MP09-15 PROGRAMMED DEATH-LIGAND 1 POSITIVE AND NON-EPITHELIAL SUBTYPE IN CIRCULATING TUMOR CELLS PREDICT LOCALLY ADVANCED PROSTATE CANCER PROGRESSION AND GUIDE THE IMMUNOTHERAPY AFTER SURGERY

Abstract

INTRODUCTION AND OBJECTIVE: Circulating tumor cells (CTCs) is considered as “liquid biopsy” for tumor prognosis, and the detection of programmed death-ligand 1 (PD-L1) expressing in CTCs could promote the predictive efficiency. However, there are not standard of cut-offs to discriminate PD-L1 positive/negative expression in CTCs in prostate cancer (PCa). This study aimed to evaluate the rates of PD-L1 positive and non-epithelial (NE) subset in CTCs isolated from patients with high-risk (HRPC) and locally advanced PCa (LAPC) before surgery, and explored the clinical utility of these markers. METHODS: Four PCa cell lines were applied in spiking experiments to establish the cut-offs of NE (hybrid and mesenchymal) and PD-L1+ CTCs. From June 2016 to December 2018, 166 and 79 patients with HRPC and LAPC were collected. All patients underwent radical prostatectomy. Preoperative CTCs were enumerated by Canpatrol CTC enrichment system. PD-L1 expressing in CTCs were identified by the RNA in situ hybridization. And the correlation between CTCs markers and other parameters in terms of clinical outcome, tumor tissues immunochemistry staining, and the effect of immunotherapy was analyzed. RESULTS: The lowest rates of NE and PD-L1+ CTCs were observed in 22Rv1 cell line, the cut-offs of NE and PD-L1+ CTCs were established in vitro, being 45% and 25%, respectively. In HRPC cohort, the NE CTCs positive group (≥45%) had a higher PSA level and more advanced pathological tumor stage than negative group (P=0.041 and P=0.004). Multivariate analysis revealed that NE CTCs rate, not total CTCs amount, was an independent prognostic factor for progression-free survival (PFS) (HR=4.68, P=0.013). In LAPC cohort, the PD-L1+ CTCs positive group (≥25%) displayed a higher PSA level and more frequently lymph node metastasis than negative group (P=0.027 and P=0.028), with median PFS of 15.6 mouths vs. 22.6 mouths, HR=2.70, P=0.018). PD-L1 expression in CTCs was not associated with its expression in tumor tissue staining. While a significant correlation was observed between PD-L1+ CTCs rate and ERG or PTEN expression in tissues (P=0.010 and P=0.009). Furthermore, we found that patients with PD-L1+ CTCs positive expression exhibited a better PSA response to Durvalumab treatment than those with negative expression. CONCLUSIONS: A novel cut-off value of PD-L1+ and NE CTCs could be utilized as powerful prognosis parameter for HRPC and LAPC patients after surgery, and adjuvant immunotherapy can be adopted accordingly. Source of Funding: None.