"Despite improvements in the diagnostic markers and imaging, overdiagnosis and particularly overtreatment continue to pose a challenge for the urologic community," writes Badar M. Mian, MD.
“Journal Article of the Month” is a new Urology Times section in which Badar M. Mian, MD (left), offers perspective on noteworthy research in the peer-reviewed literature. Dr. Mian is professor of surgery in the division of urology at Albany Medical College, Albany, NY.
The benefits and potential risks of PSA screening have remained one of the most studied and debated subjects in urology. One of the largest trials, the European Randomized study of Screening for Prostate Cancer (ERSPC), had previously demonstrated that PSA screening can reduce the mortality rate from prostate cancer, but with a high risk of overdiagnosis. In the most recent update from the ERSPC, Hugosson et al report on the effect of repeated screening rounds on mortality rate and the number of men requiring PSA testing or biopsies to achieve the mortality benefit after 16-year follow-up (Eur Urol Feb. 26, 2019 [Epub ahead of print]).
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Of the 182,160 men who were randomized for the study, 162,389 were 55 to 69 years old. PSA test interval ranged from 2 to 7 years. The primary endpoint was prostate cancer mortality, which was analyzed first starting at randomization to screening and secondarily from cancer diagnosis while on study. Of the men randomized to screening (112,553), only 64% had at least one screening test, but the data presented are based on intention to screen analysis. Of those randomized, 17% (19,308 men) had a positive test, of whom 83% (15,994) had at least one prostate biopsy.
Cumulative prostate cancer incidence at 16 years was 13.3% in the screening arm and 10.3% in the control arm. The prostate cancer incidence in the control arm compared with the screening arm increased during longer follow-up but still remained lower than the screening group. The relative risk of prostate cancer mortality between the arms remained at 0.80 (95% CI: 0.72-0.89, p<.001). However, the absolute difference between the arms increased from 0.14% at 13 years to 0.18% at 16 years. The relative risk of prostate cancer mortality was significantly lower in the screening arms at certain centers; ie, Sweden (RR: 0.63, 95% CI: 0.44-0.88, p=.008) and the Netherlands (RR: 0.67, 95% CI: 0.53-0.85, p=.001).
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The number of prostate cancer cases needed to be diagnosed with screening to avoid one prostate cancer death improved from 48 cases at 9-year follow-up to 18 cases at 16 years. Of note, in the Swedish arm of the study, this number is as low as seven cases with longer follow-up. Prostate cancer-specific survival improved during subsequent rounds of PSA testing when compared to first round. This is likely due to the prevalence of a large number of high-risk or advanced-stage cancers in the population as evident from the fact that during the first PSA round, 10% of men had PSA >20 ng/mL and only 3.2% in round three.
The ERSPC is a multicenter randomized trial of screening for prostate cancer in eight European countries, which joined the trial at different times between 1993 and 2003. Consequently, the screening frequency and intervals, as well as length of follow-up from randomization, are not uniform across all centers.
While the relative reduction in mortality for the entire study population was steady at 20%, the relative reduction in mortality in the Netherlands and Sweden was about 35%. With extended follow-up, the number of new cases needed to diagnose to avert prostate cancer death will likely continue to decrease. Despite improvements in the diagnostic markers and imaging, overdiagnosis and particularly overtreatment continue to pose a challenge for the urologic community.