Topic: Biomarkers

In My Opinion: Biomarkers for the Diagnosis of Prostate Cancer

Michael A. Gorin, MD, discusses biomarkers for diagnosing prostate cancer, including PSA, mpMRI, and serum and urine tests. He gives an overview of the history of prostate specific antigen (PSA), emphasizing that PSA screening is beneficial even as he acknowledges that PSA’s high sensitivity and low specificity result in many unnecessary biopsies. There are now many serum and urine biomarker tests that can help provide more specificity, including 4KScore, Prostate Health Index, SelectMDx, and ExoDx Prostate IntelliScore (EPI), all of which are endorsed by the NCCN Guidelines. Dr. Gorin notes that, when price is considered, SelectMDx and EPI outperform the other tests. Dr. Gorin concludes the presentation by discussing how multiparametric MRI should be used in prostate cancer diagnosis, noting that while there is little official guidance on this yet, he uses it in his own practice if a patient has a PSA ≥3 and receives an abnormal result from a serum or urine biomarker test.

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Trials in Neoadjuvant Therapy for Patients with High-Risk Localized Prostate Cancer

Brian T. Helfand, MD, PhD, Chief of the Division of Urology at NorthShore University HealthSystem in Evanston, Illinois, discusses the growing role of genetic assessment in prostate cancer screening, emphasizing the benefits of finding patients’ single nucleotide polymorphism (SNP)-based polygenic risk score (PRS). He acknowledges the roles of family history and testing for rare pathogenic mutations like BRCA2, ATM, and CHEK2, but observes that the former can change over time and be difficult to accurately obtain, while the latter is only relevant to a small percentage of patients. PRS, or genetic risk score, is a number calculated based on the cumulative variation across multiple SNPs, which is then used to provide an easily interpreted estimate of disease risk that is more informative than family history, improves predictive performance, and is significantly associated with both prostate cancer incidence and mortality. Dr. Helfand concludes by noting that there are currently no agreed upon guidelines for timing and frequency of PSA testing, but genetic assessment, and particularly PRS, could clarify who would benefit from early screening.

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Updates in PARP Inhibition and Germline Testing in Prostate Cancer

Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, outlines recent treatment updates for prostate cancer patients, beginning with a brief review of germline testing recommendations. Following this, Dr. Bryce discusses two newly-approved PARP inhibitors that target mutations: rucaparib and olaparib. Dr. Bryce then poses a series of questions and challenges that physicians should consider as ongoing trials for various disease states and combinations (neoadjuvant, metastatic castrate sensitive prostate cancer, firstline metastatic castrate resistance prostate cancner, PARP inhibition + immunotherapy, etc.) continue.

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Panel Discussion: Next Generation Genomics and Prostate Cancer Biomarkers

Leonard G. Gomella, MD, FACS, leads a panel discussion with Gerald L. Andriole, Jr., MD; Alan H. Bryce, MD; Brian F Chapin, MD; E. David Crawford, MD; Steven E. Finkelstein, MD, FACRO; A. Karim Kader, MD, PhD; and Neal D. Shore, MD, FACS on how biomarkers are being used to treat prostate cancer. Biomarkers are used to diagnose PCa and to decide whether or not to biopsy or repeat biopsy. They also discuss how biomarkers are used to treat localized disease and advanced disease. Both tissue and liquid biopsies are used for somatic DNA mutations, with liquid biopsies becoming increasingly important since it gives real-time results. Guidelines for germline testing and counseling are being updated, and germline testing for family members is becoming increasingly important. PARP inhibitors are now approved for detecting BRCA mutations. There is broader approval for the medication olaparib for both germline and somatic testing. They also review the updated biomarker map. They discuss how these changes will shape precision medicine and personalized care. It is essential for the urology community to be familiar with all these aspects of testing and clinical applications. They discuss why the PCA 3 test has been declining. They also discuss the need to send a clear message to primary care physicians.

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Genetics and Biomarkers for Prostate Cancer and Bladder Cancer

Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, discusses genetics and biomarkers for prostate cancer and bladder cancer. Genetic testing is now considered part of best practice for the treatment of cancer, but even still the topic can be confusing due to the number of different test types and scenarios. In order to combat this confusion, it is important that urologists continue to educate themselves on the matter. Dr. Bryce discusses the purpose of using either germline or somatic tests and the different information they can tell us. He goes into particular detail about the somatic test and how useful it can be in determining which targeted therapies to use for both prostate and bladder cancer. Finally, he also offers some advice on best practices for utilizing the somatic test including: testing every patient, always using a fresh biopsy, and retesting before each line of systemic therapy.

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Germline Testing for Active Surveillance

Brian T. Helfand, MD, PhD, Chief of the Division of Urology at NorthShore University HealthSystem in Evanston, Illinois, discusses the growing role of genetic assessment in prostate cancer screening, emphasizing the benefits of finding patients’ single nucleotide polymorphism (SNP)-based polygenic risk score (PRS). He acknowledges the roles of family history and testing for rare pathogenic mutations like BRCA2, ATM, and CHEK2, but observes that the former can change over time and be difficult to accurately obtain, while the latter is only relevant to a small percentage of patients. PRS, or genetic risk score, is a number calculated based on the cumulative variation across multiple SNPs, which is then used to provide an easily interpreted estimate of disease risk that is more informative than family history, improves predictive performance, and is significantly associated with both prostate cancer incidence and mortality. Dr. Helfand concludes by noting that there are currently no agreed upon guidelines for timing and frequency of PSA testing, but genetic assessment, and particularly PRS, could clarify who would benefit from early screening.

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Kaiser Permanente Prostate Cancer Risk Calculator 1.0

Joseph C. Presti, Jr., MD, FACS, Regional Leader of Urologic Oncology Surgery at Kaiser Permanente Northern California, discusses the development of Kaiser Permanente’s new prostate cancer risk calculator and its merits. Dr. Presti explains that older risk calculators tend to oversimplify variables like race, are based on outdated systematic biopsy schemes, and are often poorly calibrated due to the sampling frame used. Using TRIPOD guidelines (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) and the LASSO (least absolute shrinkage and selection operator) system of selection, Kaiser Permanente researchers determined that the variables that ought to be included in a prostate cancer prediction model are age, race, PSA, body-mass index, family history, number of prior negative biopsies, digital rectal exam (DRE), and prostate volume. They created 3 different models based on this, with the simplest but least accurate including clinical core variables but no DRE and no prostate volume, the second-most accurate including DRE but no prostate volume, and the most accurate including DRE and prostate volume. Dr. Presti notes that all of these models compare favorably to other risk calculators.

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Updates in Screening: Prostate Cancer Guidelines

Gerald L. Andriole, Jr., MD, a 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, reviews guidelines for prostate cancer screening, including the unchanged 2018 AUA guidelines and the 2020 updates to the NCCN and EAU guidelines. Following this, he explains why he disagrees with a 2020 article that suggests physicians use a PSA level of 10 ng/mL as the threshold when referring PCa patients to urology and thus biopsy. Lastly, he outlines five ways physicians can improve the early detection of prostate cancer.

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Genetic Risk Score for Prostate Cancer Screening

Brian T. Helfand, MD, PhD, Chief of the Division of Urology at NorthShore University HealthSystem in Evanston, Illinois, discusses the growing role of genetic assessment in prostate cancer screening, emphasizing the benefits of finding patients’ single nucleotide polymorphism (SNP)-based polygenic risk score (PRS). He acknowledges the roles of family history and testing for rare pathogenic mutations like BRCA2, ATM, and CHEK2, but observes that the former can change over time and be difficult to accurately obtain, while the latter is only relevant to a small percentage of patients. PRS, or genetic risk score, is a number calculated based on the cumulative variation across multiple SNPs, which is then used to provide an easily interpreted estimate of disease risk that is more informative than family history, improves predictive performance, and is significantly associated with both prostate cancer incidence and mortality. Dr. Helfand concludes by noting that there are currently no agreed upon guidelines for timing and frequency of PSA testing, but genetic assessment, and particularly PRS, could clarify who would benefit from early screening.

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What Role Do Markers Play in Establishing Active Surveillance or Definitive Care?

Gerald L. Andriole, Jr., MD, explains that while active surveillance is on the rise, doctors can do a better job of selecting patients for it. He points out that NCCN and ASCO guidelines indicate that routine ordering of molecular biomarker tests is not recommended, and state that doctors should only perform active surveillance on low- and favorable-risk patients. He concludes that clinical criteria are very useful in determining when to use active surveillance, and notes that MRI and gene expression classifiers add some certainty to the decision. There are other markers that may aid in decision making, but the current data is sparse.

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Next Generation Biomarkers – As Reflex, Combination, or First Line?

E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at University of California, San Diego, gives his expertise on next generation biomarkers in prostate cancer screening. Firstly, Dr. Crawford qualifies the new standard of PSA >1.5 ng/mL, specifically how it aids in early detection of disease and acts as a surrogate for BPH, prostate cancer, and prostatitis. Following this, Dr. Crawford reviews the clinical needs and genomic markers of prostate cancer. In conclusion, he describes his algorithm for PSA screening.

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The Live Primary Cell Phenotypic Test (LPCP) for Prostate Cancer

David M. Albala, MD, Chief of Urology at Crouse Hospital in Syracuse, New York, discusses the experimental live primary cell phenotypic test (LPCP) for prostate cancer. He details how live, unfixed cancer cells are taken from tissue, plated out on an extracellular matrix, and grown in a single cell monolayer. The LPCP looks at 14 different biomarkers from both normal and malignant cells, and machine learning algorithms generate scores that, according to preliminary research, can accurately predict general, local, and metastatic adverse pathology potential.

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