Accurate Quantification of Residual Cancer Cells in Pelvic Washing Reveals Association with Cancer Recurrence Following Robot-Assisted Radical Cystectomy.

Citation:
Wei, L., A. A. Hussein, Y. Ma, G. Azabdaftari, Y. Ahmed, L. P. Wong, Q. Hu, W. Luo, V. N. Cranwell, B. L. Bunch, et al., "Accurate Quantification of Residual Cancer Cells in Pelvic Washing Reveals Association with Cancer Recurrence Following Robot-Assisted Radical Cystectomy.", The Journal of urology, 2019 Feb 05.

Abstract:

BACKGROUND: Bladder cancer recurrence following cystectomy remains a significant cause of bladder cancer-specific mortality. Residual cancer cells (RCCs) contribute to cancer recurrence due either to tumor spillage or undetectable pre-existing micrometastatic tumor clones. We sought to detect and quantify RCCs in pelvic washing using ultra-deep targeted sequencing (UTS) and compare the levels of RCCs with clinical variables and cancer recurrence.

METHODS: 17 patients underwent robotic-assisted radical cystectomy (RARC) with primary tumor specimen available. All tumors had negative surgical margins. Pelvic washes and blood were collected intra-operatively: before RARC, after RARC, after pelvic lymph node dissection (PLND), and in the suction fluid collected during the procedure. A two-step sequencing, including whole-exome sequencing (WES) followed by UTS (>50,000X), was used to quantify RCCs in each sample. Eight patients were excluded due to sample quality issues. The final analysis cohort included nine patients. RCC level was quantified for each sample as the relative cancer cell fraction (RCCF), and compared between different time points. The peak RCCF (pRCCF) of each patient was correlated with clinical and pathological variables.

RESULTS: RCCs were detected in approximately half of the pelvic washing specimens during or after RARC, but not before it. Higher levels of RCCs were associated with aggressive variant histology and cancer recurrence. Verifying the feasibility of using RCCs as a novel biomarker for recurrence requires larger cohorts.

CONCLUSIONS: Detection of RCCs in intra-operative peritoneal washes of bladder cancer patients undergoing radical cystectomy may represent a robust biomarker of tumor aggressiveness and metastatic potential.

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