Whole blood FOLH1 mRNA expression and treatment response in metastatic castration-resistant prostate cancer (mCRPC).

Background: Identifying predictive biomarkers for mCRPC patients receiving androgen receptor signalling inhibitors (ARSI) or chemotherapy remains an unmet clinical need. FOLH1 encodes for ProstateSpecific Membrane Antigen (PSMA), a type II glycoprotein highly expressed on prostate cancer cells. We designed a whole blood assay to detect FOLH1 mRNA, and correlated expression with clinical outcomes in patients commencing ARSI (abiraterone or enzalutamide) or chemotherapy (docetaxel or cabazitaxel). Method(s): mCRPC patients commencing ARSI or chemotherapy were prospectively recruited at three Australian centres from June 2016 to July 2018. A quantitative reverse transcription polymerase chain reaction assay was used to detect FOLH1 transcript from whole blood samples collected in PAXgene RNA tubes. Pre-treatment FOLH1 expression was correlated with PSA response rate (Fisher's exact test) and PSA progression-free survival (PSA-PFS) (log-rank test). Result(s): Median follow-up was 13.6 months (IQR 9.7-19.3). In total, 88 pretreatment samples were analysed, of which 75 (85%) were FOLH1-positive. In patients receiving ARSI, outcomes favoured FOLH1-positive patients compared to FOLH1negative patients, with higher PSA response rates (39/60, 65% vs. 2/7, 29%; p = 0.1) and longer PSA-PFS (median 9.0 months [95% CI, 7.210.8] vs. 2.8 months [95% CI, 2.33.3] ; p = 0.03). Conversely, in chemotherapy-treated patients, inferior outcomes were observed in FOLH1-positive patients compared to FOLH1negative patients, with lower PSA response rates (4/15, 27% vs. 5/6, 83%, p = 0.05) and shorter PSA-PFS (median 2.9 months [95% CI, 2.83.0] vs. 4.1 months [95% CI, 3.74.5] ; p = 0.32). Conclusion(s): Pre-treatment FOLH1 expression may differentiate between outcomes on ARSI vs. chemotherapy in mCRPC patients. The utility of FOLH1 as a predictive biomarker in mCRPC warrants further evaluation in larger, independent cohorts. (Table Presented) .