# PROSPECT: neoadjuvant FOLFOX with selective use of chemoradiotherapy for locally advanced rectal cancer

Source: https://onco.cc/key-papers/paper-prospect-nejm-2023/  
OnCo record `paper-prospect-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

For rectal cancers of intermediate risk suitable for sphincter-sparing surgery, six cycles of FOLFOX chemotherapy, with radiotherapy only if the tumour did not shrink, was as effective as routine chemoradiation and spared nine in ten patients pelvic radiotherapy.

## Summary

Phase 3 non-inferiority trial of 1,194 patients with cT2 node-positive, cT3 node-negative or cT3 node-positive rectal cancer candidates for sphincter-sparing surgery, randomised to neoadjuvant FOLFOX with chemoradiotherapy only for poor response, or standard pelvic chemoradiotherapy.

Five-year disease-free survival was 80.8 versus 78.6 percent (non-inferior), local recurrence 1.8 versus 1.6 percent, and only 9 percent of FOLFOX patients needed chemoradiotherapy; quality of life differed in bowel, sexual and neuropathy domains by arm.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/NEJMoa2303269
- Authors: Schrag D, Shi Q, Weiser MR, et al.
- Findings: Five-year disease-free survival 80.8 percent vs 78.6 percent (non-inferior).; Chemoradiotherapy avoided in 91 percent of the FOLFOX arm.
- What it means: Selected patients with intermediate-risk rectal cancer can avoid radiotherapy altogether, with chemotherapy alone before surgery, trading neuropathy for better long-term bowel and sexual function.
- Caveats: Excluded T4 tumours, threatened mesorectal fascia and low tumours needing abdominoperineal resection.; Non-inferiority margin allowed a modest loss of efficacy.

## Sources

- N Engl J Med 2023: https://doi.org/10.1056/NEJMoa2303269
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37272534/

## Connected records

- cancers: [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- trials: [PROSPECT (Alliance N1048)](https://onco.cc/trials/prospect/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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