One may wonder how the management of prostate cancer could have evolved differently if it had followed a path similar to breast cancer. In breast cancer, early detection in the 1970s relied heavily on imaging because no reliable circulating biomarker was available, and this practice continues today. Prostate cancer, by contrast, saw landmark studies that focused on the utility of prostate-specific antigen (PSA) testing in largely unscreened populations (except for digital rectal examination [DRE]) to identify the disease. A key question arises: how might screening practices have developed if multiparametric MRI had been established before PSA testing? Would starting with imaging and using PSA as a secondary marker to determine the need for biopsy have been a more effective strategy? Another relevant issue is the definition of “indolent prostate cancer.” Even before PSA screening became common, autopsy studies revealed high rates of prostate cancer in men who died of other causes. However, in the early days of PSA screening, most cancers detected were treated aggressively with surgery or radiation. Despite visionary efforts by urologic oncologists like Dr Willet Whitmore, who advocated for ‘watchful waiting’ in men with even advanced-stage tumours (cT2c) as early as the 1950s and 1960s, active surveillance did not gain widespread acceptance as a management strategy for low-grade tumours until the early 2000s. In a recent study published in European Urology, Möller and colleagues explored how MRI could be integrated into population-based screening programmes for prostate cancer. Initially, MRI was only used in patients with high PSA levels who had undergone one or more unsuccessful biopsies. However, current practice increasingly involves performing MRI before biopsy to assess the need for and guide the procedure. Möller et al. focused on men with PSA levels between 1.8 and 3.0ng/ml, investigating the question of how low the PSA threshold should be to prompt an MRI for detecting clinically significant prostate cancer. The study found that within this PSA range, 4.6% of the 670 men studied had Gleason 3+4 tumours, compared to a rate of 9.3% in men with PSA levels between 3.0 and 10.0ng/ml. This finding suggests a possible reconsideration of the PSA threshold for triggering further diagnostic steps like MRI. Lowering the PSA threshold for MRI to the 1.8-3.0ng/ml range could have far-reaching consequences. Although historical data indicate that about 8% of the population has a PSA level above 4.0ng/ml, lowering the threshold would likely encompass a significantly larger proportion of men. One challenge of this approach is distinguishing between indolent and aggressive cancers. While Gleason 3+3 tumours are considered indolent, there is growing acceptance of offering active surveillance to men with Gleason 3+4 tumours, many of whom may have an indolent course. However, if the focus is limited to Gleason 4+3 tumours, the detection rate would drop to just 2%. Furthermore, MRI-based screening may detect more Gleason 3+3 cancers, and while active surveillance is an option, evidence suggests that over 60% of men on surveillance eventually undergo treatment, which carries a risk of side effects affecting quality of life. As Dr Bernard Lytton once insightfully asked, “Did you prevent deaths?”. The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated a relative reduction in prostate cancer deaths, but the absolute reduction in mortality was small (0.18%). Thus, we face a dilemma: should we biopsy men with lower PSA values based on MRI or other biomarkers to reduce prostate cancer mortality? Doing so may prevent some deaths but could also lead to an increase in men experiencing treatment-related side effects. A prospective, randomised trial comparing standard and more intensive screening, while monitoring mortality, complications, and quality of life, is the only way to provide the evidence needed for informed decision-making.
PSA screening in limbo: how low should we go?
Reviewed by Asif H Ansari
Prostate-specific antigen screening in limbo: how low should we go?
