PSA screening reduced prostate cancer death by 21%, yet risks remain

Routine PSA testing for prostate cancer was associated with a significant reduction in death, according to 13-year follow-up from a randomized study in Europe.

However, due to risks for overdiagnosis and overtreatment of prostate cancers, researchers do not recommend population-based screening based on these data.

“PSA screening delivers a substantial reduction in prostate cancer deaths, similar or greater than that reported in screening for breast cancer,” Fritz Schröder, MD, of Erasmus University Medical Center in the Netherlands, said in a press release. “However, overdiagnosis occurs in roughly 40% of cases detected by screening, resulting in a high risk of overtreatment and common side effects such as incontinence and impotence.”

In the European Randomized Study of Screening for Prostate Cancer (ERSPC), Schröder and colleagues evaluated data from more than 160,000 men from eight countries (median age, 60.2 years; range, 55 to 69 years). Researchers assigned men to routine PSA testing (n=72,891) or no screening (n=89,352).

Those assigned to the intervention arm underwent an average of two to three screenings. Men underwent a diagnostic biopsy if their PSA was ≥3 ng/mL.

Overall, 7,408 men in the intervention arm and 6,107 men in the control arm were diagnosed with prostate cancer during 13 years of follow-up. Prostate cancer incidence was 9.55 per 1,000 person-years in the intervention arm, and 6.23 per 1,000 person-years in the control arm.

Researchers reported significantly lower prostate cancer mortality in the intervention arm than the control arm (0.43 per 1,000 person-years vs. 0.54 per 1,000 person-years). Using these data, researchers calculated a rate ratio of 0.79 (95% CI, 0.69-0.91), or a 21% reduction in prostate cancer death associated with PSA screening.

When researchers excluded non-participators from the data, PSA screening was associated with a 27% reduction in prostate cancer mortality (rate ratio, 0.73; 95% CI, 0.61-0.88).

The number needed to invite (NNI) for screening and the number needed to diagnose (NND) to avoid one prostate cancer death declined with longer follow-up. Researchers calculated NNIs of 1,410 at 9 years follow-up, 979 (95% CI, 594-2,770) at 11 years follow-up, and 781 (95% CI, 490-1,929) at 13 years follow-up. Researchers calculated NNDs of 48 at 9 years follow-up, 35 (95% CI, 21-96) at 11 years follow-up, and 27 (95% CI, 17-66) at 13 years follow-up.

Results of a modeling study indicated the risk for prostate cancer overdiagnosis was 41%. Although results of the modeling study indicated a favorable balance between screening harms and benefits, more research is needed to address these risks, researchers wrote.

“The time for population-based screening has not arrived,” Schröder said. “Further research is urgently needed on ways to reduce overdiagnosis, preferably by avoiding unnecessary biopsy procedures, and reducing the very large number of men who must be screened, biopsied and treated to help only a few patients. One promising approach is multiparametric MRI technology, which may be able to selectively diagnose aggressive prostate cancers and avoid the diagnosis of many inconsequential tumors that generally grow so slowly that most men will die of other causes. But for now, men must to be given well-balanced information including the screening harms of overdiagnosis and overtreatment.”

Longer follow-up might improve the benefits associated with screening, Ian M. Thompson, MD, of the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio, and Catherine M. Tangen, DrPH, of Fred Hutchinson Cancer Research Center, wrote in an accompanying editorial.

“The new findings from ERSPC are crucially important,” Thompson and Tangen wrote. “In future publications from the study, the distribution of prostate cancer deaths by Gleason score and PSA at diagnosis will be important to understand how to tailor screening and treatment. Because the median follow-up from diagnosis of prostate cancer was 6.4 years for the intervention group and 4.3 years in the control group, and because high-risk disease often requires 12 to 15 years to cause death, we would not be surprised if the benefit of screening becomes more apparent with longer follow-up.”

Disclosure: Tangen reports a consultant role with Exosome Diagnostics. See the study for a full list of the researchers’ relevant financial disclosures.