AUA 2017: Association Between Germline Genetic Variation And Progression In Men With Low-risk Prostate Cancer On Active Surveillance

Boston, MA ( Viranda Jayalath, a medical student from Princess Margaret Cancer Center in Toronto, Canada, elegantly presented his study assessing the association between germline genetic variation and progression in men with low risk prostate cancer (PC) on active surveillance (AS). AS is the preferred initial treatment strategy for men with localized, low-risk PC. Known challenges in AS include: determining ideal candidates, improving risk stratification of AS patients, and defining clinically significant progression. Although the association between germline genetic variation and PC risk and PC-specific outcomes has been investigated, their influence on AS is unclear.

The authors aimed to study the association between germline single nucleotide polymorphisms (SNPs) and time to pathological progression (TTP) in a cohort of men undergoing AS for low-risk, localized, PC. To achieve this, DNA from peripheral blood samples of 362 men followed for AS at Princess Margaret Cancer Center was available for analysis. After imputations and quality control, 6.5 million SNPs were analyzed using a custom array (OncoArray); with a call rate of 95% and a minor allelic frequency of 1%. The authors performed a multivariate Cox proportional hazards assessing genetic variants and time to pathological progression (failing to meet low-risk criteria at biopsy) and therapeutic progression (first of pathological progression or initiation of active therapy for any reason).

Over a median 61-months of follow-up with a median age of 62, 78/362 patients (21%) progressed. 7 susceptibility loci (52 SNP) on 5 chromosomes were identified, significantly being associated with time to pathological progression in men on AS. The authors also showed that these SNPs were independent of established clinical factors. It was demonstrated that patients with 1-2 loci and those with >=3 loci were 5 times and 27 times more, respectively, likely to progress than men without these loci, independent of all other known clinical variables. Study limitations included the retrospective nature of the study, the relatively small sample size and the fact that the majority of patients were white.

Viranda summarized his intriguing presentation by emphasizing the fact that external validation is required before his data could be used. After successful validation of these findings, usage of germline genetic variations should be seriously considered, as part of a much needed effort to improve patient selection for AS.

Presented by: Viranda Jayalath, Toronto, Canada

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre

Twitter: @Goldberghanan

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA