Guidelines now recommend multiparametric magnetic resonance imaging before prostate biopsy in the work-up for patients with elevated prostate specific-antigen. However, use of magnetic resonance imaging for early detection of prostate cancer is not justified by the clinical trial evidence.

Kallikreins are a family of serine proteases with a range of tissue-specific and essential proteolytic functions. Among the best studied are the prostate tissue-specific KLK2 and KLK3 genes and their secreted protease products, human kallikrein 2, hk2, and prostate-specific antigen (PSA). Members of the so-called classic kallikreins, these highly active trypsin-like serine proteases play established roles in human reproduction. Both hK2 and PSA expression is regulated by the androgen receptor which has a fundamental role in prostate tissue development and progression of disease. This feature, combined with the ability to sensitively detect different forms of these proteins in blood and biopsies, result in a crucially important biomarker for the presence and recurrence of cancer. Emerging evidence has begun to suggest a role for these kallikreins in critical vascular events. This review discusses the established and developing biological roles of hK2 and PSA, as well as the historical and advanced use of their detection to accurately and non-invasively detect and guide treatment of prostatic disease.

Background

Active surveillance (AS) is an accepted means of managing low-risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) ≤6 disease and risk profiles similar to those in North American AS cohorts.

Methods

Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life-years (LYs), and quality-adjusted LYs.

Results

Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5-year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5-year biopsy schedules in terms of LYs (range of differences, 0.04-0.16 LYs) and quality-adjusted LYs (range of differences, -0.02 to 0.09 quality-adjusted LYs).

Conclusions

Among men diagnosed with GS ≤6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules.