Genomic/genetic testing patterns for patients with metastatic castrate-resistant prostate cancer: Results from a real-world study in the United States.
Authors: Leith Andrea , Ribbands Amanda , Last Matthew , Gayle Alicia , Payne Sarah , McCrea Charles , Yang Lingfeng , Burgents Joseph E. , Ghate Sameer 
Published: March 2021

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Background: In May 2020, Olaparib was approved for HRRm mCRPC post progression on abiraterone and enzalutamide, and rucaparib was approved for BRCAm mCPRC following progression on androgen receptor targeted inhibitors and prior taxane therapy for mCRPC. HRRm are associated with approximately 25% of mCRPC and may be derived from germline or somatic origin. Somatic and germline alterations can be detected by tumour testing, but to differentiate between these, independent germline testing is needed. This study examined real-world genomic/genetic testing (GT) patterns in patients (pts) diagnosed with mCRPC in the United States (US). Methods: Data were drawn from the Adelphi Prostate Cancer Disease Specific Programme; a point-in-time survey administered to oncologists (onc), urologists (uro) and surgeons (sur) between January and August 2020 in the US. Physicians (phys) completed an attitudinal survey and a patient record form for the next four to nine mCRPC pts seen. Study variables included patient demographics, clinical factors and GT patterns. HRRm testers were defined as phys who tested for HRRm. Pts were identified as positive, negative or unknown depending on the outcome of the HRRm test. Results: A total of 72 phys (69% onc/ 29% uro/ 1% sur; 40% academic vs. 60% community) reported on 346 mCRPC pts. 41% of phys were based in the Northeast, 24% Midwest, 23% South and 13% in the West region of the US. 65 phys (90%) reported having access to overall GT; of these 5% identified as having access to germline tests only, while 94% were able to test for germline and somatic mutations. Challenges to conducting GT overall were ‘cost per test’ (50%), ‘having to send out for the tests (within country)’ (25%), ‘inadequate sample available’ (25%) and ‘patient refusal’ (25%). GT was typically conducted at identification of castrate-resistance (52%), metastases (51%) and at initial diagnosis (49%). 72% of total phys were HRRm testers; for these, patient characteristics primarily driving HRRm testing included Ashkenazi Jewish heritage (63%) and ECOG of 2-4 (58%). Other common drivers were family history, young diagnosis age and hormone therapy failure (all 46%). 132 (38% of 326) mCRPC pts were tested for HRRm; 39% of tested pts were identified with a HRRm. Most common HRRm tested were BRCA1 (90%), BRCA2 (89%) and ATM (55%). Conclusions: In this study majority of US phys had access to GT, but testing was only performed in 38% of pts with mCRPC. The higher than expected % of pts identified with an HRRm suggest that molecular testing was prioritised in high risk populations, as identified by the phys. With the recent approval of olaparib and rucaparib, GT may become more routine in clinical practice to identify eligible pts. Broader testing may also depend on addressing other barriers to testing including cost and testing logistics/practicalities.