Risk-Adapted Selective Elective Nodal Irradiation in the Total Neoadjuvant Therapy Era for Rectal Cancer

With the introduction of total neoadjuvant therapy (TNT) in locally advanced rectal cancer treatment, multidisciplinary treatment options have become more diverse than before, and many challenges remain unresolved. A randomized clinical study in intermediate-risk locally advanced rectal cancer showed that neoadjuvant full-dose systemic chemotherapy with response-adapted omission of radiation therapy is non-inferior to concurrent chemoradiotherapy. Given that preoperative systemic chemotherapy provides an additional layer of local disease control, the traditional role and extent of neoadjuvant radiation therapy could be strategically re-evaluated within the TNT framework. In this context, a risk-adapted approach featuring selective reduction in elective nodal irradiation volume, particularly of the lateral pelvic lymph nodes, may offer a promising middle ground for treatment personalization. Drawing parallels from surgical practice-where total mesorectal excision is standard but lateral pelvic lymph node dissection is reserved for selected cases-this perspective advocates for similar selectivity in radiation therapy targeting, focusing on mesorectal and presacral regions while judiciously omitting lateral nodes in appropriately selected patients. This approach could maintain oncologic safety by focusing radiation therapy on limited but essential volumes. With modern intensity-modulated radiation therapy, reducing the target volume translates directly to enhanced organs-at-risk sparing, thereby mitigating radiation-induced toxicity. When combined with induction chemotherapy response assessment to refine patient selection, this approach can offer a biologically informed, personalized treatment paradigm that balances disease control with quality of life.