Histomic and transcriptomic features of MRI‐visible and invisible clinically significant prostate cancers are associated with prognosis

Abstract Magnetic resonance imaging (MRI) is increasingly used to triage patients for prostate biopsy. However, 9% to 24% of clinically significant (cs) prostate cancers (PCas) are not visible in MRI. We aimed to identify histomic and transcriptomic determinants of MRI visibility and their association to metastasis, and PCa‐specific death (PCSD). We studied 45 radical prostatectomy‐treated patients with csPCa (grade group [GG]2‐3), including 30 with MRI‐visible and 15 with MRI‐invisible lesions, and 18 men without PCa. First, histological composition was quantified. Next, transcriptomic profiling was performed using NanoString technology. MRI visibility‐associated differentially expressed genes (DEGs) and Reactome pathways were identified. MRI visibility was classified using publicly available genes in MSK‐IMPACT and Decipher, Oncotype DX, and Prolaris. Finally, DEGs and clinical parameters were used to classify metastasis and PCSD in an external cohort, which included 76 patients with metastatic GG2‐4 PCa, and 84 baseline‐matched controls without progression. Luminal area was lower in MRI‐visible than invisible lesions and low luminal area was associated with short metastasis‐free and PCa‐specific survival. We identified 67 DEGs, eight of which were associated with survival. Cell division, inflammation and transcriptional regulation pathways were upregulated in MRI‐visible csPCas. Genes in Decipher, Oncotype DX and MSK‐IMPACT performed well in classifying MRI visibility (AUC = 0.86‐0.94). DEGs improved classification of metastasis (AUC = 0.69) and PCSD (AUC = 0.68) over clinical parameters. Our data reveals that MRI‐visible csPCas harbor more aggressive histomic and transcriptomic features than MRI‐invisible csPCas. Thus, targeted biopsy of visible lesions may be sufficient for risk stratification in patients with a positive MRI.