$Background:$ Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates.

$Objective:$ To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial.

$Design,\; setting,\; and\; participants:$ Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN.

$Outcome\; measurements\; and\; statistical\; analysis:$ PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox’s proportional hazards regression.

$Results\; and\; limitations:$ Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0 = 5, M1 = 32) and 305 had locally advanced disease (62%). The median PSA was 17 $\mu$g/l. Treatments included radical prostatectomy (RP; $n$ = 54; 11%), radiotherapy (RT; $n$ = 245; 50%), androgen deprivation therapy (ADT; $n$ = 122; 25%), other treatments ($n$ = 11; 2%), and unknown ($n$ = 60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38–0.83; $p$ = 0.0037), but mortality was similar in those treated radically. The non-randomised design is a limitation.

$Conclusions:$ Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding.

$Patient\; summary:$ Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.