Abstract 3971: Non-invasive assessment of prostate-specific membrane antigen (PSMA) expression as a prognostic marker in men with metastatic castration-resistant prostate cancer (mCRPC) (2016)

Abstract Background: PSMA is nearly universally expressed by PC, has a correlation with androgen receptor (AR) pathway dysregulation, and some studies have pointed towards PSMA expression as a prognostic marker. Non-invasive measurement of PSMA expression may be biomarker of AR activity in animal models.[Evans et al, PNAS 2011] Anti-PSMA monoclonal antibody J591 has been utilized both for imaging as well as therapeutics and we have published semi-quantitative scoring in the setting of therapeutic clinical trials. Methods: Patients with mCRPC underwent planar gamma camera imaging following radiolabeled (RL) J591 injection (177Lu- or 111In-J591). RL-J591 images were semi-quantitatively scored using a 5-point visual score (VS) system [Tagawa et al, Clin Cancer Res 2013]. Overall survival (OS) was calculated from the date of imaging to death or last follow up. As several life-prolonging treatments (docetaxel, sipuleucel-T, cabazitaxel, abiraterone (Abi), enzalutamide (Enza), radium-223) became available during the study time period, treatment following RL-J591 imaging was recorded and used in multivariate analysis. Results: Between 2000 and 2015, 165 patients with mCRPC were imaged following RL-J591 and semi-quantitatively scored for PSMA expression by VS. Baseline demographics included median age of 71.3 years (44.5-85.9); bone metastases present in 86.7%, 52.7% with LN mets, 17% with lung mets, 7.9% with liver mets, 1.8% other mets. Fifty three (32.2%) had low PSMA expression by imaging (VS 0-1) and 112 (67.8%) had high PSMA expression (VS 2-5). Post RL-J591 imaging, 41.2% (68/165) patients received life prolonging therapy, including taxane chemotherapy (33.9%), Abi/Enza (14.5%), sipuleucel-T (1.2%), or radium-223 (1.2%). At last follow up 12.7% (21/165) patients were alive. Median OS was 22.6 months in patients with low PSMA expression and 16.6 mo with high PSMA expression (P = 0.07). Those with subsequent receipt of life prolonging therapy had OS of 23.6 months vs 14.3 mo (P = 0.002). On multivariable analysis controlling for life prolonging therapy, higher PSMA expression by imaging was a significant predictor for poorer OS (adjusted hazard ratio = 1.60; 95% CI = 1.10, 2.31; P = 0.01). Conclusion: Non-invasive measurement of PSMA expression may be evaluated on a semi-quantitative basis via planar imaging. The level of PSMA expression is inversely associated with survival when controlling for receipt of known life-prolonging therapy. With the introduction of newer quantitative molecular imaging (i.e. PET), quantitative PSMA imaging may prove to be a useful prognostic tool. Citation Format: Kavya Pinto-Chengot, Yuliya Jhanwar, Jaspreet Batra, Beerinder Karir, Shankar Vallabhajosula, Paul Christos, Ana Molina, Himisha Beltran, David M. Nanus, Stanley J. Goldsmith, Neil H. Bander, Scott T. Tagawa. Non-invasive assessment of prostate-specific membrane antigen (PSMA) expression as a prognostic marker in men with metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3971.