PROSTATE CANCER SCREENING-NO EFFECT ON OVERALL SURVIVAL

Routine prostate-specific antigen (PSA)–based screening for prostate cancer remains controversial, as the debate continues over the balance between potential benefits and potential harm.

A new systematic review and meta-analysis has found that at best, prostate cancer screening using a PSA blood test leads to a small reduction in disease-specific mortality over 10 years, but it is no effect on overall mortality.

The article was published online September 5 in the BMJ.

PSA screening was also associated with considerable biopsy-related and cancer treatment–related complications. Using modeling, the authors estimated that for every 1000 men screened, approximately one man would require hospitalization for sepsis, three men would require pads for urinary incontinence, and 25 men would experience erectile dysfunction.

So when men ask about prostate cancer screening, what should their physicians tell them?

That question is addressed in an accompanying editorial by Martin Roland, BM, BCh, DM, FRCGP, FRCP, FMedSci, professor emeritus of health services research at the University of Cambridge, United Kingdom, and colleagues.

The editorialists note that in the United Kingdom, there are more deaths from prostate cancer than from breast cancer, and men will continue to ask their general practitioners (GPs) about testing. How GPs respond varies greatly, they write. Some GPs will offer the test with little or no discussion, whereas others will decline to order PSA testing and advise their patients that the test has little or no value.

"The problem is that the PSA test, the only test currently available, has a high incidence of false positive and false negative results, and many cancers detected through PSA are indolent and would never cause the patient any harm," the editorialists write.

When patients request a PSA test, conversations "should explore their reasons for requesting a test and include evidence-based discussions about possible harms and benefits of PSA testing," Roland and colleagues comment.

These discussions should also be "informed by the patient's ethnicity and family history" and include information about recent advances in multiparametric MRI before biopsy and active surveillance. Multiparametric MRI is improving diagnosis and may reduce the number of men needing biopsy. Both of these interventions can reduce the harms of testing, the editorialist note.

Little Impact on Mortality

The new meta-analysis was conducted by Dragan Ilic, PhD, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia, and colleagues from around the world.

It included five randomized controlled trials with a total cohort of 721,718 men. Included were the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP) study, conducted in the United Kingdom; the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted in the United States; trials conducted in Canada and Sweden; and the European Randomized Study of Screening for Prostate Cancer (ERSPC), which was a multicenter study across eight European countries.

Four studies reported on all-cause mortality, and PSA screening did not appear to have any effect (incidence rate ratio [IRR], 0.99; 95% confidence interval [CI], 0.98 - 1.01; moderate-quality evidence). This extrapolated to one fewer deaths from any cause per 1000 participants screened.

In addition, the results from the five trials indicate that PSA screening had little or no effect on prostate cancer–specific mortality (IRR, 0.96; 95% CI, 0.85 - 1.08; low-quality evidence). This corresponded to zero fewer deaths from prostate cancer per 1000 participants screened.

The authors note that a sensitivity analysis of studies at lower risk for bias (n = 1) demonstrated that screening seems to have no effect on all-cause mortality (IRR, 1.0; 95% CI, 0.98 - 1.02; moderate certainty) but may have a small effect on prostate-specific mortality (IRR, 0.79; 95% CI, 0.69 - 0.91; moderate certainty). This corresponds to one fewer deaths from prostate cancer per 1000 men screened over 10 years.

Screening did, however, increase the detection of prostate cancer of any stage (IRR, 1.23; 95% CI, 1.03 - 1.48, low-quality evidence). This finding corresponded to seven more diagnoses of prostate cancer per 1000 men screened.

"This systematic review provides important information for an individual man's decision making about prostate cancer screening," note the authors. Their analysis indicates that, at best, screening yields "only a small benefit in prostate cancer specific mortality but does not reduce overall mortality.

"This small benefit should be weighed against the potential short term complications (biopsy related, false positive and false negative findings) and long term downstream effects (treatment related side effects, in particular related to urinary and sexual function)," they add.

What Do Men Want?

While the debate over PSA screening continues among physicians and professional organizations, the preferences of the patients themselves, when presented with information about the potential benefits and harms, remain unclear.

To address that question, Robin W. M. Vernooij, PhD, of the Netherlands Comprehensive Cancer Organisation, Utrecht, and an international team of colleagues conducted a systematic review that examined men's values and preferences regarding prostate cancer screening.

This study was published online September 5 in the BMJ Open.

The review included 11 studies. Five of the studies investigated PSA screening using a direct choice study design; the remaining six employed decision aids that displayed patient-important outcomes.

The authors note that a meta-analysis was not possible because the objectives of the studies differed and the outcomes reported were heterogeneous.

Overall, there was considerable variation across men's values and preferences regarding the important benefits and harms related to prostate cancer screening. Several studies reported that among many men in the general population, there was willingness to accept considerable risk for harm, such as unnecessary biopsies, risk for impotence, and risk for incontinence, to achieve a small reduction in their risk for death from prostate cancer. It was unclear how much of this variation was due to differences in study methodology and reporting.

For example, one study reported that men aged 50 to 59 years were willing to accept 233 unnecessary biopsies to avoid one prostate cancer death in 10,000 men screened. However, both younger patients (aged 40-49 years) and older patients (aged 60-69 years) accepted fewer unnecessary biopsies.

Men aged 50 to 59 years were also willing to accept 72 in 10,000 extra cases of incontinence or bowel problems to avoid one prostate cancer death in 10,000 men screened. Other age groups differed.

Another study evaluated the number of cases of overdetection that patients were willing to accept for a reduction in cancer-specific mortality. To lower the risk for prostate cancer mortality by 10% and 50%, study participants were willing to accept 126 and 231 cases of overdetection, respectively, in 1000 people screened.

The authors conclude that the "variability of men's values and preferences, particular to the degree that their information needs are met, reflect that the decision to screen is highly preference sensitive.

"As a consequence, men considering screening should be assisted through shared decision making to ensure that they are reaching a decision in line with their values," they add.

The two studies received no outside funding, and the authors have disclosed no relevant financial relationships. Editorialists Dr Roland and David Neal are trustees of the charity Prostate Cancer UK. Editorialist Richard Buckley is a patient representative on the charity's Research Advisory Committee.