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MP68-05 “SEQUENCING IS MY CO-PILOT”: USING NEXT-GENERATION SEQUENCING TO GUIDE THE SENTINEL NODE CONCEPT IN PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Sentinel node (SLN) based pelvic lymph node dissection (PLND) in prostate cancer (PC) is investigational. Classically, SLN technique involves tracer injection into the origin tumor to delineate nodal drainage. A major technical challenge in SLN based PLND efforts for PC is disease multifocality within the gland. Using next-generation sequencing (NGS), we correlated PC primary (i.e. index/dominant) and secondary (i.e. non-index) intra-prostatic lesions to their LN metastases (LNM) and report our findings on the role of the index PC lesion in identifying potential SLNs. METHODS: Paired prostate tumor and LNM archival tissue was obtained from 15 men with pN1 PC (range 1-8 positive nodes) after robotic radical prostatectomy (RARP) plus extended PLND, for 74 total samples. N=10 men with multi-focal (MF) disease, defined as minimum 2 distinct regions of cancer on the RP specimen. The primary (or index) lesion was determined based on tumor volume in RP specimen. We sampled each tumor focus and LNMs across the patients. Each sample was microdissected and assayed using microRNA (miRNA) NGS. Expression profiles were then used to make phylogenetic relationships among intraprostatic tumor foci and LNMs. For 9 men, additional RNA expression profiles were used to perform a deconvolution analysis to quantify the degree of immune cell infiltrates within each sample. RESULTS: For the MF men, the dominant lesion showed a greater genetic expression profile match to the positive LNs, than did the secondary lesion. In a sample patient, see figure 1, correlation coefficients from the primary/index lesion were higher, indicating increased similarity, to each LNM site; the left internal iliac (LII) region had the highest similarity to the index lesion (thickest arrow from the index lesion on the anatomic vascular template). LNMs had greater similarity among themselves. RNA transcriptome deconvolution analysis identified a lower number of CD8+ T-cells in the index foci as compared to the secondary foci and positive LNs(ANOVA, p=0.002). CONCLUSIONS: The index prostate lesion had higher genetic signature match with LNMs. Preoperative demarcation of the dominant intraprostatic lesion may improve the success of PC SLN-based PLND. The results also suggest PC LNM is related to poorer tumor-infiltrating immune responses. Figure. No caption available. Source of Funding: None