Heterogeneity in Genomic Risk Assessment from Tissue Based Prognostic Signatures Used in the Biopsy Setting and the Impact of Magnetic Resonance Imaging Targeted Biopsy

Abstract

Purpose: Genomic prognostic signatures are used on prostate biopsy tissue for cancer risk assessment, but tumor heterogeneity and multifocality may be an issue. We evaluated the variability in genomic risk assessment from different biopsy cores within the prostate using 3 prognostic signatures (Decipher, CCP, GPS).

Materials and methods: Men in this study came from 2 prospective prostate cancer trials of patients undergoing multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy with genomic profiling of positive biopsy cores. We explored the relationship among tumor grade, magnetic resonance imaging risk and genomic risk for each signature. We evaluated the variability in genomic risk assessment between different biopsy cores and assessed how often magnetic resonance imaging targeted biopsy or the current standard of care (profiling the core with the highest grade) resulted in the highest genomic risk level.

Results: In all, 224 positive biopsy cores from 78 men with prostate cancer were profiled. For each signature, higher biopsy grade (p <0.001) and magnetic resonance imaging risk level (p <0.001) were associated with higher genomic scores. Genomic scores from different biopsy cores varied with risk categories changing by 21% to 62% depending on which core or signature was used. Magnetic resonance imaging targeted biopsy and profiling the core with the highest grade resulted in the highest genomic risk level in 72% to 84% and 75% to 87% of cases, respectively, depending on the signature used.

Conclusions: There is variation in genomic risk assessment from different biopsy cores regardless of the signature used. Magnetic resonance imaging directed biopsy or profiling the highest grade core resulted in the highest genomic risk level in most cases.

Keywords: biomarkers; genomics; magnetic resonance imaging; prostatic neoplasms.

Figure 1:

Box plot of genomic risk scores by grade group for each tissue-based genomic prognostic signature (Decipher, CCP, GPS) showing higher score in higher grade groups. Red circles depict biopsies from MAST trial; Blue dots – from BlastM.

Figure 2:

Boxplot of genomic risk scores by template and MRI guided biopsies for each tissue-based genomic prognostic signatures (Decipher, CCP, GPS) showing higher CCP scores in MRI targeted compared to template biopsies, but no difference in GPS and Decipher scores. Within MRI targeted biospies all signatures showed higher scores with higher PIRADS levels. Red circles depict biopsies from MAST trial; Blue dots – from BlastM.

Figure 3:

Plot of genomic risk scores per biopsy core and patient for each genomic prognostic signature. Grade group of biopsy core is reflected by the different color circles.

Figure 4:

a) shows how often the genomic risk level assignment for each signature was consistent among the biopsy cores and how often they differed by one or two risk levels. Variance in Decipher and GPS scores appeared similar (p=0.77), while they both differed from variance in CCP scores (p<0.01). b) shows how often the core with largest volume of highest grade cancer found the highest genomic risk level among the biopsy cores and how often one or two risk levels higher are found in a different core for each signature. There was no difference between signatures in this distribution (p>0.1). c) shows the how often MRI guided and template biopsy identified the highest genomic risk level among the biopsy cores for each signature. There was a significant difference between all the signatures in this distribution (p<0.01).