1. Staging and Risk Stratification
What is the role of high-resolution pelvic MRI?
High-resolution pelvic MRI is the preferred imaging modality for local staging of rectal cancer. It assesses T and N stage, the relationship of the tumour to the mesorectal fascia/CRM, EMVI, tumour location and involvement of adjacent structures, thereby guiding neoadjuvant treatment and surgical planning.
What is the significance of threatened CRM/MRF and positive EMVI?
A threatened CRM/MRF (≤1 mm) indicates a high risk of an involved surgical margin and local recurrence. EMVI positivity is an adverse prognostic factor associated with a higher risk of systemic/distant metastases. Together with T3cN2a disease, these features place this patient in a high-risk locally advanced rectal cancer group.
2. Neoadjuvant Treatment
TNT versus conventional chemoradiotherapy
Total neoadjuvant therapy (TNT) delivers both systemic chemotherapy and pelvic radiotherapy/chemoradiotherapy before surgery. Compared with conventional chemoradiotherapy followed by surgery and postoperative chemotherapy, TNT improves chemotherapy completion and reduces the risk of distant relapse, with higher rates of complete response in many studies.
For this patient with T3cN2a disease, threatened CRM and EMVI, TNT would be a strong preferred approach.
Short-course RT versus long-course chemoradiotherapy
Short-course RT (5 × 5 Gy) is completed in one week and can be followed by chemotherapy and surgery. It provides good local control and is considerably shorter.
Long-course chemoradiotherapy generally involves approximately 5–6 weeks of pelvic radiation with concurrent fluoropyrimidine. It provides greater tumour regression and may be particularly useful when CRM is threatened, where downstaging is important.
pCR, distant control and organ preservation
TNT generally produces higher compliance with systemic chemotherapy and higher complete-response rates than conventional sequencing. Both short- and long-course approaches can provide good disease control, but long-course treatment may offer greater tumour shrinkage.
A higher clinical complete response (cCR) after TNT can increase opportunities for organ preservation through Watch-and-Wait, although this requires careful selection and intensive surveillance.
3. Surgery and Organ Preservation
Is sphincter preservation feasible for a tumour 4 cm from the anal verge?
Yes, it may be feasible, particularly if TNT produces good tumour regression and an adequate distal margin can be achieved while maintaining sphincter function. However, the final decision depends on tumour relationship to the sphincter complex, levator muscles, CRM and response to treatment.
LAR or APR?
If the sphincter and levator complex can be preserved with an adequate oncological margin, ultralow LAR with total mesorectal excision (TME) may be possible. If the tumour directly involves the sphincter/levator complex or adequate margins cannot be achieved, APR may be required.
When is Watch-and-Wait appropriate?
Watch-and-Wait is an option for carefully selected patients who achieve a clinical complete response after neoadjuvant treatment, with no residual tumour on DRE, endoscopy and appropriate MRI assessment.
It should only be undertaken where there is experienced multidisciplinary assessment and intensive surveillance, because local regrowth can occur and salvage surgery must be available.
4. Resource-Constrained Setting
How can short-course RT or TNT reduce treatment time and costs?
Short-course RT reduces radiation treatment from approximately 5–6 weeks to 1 week, decreasing transport, accommodation, time away from work and hospital-related costs. TNT can also complete systemic treatment before surgery, potentially reducing postoperative chemotherapy requirements and improving treatment completion.
Practical adaptations in an out-of-pocket system
- Prefer evidence-based regimens that minimize hospital visits without compromising outcomes.
- Consider short-course RT when clinically appropriate and radiotherapy capacity is limited.
- Use affordable generic CAPOX/FOLFOX where appropriate.
- Coordinate chemotherapy, imaging and surgical appointments to reduce travel.
- Provide clear counselling about expected costs before treatment.
- Establish multidisciplinary review to avoid unnecessary investigations and treatment delays.
- Ensure MRI, radiotherapy and surgery are coordinated before starting treatment.
For this particular patient, because he has T3cN2a disease, threatened CRM and EMVI-positive disease, I would favour TNT with an approach designed to achieve maximal tumour regression and systemic disease control, while considering short-course RT if local resources and patient finances make prolonged chemoradiotherapy difficult.
references
- Glynne-Jones R, Wyrwoll M, Tiret E, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2017;28(suppl 4):iv22–iv40.
- ESMO. Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology. 2025.
- Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus standard treatment in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncology. 2021;22(1):29–42.
- Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23). Lancet Oncology. 2021;22(5):702–715.