Dr Miron on Molecular Alterations in Intraductal Carcinoma of the Prostate

Benjamin Miron, MD, medical oncologist, researcher, Fox Chase Cancer Center, discusses findings and clinical implications from a study investigating molecular alterations in patients with intraductal carcinoma of the prostate.

Dr Miron on the Molecular Landscape of Intraductal Carcinoma of the Prostate

This study evaluated patients with intraductal carcinoma of the prostate who had available tissue-based RNA and DNA sequencing from a commercially available assay. The investigators analyzed these tumor specimens using next-generation sequencing to confirm intraductal histology.

The most prevalent alterations in this cohort of patients with intraductal carcinoma of the prostate were TMPRSS2 fusions (38.7%), TP53 alterations (38.7%), FOXA1 alterations (16.1%), SPOP alterations (9.7%), CDK12 alterations (9.7%), and PIK3CAalterations (9.7%). In addition, BRCA1 mutations were found in 3.2% of patients, and BRCA2 mutations were found in 3.3% of patients. CDK12 and BRCA1/2 mutations are actionable and can guide clinical decision making in prostate cancer, as agents such as PARP inhibitors are approved for patients with these mutations, Miron says.

This study also compared the incidence of alterations found in intraductal carcinoma of the prostate with the incidence of alterations found in localized prostate adenocarcinoma and in metastatic castration-sensitive prostate cancer (mCSPC). This analysis found that intraductal carcinoma of the prostate has a genetic landscape that is more similar to metastatic disease than localized disease, Miron explains. For instance, TP53 mutations were observed in 38.7% of patients with intraductal carcinoma and 33% of those with mCSPC compared with 3.4% of those with localized disease. 

Dr Miron on Genetic Sequencing in Prostate Cancer

These findings warrant further investigation of the molecular landscape of intraductal carcinoma of the prostate, Miron emphasizes. Comparing the incidence of alterations in this population with that in a population of patients with pure adenocarcinoma of the prostate may reveal additional information about intraductal disease, Miron notes.

For now, however, the actionable mutations found in this study confirm the benefits of early or up-front comprehensive RNA sequencing in patients with intraductal carcinoma of the prostate and support the continued use of germline testing in this population per guideline recommendations, Miron concludes.