Technology-enhanced acceleration of germline evaluation for therapy (TARGET): Results of a randomized controlled trial of a pretest patient-driven webtool vs. genetic counseling for prostate cancer germline testing.

person Veda N. Giri Yale Cancer Center, Yale School of Medicine, New Haven, CT info_outline Veda N. Giri, Scott W. Keith, Heather H. Cheng, Amy Leader, Laura Gross, Tatiana Sanchez Nolasco, Nataliya Byrne, Rebecca Hartman, Lauren Brown, Christopher Michael Pieczonka, Leonard G. Gomella, William Kevin Kelly, Costas D. Lallas, Nathan Handley, Patrick Johnston Mille, James Ryan Mark, Gordon Andrew Brown, Sameer Chopra, Alexandra McClellan, Stacy Loeb

Authors person Veda N. Giri Yale Cancer Center, Yale School of Medicine, New Haven, CT info_outline Veda N. Giri, Scott W. Keith, Heather H. Cheng, Amy Leader, Laura Gross, Tatiana Sanchez Nolasco, Nataliya Byrne, Rebecca Hartman, Lauren Brown, Christopher Michael Pieczonka, Leonard G. Gomella, William Kevin Kelly, Costas D. Lallas, Nathan Handley, Patrick Johnston Mille, James Ryan Mark, Gordon Andrew Brown, Sameer Chopra, Alexandra McClellan, Stacy Loeb Organizations Yale Cancer Center, Yale School of Medicine, New Haven, CT, Division of Biostatistics, Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, University of Washington Medical Center, Seattle, WA, Department of Medical Oncology, Division of Population Science, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, NYU Medical Center-Perlmutter Cancer Center, New York, NY, Thomas Jefferson University, Philadelphia, PA, Fred Hutchinson Cancer Center, Seattle, WA, Associated Medical Professionals of NY, Syracuse, NY, Jefferson Kimmel Cancer Center, Philadelphia, PA, Thomas Jefferson University Hospital, Philadelphia, PA, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, Delaware Valley Urol, Sewell, NJ, New Jersey Urology, Stratford, NJ, Yale School of Medicine, New Haven, CT, New York University and Manhattan Veterans Affairs, New York, NY Abstract Disclosures Research Funding Other Foundation Prostate Cancer Foundation Background: Germline genetic testing is important for prostate cancer management, clinical trial eligibility and hereditary cancer risk assessment. Despite this, genetic testing is underutilized and there is a shortage of genetic counselors. To address these gaps, we designed a webtool to provide patient-driven genetic education and conducted a randomized non-inferiority trial to compare it with traditional pre-test genetic counseling. Methods: TARGET is a multi-center randomized controlled trial comparing standard pre-test genetic counseling versus web-based genetic education (intervention) (NCT04447703). The study protocol was previously published (PMID 35710085). Briefly, patients with prostate cancer who met criteria for germline testing (based on tumor features, ancestry or family history) were randomized to pre-test genetic education through genetic counseling vs a 9-module webtool created by the study team and Prostate Cancer Foundation. The primary endpoint was non-inferiority in reducing decisional conflict between the webtool and genetic counseling by a margin of 4 (set in advance) on the validated Decision Conflict Scale. Analysis of covariance was used to compare decisional conflict between groups. All participants opting for testing received a 51-gene Invitae panel, with results delivered to the patient and their provider. Results: 346 patients with prostate cancer with a mean age of 63.7 years were randomized to genetic counseling (n=174) or web-based genetic education (n=172). Compared to baseline, there were reductions in decisional conflict in both arms following pre-test genetic education (Table). Adjusting for study site and baseline decisional conflict, the test of non-inferiority in reducing decisional conflict between arms was statistically significant (difference = -0.04, 95% CI: -∞ to 1.95, p<0.001). Overall 265 (76.6%) participants underwent genetic testing, including 146 (83.9%) in the genetic counseling and 119 (69.2%) in webtool arm, with the following results: negative (49.4%), variant of uncertain significance (35.5%) and pathogenic variant (15.1%). Conclusions: Delivery of pre-test genetic education through a webtool was non-inferior to genetic counseling in reducing decisional conflict. These results support a new standard of care for the use of patient-driven digital webtools for expanding access to pretest genetic education and informed decision-making for prostate cancer genetic testing. Clinical trial information: NCT04447703. Decisional conflict (*higher score: greater decisional conflict). Total Genetic Counseling Web Based Genetic Education Mean (sd) Mean (sd) Mean (sd) Baseline 36.73 (12.99) 36.69 (12.84) 36.77 (13.19) After Pre-Test Education 28 (10.78) 28.06 (11.17) 27.93 (10.37) *Mean Difference -8.16 (13.13) -8.21 (13.34) -8.11 (12.93)

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