Assessing the Molecular Heterogeneity of Prostate Cancer Biopsy Sampling: Insights from the MAST Trial.

Background and objective: Prostate cancer (PC) heterogeneity can result in sampling discrepancies during biopsy, leading to inaccurate molecular classifications that affect treatment decisions. We evaluated transcriptomic profile variability between multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TBx) and systematic biopsy (SBx) methods using the Decipher GRID platform.

Methods: The study included 205 men from the MAST trial. We analyzed 408 biopsy samples, of which 149 were TBx and 259 were SBx samples. Three prognostic signatures-the Decipher genomic classifier (DGC), cell cycle progression (CCP), and Genomic Prostate Score-were assessed in relation to grade group (GG) and MRI phenotype. Multivariable linear regression was conducted to adjust for the confounding effects of GG and tumor purity.

Key findings and limitations: Unpaired analysis revealed that TBx samples had higher derived GPS and CCP scores than SBx samples (p < 0.05), but the difference was no longer significant after multiple-test adjustment. There was no significant difference in scores between SBx and TBx samples in the subgroup with GG 1 disease. For TBx cores, higher genomic scores were associated with higher Prostate Imaging-Reporting and Data System (PI-RADS) scores in the overall cohort, but not in the GG 1 subgroup. Multivariable analysis revealed significant associations between DGC and CCP scores and PI-RADS scores (p < 0.01). Higher DGC score concordance between TBx and SBx lesions was observed in the low-risk subgroup. A limitation of the study is the small sample size, so further validation is required.

Conclusions and clinical implications: TBx samples yield higher genomic scores than SBx samples, with grade influencing the association between PI-RADS score and genomic risk. For the GG 1 subgroup, there was no correlation between PI-RADS and genomic scores. These findings need further validation to assess the impact of TBx on genomic risk assessment in active surveillance.

Patient summary: We examined the effectiveness of two different biopsy methods in assessing the risk of prostate cancer (PC) progression. We found that while biopsy samples guided by MRI (magnetic resonance imaging) scans often showed higher genetic risk scores than biopsy samples without MRI guidance, the difference was not significant for men with lower-grade PC. Our findings suggest that MRI targeting for biopsy might not always provide additional information about cancer aggressiveness for patients with low-risk PC.