Dose Escalation in Neoadjuvant Chemoradiotherapy for Rectal Cancer: Short-Term Efficacy and Toxicity of VMAT–SIB vs. 3D-CRT

<i>Background and Objectives</i>: The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT), followed by surgery with or without adjuvant chemotherapy (CT). This study evaluated the efficacy and safety of dose-escalated radiotherapy (RT) using the volumetric modulated arc therapy-simultaneous integrated boost (VMAT-SIB) technique in patients with LARC compared to 3D conformal radiotherapy (3D-CRT). <i>Materials and Methods</i>: This study prospectively enrolled 75 patients with LARC. All patients received nCRT using VMAT-SIB, delivering a tumor dose (TD) of 54 Gy in 25 fractions, with concomitant CT following the 5-fluorouracil and leucovorin (5-FU-LV) protocol. To compare the treatment outcomes and toxicity associated with the increased RT dose, a retrospective cohort of 62 patients treated with the 3D-CRT technique was analyzed. The 3D-CRT group received a TD of 50.4 Gy in 28 fractions with the same CT. Outcomes, including pathological complete response (pCR), tumor regression grade (TRG), and sphincter preservation rates, were compared. <i>Results</i>: Among operated patients, the group treated with VMAT-SIB demonstrated improved rates of pCR (20.6% vs. 8.9%), with a statistically significant trend (<i>p</i> = 0.06). Sphincter-preserving surgeries were performed in 49 out of 63 operated patients (77.8%) in the VMAT-SIB group, compared to 35 out of 56 (62.5%) in the 3D-CRT group. Analysis of the definitive postoperative stage revealed a significantly higher prevalence of lower T categories (T0-2) (<i>p</i> < 0.01), negative N status (<i>p</i> < 0.05), and lower stages (I + II) (<i>p</i> < 0.05) in patients treated with the intensified RT approach. However, no significant differences in acute toxicity were observed. <i>Conclusions</i>: The implementation of intensified treatment with a higher dose using the VMAT-SIB technique demonstrated significant benefits in downsizing and downstaging compared to the standard treatment approach. These findings support its integration into clinical practice. However, further prospective, multi-center studies are needed to validate these results and assess long-term outcomes.