Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial

Abstract

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 17μg/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 nonrandomised 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.

Keywords: Prostate cancer; Prostate-specific antigen screening; Survival.

Fig. 1

Diagram of patient flow through study. KM = Kaplan-Meier; PSA = prostate-specific antigen.

Fig. 2

(A) Prostate cancer–specific survival and (B) overall survival according to primary treatment groups among ProtecT cases. Death from prostate cancer occurred in two (4%) of the RP and 12 (5%) of the RT group (HR 0.95, CI 95% 0.22–4.12; p = 0.94). Death from all causes occurred in four (7%) of the RP and 37 (15%) of the RT group (HR 0.69, 95% CI 0.29–1.67; p = 0.41). A significantly greater proportion of the ADT group died from prostate cancer (n = 27, 22%) and all causes (n = 49, 40%) compared to men treated with radical therapy (p < 0.0001). RP = radical prostatectomy; RT = radical radiotherapy; ADT = androgen deprivation therapy; HR = hazard ratio; CI = confidence interval.

Fig. 3

Kaplan-Meier plots of (A) prostate cancer–specific survival and (B) overall survival among matched ProtecT cases and Anglia Cancer Network (ACN) controls. By the end of the study, 37 matched cases (9%) and 64 controls (16%) died from prostate cancer. Death from all causes occurred in 89 cases (22%) and 103 controls (26%). HR = hazard ratio; CI = confidence interval.