Neoplasms of the Prostate

Abstract

Overview Cancer of the prostate is the most commonly diagnosed nonskin neoplasm and the second leading cause of cancer‐related mortality in men in the United States. Considerable advances have been made in screening, diagnosis, and therapy options, particularly in advanced disease, but controversies about the diagnosis and management of prostate cancer, especially in the areas of screening and choice of therapy, continue to evolve. Research initiatives in advanced disease have shifted from prognostication to prediction, and current treatment considerations are focused on optimization of therapy sequence, development of rational combinations, biomarker‐driven patient selection, determining the role of local disease control in patients with metastases, and bone targeting therapies. Despite progress, prostate cancer survival has not improved at the same pace as other cancer subtypes. It is anticipated that addressing knowledge gaps will lead to the development of novel agents with unique mechanisms of action and optimization of integrated strategies (surgical, radiation, and medical) to improve overall survival. Prostate cancer awareness, clinical application of improved biopsy schemes, and advances in imaging combined with the widespread use of prostate‐specific antigen (PSA) have resulted in increased detection of early prostate cancer. The question of whether PSA screening would reduce mortality from prostate cancer has now been tested in the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial first published in 2009. Though many of the apparent discrepancies between these trials can be accounted for by trial design and patient cross‐contamination, they brought to the forefront the dilemma of overdiagnosis and overtreatment, as well as the heterogeneous nature of prostate cancer and the urgent need to improve the accuracy of identifying clinically significant early disease with lethal potential. It is hoped that enhancing the current morphologic and anatomic classification of prostate cancer with a better understanding of the molecular underpinnings of diverse disease states will lead to a more refined taxonomy of prostate cancer and ultimately improve outcomes while minimizing treatment‐related morbidity. Salient features that distinguish prostate cancer from other malignancies and frame the dilemmas surrounding it are its striking age‐dependent incidence, with progressively increasing frequency with increasing age, a strong familial and hereditary component, the variable lethality of morphologically identical cancers, the central role of androgen signaling, the preponderance of bone‐forming metastases, and metabolic derangements contributing to lethal progression. Important advances made in each of these areas will modify the approaches currently used to prevent, prognosticate, predict, and treat prostate cancer.