CTC Quantification During TURBT and PKVBT of Transitional Cell Carcinoma in Purging Fluid and Blood

Bladder cancer is the 9th most commonly diagnosed cancer in men worldwide, with a standardized incidence rate of 9.0 per 100,000 person-years for men and 2.2 per 100,000 person-years for women. Amongst any caner entity, bladder cancer is the most expensive cancer regarding follow-up and life-time treatment costs due to the high probability of recurrence. Up to 85% of patients initially present with non muscle-invasive bladder cancer (NMIBC). Progression to muscle-invasive bladder cancer (MIBC) is up to 10-20%. NMIBC is characterized by a high risk of recurrence after transurethral resection of bladder tumor (TURBT): the 1-yr recurrence rate is 15-61% and the 5-yr recurrence rate is 31-78%. These numbers represent the heterogeneity of NMIBC.

Against any existing oncological principle, during TURBT bladder tumors are resected in a piecemeal manner. This results in tumor fragmentation and floating cancer cells inside the bladder during surgery. These cells may have the ability to re-attach on and re-implant into the bladder wall and may be responsible for early disease recurrence which is commonly seen after initial surgery. It has been shown that tumor cells may access the circulatory system through cut vessels. Circulating tumor cells (CTCs) can be detected in up to 20% in T1 high grade disease and are commonly seen in metastasized disease. They have shown to be an independent predictor of disease progression and relapse in several studies and reflect biological aggressiveness.

In the current study the investigators want to quantify CTCs for recurrent intermediate risk transitional cell carcinoma in purging fluid and blood for two different surgical methods: TURBT and Plasma-kinetic vaporisation of bladder tumors (PKVBT). Also correlations for recurrence will be investigated for the two different surgical methods.

In 2 urological centers (LKH Hall, LKH Salzburg) participants with diagnosed intermediate risk recurrent transitional cell carcinoma of the bladder will be randomly enrolled for either TURBT or PKVBT. Before surgery CTCs will be analyzed in peripheral blood and purging fluid. (preoperative CTCs blood and purging fluid, morphological aspect of CTCs in purging fluid) After resection for TURBT and vaporization for PKVBT, a tumor ground biopsy will be taken for both groups. After coagluation, CTCs will again be drawn in peripheral blood (intraoperative CTCs blood). After completion of surgery an indwelling catheter is inserted and purging fluid is again analyzed (postoperative CTCs purging fluid, morphological aspect of CTCs in purging fluid). Blood is again taken on day 2 after surgery during the morning routine to assess CTCs after surgery (postoperative CTCs blood). Patients will be dismissed on earliest day 2 after surgery after indwelling catheter removal.

Recurrence will be assessed during follow-up by cystoscopic controls (From 3 to 36 months after surgery). If recurrence is detected the study is terminated. If no recurrence is detected up to 36 months after surgery, the study is likewise terminated.

Inclusion criteria

• female and male patients
• recurrent bladder tumor
• preoperative cystoscopy
• CT or MRI scan of abdomen not older than 30 days prior to surgery without suspicion of advanced disease (MIBC, metastasis)
• max. non-invasive papillary tumor (pTa) staging in prior histology
• max. low grade grading in prior histology
• max. 5 lesions in actual cystoscopy (all < 3cm)
• exophytic tumors
• transitional cell cancer of urinary bladder
• patient able to give consent
• signed consent form

Exclusion criteria

• initial tumor
• flat lesion
• > 3cm
• carcinoma in situ (CIS) in prior histology or suspicious CIS-finding in actual cystoscopy
• high grade grading in prior histology
• ≥ pT1 (tumor infiltration into subepithelial connective tissue) staging in prior histology
• > 5 lesions
• different entity from transitional cell carcinoma of urinary bladder
• prior radiation
• emergency surgery
• prior indwelling catheter (extraction < 1 week prior to surgery)
• pregnancy
• orthotopic neobladder