Comparative yield of three models to evaluate germline genetic risk in patients (pts) with pancreatic cancer (PCA): A single-institution study.

Abstract

e22647 Background: ~10% of PCA patients (pts) have a germline pathogenic variant (gPV) in a hereditary CA risk gene. After the POLO trial reported efficacy of PARP inhibitor olaparib in BRCA1/2+ metPAC at ASCO 2019, updated NCCN guidelines recommended universal genetic counseling/testing (GC/GT) in all PAC pts. Various care delivery models have examined approaches to improve rates of GC/GT in PAC. In the current study, we compared 3 models in PAC pts: 1) non-universal GC/GT provider-initiated referral (PR) to genetics; 2) universal mainstream genetic testing (MT) conducted by oncologists in clinic; 3) universal direct scheduling (DS) of all new PAC pts to genetics (no referral). We hypothesized that universal DS would improve uptake of GC/GT and improve yield of gPV identified. Methods: Demographic, GC/GT, and clinical follow-up data were retrospectively extracted from the EMR for 3 unique one-year time periods: 1) PR (11/1/2017-10/31/2018), 2) MT (11/1/2022-10/31/2023) and 3) DS (11/1/2024-10/31/2025). Universal GT for PAC began 11/2019. Summary descriptive statistics and chi-square tests used in data reporting. Results: Under PR model, 117 eligible new PAC pts were evaluated (mean age 69 yrs, 50% F, 19% non-White) and 19% (n = 21) had pretest GC followed by GT. Notably 9% pts were referred to genetics but declined. gPVs in ATM, BRCA1, CDKN2A, RAD51D, MUTYH and CFTRx2 were identified, and 9% had a gVUS. Overall, 84% with a gPV+/gVUS+ had posttest GC. Under MT model, 56% (57/102) PAC pts (mean age 67 yrs, 49% F, 32% non-White) had GT sent by their oncologist: 8% had a gPV (ATM, BRCA2, PALB2, CFTRx3, MUTYHx2, PALB2) and 12% had a gVUS. Overall, 30% pts were referred to genetics, but only 19% pts had GC, and only 50% of those with a gPV+/gVUS+. Nearly 1 in 3 untested pts lacked EMR documentation by oncology explaining lack of GT. Under DS model, 235 pts were EMR routed to genetics. Of these, 60% (n = 141) were appropriate for DS GT (mean age 64 yrs, 50% F, 32% non-White) and 50% (n = 71) were scheduled for GC/GT. Reasons for non-scheduling included: previous GT (23%), GC/GT active decline (33%) and passive decline/non-response (11%), pursuit of care elsewhere (10%) rapid decline/death (7%), or non-PAC diagnosis (17%). gPV were identified in 8%: APC, APC/FH, ATMx3, BRCA1, BRIP1, MSH2, MUTYHx2, PMS2 and 7% had gVUS. 95% pts with gPV+/gVUS+ had post-test GC. Conclusions: Universal GT + direct scheduling improves rates of GC/GT in PAC over the non-universal provider referral model and improves completion of post-test GC in PV+/VUS+ pts over universal mainstream GT; nonetheless, nearly half of eligible PAC pts fail to receive GC/GT with universal direct scheduling. Provider referral (PR) n=117 Universal mainstream (MT) n=102 Universal direct scheduling (DS) n=141 p Had GT 19%* 56% 50%* <0.001* Any GC 19% 19%* 50%* <0.001* Post-test GC for PV+VUS+ 84% 50%* 95%* <0.05* PV n(%) 7 (6%) 9 (8%) 12 (8%) NS VUS 9% 12% 7% NS