Source: Djulbegovic, M., Beyth, R., Neuberger, M.M. et al. Screening for prostate cancer: Systematic review and meta-analysis of randomized controlled trials. BMJ 2010;341:c4543 doi:10.1136/bmj.c4543
Lin K, Lipsitz R, Miller T, Janakiraman S. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008 Aug 5;149(3):192-9
U.S. Preventive Services Task Force: Screening for prostate cancer.
Andriole et al. Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after 13 Years of Follow-up. JNCI J Natl Cancer Inst (2012) doi: 10.1093/jnci/djr500 (published online 1/6/12)

Efficacy Endpoints: Detection of prostate cancer, prevention of death or metastasis

Harm Endpoints: Need for biopsy (when given the risk of PSA false-positive)

Narrative: The prostate is a kiwi-sized gland that secretes fluid into male semen. The cells of the prostate have a propensity to become cancerous: U.S. men have a 16% chance of being diagnosed with prostate CA in their lifetime and a 3% chance of dying from prostate cancer.1Autopsy studies have shown that up to 2/3 of elderly men will be found to have asymptomatic prostate cancer. It appears that if they live long enough, most men will develop prostate cancer, though it will not affect their longevity.

Given the high incidence of prostate cancer, there have been aggressive efforts to screen patients with the hopes of diagnosing local (non-metastatic) cancer that can be treated before it gets worse and is potentially lethal. Elevated serum prostate-specific antigen (PSA) levels, a protein found in the prostate, are loosely correlated with prostate cancer. Routine PSA screening was widely adopted on the theory that tracking PSA levels would identify prostate cancer; broad screening for prostate cancer was started in many Western countries without any medical/scientific data to support this theory.

In the systematic review summarized here researchers pooled the data from 6 randomized controlled trials with a total of 387,286 patients (poorly designed trials were excluded). The studies randomized patients to screening with PSA versus no screening. Pre-defined outcomes of interest were: All cause mortality and death from prostate cancer, diagnosis of prostate cancer, effect of screening on stage at diagnosis, false positive and false negative results, harms of screening, quality of life, and cost effectiveness.

All cause mortality and prostate cancer mortality were statistically unaffected by PSA screening. There were more cancers detected in the PSA screened groups (6.4% versus 4.4%), suggesting a 2% difference and a NNT of 50 if diagnosing a cancer in the absence of a mortality benefit is considered important. There was a slight increase in diagnosis of stage 1 and 2 prostate cancer, but no increase in the diagnosis of higher stage (3, 4, and 5) prostate cancer. Many of the trials did not report complication or quality of life measures. One trial2 reported a complication rate of 0.7% for prostate biopsy including infection, bleeding, clot formation, and urinary difficulties. Another3 reported 76% of PSA ‘positives’ to be false positives, verified by subsequent prostate biopsy.

Caveats: The quality of the mortality data in the systematic review was considered “moderate” by the GRADE approach (a method of grading the quality of the data; see The GRADE Working Group). The quality of the data for diagnosing cancer and effect of screening on stage of cancer was “low”, and there unfortunately remains no good data to answer whether PSA screening is useful for high-risk populations or persons.

This review also did not address quality of life factors. Findings in the USPSTF review of these and other PSA data suggest significant increases in anxiety due to false positive PSA results. With false positive rates of 75% (other sources have similar or higher rates) it is clear that this is not a specific test. Most men who undergo prostate biopsy do so needlessly. Significant complications from biopsy are low however economic costs and short term pain/complication should not be overlooked. More concerning (and unclear) is the number of men who undergo unnecessary prostatectomy, a procedure known to be associated with long-term sequelae: erectile dysfunction rates as high as 70%, partial urinary incontinence (leaking) as high as 40%, and total urinary incontinence as high as 2% (reported rates vary considerably in the literature).

Why does detection of prostate cancer not lead to increased survival? This is not clear, but the data from this large review strongly argue against routine PSA screening. The strategy of routinely screening all men with PSA tests leads to interventions that are not saving lives and may be causing harm.

Author: Joshua Quaas, MD

Published/Updated: November 23, 2010