| Summary: | That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort study by using propensity score matching (PSM) to evaluate the clinical outcomes of RP and IMRT-ADT in relatively young patients with HR/VHR-LPC. <i>Methods</i>: We used the Taiwan Cancer Registry database to evaluate clinical outcomes in relatively young (aged ≤ 65 years) patients with HR/VHR-LPC, as defined by the National Comprehensive Cancer Network risk strata. The patients had received RP or IMRT-ADT (high-dose, ≥72 Gy plus long-term, 1.5–3 years, ADT). Head-to-head PSM was used to balance potential confounders. A Cox proportional hazards regression model was used to analyze oncologic outcomes. <i>Results</i>: High-dose IMRT-ADT had a higher risk of biochemical failure (adjusted hazard ratio [aHR] = 2.03, 95% confidence interval [CI] 1.56–2.65, <i>p</i> < 0.0001) compared with RP; IMRT-ADT did not have an increased risk of all-cause death (aHR = 1.2, 95% CI 0.65–2.24, <i>p</i> = 0.564), locoregional recurrence (aHR = 0.88, 95% CI 0.67–1.06, <i>p</i> = 0.3524), or distant metastasis (aHR = 1.03, 95% CI 0.56–1.9, <i>p</i> = 0.9176) compared with RP. <i>Conclusion</i>: In relatively young patients with HR/VHR-LPC, RP and IMRT-ADT yielded similar oncologic outcomes and RP reduced the risk of biochemical failure compared with IMRT-ADT.
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