No effect on overall mortality

Prostate-specific prostate (PSA) -defined prostate cancer screening remains controversial, as debate continues over the balance between potential benefits and potential harm.

A new systematic review and meta-analysis have shown that at best, screening for prostate cancer using a PSA blood test results in a slight reduction in disease-specific mortality over 10 years, but no effect on overall mortality.

The article was published online on September 5 in the BMJ.

Screening for PSA was also associated with considerable complications related to biopsy and cancer treatment. Using modeling, the authors estimated that for every 1,000 men screened, about one man would require hospitalization for sepsis, three men would require an electrode for urinary incontinence and 25 men would exhibit erectile dysfunction.

So when men ask questions about prostate cancer screening, what should doctors tell them?

Martin Roland, BM, BCh, DM, FRCGP, FRCP, FMedSci, Emeritus Professor of Health Services Research at the University of Cambridge (UK) and colleagues address this issue.

The editorialists note that in the UK, the number of deaths from prostate cancer is higher than that of breast cancer, and that men will continue to question their GPs about screening. How do general practitioners react to vary considerably, they write. Some GPs will offer the test with little or no discussion, while others will refuse to order the PSA test and will 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 positives and false negatives, and many cancers detected by PSA are indolent and would not cause any harm to the patient," write editorialists.

When patients request a PSA test, the conversations "should explore why they are asking for a test and include evidence-based discussions about the potential damage and benefits of the PSA test," commented Roland and his colleagues.

These discussions should also be "informed by the patient's ethnicity and family background" and include information on recent advances in multiparametric MRI before biopsy and active surveillance. Multiparametric MRI improves diagnosis and can reduce the number of men needing a biopsy. These two interventions can reduce the disadvantages of the tests, notes the editorialist.

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 study of the cluster randomized trial of the PSA test for prostate cancer (CAP) conducted in the United Kingdom; Prostate Cancer, Lung Cancer, Colorectal Cancer and Ovarian (PCO) Screening Test, conducted in the United States; trials conducted in Canada and Sweden; and the European Randomized Study on Prostate Cancer Screening (ERSPC), a multicentre study conducted in eight European countries.

Four studies reported all-cause mortality and PSA screening did not appear to have an effect (incidence rate ratio). [IRR], 0.99; 95% confidence interval [CI]0.98 – 1.01; evidence of average quality). This extrapolation to a death of less than any cause per 1000 participants screened.

In addition, the results of the five trials indicate that PSA screening had little or no effect on prostate cancer specific mortality (TRI: 0.96, 95% CI: 0.85 – 1.08, low quality data). This corresponds to zero deaths from prostate cancer per 1000 screened participants.

The authors note that a sensitivity analysis of studies at low risk of bias (n = 1) showed that screening does not appear to have any effect on all-cause mortality (IRR 1.0, 95% CI : 0.98 to 1.02). have a small effect on prostate specific mortality (IRR, 0.79, 95% CI, 0.69 – 0.91, moderate certainty). This corresponds to fewer prostate cancer deaths per 1000 men screened over 10 years.

Screening, however, increased the detection of prostate cancer at all stages (IRR: 1.23, 95% CI, 1.03 to 1.48, low quality data). This discovery corresponds to seven other prostate cancer diagnoses per 1000 men screened.

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

"This small advantage should be weighed against potential short-term complications (biopsy-related, false-positive and false-negative) and long-term downstream effects (treatment-related side effects, particularly with respect to function). urinary and sexual), "they add.

What do men want?

As the debate about 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 answer this question, Robin WM Vernooij, PhD, Netherlands Organization Against Cancer, Utrecht, and an international team of colleagues conducted a systematic study of men's values ​​and preferences for cancer screening. of the prostate.

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

The review included 11 studies. Five of the studies focused on PSA screening using a choice direct study design; the other six decision aids used showed important results for the patient.

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

Overall, men 's values ​​and preferences varied considerably with respect to the significant advantages and disadvantages of screening for prostate cancer. Several studies have shown that among many men in the general population, there was a willingness to accept considerable risk, such as unnecessary biopsies, the risk of impotence and the risk of incontinence, for slightly reduce the risk of death from prostate cancer. It was unclear to what extent this variation was due to differences in methodology and reporting.

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

Men aged 50 to 59 were also willing to accept 72 out of 10,000 cases of incontinence or intestinal problems to prevent death from prostate cancer in 10,000 men screened. Other age groups differed.

Another study evaluated the number of cases of over-detection that patients were willing to accept for a reduction in cancer mortality. To reduce the risk of death from prostate cancer by 10% and 50%, study participants were prepared to accept respectively 126 and 231 cases of over-detection in 1000 screened individuals.

The authors conclude that the "variability in men's values ​​and preferences, especially to the extent that their information needs are met, shows that the decision to detect is very sensitive to preferences.

"As a result, men who are considering screening should be helped by shared decision-making to ensure that they reach a decision that is in line with their values," they add.

Both studies received no outside funding and the authors did not reveal any relevant financial relationship. Editorials Dr. Roland and David Neal are directors of the Prostate Cancer UK charity. Editorialist Richard Buckley is a patient representative on the charity's Research Advisory Committee.

BMJ. Posted online September 5, 2018. Full text , Editorial

BMJ Open. Posted online September 5, 2018. Full text