This protocol covers patients with localised rectal cancer situated in the lower or middle third of the rectum in whom organ preservation is the intended goal. The tumour is mismatch repair proficient (MMR-p) and microsatellite stable (MSS). Treatment planning centres on multimodal strategies designed to achieve tumour regression while avoiding surgical resection.

Treatment Approach

Radiotherapy-based strategies — selected according to tumour and nodal staging — form the backbone of treatment, with the addition of chemotherapy in certain presentations. The specific combination, sequence, and intensity differ meaningfully by stage. The full protocol specifies which approach applies and how treatment decisions are structured.

Primary Clinical Goal

The aim is clinical complete response (cCR), evaluated by digital rectal examination, sigmoidoscopy, and MRI at restaging 12 weeks after the start of radiotherapy. Where near-cCR is found, further restaging after an additional interval is recommended.

References

DOI: 10.1016/j.annonc.2025.05.528

Management of localised rectal cancer located in the lower or middle third of the rectum when organ preservation is intended.
Multimodal treatment strategies for patients with rectal cancer are increasingly incorporating a watch-and-wait approach for organ preservation.
SCRT or CRT can be recommended for patients with cT1-cT2 N0 tumours [II, B].
Standard external CRT followed by RT dose escalation using endorectal brachytherapy is recommended for patients with cT1-cT2 N+ or cT3 N0-1 tumours <5 cm [I, A].
TNT is recommended for patients with high-risk criteria and patients with cT2 N+ or cT3 Nany tumours [I, A].
Upfront CRT followed by consolidation ChT can be recommended to increase the likelihood of cCR [I, B].
RT should be offered as long-course CRT (50-50.4 Gy in 25-28 fractions with concomitant capecitabine or infusional 5-FU) or SCRT (25 Gy in five fractions) [I, A].
Consolidation or induction ChT (CAPOX or FOLFOX) should be administered for 3-4.5 months [I, A].
12 weeks after the start of RT in SCRT or CRT; in case of near cCR, further restaging can be recommended after another 4-8 weeks [I, B].
The cCR is assessed by a combination of DRE, sigmoidoscopy and MRI to assess the MRI tumour regression grade.

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Treatment of Localised Rectal Cancer in the Lower or Middle Third of the Rectum with Organ Preservation Intent

References