(UroToday.com) The 2025 SESAUA annual meeting featured a prostate cancer session and a presentation by Dr. Mary Rostom discussing a subgroup analysis from the MAST trial assessing molecular heterogeneity of prostate cancer biopsy sampling. Due to prostate cancer heterogeneity, biopsy sampling often under samples different tumor foci.
This can lead to inaccurate molecular classifications of tumor biology on tissue-based prognostic tests, impacting treatment in localized prostate cancer. At the SESAUA 2025 annual meeting, Dr. Rostom and colleagues evaluated the degree of variability in transcriptomic profiles when assessing genomic profiles from MRI guided versus template biopsy using the Decipher GRID platform.
A total of 205 men enrolled in the Miami MRI selection for Active Surveillance versus Treatment (MAST) trial. MAST is a prospective, single-center protocol of men with low to intermediate risk prostate cancer who underwent a rigorous MRI and biopsy follow-up schedule. For this study, 408 biopsy samples from 159 patients with successful genomic profiling were included. All biopsy cores with successful gene expression profiling were categorized by mpMRI targeted (149 samples) or template (259 samples) sampling. Three main prognostic signatures (i) Decipher genomic classifier, (ii) derived cell cycle progression (CCP), and (iii) derived Genomic Prostate score (GPS) were used to assess the variation in genomic risk between MRI targeted and template cores.
In unpaired analyses comparing all targeted biopsies to all template biopsies, targeted lesions showed higher CCP and GPS scores, but Decipher scores were not significantly different. In paired analyses comparing targeted and template lesions, there was no difference between genetic signatures. There was also no significant difference in scores between template biopsies and targeted biopsy samples in the subgroup with Gleason Group 1 disease. The following is a comparison of genomic classifier scores for systematic versus targeted biopsies in the overall cohort according to (A) unpaired and (B) paired analysis, and the subgroup with Grade Group 1 disease on (C) unpaired and (D) paired analysis:
For targeted biopsy cores, higher genomic scores were associated with higher PI-RADS scores in the overall cohort, but not in the Gleason Group 1 subgroup. Multivariable analysis showed a significant association between Decipher genomic classifier and CCP score and PI-RADS scores (p < 0.01). The following Sankey diagram shows the flow of risk groups according to the Decipher genomic classifier score between systematic biopsy and targeted biopsy in paired analysis for the overall cohort (A) and the subgroup with Gleason Group 1 disease (B):
Dr. Rostom concluded her presentation discussing a subgroup analysis from the MAST trial assessing molecular heterogeneity of prostate cancer biopsy sampling with the following take-home points:
- Targeted biopsy samples yield higher genomic scores than template biopsy samples, with grade influencing the association between PI-RADS score and genomic risk
- Patients with higher cancer grade on biopsy had higher genomic risk, regardless of their MRI phenotype
- For the Grade Group 1 subgroup, there was no correlation between PI-RADS and genomic scores
- These findings suggest that the molecular profile of high risk tumors is correlated more to grade, and that the features of the prostate observable on imaging are not associated with higher genomic risk in the case of low grade disease
- Incorporation of genomic signatures in active surveillance protocols could add a potential tool for risk classification and assessment of disease
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Southeastern Section of the American Urological Association (SESAUA) 2025 Annual Meeting, Nashville, TN, Wed, Mar 12 – Sat, Mar 15, 2025.