Goal-directed neoadjuvant therapy: What should we offer in each case?

Abstract

The management of rectal cancer has undergone significant evolution, driven by advancements in staging, treatment strategies, and understanding tumor biology. Initially dominated by total mesorectal excision (TME) with or without neoadjuvant chemoradiation (nCRT), the landscape shifted with the advent of high-resolution magnetic resonance imaging (MRI), which refined locoregional staging and identified prognostic markers such as extramural venous invasion (EMVI) and mesorectal fascia involvement. Tumor response to therapy, particularly complete clinical response (cCR), enabled organ-preserving strategies like the Watch & Wait approach and transanal local excision. Total neoadjuvant therapy (TNT) emerged as a strategy to improve systemic outcomes, though controversies persist regarding its optimal sequencing and survival benefits. Recent breakthroughs, such as immunotherapy for microsatellite instability-high tumors, demonstrate promising non-surgical management options. Current treatment objectives prioritize personalized approaches based on tumor location, risk factors, and the potential for organ preservation, reflecting a nuanced balance between efficacy, functional outcomes, and patient quality of life.