Abstract 1377P
Background
Multiple targeted therapies have been shown to extend overall survival among men with metastatic castrate resistant prostate cancer including androgen axis modulators, PARP inhibitors, and PSMA theranostics. These and other treatments are being trialed in earlier disease states including in clinically localized prostate cancer. When moved earlier in disease course, therapeutic index and drug effect become more salient. As these therapies are molecularly based, patient subgroups with superior oncological responses might be defined by genomic signatures of their cancer.
Methods
We analyzed the transcriptomes of 52,217 men diagnosed with non-metastatic hormone sensitive prostate cancer for predefined signatures of androgen receptor activity (AR-A), PTEN loss, homologous repair deficiency, RB loss, immune activity, and PSMA expression. We compared signature readouts across NCCN / EAU prostate cancer risk categories.
Results
Median AR-A was highest among men with very low risk prostate cancer and decreased progressively as disease risk/stage increased (P<0.001). Conversely, selected signatures for PTEN loss, homologous recombination deficiency, immune activity, and PSMA expression all increased with disease risk (all P<0.001). PTEN loss rates and rates of homologous recombination deficiency nearly doubled between men suitable for active surveillance and those with unfavorable intermediate disease or greater (7.5% vs 15.3% and 32.2% vs 59.7%, respectively, both P<0.001). While an increase in rates for RB loss was observed among men with very high risk disease at diagnosis, rates remained low at 6.3%.
Conclusions
When considering use of novel targeted therapeutics in localized prostate cancer, agents affecting the androgen axis may be most suited for favorable risk disease while those targeting DNA damage repair deficient tumors, the PI3K/AKT pathway, and PSMA targeted agents are more suitable for exploration in higher risk patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Ashley Ross.
Funding
Has not received any funding.
Disclosure
J.A. Proudfoot, A. Hakansson: Financial Interests, Personal, Full or part-time Employment: Veracyte. X. Zhao, Y. Liu, E. Davicioni: Financial Interests, Personal and Institutional, Full or part-time Employment: Veracyte. A. Ross: Financial Interests, Personal, Advisory Role: Veracyte. All other authors have declared no conflicts of interest.