By Lynda Williams, medwireNews Reporter
medwireNews: A polygenic risk score (PRS) may help to identify patients undergoing active surveillance for clinically localised prostate cancer who are at particular risk of an increase in their Gleason grade, US research shows.
Each 1-standard deviation (SD) unit increase in the multi-ancestry PRSs used was associated with up to a 27% increased risk for Gleason upgrading, report Burcu Darst (Fred Hutchinson Cancer Center, Seattle, Washington) and co-workers.
The study included 1220 participants of the Canary Prostate Active Surveillance Study, aged a median 63 years, who had cT1–T2 disease and underwent repeat biopsy at 6–12 and 24 months after their initial positive biopsy, with further biopsies taken every 2 years.
Over a median follow-up of 5.3 years, 470 of the patients received an upgrade in their Gleason grade, with 17.7% occurring within 2 years of initial diagnosis and 33.3% within 5 years. An extreme upgrade, defined as an increase from grade group 1 or 2 to grade group 3 or higher, occurred in 152 of the participants, within 2 years in 5.0% of patients and within 5 years in 11.1%.
Genome-wide genotyping showed that each 1-SD unit increase in the PRS of 451 prostate cancer risk gene variants, including 51 prostate-specific antigen (PSA) variants linked to aggressive prostate cancer (PRS-451), was associated with a 23% increase in the likelihood of Gleason upgrading at any time during follow-up, while the PRS-400, excluding the PSA-specific genes, was associated with a 27% increase.
And each 1-SD unit increase in the PRS-451 and PRS-400 was associated with a significant 19% and 22% increase in the risk of extreme upgrade, respectively.
Compared with patients in the lowest PRS-400 quintile, those in the top quintile were twice as likely to experience upgrading and extreme upgrading, report Darst and co-workers in JAMA Oncology.
In addition, each 1-SD unit increase in PRS-400 was significantly associated with a 1.38 percentage point increase in cancerous biopsy cores, a 1.48 cc reduction in prostate volume, and a 0.18 ng/mL increase in PSA, as well as a 0.01 ng/mL2 increase in PSA density. “Except for PSA, associations were similar or weaker for PRS-451”, the researchers note.
The investigators conclude: “In this cohort study, among patients undergoing active surveillance, high PRS was associated with increased risk of upgrading, smaller prostate volume, and possibly tumor multifocality.
“As such, PRS could inform surveillance strategies for patients with low-risk [prostate cancer], potentially reducing active surveillance burdens for patients with decreased risk of upgrading.”
However, Konrad Stopsack (Massachusetts General Hospital and Harvard Medical School, Boston, USA) observes in an accompanying comment that Gleason upgrading during active surveillance is a “surrogate” and “may not reflect an actual grade change in the tumor over a few years and could also result from sampling high-grade tumor nodules that were present for decades.”
He continues: “The low absolute risk of metastasis among patients often selected for active surveillance and the modest discriminatory ability of the PRS in this setting puts into question how successful clinical effectiveness trials of PRS implementation would be.”
The commentator concludes that it is “critical to ensure that PRS guidance does not detract from prevention strategies that are favorable across multiple health outcomes or from the generally small absolute risk of distant metastasis while receiving active surveillance.”
News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
JAMA Oncol 2024; doi:10.1001/jamaoncol.2024.5398
https://pubmed.ncbi.nlm.nih.gov/39666350
JAMA Oncol 2024; doi:10.1001/jamaoncol.2024.5203