Heterogeneity in Genomic Risk Assessment from Tissue Based Prognostic Signatures Used in the Biopsy Setting and the Impact of Magnetic Resonance Imaging Targeted Biopsy
This article is commented on by the following:
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.
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.
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.
- 1. : Active surveillance for prostate cancer: a systematic review of the literature. Eur Urol 2012: 62: 976. Google Scholar
- 2. : Adverse pathologic findings for men electing immediate radical prostatectomy. JAMA Oncol 2018; 4: 89. Google Scholar
- 3. : MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis. N Engl J Med 2020; 382: 917. Google Scholar
- 4. : What is the negative predictive value of multiparametric magnetic resonance imaging in excluding prostate cancer at biopsy? A systematic review and meta-analysis from the European Association of Urology prostate cancer guidelines panel. Eur Urol 2017: 72: 250. Google Scholar
- 5. : Incorporation of tissue-based genomic biomarkers into localized prostate cancer clinics. BMC Med 2016: 14: 67. Google Scholar
- 6. : Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol 2013; 31: 1428. Google Scholar
- 7. : A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol 2014; 66: 550. Google Scholar
- 8. : Decipher genomic classifier measured on prostate biopsy predicts metastasis risk. Urology 2016; 90: 148. Google Scholar
- 9. : Intratumoral and intertumoral genomic heterogeneity of multifocal localized prostate cancer impacts molecular classifications and genomic prognosticators. Eur Urol 2017: 71: 183. Google Scholar
- 10. : Transcriptomic heterogeneity in multifocal prostate cancer. JCI Insight 2018; 3: 3. Google Scholar
- 11. : Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer 2012; 106: 1095. Google Scholar
- 12. : Tissue-based genomics augments post-prostatectomy risk stratification in a natural history cohort of intermediate- and high-risk men. Eur Urol 2016; 69: 157. Google Scholar
- 13. : Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One 2013; 8: e66855. Google Scholar
- 14. : A critical appraisal of biomarkers in prostate cancer. World J Urol 2020: 38: 547. Google Scholar
- 15. : Image-guided prostate biopsy using magnetic resonance imaging–derived targets: a systematic review. Eur Urol 2013; 63: 125. Google Scholar
- 16. : Transcriptome wide analysis of magnetic resonance imaging-targeted biopsy and matching surgical specimens from high-risk prostate cancer patients treated with radical prostatectomy: the target must be hit. Eur Urol Focus 2018: 4: 540. Google Scholar
Supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA240139, RO1CA189295, R01CA190105 and U01CA239141 and Paps Corps Champions for Cancer Research Endowed Chair in Solid Tumor Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Editor's Note: This article is the second of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1537 and 1538.