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Prostate Cancer Molecular Heterogeneity: MAST Trial Insights

January, 01, 2024 | Genitourinary Cancer, Prostate Cancer

KEY TAKEAWAYS

  • An interventional trial aimed to investigate the extent of genetic heterogeneity and genomic risk variation among PCa biopsy cores, comparing sampling methods.
  • The study observed improved genomic assessment with mpMRI sampling, highlighting potential advancements in accurate risk stratification for localized PCa.

Prostate cancer (PCa) exhibits heterogeneity and multifocality, with biopsy sampling frequently inadequately representing the entire tumor or capturing various tumor foci. This multiple sampling approach can introduce molecular heterogeneity, potentially resulting in underestimated risk assessments. Consequently, it has implications for treatment decision-making and management strategies in localized PCa.

Sanoj Punnen and his team aim to assess the differences between magnetic resonance imaging-guided biopsy (mpMRI) and template biopsy in capturing the molecular landscape of prostate tumors. The objective was to quantify and compare the degree of molecular heterogeneity among different biopsy cores, shedding light on the potential underestimation of risk associated with multiple sampling approaches.

In this study, about 348 biopsy samples from 156 patients enrolled in the Miami MRI selection for Active Surveillance versus Treatment (MAST) trial (NCT02242773) were used. Throughout the entire time-course, all biopsy cores that successfully underwent gene expression profiling were systematically categorized based on the sampling method—mpMRI targeted (110 samples) or template (187 samples). Specifically, cores with higher Gleason scores were selectively chosen from each sampling group. The analysis focused on investigating the variation in gene expression across biopsy samples derived from the same patients.

In methods, a comparative analysis was conducted on the Decipher genomic scores obtained from template and targeted biopsies, utilizing unpaired statistical methods (P=0.02). However, no statistically significant difference was observed in the paired analysis between these biopsy approaches. The investigation further explored various molecular pathways, revealing consistent gene expression profiles in both groups, with the notable exception of the E2F transcription factor.

Examining the relationship between MRI-targeted biopsy Decipher genomic scores and PIRADS scores, a non-significant variation was found (P=0.6). Notably, PIRADS 5 lesions exhibited heightened expression in the angiogenesis pathway, E2F transcription factor pathway, and G2/M checkpoint pathway, while the estrogen response signaling was comparatively lower in PIRADS 5.

The reported outcome suggested  that mpMRI sampling may enhance genomic assessment in prostate cancer. However, the study revealed no correlation between radiologic lesion scoring and genomic risk. The findings from this study are crucial for informing more accurate risk assessments and enhancing the precision of treatment decision-making.  The study is sponsored by University of Miami

Source: https://suo-abstracts.secure-platform.com/a/gallery/rounds/18/details/2763

Clinical Trial: https://clinicaltrials.gov/study/NCT02242773

Tarek Ajami T, Yu H, Prakash N.S et al.,”Assessing Molecular Heterogeneity of Prostate Cancer Biopsy sampling: insights from the MAST trial.” Presented at SUO 2023 (Poster 214)

 

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