Prostate Cancer Tumor Volume and Genomic Risk

BACKGROUND: Despite the historic association of higher prostate cancer volume with worse oncologic outcomes, little is known about the impact of tumor volume on cancer biology. OBJECTIVE: To characterize the relationship between tumor volume (measured by percent positive cores [PPC]) and cancer biology (measured by Decipher genomic risk classifier [GC]) in men who underwent prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: Prostate biopsies from 52 272 men profiled with Decipher captured in a population-based prospective tumor registry were collected from 2016 to 2021. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The degree of distribution and correlation of PPC with a GC score across grade group (GG) strata were examined using the Mann-Whitney U test, Pearson correlation coefficient, and multivariable linear regression controlled for clinicopathologic characteristics. RESULTS AND LIMITATIONS: A total of 38 921 (74%) biopsies passed quality control (14 331 GG1, 16 159 GG2, 5661 GG3, 1775 GG4, and 995 GG5). Median PPC and GC increased with sequentially higher GG. There was an increasingly positive correlation (r) between PPC and GC in GG2–5 prostate cancer (r [95% confidence interval {CI}]: 0.07 [0.5, 0.8] in GG2, 0.15 [0.12, 0.17] in GG3, 0.20 [0.15, 0.24] in GG4, and 0.25 [0.19, 0.31] in GG5), with no correlation in GG1 disease (r = 0.01, 95% CI [–0.001, 0.03]). In multivariable linear regression, GC was significantly associated with higher PPC for GG2–5 (all p < 0.05) but was not significantly associated with PPC for GG1. Limitations include retrospective design and a lack of final pathology from radical prostatectomy specimens. CONCLUSIONS: Higher tumor volume was associated with worse GC for GG2–5 prostate cancer, whereas tumor volume was not associated with worse GC for GG1 disease. The finding that tumor volume is not associated with worse cancer biology in GG1 disease encourages active surveillance for most patients irrespective of tumor volume. PATIENT SUMMARY: We studied the relationship between prostate cancer tumor volume and cancer biology, as measured by the Decipher genomic risk score, in men who underwent prostate biopsy. We found that tumor volume was not associated with worse cancer biology for low-grade prostate cancer. Our findings reassuringly support recent guidelines to recommend active surveillance for grade group 1 prostate cancer in most patients, irrespective of tumor volume.