A hybrid radioactive and fluorescence approach is more than the sum of its parts; outcome of a phase II randomized sentinel node trial in prostate cancer patients

Objective To determine the diagnostic accuracy of the hybrid tracer indocyanine green (ICG)-Technetium-99 m( 99m Tc)-nanocolloid compared to sequential tracers of 99m Tc-nanocolloid and free-ICG in detecting tumor-positive lymph nodes (LN) during primary surgery in prostate cancer (PCa) patients. Introduction Image-guided surgery strategies can help visualize individual lymphatic drainage patterns and sentinel lymph nodes (SLNs) in PCa patients. For lymphatic mapping radioactive, fluorescent and hybrid tracers are being clinically exploited. In this prospective randomized phase II trial, we made a head-to-head comparison between ICG- 99m Tc-nanocolloid (hybrid group) and 99m Tc-nanocolloid and subsequent free-ICG injection (sequential group). Methods PCa patients with a >5% risk of lymphatic involvement according to the 2012 Briganti nomogram and planned for prostatectomy were included and randomized (1:1) between ultrasound-guided intraprostatic tracer administration of ICG- 99m Tc-nanocolloid ( n = 69) or 99m Tc-nanocolloid ( n = 69) 5 h before surgery. Preoperative lymphoscintigraphy and SPECT/CT were performed to define the locations of the SLNs. Additionally, all participants in the sequential group received an injection of free-ICG at time of surgery. Subsequently, all (S)LNs were dissected using fluorescence guidance followed by an extended pelvic lymph node dissection (ePLND). The primary outcome was the total number of surgically removed (S)LNs and tumor-positive (S)LNs. Results The total number of surgically removed (S)LN packages was 701 and 733 in the hybrid and sequential groups, respectively ( p = 0.727). The total number of fluorescent LNs retrieved was 310 and 665 nodes in the hybrid and sequential groups, respectively ( p < 0.001). However, no statistically significant difference was observed in the corresponding number of tumor-positive nodes among the groups (44 vs. 33; p = 0.470). Consequently, the rate of tumor-positive fluorescent LNs was higher in the hybrid group (7.4%) compared to the sequential group (2.6%; p = 0.002), indicating an enhanced positive predictive value for the hybrid approach. There was no difference in complications within 90 days after surgery ( p = 0.78). Conclusions The hybrid tracer ICG- 99m Tc-nanocolloid improved the positive predictive value for tumor-bearing LNs while minimizing the number of fluorescent nodes compared to the sequential tracer approach. Consequently, the hybrid tracer ICG- 99m Tc-nanocolloid enables the most reliable and minimal invasive method for LN staging in PCa patients.