Brian T. Helfand, MD, PhD

Brian T. Helfand, MD, PhD

NorthShore University Health System

Evanston, Illinois

Brian T. Helfand, MD, PhD, is Chief of the Division of Urology and the Ronald L. Chez Family and Richard Melman Family Endowed Chair at NorthShore University HealthSystem. He is Director of the Personalized Prostate Program and Director of Clinical Research in the Program for Personalized Cancer Care (PPCC). He is also an active surgical scientist who is involved in the care of patients with prostate cancer. His clinical care and research is focused on the implementation of genetic tests and biomarker studies for prostate cancer. Dr. Helfand completed his undergraduate degree at Emory University. He received his medical training and PhD in Cell and Molecular Biology and Genetics from Northwestern University. He is a fellowship-trained urologic oncologist who has focused his research career on prostate cancer. He was recruited in 2011 from Northwestern University’s Feinberg School of Medicine, where he was faculty in the Department of Urology. Dr. Helfand is an internationally-known urologist and genomic translational researcher. He has received multiple grants from the NIH and has published over 140 peer-reviewed manuscripts in journals such as Nature Genetics, The Journal of Cell Biology, and Science Translational Medicine. Dr. Helfand is involved in national and international research collaborations as an active member of the International Consortium for Prostate Cancer Genetics (ICPCG), the Prostate Cancer Specialized Program of Research Excellence (SPORE), the IMPACT) study, and the Lower Urinary Tract Dysfunction Research Network (LURN). His current research goals are focused on germline genetic variations and mutations. He is determined to use this information to assist in personal and informed clinical decision making about prostate cancer screening and treatment for patients and their family members.

Disclosures:

Advisory Board and Speaker at Ambry Genetics

Talks by Brian T. Helfand, MD, PhD

Overview of the State of Genetic Testing and Future Applications in Prostate Cancer

Brian T. Helfand, MD, PhD, Chief of the Division of Urology and the Ronald L. Chez Family and Richard Melman Family Endowed Chair at NorthShore University HealthSystem in Evanston, Illinois, discusses current and potential future applications of genetic testing in prostate cancer screening and treatment. He explains that genetic testing has applications throughout the patient journey. At the prevention and screening stage, genetic testing can determine which men will benefit from screening. At the diagnosis stage, it can determine which men will benefit from biopsy. During early-stage disease, genetic testing can help identify which men will benefit from definitive treatment. Finally, during late-stage disease, genetic testing can identify the men that will benefit from advanced therapies. Dr. Helfand notes that there are two kinds of genetic testing, germline and somatic, and not all tests are relevant at all stages of the patient journey. He then gives an overview of germline genetic testing’s role in screening, arguing that because family history, rare pathogenic mutations (RPMs), and genetic risk score (GRS) all measure risk independently, a comprehensive inherited risk assessment should include all three tools. Dr. Helfand particularly focuses on GRS, defining it as a number calculated based on the cumulative variation across multiple single nucleotide polymorphisms (SNPs), which is then used to provide an estimate of disease risk. He notes that GRS is simple to interpret and more informative than family history. Dr. Helfand also observes that GRS is correlated with number and laterality of tumor cores. GRS, he argues, is useful for risk stratification for both screening and active surveillance. He notes that RPMs can help with stratification in terms of disease aggressiveness. Dr. Helfand concludes by arguing that genetic testing for prostate cancer will be pivotal in the future and should be included in guidelines for both prevention and screening.

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Next Generation Imaging for Localization of Recurrent Prostate Cancer

Brian T. Helfand, MD, PhD, Chief of the Division of Urology and the Ronald L. Chez Family and Richard Melman Family Endowed Chair at NorthShore University HealthSystem in Evanston, Illinois, discusses the efficacy of next generation imaging options for localization of recurrent prostate cancer. He states that conventional imaging is consistently lacking in the sensitivity necessary to localize recurrence in patients with PSA levels below 10 ng/ml and that waiting for PSA levels to become this high produces worse oncologic outcomes in patients. Dr. Helfand suggests that next generation imaging is superior to conventional imaging due to the ability of MRI and PET CT scans to produce more accurate results at lower PSA levels. He then looks at the different available next generation imaging agents, focusing on choline C-11, fluciclovine, gallium, and DCFPyl, and expresses a need to understand how these agents compare to one another. Dr. Helfand reviews data on choline C-11 PET imaging which shows positive scans in 36% of patients at PSA levels below 1 ng/ml. He then discusses data from the LOCATE trial showing a 30% detection rate at 0 to 0.5 ng/ml, and evidence of PSMA having a 57.89% detection rate at 0.2 to 0.5 ng/ml. Dr. Helfand shows comparative data of the agents wherein PSMA has a better detection rate than choline C-11 of 86% vs. 70%, respectively, and a better detection rate than fluciclovine of 80% vs. 62%, respectively. He concludes that all next generation imaging options are superior to conventional imaging but more data is needed on how they improve oncological outcomes and on situational use of imaging agents.

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Germline Genetics in Prostate Cancer

Brian T. Helfand, MD, PhD, Chief of the Division of Urology and the Ronald L. Chez Family and Richard Melman Family Endowed Chair at NorthShore University HealthSystem, Director of the Personalized Prostate Program, and Director of Clinical Research in the Program for Personalized Cancer Care, discusses germline genetic testing and its ability to support prostate cancer (PCa) diagnosis and prognosis when used effectively. He begins with the NCCN guidelines for PCa germline testing, detailing its recommended use for patients with: intermediate-risk, high-risk, regional or metastatic disease; intraductal histology; Ashkenazi Jewish ancestry; family history (FH) of high-risk germline mutations; and positive family history of cancer. Dr. Helfand then considers genetic assessments, stressing the importance of FH, rare pathogenic mutations (RPMs), and SNPs in reaching conclusions. He continues with an explanation of genetic risk score (GRS), a number calculated based on the cumulative variation across multiple SNPs which is then used to provide an estimate of disease risk, and shows data supporting the idea that GRS is more informative than FH. He looks at how to complete genetic testing with intention, suggesting screening with the goal of identifying men at risk of PCa and aggressive cancer, as well as identifying men who are likely to respond to specific chemotherapies. Dr. Helfand also reviews data from the UK biobank showing the associations FH, RPMs, and GRS have with PCa incidence and mortality. He also presents data on active surveillance showing that it should be used with caution if patients have any DNA damage repair genes. Dr. Helfand reviews data on DNA damage response and cancer therapy, showing that men with DNA double repair gene mutations are more responsive to PARP inhibitors and platinum-based chemo, while men with mismatch mutations are more responsive to immune checkpoint inhibitors. Dr. Helfand concludes by saying that genetic testing should be included in PCa decision-making more often and used to understand the future of PCa patients.

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All Men with Prostate Cancer and All Patients with Advanced Disease Should Undergo Germline Testing

Brian T. Helfand, MD, PhD, Chief of the Division of Urology and the Ronald L. Chez Family and Richard Melman Family Endowed Chair at NorthShore University HealthSystem in Evanston, Illinois, takes the pro side in a point-counterpoint debate on the merits of germline testing for all patients with prostate cancer, from the screening stage to the advanced treatment stage. Dr. Helfand argues that germline testing is beneficial during screening since the identification of rare pathogenic mutations can indicate which patients are at high risk for more aggressive prostate cancer. Germline testing for patients with localized disease is also useful since if a patient has a genetic variant it is more advisable to proceed to definitive treatment with surgery or radiation as opposed to putting them on active surveillance. Dr. Helfand concludes by observing that it can be particularly useful for patients with advanced disease to undergo germline testing since some genetic variants are associated with increased response to certain treatments, such as PARP inhibitors and platinum-based therapies for men with DNA damage repair mutations and immunotherapies for DNA mismatch repair mutations.

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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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