Molecular Hallmarks of Multiparametric Magnetic Resonance Imaging Visibility in Prostate Cancer

Genetic correlates of prostate cancer visibility (and invisibility) on multiparametric magnetic resonance imaging: it's time to take stock

“…Decipher scores were significantly higher in mpMRI-visible lesions (mean difference 0.22, 95% CI 0.13-0.32; P < 0.001), indicating an enrichment of genes associated with high-risk prostate cancer (in this case, elevated risk of early metastatic spread) in mpMRI-visible disease; however, in this study, they did not control for the dominant effect that tumour grade and size has on mpMRI visibility. Similar findings were confirmed by Houlahan et al [4], who took a cohort of men who underwent RP (n = 40), defining tumours as mpMRI-visible (PI-RADSv2 score 5) or mpMRI-invisible (PI-RADSv2 score 1-2). Unlike Purysko et al [3], they stipulated inclusion of only 'clinically significant' cancer (using their definition of Gleason score 3+4 with a minimum tumour diameter of 1.5 cm).…”

“…Purysko et al [3], recently sought to address this challenge by correlating the Decipher Genomic Classifier with mpMRI phenotypes for men undergoing radical prostatectomy (RP, n = 72). Lesions were classified as either mpMRI-visible (Prostate Imaging Reporting and Data System version 2 [PI-RADSv2] scores [3][4][5] or mpMRI-invisible (PI-RADSv2 scores 1-2) and were microdissected from RP specimens and profiled with the Decipher gene panel. Decipher scores were significantly higher in mpMRI-visible lesions (mean difference 0.22, 95% CI 0.13-0.32; P < 0.001), indicating an enrichment of genes associated with high-risk prostate cancer (in this case, elevated risk of early metastatic spread) in mpMRI-visible disease; however, in this study, they did not control for the dominant effect that tumour grade and size has on mpMRI visibility.…”

“…Parry et al [6] recently took RP specimens (n = 6) and obtained clock-face punch biopsies from the mid-gland level. After retrospectively assigning each punch biopsy as mpMRI-visible (PI-RADSv2 score [3][4][5] or mpMRI-invisible (PI-RADSv2 score 1-2), they compared them using low-pass whole genome sequencing, methylation arrays and RNAseq, to gain detailed molecular profiles. There was a high intra-patient molecular heterogeneity, but they found that three of six cores obtained from mpMRI-invisible tumours harboured genetic alterations observed in metastatic castration-resistant prostate cancer.…”

Avoiding biopsy in men with PI‐RADS scores 1 and 2 on multiparametric MRI of the prostate, ready for prime time?

“…Perhaps the future lies in the genomics of mpMRI‐visible vs ‐invisible lesions, with a recent study showing that there is a confluence of aggressive molecular and pathological features in lesions visible on MRI. Future research may be able to determine if indeed it is safe to leave some Gleason 3 + 4 = 7 cancers undetected if invisible on mpMRI because of their lack of genomic and metabolic aggression rather than based on their Gleason pattern .…”

A NICE change? The evidence for mpMRI triage in prostate cancer

“…13 Approximately 20% of primary prostate tumours are 'invisible' on mpMRI, though transcriptomic analysis suggests that these have a lower mutational burden and fewer genetic aberrations, resulting in a less aggressive phenotype than mpMRI visible tumours. 14 The prospective 'MRI-FIRST' study showed that pre-biopsy mpMRI didn't negate the need for systematic biopsy in 'mpMRI negative' patients. 15 Authors reported 37% detection of clinically significant disease in patients who had mpMRI showing Likert ≤2 lesions.…”