Molecular lymph node status for prognostic stratification of prostate cancer patients undergoing radical prostatectomy with extended pelvic lymph node dissection

Purpose: Molecular lymph node (LN) analysis using quantitative polymerase chain reaction (qPCR) detects LN metastases with higher sensitivity than histopathology. However, the prognostic role of molecular LN status in prostate cancer (PCa) patients treated with radical prostatectomy (RP) and extended pelvic LN dissection (ePLND) is unclear. To investigate the association of molecular compared to histopathologic LN status with biochemical recurrence. Experimental Design: Patients with intermediate and high risk PCa were prospectively enrolled and underwent RP with ePLND including obturator, internal, external and common iliac region. LNs ≥3mm were bisected and examined by standard histopathology and qPCR for Kallikrein3 (KLK3) expression. Biochemical recurrence was defined by confirmed postoperative PSA>0.2ng/ml. Results: In 111 patients, 2411 of 3173 removed LNs were examined by both methods. Histopathology detected 68 LN metastases in 28 (25%) patients. Molecular analysis confirmed elevated KLK3 expression in 65 histopathologic LN metastases of all 28 pN1-patients (pN1/molN1) and additionally reclassified 224 histopathologic negative LNs and 32 (29%) pN0-patients as LN-positive (pN0/molN1). At a median follow-up of 48 months 52 (47%) patients developed biochemical recurrence. Median biochemical recurrence-free survival (bRFS) was 9 months [95%CI0.0-20.1] in pN1/molN1-patients, 24 months [95%CI1.7-46.3] in pN0/molN1 patients and was not reached in pN0/molN0 patients (p<0.001). On multivariable Cox regression analysis, molecular LN status (HR 4.1 [95%CI1.9-8.8],p<0.001) but not histopathologic LN status (HR 1.5 [95%CI0.8-3.0],p=0.198) was confirmed as independent predictor of biochemical recurrence. Conclusion: Molecular LN analysis identified pN0-patients with a high risk of biochemical recurrence and provided superior prognostic information in comparison with histopathology alone.

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