Prospective clinical study of sentinel node detection in bladder cancer using a hybrid tracer - Towards replacement...

Nodal staging in patients with muscle invasive bladder cancer (MIBC) or very high risk non-muscle invasive bladder cancer (vhNMIBC) aids to predict survival. The sentinel node (SN) procedure holds the promise to identify the diagnostically relevant first tumor-draining nodes while limiting the complication rate associate with a pelvic lymph node dissection (PLND), still considered the gold standard of nodal staging. Following an initial technical feasibility study, we prospectively evaluated the clinical impact of using peri-tumoral injections with the hybrid tracer indocyanine green (ICG)-^99mTc-nanocolloid for SN procedures in bladder cancer.

A total of 30 patients with vhNMIBC or MIBC, cN0M0 (with or without neo-adjuvant systemic therapy) scheduled for radical cystectomy with pelvic lymph node dissection (PLND) were enrolled in a prospective study. Patients received four to six transurethral peritumoral injections of ICG-^99mTc-nanocolloid into the bladder for SN tracing. Preoperative lymphoscintigraphy and Single Photon Emission Computed Tomography (SPECT)/CT was performed the day before surgery. The intraoperative detection of SNs was supported by both fluorescence (utilizing a hand-held camera or fluorescence laparoscope) and radio-guidance (using hand-held, laparoscopic or DROP-IN probe tracing). Resected specimens, comprising both SNs and PLND tissue, were analyzed by the pathologist. Complications related to the tracer injection were documented and cancer-specific survival (CSS) and overall survival (OS) were studied using Kaplan-Meier survival curves.

SPECT/CT imaging revealed 31 SNs in 19 patients with non-visualization of SN in 11 patients (36.7%). During surgery, 4 additional SNs were identified based on fluorescent signals in 3 patients. In 1 patient who underwent open cystectomy, ex vivo evaluation of the PLND-specimen revealed an additional radioactive SN. The PLND yielded 592 lymph nodes (LNs; median 17 LNs/patient). In 5 out of 35 SNs (14.2%; no additional tumor positive LN in complementary PLND) and 3 out of 592 LNs (0.5%; 2 patients with non-visualization of SN) were identified as tumor-positive upon pathological evaluation. At mean follow up of 82 months (SD ± 7.1 months) 17% of patients died of disease. The 2 patients with non-visualization of SN and nodal metastases (0%) did worse than SN positive patients (75%). Of the 24 patients classified as pN0 8% died.

Preoperative SN-visualization on SPECT/CT was achieved in the majority of patients. Patients with SN non-visualization had an increased risk of nodal metastases and poorer outcome. In patients with metastases in the SN no additional nodal metastases were found in the complementary PLND.