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

NCT04811846 | Active Not Recruiting

• 1 other identifier: 1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Transurethral resection of bladder tumor (TURBT) is usually performed in a piecemeal technique. Tumor fragmentation and cell spilling could be responsible for high recurrence rates. Circulating tumor cells (CTCs) have been shown to be a prognostic predictor in disease progression in transitional cell carcinoma. In the current study the investigators aim to quantify CTCs in purging fluid and blood for recurrent intermediate risk bladder cancer during surgery for two different methods: TURBT and Plasma-kinetic vaporization of bladder tumor (PKVBT). Also correlations for recurrence will be investigated for the two different surgical methods.

Conditions

Urinary Bladder Neoplasm; Transitional Cell Carcinoma; Urogenital Neoplasms; Circulating Tumor Cell; Neoplasms

Keywords

Bladder cancer; NMIBC; CTC; Circulating tumor cell; Transurethral resection; Plasma kinetic vaporization; TURBT; PKVB

Outcome Measures

Primary Outcomes (8)

• intraoperative CTC-number in blood [n/ml]

  Circulating tumor cells (CTCs) are measured in 15ml of peripheral blood which is taken during surgery. CTCs are quantified via automated immunofluorescence-microscopy. CK20+, p53+, DAPI+ and CD45- cells will be classified transitional cancer CTCs.

  During surgery: after evacuation of snippets for TURBT and after full vaporization for PKVBT.

• postoperative CTC-number in blood [n/ml]

  Circulating tumor cells (CTCs) are measured in 15ml peripheral blood which is taken after surgery. CTCs are quantified via automated immunofluorescence-microscopy. CK20+, p53+, DAPI+ and CD45- cells will be classified transitional cancer CTCs.

  2nd postoperative day during morning routine.

• postoperative CTC-number in purging fluid [n/ml]

  Circulating tumor cells (CTCs) are measured in purging fluid after the surgical intervention. After insertion of a new indwelling catheter the bladder is fully emptied and 100ml of sterile NaCl 0,9% is injected and extracted 5 times into and out of the bladder to mix CTCs. CTCs are quantified via automated immunofluorescence-microscopy. CK20+, p53+, DAPI+ and CD45- cells will be classified transitional cancer CTCs.

  For both gruops (TURBT and PKVB) after insertion of indwelling catheter before finishing surgery.

• postoperative CTC morphology in purging fluid

  Cytological morphology of CTCs in purging fluid. CTCs will be examined for both groups and their morphological aspect (e.g. vital, non-vital, necrotic, deformed) is classified.

  After insertion of indwelling catheter before finishing the surgery.

• pre-to-intraoperative change of CTC-number in blood [n/ml]

  The difference of the preoperative and intraoperative CTC-number in blood is calculated. Due to the intervention in both groups a difference in CTC-number is to be expected.

  Preoperative CTCs will be taken right before the start of surgery. Intraoperative CTCs will be taken after evacuation of snippets for TURBT and after full vaporization for PKVBT.

• pre-to-postoperative change of CTC-number in blood [n/ml]

  The difference of the preoperative and postoperative CTC-number in blood is calculated. Due to the intervention in both groups a difference in CTC-number is to be expected.

  Preoperative CTCs will be taken right before the start of surgery. Postoperative CTCs will be taken on day 2 after surgery during the morning routine.

• intra-to-postoperative change of CTC-number in blood [n/ml]

  The difference of the intraoperative and postoperative CTC-number in blood is calculated. Due to the intervention in both groups a difference in CTC-number is to be expected.

  Intraoperative CTCs will be taken after evacuation of snippets for TURBT and after full vaporization for PKVBT. Postoperative CTCs will be taken on day 2 after surgery during the morning routine.

• pre-to-postoperative change of CTC-number in purging fluid [n/ml]

  The difference of the preoperative and postoperative CTC-number in purging fluid is calculated. Due to the intervention in both groups a difference in CTC-number is to be expected.

  Preoperative CTCs in purging fluid are taken via an indwelling catheter right before start of the surgery. Postoperative CTCs in purging fluid are taken after insertion of a new indwelling catheter before finishing the surgery.

Secondary Outcomes (5)

• Tumor recurrence [yes/no]

  According to follow up cystoscopy at 3, 6, 12, 24, 36 months after intervention.

• Time to recurrence [days]

  Through study completion, recurrence can occur within a maximum follow up of 36 months.

• preoperative CTC-number in purging fluid [n/ml]

  Right before surgery.

• preoperative CTC-number in blood [n/ml]

  Right before start of surgery.

• preoperative CTC morphology in purging fluid

  Right before start of surgery.

Study Arms (2)

TURBT (Transurethral Resection of Bladder Tumor)

ACTIVE COMPARATOR

For patients undergoing bipolar transurethral resection, bladder tumor is resected in a piecemeal manner.

Device: Bipolar transurethral resection of bladder tumor (TURBT)

PKVB (Plasma Kinetic Vaporization of Bladder Tumor)

ACTIVE COMPARATOR

For patients undergoing bipolar plasma kinetic vaporization of bladder tumor, bladder tumor is vaporized.

Device: Bipolar transurethral plasma kinetic vaporization of bladder tumor (PKVBT)

Interventions

Bipolar transurethral resection of bladder tumor (TURBT) DEVICE

Standard resection in piecemeal technique with standard bipolar cutting loop. (Storz medical, 27040 GP1)

TURBT (Transurethral Resection of Bladder Tumor)

Bipolar transurethral plasma kinetic vaporization of bladder tumor (PKVBT) DEVICE

Vaporization of bladder tumor with standard bipolar vaporization electrode. (Storz medical, 27040 NB)

PKVB (Plasma Kinetic Vaporization of Bladder Tumor)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Teaching Hospital Hall in Tirol: lead
• Salzburger Landeskliniken: collaborator

Study Sites (2)

LKH Hall in Tirol, Department of Urology and Andrology

Hall in Tirol, 6060, Austria

Location

LKH Salzburg, Department of Urology and Andrology

Salzburg, 5020, Austria

Location

Related Publications (11)

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  PMID: 22877502 BACKGROUND

• Comperat E, Larre S, Roupret M, Neuzillet Y, Pignot G, Quintens H, Houede N, Roy C, Durand X, Varinot J, Vordos D, Rouanne M, Bakhri MA, Bertrand P, Jeglinschi SC, Cussenot O, Soulie M, Pfister C. Clinicopathological characteristics of urothelial bladder cancer in patients less than 40 years old. Virchows Arch. 2015 May;466(5):589-94. doi: 10.1007/s00428-015-1739-2. Epub 2015 Feb 20.

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• Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, Newling DW, Kurth K. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006 Mar;49(3):466-5; discussion 475-7. doi: 10.1016/j.eururo.2005.12.031. Epub 2006 Jan 17.

  PMID: 16442208 BACKGROUND

• Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM, Hernandez V, Kaasinen E, Palou J, Roupret M, van Rhijn BWG, Shariat SF, Soukup V, Sylvester RJ, Zigeuner R. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. 2017 Mar;71(3):447-461. doi: 10.1016/j.eururo.2016.05.041. Epub 2016 Jun 17.

  PMID: 27324428 BACKGROUND

• Wilby D, Thomas K, Ray E, Chappell B, O'Brien T. Bladder cancer: new TUR techniques. World J Urol. 2009 Jun;27(3):309-12. doi: 10.1007/s00345-009-0398-9. Epub 2009 Mar 4.

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• Rink M, Schwarzenbach H, Vetterlein MW, Riethdorf S, Soave A. The current role of circulating biomarkers in non-muscle invasive bladder cancer. Transl Androl Urol. 2019 Feb;8(1):61-75. doi: 10.21037/tau.2018.11.05.

  PMID: 30976570 BACKGROUND

• Engilbertsson H, Aaltonen KE, Bjornsson S, Kristmundsson T, Patschan O, Ryden L, Gudjonsson S. Transurethral bladder tumor resection can cause seeding of cancer cells into the bloodstream. J Urol. 2015 Jan;193(1):53-7. doi: 10.1016/j.juro.2014.06.083. Epub 2014 Jul 1.

  PMID: 24996129 BACKGROUND

• Zare R, Grabe M, Hermann GG, Malmstrom PU. Can routine outpatient follow-up of patients with bladder cancer be improved? A multicenter prospective observational assessment of blue light flexible cystoscopy and fulguration. Res Rep Urol. 2018 Oct 9;10:151-157. doi: 10.2147/RRU.S141314. eCollection 2018.

  PMID: 30349812 BACKGROUND

• Donat SM, North A, Dalbagni G, Herr HW. Efficacy of office fulguration for recurrent low grade papillary bladder tumors less than 0.5 cm. J Urol. 2004 Feb;171(2 Pt 1):636-9. doi: 10.1097/01.ju.0000103100.22951.5e.

  PMID: 14713776 BACKGROUND

• Gazzaniga P, de Berardinis E, Raimondi C, Gradilone A, Busetto GM, De Falco E, Nicolazzo C, Giovannone R, Gentile V, Cortesi E, Pantel K. Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer. Int J Cancer. 2014 Oct 15;135(8):1978-82. doi: 10.1002/ijc.28830. Epub 2014 Mar 13.

  PMID: 24599551 BACKGROUND

• Sievert KD, Amend B, Nagele U, Schilling D, Bedke J, Horstmann M, Hennenlotter J, Kruck S, Stenzl A. Economic aspects of bladder cancer: what are the benefits and costs? World J Urol. 2009 Jun;27(3):295-300. doi: 10.1007/s00345-009-0395-z. Epub 2009 Mar 7.

  PMID: 19271220 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urogenital Neoplasms; Neoplastic Cells, Circulating; Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Udo Nagele, MD, Prof.

  Head of Department LKH Hall in Tirol

  STUDY CHAIR

• Lukas Lusuardi, MD, Prof.

  Heas of Department LKH Salzburg

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sub-Investigator

Model Details: Pilot trial with parallel group design and comparison of 2 established techniques (TURBT, PKVB)

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 23, 2021
• Study Start: March 14, 2021
• Primary Completion: May 31, 2025
• Study Completion: October 1, 2025
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)