Clinical Edge Journal Scan

Clinical Edge Journal Scan Commentary: Prostate Cancer June 2021

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Mark Klein, MD

Ongoing studies continue to add to the somewhat complicated and nuanced areas of prostate cancer diagnosis and prediction of risk of varying outcomes. The introduction of PSA screening in the mid-1990s, while well-meaning, also led to the ongoing debate about the appropriate use of PSA and the recognition that prostate cancer is quite heterogenous. Numerous studies have demonstrated evidence for or against early prostate cancer detection. Bergengren et al sought to take a slightly different approach compared to previous studies by utilizing a simulation model, the PRISM-PC, to analyze data on all Swedish men diagnosed with prostate cancer from 1996-2016 and compare the outcomes between a hypothetical and simulated scenario with a more restrictive diagnostic activity and a scenario with higher diagnostic activity. In this simulation, they determined that a higher-diagnostic activity scenario results in 48% more prostate cancer diagnoses, 148% more low- or intermediate-risk cancers, 108% more curative treatments, but up to 15% fewer prostate cancer deaths. Thus, the simulation, while innovative and nuanced, has similar findings in general that already observed that there is a balance between higher PSA screening rates and overtreatment balanced by a modest decrease in mortality.


Due to the heterogeneity of outcomes and study designs, consensus on definitive prostate cancer risk assessment has been somewhat elusive. Differences in outcomes based on ethnicity and race have been observed, but much data on risk has originally been obtained in populations with lower ethnic and racial diversity, complicating extrapolation to larger populations. Huynh-Le et al developed an updated polygenic hazard score (PHS2) based on a single nucleotide polymorphism (SNP) panel (46 total SNPs) for prostate cancer patients with multiple ethnicities (African, Asian, and European ancestries). This updated PHS2 score stratified men into higher and lower risks for any, aggressive, and fatal prostate cancers in a statistically significant way. Camargo et al took a different approach and evaluated whether 2 SNPs were prognostic in prostate cancer: rs1834306 corresponding to microRNA 100 (miR 100) and rs2910164 from miR 146a. There were no differences in miR 100 or miR 156a between patients with local prostate cancer or a control group of men without prostate cancer. In addition, there were no differences in the chance of particular genotypes between the 2 groups. There was an association between lower presence of rs1834306 (miR 100) and patients with PSA > 10 mg/mL and between a higher amount of the polymorphic allele for rs2910164 (miR 146A).

The 3 studies summarized here demonstrate the ongoing challenges in how to identify nuances that will affect clinical decision-making in PSA screening and to identify prognostic features that associate with particular outcomes. The study by Bergengren confirmed the current state of PSA screening in that balancing diagnosis and potential overtreatment with modest survival outcomes is challenging. While the studies by Huynh-Le et al and Camargo et al have interesting findings, the use of SNPs and miR in prostate cancer prognosis is still not ready for routine clinical use in prostate cancer management.

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