Clinical Impact of Total Neoadjuvant Therapy Combined with Dose-Escalated Intensity-Modulated Radiotherapy for Lower...

Background: This study aimed to compare the outcomes and safety profiles of total neoadjuvant therapy (TNT) combined with dose-escalated intensity-modulated radiotherapy (IMRT) and conventional neoadjuvant chemoradiotherapy (NACRT) using three-dimensional conformal radiotherapy (3D-CRT) for locally advanced lower rectal cancer. Methods: This single-institution retrospective study included 51 patients treated with TNT using IMRT from 2018 to 2023 and 53 patients treated with conventional NACRT from 2001 to 2018. TNT consisted of IMRT at a total dose of 54 Gy with capecitabine, whereas NACRT consisted of 3D-CRT at a total dose of 45 Gy with a 5-fluorouracil-based regimen. Survival outcomes, treatment compliance, adverse events, surgical complications, and combined complete response (CR), defined as clinical CR plus pathological CR, were evaluated. Results: The combined CR rate was significantly higher in the TNT with IMRT group than in the NACRT group (43.1% vs. 5.7%). Overall survival and local recurrence-free survival did not differ significantly between the groups, whereas recurrence-free survival was significantly better in the TNT with IMRT group. Treatment compliance was comparable between the groups. Grade ≥ 3 adverse events during radiotherapy were less frequent in the TNT with IMRT group than in the NACRT group (7.8% vs. 22%), and major surgical complications did not differ significantly. Conclusions: TNT combined with dose-escalated IMRT was associated with a higher combined CR rate, favorable disease-free survival, and acceptable toxicity in this cohort. However, given the retrospective historical control design, chronological differences, follow-up imbalance, and potential residual confounding, these findings should be interpreted cautiously and require validation in prospective studies with longer follow-up.