Abstract: PD28-01
Sources of Funding: Prostate Cancer Canada_x000D_

Introduction

Active surveillance (AS) is the preferred initial treatment for men with localized, low-risk prostate cancer (PC). Challenges in AS include: determining optimal candidates, modifying follow-up by risk strata, 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.

Methods

DNA from peripheral blood samples was available in 490 men followed for AS at Princess Margaret Cancer Center. All men satisfied low-risk criteria: Gleason score <7, <4 positive cores, <50% involvement of any core, and prostate-specific antigen (PSA) level <10.0ng/dL, and had ?1 postdiagnostic biopsy. We genotyped 360,345 SNPs using a custom array (OncoArray); all SNPs had a call rate ?95% and a minor allelic frequency ?1%. Univariate Cox proportional hazards assessed genetic variants and time to pathological (failing to meet low-risk criteria at biopsy) and therapeutic progression (first of pathological progression or initiation of active therapy for any reason). Secondary analyses evaluated the same outcomes for 11 candidate SNPs previously studied for PC grade progression.

Results

Over a median 44-months of follow-up, 206 (42%) and 227 (46%) men progressed pathologically and therapeutically. Men who progressed had worse pathological characteristics at diagnosis (PSA, prostate volume, number of positive cores, and max percent of core involvement; p<0.05). Results of the 5 most highly correlated SNPs are presented in Table 1. After correcting for multiple analyses, one SNP (rs4464333) remained associated with pathological progression (HR 5.51, 95%CI 3.01-10.1, p=3x10 ^-8) and one SNP (rs6583016) remained borderline-associated with therapeutic progression (HR 2.30, 95%CI 1.67-3.17, p=3x10 ^-7). Of the 11 SNPs previously studied for grade progression, rs7141529 associated with therapeutic progression (HR 1.32 95%CI 1.02-1.73, p=0.03).

Conclusions

We identified 2 novel germline genotypic variants that significantly associated with an increased risk of progression in men undergoing AS. These findings may improve patient selection for, and follow-up on AS, and need validation in other cohorts.

Funding

Prostate Cancer Canada_x000D_