Abstract 628P
Background
Pathogenic/Likely pathogenic (P/LP) germline variants occur in 10-15% of all prostate cancer (PCa) patients. However, complex and restrictive testing criteria lead to underutilization of genetic testing. A multi center prospective observational study was conducted to determine the incidence of P/LP variants in PCa patients who met criteria (IC) and did not meet (out of criteria-OOC) personal/family history based genetic testing criteria (e.g. ESMO Clinical Practice Guidelines).
Methods
An IRB-approved, prospective registry was initiated with 15 community and academic urology centers. Consecutive, unselected PCa patients ages 18-90 were consented and underwent an 84-gene germline panel test, with clinician-collected clinical information.
Results
Of the 615 patients to date, 358 (58%) were IC and 257 (42%) were OOC. Excluding low risk findings (e.g. MUTYH heterozygotes), 8.3% of patients had a P/LP variant on an 84-gene panel: 9.5% of IC patients and 6.6% of OOC patients (p=0.19). For a 12-gene PCa panel, P/LP yield was 5.9% (36/615), with no significant difference between IC and OOC patients (p=0.29). Of 51 pts with P/LP variants, 75% were potentially eligible for precision therapy, clinical treatment trials (e.g. PARP inhibitors) and/or other clinical management interventions, 30% of whom would’ve been missed by criteria.
Conclusions
There was no statistically significant difference in the yield of P/LP variants between IC and OOC patients, reinforcing that guidelines miss a significant number of patients with P/LP variants. Current criteria for germline testing of PCa patients are an obstacle to identifying patients with precision therapy-eligible P/LP variants and should be revised.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Invitae.
Funding
Invitae.
Disclosure
M.K. Hardwick: Other, Institutional, Project Lead: Invitae. E. Esplin: Financial Interests, Personal, Full or part-time Employment: Invitae. B. Mazzerelli: Financial Interests, Institutional, Research Grant: Invitae. D. Morris: Financial Interests, Institutional, Research Grant: Invitae. S. Heron: Financial Interests, Institutional, Research Grant: Invitae. J. Veys: Financial Interests, Institutional, Research Grant: Invitae. A. Engelman: Financial Interests, Institutional, Research Grant: Invitae. P. Dato: Financial Interests, Institutional, Research Grant: Invitae. R. Bevan-Thomas: Financial Interests, Institutional, Research Grant: Invitae. D. Wise: Financial Interests, Institutional, Research Grant: Invitae. R. Cornell: Financial Interests, Institutional, Research Grant: Invitae. A. Berger: Financial Interests, Institutional, Research Grant: Invitae. S. Nielsen: Financial Interests, Personal, Full or part-time Employment: Invitae. K. Hatchell: Financial Interests, Personal, Full or part-time Employment: Invitae. R. Nussbaum: Financial Interests, Personal, Leadership Role: Invitae. M. Gazi: Financial Interests, Institutional, Research Grant: Invitae. C.M. Pieczonka: Financial Interests, Institutional, Research Grant: Invitae. L. Belkoff: Financial Interests, Institutional, Research Grant: Invitae. D.J. Cahn: Financial Interests, Institutional, Research Grant: Invitae. N.D. Shore: Financial Interests, Institutional, Research Grant: Invitae.