Longer-term outcomes of PSA screening and the diagnosis and treatment of prostate cancer

The recent publication of a secondary analysis of The Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP) study reports only a small difference in prostate cancer mortality at 15-year follow-up between groups of men (aged 50-69 years at recruitment) randomised to either standard care or invited to undergo a prostate-specific antigen (PSA) screening test. The difference was smaller than that of what is considered to be meaningful for clinical or public health significance.

Detection of low-grade and localised prostate cancer was greater in the group of men randomised to receive an invitation for PSA screening, compared to those randomised to standard care. These diagnoses relied on 10-core transrectal ultrasound-guided (TRUS) biopsies.

Men from the screening arm of the CAP study who were diagnosed with prostate cancer were recruited into the Prostate Testing for Cancer and Treatment (ProtecT) trial, which randomised participants to active surveillance, radical prostatectomy or radiotherapy. After a 15-year follow-up, “prostate cancer mortality was low regardless of treatment assigned.”

Patient-reported outcomes from ProtecT trial participants, up to 12 years after treatment, show similarities in quality of life regardless of treatment. After prostatectomy, urinary incontinence affected around one in four men and sexual function was “severely impaired”. Sexual and bowel function was reduced in men who underwent radiation therapy. Active monitoring avoided these adverse outcomes, unless, and until, radical treatment was needed.

The take-home message from all of this work seems to be that PSA screening, with subsequent diagnostic biopsy and treatment, offers little, if any, reduction in long-term prostate cancer mortality, but there are adverse health effects from radiotherapy of prostatectomy. While this conclusion is not necessarily ‘new’, the recent long-term follow-up publications are valuable for counselling patients about treatment choices.

Prostate cancer screening, diagnosis and treatment are continually evolving. For example, multiparametric MRI was not available when CAP study participants were recruited, so diagnostic procedures now are more refined. New treatments, like ¹⁷⁷Lu-PSMA, should reduce mortality from advanced metastatic disease.