Rectal adenocarcinoma, no metastases (M0)
Biopsy-proven. Staged with pelvic MRI, CT of chest, abdomen and pelvis, baseline CEA and complete colonoscopy (CT colonography if impassable). Plan at the colorectal MDT before any treatment.
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Rectal Cancer Neoadjuvant Therapy Selection
Rectal Cancer Neoadjuvant Therapy Selection: Rectal adenocarcinoma, no metastases (M0) → Tumour dMMR or MSI-H? → dMMR/MSI-H: do not start with chemother...
Pathway Overview
15 steps
Algorithm Steps
15 total
01Start 02Decision Tumour dMMR or MSI-H?
Test mismatch repair (IHC) or MSI on the biopsy in every patient before choosing neoadjuvant therapy.
- If Yes
- dMMR/MSI-H
03Warning dMMR/MSI-H: do not start with chemotherapy alone
dMMR rectal cancer can progress on neoadjuvant chemotherapy but responds well to PD-1 blockade. Chemoradiotherapy still downstaged most tumours in the same series.
- Progression on FOLFOX or CAPOX in 6 of 21 patients in one series
- Refer for Lynch syndrome assessment; MLH1 loss: test MLH1 promoter methylation
- Dostarlimab is not TGA-registered for rectal cancer
04End dMMR/MSI-H: MDT; PD-1 blockade if locally advanced (trial or off-label)
Locally advanced (cT3–T4 or node-positive): in a phase 2 study, dostarlimab every 3 weeks for 6 months gave a clinical complete response in all 49 patients who completed it. Complete response: watch-and-wait with close surveillance. Residual disease, or immunotherapy not possible: chemoradiotherapy and TME per MDT. cT1–T2 N0: surgery as for early tumours; no routine pre-op radiotherapy.
If No- pMMR/MSS
05Decision Early tumour: cT1–T2, N0?
On pelvic MRI (endorectal ultrasound can help for cT1). cT3–T4 or node-positive: locally advanced.
- If Yes
- cT1-2 N0
06End cT1–T2 N0: surgery; no routine pre-op radiotherapy
Shared decision on TME, transanal local excision (TAMIS or TEMS) or ESD for selected tumours. Pre-operative radiotherapy or chemoradiotherapy only in a clinical trial. After local excision with adverse pathology (pT2, high-risk pT1 or involved margin): MDT for completion TME.
If No- Locally advanced
07Warning Before fluoropyrimidine chemotherapy or pelvic radiotherapy
Also: warfarin with capecitabine raises INR, so monitor INR closely. Coronary artery disease: higher risk of fluoropyrimidine cardiotoxicity (angina, MI, arrhythmia). Prior pelvic radiotherapy or active IBD: radiation oncology review first. Discuss fertility preservation before pelvic radiotherapy.
- DPYD genotype before starting (MBS item 73322). Complete DPD deficiency: do not give. Partial: reduced dose
- Capecitabine: contraindicated if CrCl below 30 mL/min or severe hepatic impairment
- Pregnancy: chemotherapy and pelvic radiotherapy contraindicated. Pregnancy test first
08Decision High risk on MRI?
Any of: cT4; mesorectal fascia (MRF) involved (tumour 1 mm or less from MRF); EMVI; cN2; enlarged lateral pelvic nodes.
- If Yes
- High risk
09Action High risk: total neoadjuvant therapy (TNT)
Options: short-course RT 5 × 5 Gy, then CAPOX or FOLFOX (RAPIDO). Or long-course chemoradiotherapy with consolidation or induction FOLFOX or CAPOX (OPRA). Or FOLFIRINOX, then chemoradiotherapy (PRODIGE 23; fit, age 18–75).
- Chemoradiotherapy first, then chemotherapy: more organ preservation (OPRA)
- Short-course TNT: more locoregional recurrence at 5 years than long-course CRT (10% vs 6%, RAPIDO)
- Not fit for oxaliplatin: long-course chemoradiotherapy or short-course RT alone
- Regimen and doses: eviQ or local protocol
10Action Restage after neoadjuvant therapy
DRE, endoscopy and pelvic MRI, with CT of chest, abdomen and pelvis, about 8 weeks (4–12) after the last treatment. Short-course RT with immediate surgery (within 1 week): no restaging, go to TME.
11Decision Clinical response at restaging?
Graded as complete, near-complete or incomplete on DRE, endoscopy and MRI.
- cCR
12End Complete (cCR): offer watch-and-wait or TME
Only with informed consent (regrowth risk) and a structured surveillance programme. OPRA schedule: DRE and endoscopy every 4 months for 2 years, then every 6 months to 5 years; MRI every 6 months for 2 years, then yearly; CT of chest, abdomen and pelvis at least yearly. Regrowth: salvage TME.
- Near-complete
13End Near-complete: MDT to re-evaluate or proceed to TME
Options: reassess after a further interval and offer watch-and-wait if the response becomes complete; local excision in selected patients; or TME.
- Incomplete
14End Incomplete response: TME surgery
Low anterior resection or abdominoperineal resection by tumour level and sphincter involvement. New metastases or progression at restaging: MDT (metastatic pathway), not direct TME. After surgery: MDT review of the pathology for adjuvant therapy.
If No- Not high risk
15Action Not high risk (for example cT3, MRF clear): MDT options
Long-course chemoradiotherapy, or short-course RT then surgery, or TNT if organ preservation is a goal. cT2 N1 or cT3 N0–N1 suited to sphincter-sparing surgery: FOLFOX, with chemoradiotherapy only if poor response (PROSPECT). Upper rectum, MRF clear: upfront TME is an option.
- Long-course: 50–50.4 Gy in 25–28 fractions with capecitabine or infusional 5-FU
- Short-course: 5 × 5 Gy; delayed surgery gives more complete responses than immediate surgery
- Frail or unfit for chemotherapy: short-course RT alone
- Path rejoins step 10Shared downstream outcome
Guideline Source
ESMO Clinical Practice Guideline: Localised rectal cancer (Hofheinz et al., Ann Oncol 2025)
Clinical Safety Information
Clinical Decision Support — Not a Substitute for Clinical Judgment
Individual patient factors may require deviation from these recommendations.
Known Limitations
- For non-metastatic rectal adenocarcinoma only; not for metastatic or recurrent disease or other tumour types.
- PD-1 blockade for dMMR rectal cancer rests on phase 2 data; dostarlimab is not TGA-registered for this use.
- Regimens and doses: follow eviQ or local protocols.
- Watch-and-wait needs a centre with a structured surveillance programme.
Contraindicated Populations
Metastatic (M1) or locally recurrent rectal cancerChildren and adolescentsPregnancy (chemotherapy and pelvic radiotherapy contraindicated)Non-adenocarcinoma tumours (for example anal squamous cell carcinoma, neuroendocrine tumour, GIST)
Applicable Regions
USAUUKEU
AU: DPYD genotyping is Medicare-funded (MBS item 73322, from 1 Nov 2025). Regimens: eviQ. Dostarlimab is TGA-registered for endometrial cancer only. Optimal care pathway for colorectal cancer applies.
EU: ESMO 2025 localised rectal cancer guideline.
UK: NICE NG151: pre-operative RT or CRT for cT1-T2 N1-N2 or cT3-T4; not for cT1-T2 N0 outside trials; deferral of surgery after complete response with registry data.
US: NCCN Rectal Cancer guideline (current version).
Version 2Next review: 2027-09-30
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Frequently Asked Questions
What is the Rectal Cancer Neoadjuvant Therapy Selection?
The Rectal Cancer Neoadjuvant Therapy Selection is a management clinical algorithm for Colorectal Surgery. It provides a structured decision tree to guide clinical decision-making, based on ESMO Clinical Practice Guideline: Localised rectal cancer (Hofheinz et al., Ann Oncol 2025).
What guideline is the Rectal Cancer Neoadjuvant Therapy Selection based on?
This algorithm is based on ESMO Clinical Practice Guideline: Localised rectal cancer (Hofheinz et al., Ann Oncol 2025) (DOI: 10.1016/j.annonc.2025.05.528).
What are the limitations of the Rectal Cancer Neoadjuvant Therapy Selection?
Known limitations include: For non-metastatic rectal adenocarcinoma only; not for metastatic or recurrent disease or other tumour types.; PD-1 blockade for dMMR rectal cancer rests on phase 2 data; dostarlimab is not TGA-registered for this use.; Regimens and doses: follow eviQ or local protocols.; Watch-and-wait needs a centre with a structured surveillance programme.. Individual patient factors may require deviation from these recommendations.
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