The Impact of Radiotherapy in Rectal Neuroendocrine Carcinoma Treatment

Radiotherapy, within multimodal treatment for high-grade, poorly differentiated rectal neuroendocrine carcinoma (NEC), has been associated with improved outcomes when combined with surgery and/or chemotherapy, but current evidence is sparse and largely retrospective. Here, NEC refers to poorly differentiated, high-grade carcinomas and is distinct from well-differentiated rectal neuroendocrine tumors (NETs); unless stated otherwise, the discussion focuses on NEC. Given heterogeneity in tumor biology and staging at presentation, along with limited high-level evidence, outcomes and optimal integration of radiotherapy can vary substantially between patients.

The synergy seen in combining these treatments is associated with improved local control and survival in observational analyses. In a retrospective cohort analysis, radiotherapy was associated with an adjusted hazard ratio of approximately 0.54 for mortality (95% CI as reported after multivariable adjustment), suggesting lower mortality without establishing causality; details are available in the retrospective cohort analysis. These associations support consideration of radiotherapy within multidisciplinary management for rectal NEC, while acknowledging the limits of the current evidence base.

Within multidisciplinary care, major guidelines note that the role of radiotherapy in high-grade rectal NEC is not well defined and is often individualized, with many recommendations extrapolated from broader NEC or rectal cancer literature. In practice, potential benefits include improved local control, downstaging to facilitate resection in select cases, and palliation of bleeding or pain. Tumor biology, including proliferation indices (e.g., Ki-67) and DNA damage response features, likely influences radio- and chemosensitivity, which may partly explain variable outcomes across cohorts.

Recent observational studies and retrospective cohorts suggest that integrated therapies may be associated with improved outcomes, informing but not definitively realigning clinical protocols. Modern techniques such as IMRT, VMAT, image-guided radiotherapy, and SBRT enable more precise targeting and may improve tolerability; their specific impact in rectal NEC continues to be defined.

When adverse effects occur during pelvic radiotherapy, standard mitigation includes IMRT-based planning with attention to bowel and bladder dose constraints, bowel/bladder preparation protocols, skin care, and symptom-directed management of diarrhea, cystitis, and fatigue; dose and fractionation are individualized by center and patient factors.

Priorities for the field include clarifying sequencing of chemoradiation relative to surgery, defining indications for adjuvant versus definitive radiotherapy, and building prospective registries specific to rectal NEC to improve evidence quality.

Key Takeaways:

• Evidence for radiotherapy in high-grade rectal NEC is limited and largely retrospective; associations with improved local control and survival have been reported but are not definitive.
• Within multidisciplinary care, radiotherapy may contribute to local control, downstaging, and symptom palliation, and may be associated with improved survival in observational cohorts.
• Modern planning and delivery techniques can aid tolerability, though their specific impact in rectal NEC is still being defined.
• Personalization is essential, and prospective registries are needed to clarify sequencing and indications.