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Early Detection of Prostate Cancer: Navigating the Challenges in 2021

E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, discusses the challenges of early detection of prostate cancer (PCa) and recommends a prostate-specific antigen (PSA) cut-off of 1.5 ng/ml. He begins by briefly summarizing different screening guidelines, noting particularly that the United States Preventive Services Task Force (USPSTF) has raised concerns about PCa early detection, asserting that there is too much overtreatment. Dr. Crawford argues, however, that evidence shows that a reduction in PSA screening resulted in a rise in metastatic prostate cancer across the United States. Because most diagnostic testing is completed by family practice physicians who may not understand the nuances of PSA testing, Dr. Crawford recognizes that they need a simple message from urologists. He states that a PSA of >1.5 ng/ml is a good surrogate for benign prostatic hyperplasia (BPH), PCa, and PCa risk, and explains that patients with a PSA of 1.5 ng/ml to 4.0 ng/ml may be in a “danger zone” and require additional testing. Dr. Crawford contends that patients do not need to make an informed decision about getting a PSA test, and that PSA testing should be considered as routine as measuring a patient’s weight or cholesterol, especially since more than 70% of men will have a PSA of less than 1.5 and will not require further screening for another 5 to 10 years. He then explains that an abnormal PSA alone should not guide biopsy decisions, though, and suggests that using tests like 4Kscore and SelectMDx in conjunction with MRI can reduce unnecessary biopsies. Dr. Crawford concludes by reiterating the importance of simple messaging to move forward with effective screening and early detection of PCa.

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Panel Discussion – Focus on PSMA

Phillip J. Koo, MD, Division Chief of Diagnostic Imaging and Northwest Region Oncology Physician Executive at the Banner MD Anderson Cancer Center in Phoenix, Arizona, leads a panel discussion focused on PSMA PET-CT’s expanding role in prostate cancer screening and diagnosis. The conversation begins with a look at how PSMA ligands are produced and distributed and what this means for access. Jérémie Calais, MD, MSc, Director of the Clinical Research Program of the Ahmanson Translational Theranostics Division of the Department of Molecular and Medical Pharmacology at UCLA, explains the differences between Gallium-68 PSMA-11 and 18F-DCFPyL, noting that the capacity of production and distribution is greater for the latter than the former. He argues, however, that the tracer used does not ultimately matter. E. David Crawford, MD, Professor of Urology at UCSD, observes that there have not actually been any comparative trials of gallium vs. PyL scans, and he suggests that there might be subtle differences in efficacy. Dr. Calais agrees that there is some disparity, but he does not think they are significant enough to affect staging or clinical management decisions. The discussion continues with a brief consideration of PSMA’s potential in theranostics and a look at whether PSMA scans can be trusted without confirmation from biopsy. Dr. Crawford notes that while biopsies are important and should be obtained when possible, as trust grows in the PSMA scans they may become less necessary. Dr. Calais and Dr. Koo then consider the potential for PSMA tests to be reimbursed, observing that they are not yet covered by Medicare but that there is a potential that they will be covered by insurance relatively soon. Dr. Crawford then asks whether the older CT and bone scans will be replaced by scans like PSMA, and the panelists conclude that they inevitably will but that costs will make this shift take some time.

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Considerations to Improve Screening for Prostate Cancer

Gerald L. Andriole, Jr., MD, outgoing Robert K. Royce Distinguished Professor and Chief of Urologic Surgery at Barnes-Jewish Hospital, the Siteman Cancer Center, and Washington University School of Medicine in St. Louis, Missouri, and incoming Director of Urology in the National Capital Region at the Brady Urologic Institute at Johns Hopkins University, reviews current guidelines for prostate cancer screening and considers how screening can be improved. After an introduction from E. David Crawford, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, Dr. Andriole summarizes the AUA, EAU, and NCCN prostate cancer screening guidelines, highlighting the NCCN’s recommendation that men get an early-in-life PSA test to obtain a baseline, and interrogating the validity of the age cut-offs for testing in the AUA and EAU guidelines. He then proposes a series of concepts to improve screening, starting with recommendations on how to better identify which men are at above average risk. Dr. Andriole particularly emphasizes the utility of polygenomic risk scores, which have a high negative predictive value and can focus attention on which patients need to be further screened. He suggests that another key way to improve screening is to reduce confusion about the PSA test among patients and primary care providers by setting a cut-point of 1-1.5 as a threshold for referral to a urologist. Dr. Andriole then considers how to identify patients with clinically-significant prostate cancer earlier, focusing on the need for better biopsies. He also notes the importance of reducing unnecessary repeat and initial biopsies and suggests potentially using biomarkers, MRI, and PSMA-PET to decide whether a biopsy is necessary. After concluding his talk, Dr. Andriole further discusses polygenic risk score, the pros and cons of multiparametric MRI, the benefits of micro-ultrasound, transrectal versus transperineal biopsy, and the future of screening with Dr. Crawford.

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Final Results from ACIS Trial of Apalutamide Plus Abiraterone/Prednisone in Patients with Chemo-Naive mCRPC

Raoul S. Concepcion, MD, FACS, Chief Science Officer of U.S. Urology Partners in Nolensville, Tennessee, presents the final results of the ACIS trial, a random double-blind phase III study examining concomitant treatment with apalutamide and abiraterone plus prednisone against abiraterone and androgen deprivation therapy (ADT) in patients with chemotherapy-naïve metastatic castrate-resistant prostate cancer (mCRPC). He provides background, describes the study design and baseline characteristics, and reviews the findings. Dr. Concepcion explains the role of activated androgen receptors and intratumoral androgens in mCRPC. He also describes the concept of androgen annihilation, essentially blocking androgen at both the production and receptor level. The ACIS trial met its primary endpoint, radiographic progression-free survival (rPFS), at a median of 25.7 months of follow up, representing a 31% reduction in risk of radiographic progression or death. The risk reduction was maintained at 30% in long term follow-up at 54.8 months. However, overall survival was similar between treatment arms. Likewise, the secondary endpoints, time to initiation of cytotoxic chemotherapy, time to pain progression, and time to chronic opioid use, were also similar. Lastly, Dr. Concepcion notes that no new safety signals were observed and patient quality of life was comparable between treatment arms.

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Updates of Changes in the Early Detection of Prostate Cancer NCCN Guidelines 2021

Preston C. Sprenkle, MD, Associate Professor of Urology at Yale University School of Medicine in New Haven, Connecticut, offers an update of changes in the National Comprehensive Cancer Network (NCCN) guidelines for 2021 regarding the early detection of prostate cancer. Dr. Sprenkle first explains the rationale behind the early detection of prostate cancer guidelines, with the NCCN recognizing that prostate cancer is a spectrum of disease, that early detection is for men who opt-in to screening, and that early detection allows for treatment of aggressive cancer, realizing the challenge of not treating indolent disease. Dr. Sprenkle then displays a schematic to outline the format and elements of the NCCN guidelines before highlighting some changes made since 2020. The revised guidelines clarify language regarding race and ancestry as well as germline mutations. The revisions strengthen statements supporting the use of magnetic resonance imaging (MRI), reflecting an understanding that the benefit of MRI fusion prostate biopsy is clear and that data on multi-parametric (mp)MRI are no longer simply “emerging.” Additionally, the new recommendations remove the prostate cancer antigen 3 gene (PCA3) from the list of recommended biomarkers that further define risk. Guidelines now also recommend that high-grade prostatic intraepithelial neoplasia (HGPIN) be treated as benign disease. Dr. Sprenkle emphasizes that while these 2021 guidelines do not introduce major changes, the addition in 2020 of intraductal carcinoma (IDC) as a concerning pathological feature was a major change that merits continued attention.

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