Publications by authors named "Veda N Giri"

68 Publications

Insight into how patients with prostate cancer interpret and communicate genetic test results: implications for families.

J Community Genet 2022 Jul 22. Epub 2022 Jul 22.

Division of Population Science, Department of Medical Oncology and the Sidney Kimmel Cancer Center, Thomas Jefferson University, 834 Chestnut Street, Suite 314, Philadelphia, PA, 19107, USA.

Patients with prostate cancer (PCA) are increasingly being offered germline genetic testing for precision therapy, precision management, and clinical trial options. Genetic test results also have implications for family members. How men with PCA perceive their genetic test results and decide whether to share recommendations with family members is not well studied. We interviewed 12 patients who had PCA and genetic testing and received a positive variant/likely positive variant (PV/LPV) (n = 7) or a variant of unknown significance (VUS) (n = 5) result. The semi-structured interview had five sections: genetic testing experience, impact, and interpretation of the test result, deciding whether to communicate test results to family members, impact of communication on family members, and suggestions for genetic counselors and other PCA patients. Interviews were transcribed verbatim and thematic analysis was completed using NVivo software v10. Receipt of PV/LPV or VUS genetic test results was not as emotional as receiving the diagnosis of PCA itself. Seven of the 12 participants chose to share their test results with all relevant family members, 4 chose to share with select family members, and one chose to not disclose to any family members. The majority of family members who were aware of participants' genetic results have not undergone cascade genetic testing or sought cancer screening. Participants with PCA and positive or VUS genetic test results typically share their results with at least immediate family members, but some communication barriers exist. Understanding the best way to provide actionable and relevant information about genetic testing to family members remains a challenge.
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http://dx.doi.org/10.1007/s12687-022-00603-1DOI Listing
July 2022

Guidelines on Germline Testing for Urologic Tumor Syndromes.

Eur Urol Focus 2022 Jul 5. Epub 2022 Jul 5.

Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, USA.

In the expanding precision medicine landscape, along with improvements in and the availability of testing, the use of genetics in the evaluation and treatment of patients has increased significantly. Multiple urologic cancers in different organ systems associated with an inherited gene mutation have been described. As these mutations can impact screening and treatment decisions for patients and their families, it is important for providers to be familiar with the current guidelines for germline testing. Here we summarize the current guidelines regarding germline testing for patients with suspected urologic tumor syndromes. PATIENT SUMMARY: Several cancers of the genitourinary tract can be associated with inherited genetic mutations. Knowledge of when to test for these mutations has implications for both treatment and screening of patients and their family members at risk of genitourinary cancers.
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http://dx.doi.org/10.1016/j.euf.2022.06.010DOI Listing
July 2022

Technology-enhanced AcceleRation of Germline Evaluation for Therapy (TARGET): A randomized controlled trial of a pretest patient-driven webtool vs. genetic counseling for prostate cancer germline testing.

Contemp Clin Trials 2022 Jun 14;119:106821. Epub 2022 Jun 14.

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America; Cancer Risk Assessment and Clinical Cancer Genetics, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America; Department of Urology, Thomas Jefferson University, Philadelphia, PA, United States of America. Electronic address:

Background: Germline testing has an increasingly important role in prostate cancer care. However, a relative shortage of genetic counselors necessitates alternate strategies for delivery of pre-test education for germline testing. This study, funded by the Prostate Cancer Foundation, seeks to address the need for novel methods of delivery of pre-test germline education beyond traditional germline counseling to facilitate informed patient decision-making for germline testing.

Methods: This is a two-armed randomized controlled trial (RCT) with a target enrollment of 173 participants with prostate cancer per study arm (total anticipated n = 346). Patients who meet criteria for germline testing based on tumor features, family history or Ashkenazi Jewish ancestry are being recruited from 5 US sites including academic, private practice and Veterans healthcare settings. Consenting participants are randomized to the interactive pretest webtool or germline counseling with assessment of key patient-reported outcomes involved in informed decision-making for germline testing.

Results: Participants complete surveys at baseline, after pretest education/counseling, and following disclosure of germline results. The primary outcome of the study is decisional conflict for germline testing. Secondary outcomes include genetic knowledge, satisfaction, uptake of germline testing, and understanding of results.

Conclusion: Our hypothesis is that the web-based genetic education tool is non-inferior to traditional genetic counseling regarding key patient-reported outcomes involved in informed decision-making for germline testing. If proven, the results would support deploying the webtool across various practice settings to facilitate pre-test genetic education for individuals with prostate cancer and developing collaborative care strategies with genetic counseling.

Clinicaltrials: gov Identifier: NCT04447703.
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http://dx.doi.org/10.1016/j.cct.2022.106821DOI Listing
June 2022

Germline Variant Spectrum Among African American Men Undergoing Prostate Cancer Germline Testing: Need for Equity in Genetic Testing.

JCO Precis Oncol 2022 05;6:e2200234

Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA.

Purpose: Guidelines for prostate cancer (PCA) germline testing (GT) have expanded, with impact on clinical management and hereditary cancer assessment. African American (AA) men have lower engagement in GT, with concern for widening disparities in genetically informed care. We evaluated the germline spectrum in a cohort of men with PCA enriched for AA men who underwent GT to inform tailored genetic evaluation strategies.

Methods: Participants included AA and White men with PCA tested with a 14-gene PCA panel: , , , , , , , , , , , , , and . Germline analysis was performed per standard clinical testing and variant classification protocols. Data were compared with Fisher's exact, chi-squared, or two sample -tests, as appropriate. Multivariable analysis was conducted using Akaike's Information Criterion. The significance level was set a priori at .05.

Results: The data set included 427 men all tested using the 14-gene PCA panel: AA (n = 237, 56%) and White (n = 190, 44%). Overall, the pathogenic/likely pathogenic (P/LP) variant rate was 8.2%, with AA men having lower rates of P/LP variants then White men (5.91% v 11.05%, respectively; = .05). Borderline associations with P/LP variant status were observed by race (AA White; odds ratio = 0.51; = .07) and age (> 50 ≤ 50 years; odds ratio = 0.48; = .06). The P/LP spectrum was narrower in AA men (, , , and ) than White men (, , , , , and ). A significant difference was noted in rates of variants of uncertain significance (VUSs) between AA men and White men overall (25.32% 16.32%; = .02) and for carrying multiple VUSs (5.1% 0.53%, = .008).

Conclusion: Germline evaluation in a cohort enriched for AA men highlights the narrower spectrum of germline contribution to PCA with significantly higher rates of multiple VUSs in DNA repair genes. These results underscore the imperative to engage AA men in GT, the need for larger panel testing in AA men, and the necessity to incorporate novel genomic technologies to clarify VUS to discern the germline contribution to PCA. Furthermore, tailored genetic counseling for AA men is important to ensure understanding of VUS and promote equitable genetics care delivery.
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http://dx.doi.org/10.1200/PO.22.00234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200399PMC
May 2022

Germline testing and genetic counselling in prostate cancer.

Nat Rev Urol 2022 06 21;19(6):331-343. Epub 2022 Apr 21.

Cancer Risk Assessment and Clinical Cancer Genetics, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Genetic testing for prostate cancer is rapidly growing and is increasingly being driven by precision medicine. Rates of germline pathogenic variants have been reported in up to 15% of men with prostate cancer, particularly in metastatic disease, and results of genetic testing could uncover options for precision therapy along with a spectrum of hereditary cancer-predisposition syndromes with unique clinical features that have complex management options. Thus, the pre-test discussion, whether delivered by genetic counsellors or by health-care professionals in hybrid models, involves information on hereditary cancer risk, extent of gene testing, purpose of testing, medical history and family history, potential types of results, additional cancer risks that might be uncovered, genetically based management and effect on families. Understanding precision medicine, personalized cancer risk management and syndrome-related cancer risk management is important in order to develop collaborative strategies with genetic counselling for optimal care of patients and their families.
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http://dx.doi.org/10.1038/s41585-022-00580-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022414PMC
June 2022

Genetic testing in prostate cancer management: Considerations informing primary care.

CA Cancer J Clin 2022 Jul 24;72(4):360-371. Epub 2022 Feb 24.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Inherited genetic mutations can significantly increase the risk for prostate cancer (PC), may be associated with aggressive disease and poorer outcomes, and can have hereditary cancer implications for men and their families. Germline genetic testing (hereditary cancer genetic testing) is now strongly recommended for patients with advanced/metastatic PC, particularly given the impact on targeted therapy selection or clinical trial options, with expanded National Comprehensive Cancer Network guidelines and endorsement from multiple professional societies. Furthermore, National Comprehensive Cancer Network guidelines recommend genetic testing for men with PC across the stage and risk spectrum and for unaffected men at high risk for PC based on family history to identify hereditary cancer risk. Primary care is a critical field in which providers evaluate men at an elevated risk for PC, men living with PC, and PC survivors for whom germline testing may be indicated. Therefore, there is a critical need to engage and educate primary care providers regarding the role of genetic testing and the impact of results on PC screening, treatment, and cascade testing for family members of affected men. This review highlights key aspects of genetic testing in PC, the role of clinicians, with a focus on primary care, the importance of obtaining a comprehensive family history, current germline testing guidelines, and the impact on precision PC care. With emerging evidence and guidelines, clinical pathways are needed to facilitate integrated genetic education, testing, and counseling services in appropriately selected patients. There is also a need for providers to understand the field of genetic counseling and how best to collaborate to enhance multidisciplinary patient care.
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http://dx.doi.org/10.3322/caac.21720DOI Listing
July 2022

When to use germline genetic testing in prostate cancer.

Authors:
Veda N Giri

Clin Adv Hematol Oncol 2022 02;20(2):78-81

Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.

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February 2022

Helix: A Digital Tool to Address Provider Needs for Prostate Cancer Genetic Testing in Clinical Practice.

Clin Genitourin Cancer 2022 04 27;20(2):e104-e113. Epub 2021 Nov 27.

NYU-Langone Health, New York, NY; Manhattan Veterans Affairs Hospital, New York, NY.

Background: Prostate cancer (PCA) germline testing (GT) is now standard-of-care for men with advanced PCA. Thousands of men may consider GT due to clinical and family history (FH) features. Identifying and consenting men for GT can be complex. Here we identified barriers and facilitators of GT across a spectrum of providers which informed the development of Helix - an educational and clinical/FH collection tool to facilitate GT in practice.

Materials And Methods: A 12-question survey assessing knowledge of genetics PCA risk and FH was administered December 2017 to March 2018 in the Philadelphia area and at the Mid-Atlantic AUA meeting (March 2018). Responses were analyzed using descriptive statistics. Semi-structured interviews were conducted with medical oncologists, radiation oncologists, and urologists across practice settings from March-October 2020 as part of a larger study based on the Tailored Implementation in Chronic Diseases framework. Helix was then developed followed by user testing.

Results: Fifty-six providers (50% urologists) responded to the survey. Multiple FH and genetic knowledge gaps were identified: only 66% collected maternal FH and 43% correctly identified BRCA2 and association to aggressive PCA. Genetic counseling gaps included low rates of discussing genetic discrimination laws (45%). Provider interviews (n = 14) identified barriers to FH intake including access to details and time needed. In user testing (n = 10), providers found Helix helpful for FH collection. All providers found Helix easy to use, suggesting expanded clinical use.

Conclusion: Helix addressed multiple GT knowledge and practice gaps across a spectrum of providers. This tool will become publicly available soon to facilitate PCA GT in clinical practice.
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http://dx.doi.org/10.1016/j.clgc.2021.11.009DOI Listing
April 2022

Predictors of Population Awareness of Cancer Genetic Tests: Implications for Enhancing Equity in Engaging in Cancer Prevention and Precision Medicine.

JCO Precis Oncol 2021 3;5. Epub 2021 Nov 3.

Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Racial and ethnic disparities in genetic awareness (GA) can diminish the impact of personalized cancer treatment and risk assessment. We assessed factors predictive of GA in a diverse population-based sample to inform awareness strategies and reduce disparities in genetic testing.

Methods: A cross-sectional study was conducted from July 2019 to August 2019, with the survey e-mailed to 7,575 adult residents in southeastern Pennsylvania and New Jersey. Constructs from National Cancer Institute Health Information and National Trends Survey assessed cancer attitudes or beliefs, health literacy, and numeracy. Characteristics were summarized with mean ± standard deviation for numeric variables and frequency counts and percentages for categorical variables. Comparison of factors by race or ethnicity (non-Hispanic White and non-Hispanic Black) and sex was conducted by -tests, chi-square, or Fisher's exact tests. Multivariate logistic regression models were conducted to identify factors independently predictive of GA.

Results: Of 1,557 respondents, data from 940 respondents (the mean age was 45 ± 16.2 years, 35.5% males, and 23% non-Hispanic Blacks) were analyzed. Factors associated with higher GA included female gender ( < .001), non-Hispanic White ( < .001), college education ( < .001), middle-higher income ( < .001), stronger belief in genetic basis of cancer ( < .001), lower cancer fatalism ( = .004), motivation for cancer information ( < .001), and higher numeracy ( = .002). On multivariate analysis, college education (odds ratio [OR] 1.79; 95% CI, 1.22 to 2.63), higher motivation for cancer information (OR 1.56; 95% CI, 1.17 to 2.09), stronger belief in genetics of cancer (OR 2.21; 95% CI, 1.48 to 3.30), and higher medical literacy (OR 2.21; 95% CI, 1.34 to 3.65) predicted greater GA.

Conclusion: This population-based study conducted in the precision medicine era identified novel modifiable factors, importantly perceptions of cancer genetics and medical literacy, as predictive of GA, which informs strategies to promote equitable engagement in genetically based cancer care.
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http://dx.doi.org/10.1200/PO.21.00231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585288PMC
March 2022

Adopting Consensus Terms for Testing in Precision Medicine.

JCO Precis Oncol 2021 6;5. Epub 2021 Oct 6.

Seattle Cancer Care Alliance, Seattle, WA.

Despite the well-understood benefits of biomarker and genetic testing in precision medicine, uptake remains low, particularly for patients with low socioeconomic status and minority ethnic backgrounds. Patients report having limited familiarity with testing terminology and may not be able to accurately explain testing's role in treatment decisions. Patient confusion and lack of understanding is exacerbated by a multiplicity of overlapping terms used in communicating about testing. A LUNGevity Foundation-led working group composed of five professional societies, 23 patient advocacy groups, and 19 industry members assessed and recommended specific terms for communicating with patients on testing for tumor characteristics and germline mutations.

Methods: Members completed a precision oncology testing framework analysis (biomarkers, germline variants, testing modalities, biospecimen, and commonly used testing terms) for nine solid tumors and blood cancers. The evaluation was segmented into terms that distinguish between somatic and germline testing. Additional data were captured in a comprehensive survey (1,650 respondents) led by FORCE (Facing Our Risk of Cancer Empowered) on patient preferences on germline testing terms.

Results: Thirty-three terms were noted in patient education related to biomarker, genetic, and genomic testing. Biomarker testing was selected as the preferred term for testing for somatic (acquired) alterations and other biomarkers. Genetic testing for an inherited mutation and genetic testing for inherited cancer risk were selected as the preferred terms for testing for germline variants.

Conclusion: Democratizing comprehension about precision oncology testing through intentional use of plain language and common umbrella terminology by oncology health care providers and others in the oncology ecosystem may help improve understanding and communication, and facilitate shared decision making about the role of appropriate testing in treatment decisions and other aspects of oncology care.
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http://dx.doi.org/10.1200/PO.21.00027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509918PMC
April 2022

Pretest Genetic Education Video Versus Genetic Counseling for Men Considering Prostate Cancer Germline Testing: A Patient-Choice Study to Address Urgent Practice Needs.

JCO Precis Oncol 2021 1;5. Epub 2021 Sep 1.

Cancer Risk Assessment and Clinical Cancer Genetics Program, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Purpose: Germline testing (GT) for prostate cancer (PCA) is now central to treatment and hereditary cancer assessment. With rising demand for and shortage of genetic counseling (GC), tools to deliver pretest informed consent across practice settings are needed to improve access to GT and precision care. Here, we report on Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER), a patient-choice study for pretest video-based genetic education (VBGE) versus GC to inform urgent practice needs.

Patients And Methods: Men with PCA or at risk for PCA (family history of PCA) were eligible and could choose pretest VBGE or GC. Outcomes included decisional conflict for GT, change in genetics knowledge, satisfaction, and intention to share results with family and/or providers. Descriptive statistics summarized results with counts and percentages for categorical variables and mean ± standard deviation for continuous variables. Data were compared with Fisher's exact, chi-squared, or Wilcoxon two-sample tests. Mean change in genetics knowledge was compared with tests. The significance level was set a priori at .05.

Results: Data on the first 127 participants were analyzed. Characteristics were White (85.8%), bachelor's degree (66.9%), and PCA diagnosis (90.6%). The majority chose VBGE (71%) versus GC (29%; < .001). No differences were observed in decisional conflict for GT or satisfaction. Cancer genetics knowledge improved in both groups without significant difference (+0.9 VBGE, +1.8 GC, = .056). Men who chose VBGE had higher intention to share GT results (96.4% VBGE 86.4% GC, = .02). Both groups had high rates of GT uptake (VBGE 94.4%, GC 92%).

Conclusion: A substantial proportion of men opted for pretest VBGE, with comparable patient-reported outcomes and uptake of GT. The results support the use of pretest video to address the critical GC shortage in the precision era.
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http://dx.doi.org/10.1200/PO.21.00238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462590PMC
March 2022

Gaps in Public Awareness About BRCA and Genetic Testing in Prostate Cancer: Social Media Landscape Analysis.

JMIR Cancer 2021 Sep 20;7(3):e27063. Epub 2021 Sep 20.

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States.

Background: Genetic testing, particularly for BRCA1/2, is increasingly important in prostate cancer (PCa) care, with impact on PCa management and hereditary cancer risk. However, the extent of public awareness and online discourse on social media is unknown, and presents opportunities to identify gaps and enhance population awareness and uptake of advances in PCa precision medicine.

Objective: The objective of this study was to characterize activity and engagement across multiple social media platforms (Twitter, Facebook, and YouTube) regarding BRCA and genetic testing for PCa compared with breast cancer, which has a long history of public awareness, advocacy, and prominent social media presence.

Methods: The Symplur Signals online analytics platform was used to obtain metrics for tweets about (1) #BRCA and #breastcancer, (2) #BRCA and #prostatecancer, (3) #genetictesting and #breastcancer, and (4) #genetictesting and #prostatecancer from 2016 to 2020. We examined the total number of tweets, users, and reach for each hashtag, and performed content analysis for a subset of tweets. Facebook and YouTube were queried using analogous search terms, and engagement metrics were calculated.

Results: During a 5-year period, there were 10,005 tweets for #BRCA and #breastcancer, versus 1008 tweets about #BRCA and #prostatecancer. There were also more tweets about #genetictesting and #breastcancer (n=1748), compared with #genetic testing and #prostatecancer (n=328). Tweets about genetic testing (12,921,954) and BRCA (75,724,795) in breast cancer also had substantially greater reach than those about PCa (1,463,777 and 4,849,905, respectively). Facebook groups and pages regarding PCa and BRCA/genetic testing had fewer average members, new members, and new posts, as well as fewer likes and followers, compared with breast cancer. Facebook videos had more engagement than YouTube videos across both PCa and breast cancer content.

Conclusions: There is substantially less social media engagement about BRCA and genetic testing in PCa compared with breast cancer. This landscape analysis provides insights into strategies for leveraging social media platforms to increase public awareness about PCa germline testing, including use of Facebook to share video content and Twitter for discussions with health professionals.
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http://dx.doi.org/10.2196/27063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550715PMC
September 2021

Prostate Cancer Genetics: Changing the Paradigm of Care.

Urol Clin North Am 2021 Aug;48(3):xiii-xiv

Medical Oncology, Cancer Biology, Urology, Cancer Risk Assessment and Clinical Cancer Genetics, 1025 Walnut Street, Suite 1015, Philadelphia, PA 19107, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ucl.2021.06.001DOI Listing
August 2021

Genetic Testing Guidelines and Education of Health Care Providers Involved in Prostate Cancer Care.

Urol Clin North Am 2021 Aug 12;48(3):311-322. Epub 2021 Jun 12.

Department of Urology, Thomas Jefferson University, Philadelphia, PA, USA; Cancer Risk Assessment and Clinical Cancer Genetics, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA; Cancer Risk Assessment and Clinical Cancer Genetics, Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address:

Germline testing for prostate cancer (PCA) is revolutionizing PCA care. Two PARP inhibitors are FDA approved for men with metastatic, castration-resistant disease after progression on first-line therapies. In the screening setting, genetic test results may inform initiation and screening strategies. For men with early-stage disease, literature is emerging on the possible role of germline testing in active surveillance discussions. As such, urologists and oncologists must gain working knowledge of the principles and practice of germline testing and hereditary cancer implications for responsible implementation. Here the authors outline key learning areas and practice strategies for responsible dissemination of PCA germline testing.
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http://dx.doi.org/10.1016/j.ucl.2021.03.003DOI Listing
August 2021

Philadelphia Prostate Cancer Genetic Consensus Conference 2019 and implications for military medicine.

Can J Urol 2021 06;28(3):10659-10667

Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

INTRODUCTION The objective of our review is to summarize the 2019 Philadelphia Prostate Cancer Genetic Consensus recommendations and discuss their implications to the US Military Health System.

Materials And Methods: Literature review.

Results: Our fighting force and retired service members will significantly benefit from the Philadelphia Prostate Cancer Genetic Consensus recommendations. Moreover, the experience of the equal access US Military Health System may help advancing genetic testing for cancer at national levels.

Conclusions: Priorities recommended by the 2019 Consensus for more research on genetic predisposition to prostate cancer in racially diverse populations is a promising step. The US Military Health System has the ability of providing equal access to implement advanced germline testing for its racially diverse population.
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June 2021

Barriers and facilitators of germline genetic evaluation for prostate cancer.

Prostate 2021 08 31;81(11):754-764. Epub 2021 May 31.

Division of Population Science, Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Background: Genetic counseling and germline testing have an increasingly important role for patients with prostate cancer (PCa); however, recent data suggests they are underutilized. Our objective was to perform a qualitative study of the barriers and facilitators of germline genetic evaluation among physicians who manage PCa.

Methods: We conducted semi-structured interviews with medical oncologists, radiation oncologists, and urologists from different U.S. practice settings until thematic saturation was achieved at n = 14. The interview guide was based on the Tailored Implementation in Chronic Diseases Framework to identify key determinants of practice. Interview transcripts were independently coded by ≥2 investigators using a constant comparative method.

Results: The decision to perform or refer for germline genetic evaluation is affected by factors at multiple levels. Although patient factors sometimes play a role, the dominant themes in the decision to conduct germline genetic evaluation were at the physician and organizational level. Physician knowledge, coordination of care, perceptions of the guidelines, and concerns about cost were most frequently discussed as the main factors affecting utilization of germline genetic evaluation.

Conclusions: There are currently numerous barriers to implementation of germline genetic evaluation for PCa. Efforts to expand physician education, to develop tools to enhance genetics in practice, and to facilitate coordination of care surrounding genetic evaluation are important to promote guideline-concordant care.
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http://dx.doi.org/10.1002/pros.24172DOI Listing
August 2021

Clinical Implications of Germline Testing in Newly Diagnosed Prostate Cancer.

Eur Urol Oncol 2021 02 31;4(1):1-9. Epub 2020 Dec 31.

Cancer Risk Assessment and Clinical Cancer Genetics, Departments of Medical Oncology, Cancer Biology, and Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address:

Context: Germline testing (GT) is increasingly impacting prostate cancer (PCa) management and screening, with direct effects in urology, medical oncology, and radiation oncology. The majority of testing indications and recommendations center on men with metastatic disease, although guidelines now encompass newly diagnosed, early-stage PCa and entail assessment of personal history, pathologic features, and family history to determine eligibility for testing.

Objective: To describe current guidelines on GT for men with PCa and the impact on management. An additional objective was to review the literature on current uptake of GT across practice settings.

Evidence Acquisition: A nonsystematic review was performed of current guidelines on GT in PCa from professional societies and consensus conferences, detailing supporting evidence for these recommendations. This was supplemented by a literature review of uptake of GT and precision medicine in practice.

Evidence Synthesis: Multiple guidelines and consensus panels recommend GT for men with metastatic PCa. Guidelines endorse BRCA2 testing in metastatic PCa because of strong evidence for PCa risk, aggressiveness, and PARP inhibitor candidacy. Testing of additional DNA repair genes in metastatic disease is also endorsed across guidelines. Immunotherapy with pembrolizumab is an option in some guidelines for men with DNA mismatch repair deficiency. In localized disease, GT is recommended on the basis of histologic features and family history; criteria vary between guidelines. GT for localized disease informs hereditary cancer risk and will probably impact future PCa management. Practice gaps exist regarding utilization of GT.

Conclusions: Germline evaluation is increasingly important in the management of men with metastatic PCa and may also affect the prognosis for men with localized disease. The presence of germline mutations has important hereditary cancer implications for men and their families. Uptake of germline evaluation may be underutilized in some practice settings, so strategies for optimization are required.

Patient Summary: Patients with prostate cancer should talk to their doctor about the pros and cons of genetic testing, with attention to family history and cancer features. Genetic testing can have important implications for treatment, cancer screening, and family cancer risk.
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http://dx.doi.org/10.1016/j.euo.2020.11.011DOI Listing
February 2021

Knowledge and practice regarding prostate cancer germline testing among urologists: Gaps to address for optimal implementation.

Cancer Treat Res Commun 2020 28;25:100212. Epub 2020 Sep 28.

Cancer Risk Assessment and Clinical Cancer Genetics Program, Departments of Medical Oncology, Cancer Biology, and Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Background: Germline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown.

Materials And Methods: We conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media.

Results: Among 132 total respondents from diverse practice settings across the U.S., 12% perform germline testing, 44% refer to a genetic counselor, 11% do both, and 33% do not test/refer. Only 4% had formal education in genetics. While 98% ask about PCa family history, only 76% and 52% ask about breast and ovarian cancer. When presented with hypothetical case scenarios where germline testing is indicated, many respondents indicated they would not offer genetic counseling or testing. Younger age (p = 0,03), academic practice (p = 0.04), and specializing in PCa/oncology (p = 0.007) were significantly associated with performing or referring for germline testing. Specializing in PCa/oncology was significantly associated with recommending germline testing for all case scenarios involving metastatic PCa (p = 0.0009) CONCLUSION: Our results suggest significant gaps in knowledge of germline testing and alignment of practice with national guidelines among urologists. Germline testing education and facilitation of genetic evaluation in urologic practice is warranted.
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http://dx.doi.org/10.1016/j.ctarc.2020.100212DOI Listing
November 2021

Practical Considerations and Challenges for Germline Genetic Testing in Patients With Prostate Cancer: Recommendations From the Germline Genetics Working Group of the PCCTC.

JCO Oncol Pract 2020 12 28;16(12):811-819. Epub 2020 Sep 28.

Department of Medicine, University of California at San Diego Moores Cancer Center, La Jolla, CA.

Germline genetic testing is now routinely recommended for patients with prostate cancer (PCa) because of expanded guidelines and options for targeted treatments. However, integrating genetic testing into oncology and urology clinical workflows remains a challenge because of the increased number of patients with PCa requiring testing and the limited access to genetics providers. This suggests a critical unmet need for genetic services outside of historical models. This review addresses current guidelines, considerations, and challenges for PCa genetic testing and offers a practical guide for genetic counseling and testing delivery, with solutions to help address potential barriers and challenges for both providers and patients. As genetic and genomic testing become integral to PCa care, developing standardized systems for implementation in the clinic is essential for delivering precision oncology to patients with PCa and realizing the full scope and impact of genetic testing.
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http://dx.doi.org/10.1200/OP.20.00431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735040PMC
December 2020

Cancer Screening and Genetic Testing Recommendations for Relatives of Men Undergoing Prostate Cancer Germline Testing: Implications for Practice.

J Urol 2020 12 27;204(6):1116-1118. Epub 2020 May 27.

Division of Population Science, Departments of Medical Oncology, Cancer Biology, and Urology, and Cancer Risk Assessment and Clinical Cancer Genetics Program, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1097/JU.0000000000001150DOI Listing
December 2020

Neuroendocrine Tumors Are Enriched in Cowden Syndrome.

JCO Precis Oncol 2020 1;4. Epub 2020 Jun 1.

Department of Medical Oncology and Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

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http://dx.doi.org/10.1200/PO.19.00241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446357PMC
June 2020

Physical activity assessment among men undergoing genetic counseling for inherited prostate cancer: a teachable moment for improved survivorship.

Support Care Cancer 2021 Apr 2;29(4):2145-2151. Epub 2020 Sep 2.

Cancer Risk Assessment and Clinical Cancer Genetics Program, Departments of Medical Oncology, Cancer Biology, and Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Background: Genetic counseling (GC) presents an opportunity to address modifiable cancer risk factors, such as obesity, which is impacted by non-adherence to physical activity (PA) guidelines. Adherence to PA guidelines has not been assessed among men undergoing GC for prostate cancer (PCA). We conducted a targeted analysis of men undergoing PCA GC to assess adherence to PA recommendations.

Methods: Using a cross-sectional design, a total of 158 men from the Genetic Evaluation of Men (GEM) study at two academic cancer centers with a diagnosis or at risk for PCA completed a structured lifestyle survey, including questions about the number of days and intensity of PA over the past year. One-sample t tests assessed adherence of participants to PA recommendations. Chi-square analyses compared differences in PA adherence by PCA status, aggressiveness, family history, and body mass index. Logistic regression analyses identified predictors of PA adherence.

Results: High proportions of GEM participants were overweight (44.9%) or obese (38.0%, p = 0.002). Men with PCA engaged in less moderate (p = 0.019) and vigorous (p = 0.005) aerobic activity than men without PCA. Higher education was predictive of adherence to light (p = 0.008), moderate (p = 0.019), and vigorous (p = 0.002) intensity PA. Older age (p = 0.015) and higher education (p = 0.001) were predictive of adherence to strength-based recommendations.

Conclusions: High proportions of men receiving PCA GC were overweight/obese and lacked adherence to PA recommendations. GC represents a teachable moment to address PA to reduce cancer risk and promote cancer survivorship.
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http://dx.doi.org/10.1007/s00520-020-05667-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897228PMC
April 2021

The effect of neighborhood social environment on prostate cancer development in black and white men at high risk for prostate cancer.

PLoS One 2020 13;15(8):e0237332. Epub 2020 Aug 13.

Cancer Prevention and Control, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.

Introduction: Neighborhood socioeconomic (nSES) factors have been implicated in prostate cancer (PCa) disparities. In line with the Precision Medicine Initiative that suggests clinical and socioenvironmental factors can impact PCa outcomes, we determined whether nSES variables are associated with time to PCa diagnosis and could inform PCa clinical risk assessment.

Materials And Methods: The study sample included 358 high risk men (PCa family history and/or Black race), aged 35-69 years, enrolled in an early detection program. Patient variables were linked to 78 nSES variables (employment, income, etc.) from previous literature via geocoding. Patient-level models, including baseline age, prostate specific antigen (PSA), digital rectal exam, as well as combined models (patient plus nSES variables) by race/PCa family history subgroups were built after variable reduction methods using Cox regression and LASSO machine-learning. Model fit of patient and combined models (AIC) were compared; p-values<0.05 were significant. Model-based high/low nSES exposure scores were calculated and the 5-year predicted probability of PCa was plotted against PSA by high/low neighborhood score to preliminarily assess clinical relevance.

Results: In combined models, nSES variables were significantly associated with time to PCa diagnosis. Workers mode of transportation and low income were significant in White men with a PCa family history. Homeownership (%owner-occupied houses with >3 bedrooms) and unemployment were significant in Black men with and without a PCa family history, respectively. The 5-year predicted probability of PCa was higher in men with a high neighborhood score (weighted combination of significant nSES variables) compared to a low score (e.g., Baseline PSA level of 4ng/mL for men with PCa family history: White-26.7% vs 7.7%; Black-56.2% vs 29.7%).

Discussion: Utilizing neighborhood data during patient risk assessment may be useful for high risk men affected by disparities. However, future studies with larger samples and validation/replication steps are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237332PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425919PMC
October 2020

Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019.

J Clin Oncol 2020 08 9;38(24):2798-2811. Epub 2020 Jun 9.

Advocate Aurora Health, Milwaukee, WI.

Purpose: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.

Methods: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).

Results: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included and mismatch repair genes, with broader testing, such as , for clinical trial eligibility. was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for carriers, with consideration in , and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.

Conclusion: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.
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http://dx.doi.org/10.1200/JCO.20.00046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430215PMC
August 2020

Genetic education and practice considerations of non-genetic providers.

Authors:
Veda N Giri

Can J Urol 2019 Oct;26(5 Suppl 2):44-45

Departments of Medical Oncology, Cancer Biology and Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Germline testing for inherited prostate cancer is revolutionizing prostate cancer treatment for advanced and metastatic disease and is beginning to inform management for early-stage disease as well as prostate cancer screening discussions. Increasingly, non-genetic providers are performing genetic testing in their practices, necessitating focused efforts to address genetic education and working knowledge of genetic testing for responsible delivery of testing to men with or at risk for prostate cancer.
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October 2019

Introduction to the 2019 Philadelphia Prostate Cancer Consensus Program: 'Implementation of Genetic Testing for Inherited Prostate Cancer'.

Can J Urol 2019 10;26(5 Suppl 2):1-4

Thomas Jefferson University, Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, USA.

In 2017 the Sidney Kimmel Cancer Center of Thomas Jefferson University held the first international consensus conference on the role of genetic testing for inherited prostate cancer risk. This article outlines the key elements of our 2017 consensus meeting and discusses the rationale and design of our follow up 2019 Philadelphia Prostate Cancer Consensus titled the 'Implementation of Genetic Testing for Inherited Prostate Cancer.'
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October 2019

Exploring Asian Indian views about cancer and participation in cancer research: an evaluation of a culturally tailored educational intervention.

J Community Genet 2020 Apr 14;11(2):193-203. Epub 2019 Sep 14.

Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Asian Indians (AIs) are a growing population in the United States (US) with increased cancer incidence and mortality. However, screening rates among this population are low, and the population has been underrepresented in clinical research. This pilot study aims to address gaps in the literature in order to understand if a culturally tailored educational intervention will improve knowledge, risk perceptions, and awareness of cancer risk assessments among AIs. We delivered an educational intervention comprised of culturally tailored case studies describing risk factors for developing cancer in both males and females. We assessed knowledge gaps about cancer risk and genetic testing, cancer risk perceptions, and willingness to participate in medical research studies, pre- and post-intervention. Among 23 participants, knowledge of genetic testing use and screening recommendations significantly improved post-intervention, with increased willingness to discuss cancer with family members, participate in medical research, and undergo genetic testing for cancer risk assessment. However, findings at the 1-month follow-up time did not show significant changes, except for one knowledge item. Culturally tailored educational interventions, delivered in a community setting, can influence knowledge and risk perceptions about cancer risk and genetics among AIs. Our findings lay the groundwork to continue educational efforts in the area of cancer risk and genetic testing in the AI population, a growing population that has been understudied in the US.
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http://dx.doi.org/10.1007/s12687-019-00436-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062964PMC
April 2020

Prevalence of Suspected Hereditary Cancer Syndromes and Germline Mutations Among a Diverse Cohort of Probands Reporting a Family History of Prostate Cancer: Toward Informing Cascade Testing for Men.

Eur Urol Oncol 2020 06 3;3(3):291-297. Epub 2019 Jul 3.

Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA; Cancer Risk Assessment and Clinical Cancer Genetics, Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Background: Prostate cancer (PCa) is increasingly recognized as part of hereditary cancer syndromes (HCSs). HCS prevalence among diverse probands seeking genetic evaluation with PCa family history (FHx) has not been reported and has implications for cascade genetic testing.

Objective: To evaluate the rates of HCSs among probands reporting PCa FHx and germline mutations among probands.

Design, Setting, And Participants: A prospective genetic testing database queried for individuals with PCa FHx. Pedigrees analyzed for three HCSs: hereditary breast and ovarian cancer (HBOC), hereditary PCa, and Lynch syndrome.

Outcome Measurements And Statistical Analysis: Associations between HCS overall, and with plausible link to PCA FHx and race evaluated using Fisher's exact test. Germline mutation rates described among probands with a suspicion of an HCS connected with PCa FHx.

Results And Limitations: A total of 345 probands reported PCa FHx: 53 African American (AA) and 292 Caucasian (Wh). Overall, 220 probands (63.8%) met the criteria for at least one HCS with a potential link to PCa FHx (75.5% AA; 61.6% Wh). HBOC linked to PCa FHx was identified in a higher percentage of AA than Wh probands (90.2% vs 74.6%, p=0.04). Among probands who underwent genetic testing with any HCS potentially linked to PCa FHx (n=169), 19.5% had germline mutations identified; five AA probands had germline mutations (all in BRCA1/2), while 28 Wh probands had mutations in a spectrum of genes.

Conclusions: A significant percentage of AA probands with PCa FHx meet the criteria for HCSs, with HBOC identified at the highest rate. Although limited in sample size, our findings implicate BRCA mutations in AA families with HCSs linked with PCa, underscoring the need for greater enrollment of AA participants in genetic studies.

Patient Summary: Hereditary cancer syndromes potentially linked to prostate cancer are common in patients reporting a family history of prostate cancer. African-American patients may need special attention with regard to testing for hereditary breast and ovarian cancer syndrome, which may impact men with prostate cancer in these families.
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http://dx.doi.org/10.1016/j.euo.2019.06.010DOI Listing
June 2020

Germline Genetic Testing in Advanced Prostate Cancer; Practices and Barriers: Survey Results from the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium.

Clin Genitourin Cancer 2019 08 18;17(4):275-282.e1. Epub 2019 Apr 18.

Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA. Electronic address:

Background: Germline genetic testing increasingly identifies advanced prostate cancer (PCa) patients who are candidates for precision therapies. The Prostate Cancer Clinical Trials Consortium (PCCTC) established the Germline Genetics Working Group to provide guidance and resources to expand effective use of germline genetic testing.

Materials And Methods: A 14-item questionnaire was e-mailed to academic oncologists at 43 PCCTC sites to collect information on germline genetic testing patterns, including patients considered, choice of assays, barriers slowing adoption, and actions to overcome barriers.

Results: Twenty-six genitourinary oncologists from 19 institutions responded. Less than 40% (10 of 26) reported referring patients to a genetics department, whereas the remainder take personal responsibility for genetic testing and counseling; 16 (62%) consider testing all metastatic PCa patients, whereas 3 (12%) consider testing all patients with high-risk local disease; and 7 (27%) use multigene comprehensive pan-cancer panels, and 14 (54%) use smaller or targeted cancer gene panels. Barriers to widespread use are: (1) delayed or limited access to genetic counseling; (2) no insurance coverage; (3) lack of effective workflows; (4) insufficient educational materials; and (5) time and space constraints in busy clinics. The primary limitation was the <50% (19 of 43) response from PCCTC sites and no coverage of nonacademic cancer treatment facilities.

Conclusion: Joint efforts by urologists, oncologists, genetics counselors, insurers, and cancer centers can accelerate implementation of integrated germline genetic services for personalized treatment and clinical trial eligibility for PCa patients.
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http://dx.doi.org/10.1016/j.clgc.2019.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662206PMC
August 2019
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