, 53 people (9%) needed radiation therapy before surgery because the tumors hadn’t shrunk by 20% or more. After surgery, doctors and patients may choose to prescribe/receive additional chemotherapy. Most patients in both groups continued to receive additional postoperative modified FOLFOX6 chemotherapy.

Key Findings

After 5 years, there was no statistically significant difference between the two treatment groups in any of the endpoints studied, meaning that radiotherapy can safely be omitted before surgery if the tumor is responding to treatment with modified FOLFOX6 chemotherapy.

Five years after random assignment, the results showed that:

• Disease-free survival was 78.6% in the chemoradiotherapy group and 80.8% in the selective chemoradiotherapy modified FOLFOX6 group.
• Overall survival was 90.2% in the chemoradiotherapy group and 89.5% in the selective chemoradiotherapy modified FOLFOX6 group.
• Surgical resection rates were 97.1% in the chemoradiotherapy group and 98.8% in the selective chemoradiotherapy modified FOLFOX6 group.
• Local recurrence rates were very low and similar for both groups (2%).
• Pathologic complete response was 24.3% in the chemoradiation group and 21.9% in the selective chemoradiation-modified FOLFOX6 group.
• Only 9% of patients who received modified FOLFOX6 in the experimental group required preoperative chemoradiotherapy.

This study establishes preoperative FOLFOX therapy and only the selective use of chemoradiotherapy for patients with locally advanced rectal cancer, said lead author Dr. Schrag, chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center. Having this option is important for several reasons. First, in many parts of the world, radiation therapy is not readily available. An all-chemotherapy approach may make treatment with curative intent accessible for patients in these resource-limited settings. Additionally, given the rising rates of colorectal cancer in young patients, this offers an option for patients wishing to preserve fertility or avoid early menopause.

Radiation therapy can have significant short- and long-term toxicities that negatively impact quality of life, including infertility, ovarian failure, the need for a temporary ostomy, diarrhea, cramping, fecal incontinence, and bladder problems. Chemotherapy also has side effects including fatigue, nausea, vomiting, low white blood cell count, infection, and neuropathy (numbness and tingling in the hands and feet). This study offers patients alternative treatment options.

Next steps

The study will continue to follow participants and collect additional data on disease-free survival, overall survival, local recurrence-free survival, and other secondary endpoints for 8 years. Further studies will evaluate the biological samples collected during this study to see if there are tumor characteristics associated with an increased likelihood of responding to chemoradiotherapy or with an increased likelihood of responding to modified FOLFOX6 chemotherapy.

Disclosure: The study was funded by the National Cancer Institute of the National Institutes of Health. For complete information on the authors of the study, visit coi.asco.org.

The content of this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO) and does not necessarily reflect the views and opinions of ASCO.

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