BACKGROUND: This study evaluated the impact of radiotherapy (RT) with or without a simultaneous integrated boost (SIB) to intraprostatic lesions on survival, recurrence, and toxicity in localized prostate cancer (PCa). Key prognostic and predictive factors were also analyzed. MATERIALS AND METHODS: A retrospective analysis included 712 intermediate- and high-risk PCa patients treated with external beam RT at 78 Gy, with or without SIB (up to 86 Gy), between 2010 and 2018. Propensity score matching (PSM) was used to ensure comparability. Outcomes assessed included biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), local recurrence (LR), distant metastasis (DM), and treatment-related toxicities. RESULTS: After PSM, 417 patients were analyzed (208 with SIB, 209 without). Over a median follow-up of 8.6 years, the SIB group showed higher 8-year bDFS (93.8% vs. 83.5%
p = 0.006) and lower rates of DM (6.1% vs. 13.0%
p = 0.003) and LR (1.8% vs. 6.9%
p = 0.03). PCSS was similar between groups (95.7% vs. 92.3%
p = 0.38). Advanced T stage and absence of SIB were predictors of worse bDFS, DM, and LR, while higher Gleason score were associated with poorer PCSS and DM in multivariable analysis. There were no significant differences in 8-year Grade ≥ 2 GU (10.1% vs. 10.5%
p = 0.98) or GI (7.8% vs. 6.5%
p = 0.64) toxicities between the SIB and non-SIB groups. CONCLUSIONS: SIB with external beam RT significantly improves bDFS and reduces LR and DM in intermediate- and high-risk PCa, with no increase in significant toxicities. These findings emphasize the value of dose escalation in achieving better local control and long-term outcomes while maintaining patient safety.