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Randomized Controlled Trial
. 2024 May 7;331(17):1460-1470.
doi: 10.1001/jama.2024.4011.

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial

Richard M Martin  1   2   3 , Emma L Turner  1 , Grace J Young  1 , Chris Metcalfe  1 , Eleanor I Walsh  1 , J Athene Lane  1 , Jonathan A C Sterne  1   2   4 , Sian Noble  1 , Peter Holding  5 , Yoav Ben-Shlomo  1 , Naomi J Williams  1 , Nora Pashayan  6 , Mai Ngoc Bui  6 , Peter C Albertsen  7 , Tyler M Seibert  8   9   10 , Anthony L Zietman  11 , Jon Oxley  12 , Jan Adolfsson  13 , Malcolm D Mason  14 , George Davey Smith  1   3 , David E Neal  5 , Freddie C Hamdy  5 , Jenny L Donovan  1 ; CAP Trial Group
Collaborators, Affiliations
Randomized Controlled Trial

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial

Richard M Martin et al. JAMA. .

Abstract

Importance: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.

Objective: To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening.

Design, setting, and participants: This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021.

Intervention: Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation).

Main outcomes and measures: The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.

Results: Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.

Conclusions and relevance: In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.

Trial registration: isrctn.org Identifier: ISRCTN92187251.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lane reported receiving grants from the UK National Institute for Health and Care Research (NIHR) during the conduct of the study. Dr Sterne reported receiving grants from the NIHR and Health Data Research UK during the conduct of the study. Dr Seibert reported receiving personal fees from Varian Medical Systems; receiving personal fees from, having stock options in, and serving on the scientific advisory board for Cortechs; and receiving grants to the institution from GE Healthcare outside the submitted work. Dr Adolfsson reported being a member of the National Screening Council giving advice on screening to the Swedish National Board of Health and Welfare. Dr Davey Smith reported receiving grants from the Medical Research Council during the conduct of the study and serving on the scientific advisory board for Relation Therapeutics and Insitro outside the submitted work. Dr Hamdy reported receiving grants from the NIHR during the conduct of the study and receiving personal fees from British Journal of Urology International and the UK Policy Advisory Board, Intuitive Surgical and grants from Prostate Cancer UK outside the submitted work. Dr Donovan reported receiving grants from the NIHR for the linked ProtecT study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Recruitment, Randomization, and Flow of Practices and Patients
Follow-up was through routine National Health Services (NHS) electronic vital status and cancer registry databases for diagnoses and deaths notified by November 17, 2021, but that occurred up to March 31, 2021. aPractices were randomized prior to invitation to take part in the trial. Randomization details are given in the Randomization subsection of the Methods section. bNumbers of men are as of November 17, 2021, and are subject to small changes over time because of continued updates from NHS Digital (eg, changes to the trace status of the men, men newly successfully traced). Note that not all men traced at 15 years were traced at 10 years. cPseudo-anonymized follow-up. dNHS digital national data opt-outs (previously type 2 opt-outs) preventing NHS data being used for research.
Figure 2.
Figure 2.. Effect of the Trial Intervention on the Cumulative Incidence (95% CI) of Prostate Cancer Mortality and Diagnosis and All-Cause Mortality After a Median 15-Year Follow-Up
P values are from a random-effects Poisson model (see Statistical Analysis subsection of the Methods section).
See this image and copyright information in PMC

Comment in

References

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