Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality
Authors: Martin Richard M. , Turner Emma L. , Young Grace J. , Metcalfe Chris , Walsh Eleanor I. , Lane J. Athene , Sterne Jonathan A. C. , Noble Sian , Holding Peter , Ben-Shlomo Yoav , Williams Naomi J. , Pashayan Nora , Bui Mai Ngoc , Albertsen Peter C. , Seibert Tyler M. , Zietman Anthony L. , Oxley Jon , Adolfsson Jan , Mason Malcolm D. , Davey Smith George , Neal David E. , Hamdy Freddie C. , Donovan Jenny L. ,   CAP Trial Group, Oliver  Steven , Brindle  Peter  , Evans Simon , Frankel Stephen , Down Liz , Tazewell Marta , Shiarly Pete , Thorn Joanna , Harrison  Sean , Hounsome Luke , Davies Charlotte , Hughes Laura , Rowlands Mari-Anne , Bell Lindsey , Hill Elizabeth , Ng Siaw Yein , Williams Naomi , Toole Jessica , Baum Michael , Roberts Tracy , Robinson Mary , Dearnaley David  , Schröder Fritz , Peters Tim , Lennon Teresa , Bonnington Sue , Holmberg Lars , Pickard Robert , Thompson Simon , Menon Usha , McFarlane Jon , Bryant Richard , Dormer John , Reid Colette , Bahl Amit , Koupparis Anthony , Gunnell David 
Published: April 2024

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 &amp;lt; .001) and localized (T1/T2: 3.6% vs 3.1%;P &amp;lt; .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