Target trial emulation of survival outcomes for clinically localized prostate cancer treatments

BACKGROUND: The ProtecT randomized trial found similar survival between active surveillance (AS), radiotherapy (RT), and radical prostatectomy (PT) in localized prostate cancer (PC), but observational studies yielded conflicting results. This study aims to emulate ProtecT by comparing survival outcomes of men with localized PC undergoing PT or RT versus AS/watchful waiting (WW). METHODS: This target trial emulation study used the Korean Nationwide Health Insurance, Cancer Registry, and Death Registry linkage data (2012-2020). We included men (50-69 years) diagnosed with a first malignant localized PC. Primary outcome was PC-specific death, and secondary outcomes were all-cause death, metastasis, and antidepressant initiation. Two cohorts (PT vs. AS/WW and RT vs. AS/WW) were analyzed using Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 8,036 localized PC patients, 1,191 PT vs. 1,191 AS/WW and 428 RT vs. 428 AS/WW individuals were identified. During a mean follow-up of 4.4 years, PC-specific death occurred in 2 men (0.2%) in PT and 2 men (0.2%) in AS/WW, and 3 men (0.7%) in RT with 1 man (0.2%) in AS/WW. AS/WW showed comparable risks of PC-specific and all-cause death and metastasis as PT and RT. Compared to AS/WW, PT and RT showed lower risks of antidepressant initiation (HR [95% CI] 0.73 [0.58-0.93] for PT and HR 0.38 [0.24-0.61] for RT, respectively). CONCLUSIONS: In this target trial emulation study, AS/WW showed similar risks of mortality and metastasis as PT and RT, while PT and RT showed favorable outcomes with antidepressant initiation in Asian men with localized PC.