Precision management of localized prostate cancer

Abstract

Introduction The vast majority of men who are diagnosed with prostate cancer die of other causes, highlighting the importance of determining which patient has a risk of death from prostate cancer. Precision management of prostate cancer patients includes distinguishing which men have potentially lethal disease and employing strategies for determining which treatment modality appropriately balances the desire to achieve a durable response while preventing unnecessary overtreatment. Areas covered In this review, we highlight precision approaches to risk assessment and a context for the precision-guided application of definitive therapy. We focus on three dilemmas relevant to the diagnosis of localized prostate cancer: screening, the decision to treat, and postoperative management. Expert commentary In the last five years, numerous precision tools have emerged with potential benefit to the patient. However, to achieve optimal outcome, the decision to employ one or more of these tests must be considered in the context of prevailing conventional factors. Moreover, performance and interpretation of a molecular or imaging precision test remains practitioner-dependent. The next five years will witness increased marriage of molecular and imaging biomarkers for improved multi-modal diagnosis and discrimination of disease that is aggressive versus truly indolent.

Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer

“…Over the last two decades, prostate cancer remains the most diagnosed neoplasm in American men, representing approximately 20% of all new diagnoses in 2019 [1]. Overtreatment of newlydiagnosed, indolent prostate cancers detected by rising levels of prostate-specific antigen (PSA) has been mitigated by increasingly widespread adoption of active surveillance, MRI-targeted biopsies, nomograms, and molecular tests for assessing the risk posed by unsampled higher grade disease [2][3][4][5]. While the absence of adverse pathological features, such as high Gleason score or seminal vesicle invasion, from biopsy is associated with improved outcomes following definitive therapy (surgery or radiation), sampling errors may lead to underestimation of the risk of biochemical recurrence.…”

Molecular correlates of intermediate- and high-risk localized prostate cancer

“…Historically, the greatest value of biopsy was in the positive predictive power of the pathology (tumor grade and volume) for disease aggressiveness, guiding patient counseling and decision making. Historic undersampling is expected to decrease by application of advanced imaging modalities such as multi-parametric MRI, which has an increased sensitivity in detecting higher grade disease [9–11]. Based on the findings that the adjacent Gleason grade 3 and grade 4 components in intermediate to high risk PCa are clonally related and share some common molecular features, commercial molecular tests and in-house ancillary tests have been developed and increasingly used to predict final pathology on radical prostatectomy (RP).…”