Molecular Landscape of Aggressive Histologic Subtypes of Localized Prostate Cancer

Despite incredible progress in describing the molecular underpinnings of prostate cancer over the last decades, pathologic examination remains indispensable for predicting aggressive behavior in the localized setting. Beyond pathologic grade, specific histologic findings have emerged as critical prognostic or predictive indicators. Here, the authors review molecular correlates of aggressive histologic subtypes of prostate cancer in the localized setting, demonstrating that many of the signature molecular alterations found in metastatic disease-such as tumor suppressor gene loss and DNA repair defects-are enriched in primary disease with adverse histologic features, presaging aggressive behavior, and presenting opportunities for earlier germline screening or targeted therapies.