Democratizing germline genetic testing and its impact on prostate cancer clinical decision-making.

Authors

null

Neal D. Shore

Carolina Urologic Research Center, Myrtle Beach, SC

Neal D. Shore , Mukaram Gazi , Christopher Michael Pieczonka , Sean Heron , David J Cahn , Laurence Belkoff , Aaron D. Berger , Brian Mazzarella , Joseph Veys , David Morris , Alexander Engelman , Paul Dato , Richard Bevan-Thomas , Robert Cornell , Paige Layman , Kathryn E. Hatchell , Brandie Heald , Sarah M. Nielsen , Robert Luke Nussbaum , Edward D. Esplin

Organizations

Carolina Urologic Research Center, Myrtle Beach, SC, University Urology Associates, Howell Township, NJ, Associated Medical Professionals, Syracuse, NY, AUI Health—Advanced Urology Institute, St. Petersburg, FL, Colorado Urology, Golden, CO, MidLantic Urology LLC, Bala Cynwyd, PA, Associated Urological Specialists, Chicago Ridge, IL, Urology Austin, Austin, TX, North Georgia Urology, Dalton, GA, Urology Associates, P.C., Nashville, TN, Cancer Center of South Tampa, Tampa, FL, Genesis Healthcare Partners, San Diego, CA, Urology Partners, Arlington, TX, Urosurgery Houston, Houston, TX, Invitae, San Francisco, CA

Research Funding

Other

Background: Approximately 10-15% of prostate cancer (PCa) patients (pts) have a pathogenic germline variant (PGV). Identification of a PGV has important implications affecting decisions regarding cancer screening, treatment selection, and family cascade testing. There exists limited data documenting real world recommendations post germline genetic testing (GGT). This study was designed to collect clinician reported outcomes from PCa pts who underwent GGT. Methods: An IRB-approved, nationwide, prospective registry recruited unselected PCa pts from 15 community and academic urology practices. Pts underwent an 84-gene panel test, with clinical outcomes collected via clinician-completed case report forms > 1-month post GGT. Statistical significance was determined by two-tailed Fisher’s exact test. Results: 982 predominantly white (75.9%), non-metastatic (80.7%) males with PCa were recruited; 56.9% met National Comprehensive Cancer Network (NCCN) GGT criteria. Average age was 65.3 years at PCa diagnosis. PGVs, most commonly CHEK2 (17) and BRCA2 (10), were identified in 100 (10.2%) pts; 34 (34%) of these did not meet NCCN GGT criteria. Among PGV positive pts, 241 recommendations were made (Table). They were more likely to have changes to treatment (p < 0.0001), follow up (p < 0.0001) and cascade testing recommendations (p < 0.0001) than those with negative/variant of uncertain significance (VUS) results. There were no significant differences in changes to treatment (p = 0.4471) or follow up (p = 0.861) for pts who met NCCN criteria versus those who did not. 7 pts with PGVs received targeted therapy or were referred to a clinical trial. 5 pts with VUS results were also referred to a clinical trial. Among these 12 pts, 6 (50%, 2 CHEK2 PGV, 1 ATM PGV, 1 VUS each ATM, BLM, CHEK2) did not meet NCCN GGT criteria. Referral to a genetic counselor was the most common follow up recommendation for those with PGV (38 patients, 38%) and VUS results (66, 13.7%). The most commonly reported impact to health outcomes for those with negative results was knowledge/reassurance (38, 7.88%). Conclusions: This study showed that GGT did influence PCa pts care. Appropriately, pts with PGVs received a greater number of recommendations for relatives, changes to follow up and treatment.

# pts
# positive
%
# negative
%
# vus
%
total
%
100
10.2%
400
40.7%
482
49.1%
982
100%
# yes, GGT impacted pt health outcome
67
67.0%
100
25.0%
188
39.0%
356
36.3%
# pts, change to treatment recommendations
18
18.0%
1
0.3%
10
2.1%
29
3.0%
# changes to treatments recommendations
21
-
1
-
11
-
33
-
# pts, change to follow up
62
62.0%
7
1.8%
92
19.1%
161
16.4%
# changes to follow up
82
-
7
-
92
-
181
-
# pts, GC recommended for family
67
67.0%
4
1.0%
35
7.3%
106
10.8%
# pts, GGT recommended for family
71
71.0%
7
1.8%
41
8.5%
119
12.2%
Total # health outcome evaluations
241
-
19
-
179
-
439
-

GC, genetic counseling; GGT, germline genetic testing; pt(s), patient(s); VUS, variant of uncertain significance.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Prevention, Risk Reduction, and Hereditary Cancer

Track

Prevention, Risk Reduction, and Genetics

Sub Track

Germline Genetic Testing

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 10500)

DOI

10.1200/JCO.2022.40.16_suppl.10500

Abstract #

10500

Abstract Disclosures