Safety Analysis and Oncological Outcomes in HoLERT vs TURBT

Bladder Cancer Clinical Trial

Official title:

Safety Analysis and Oncological Outcomes in Endoscopic Bladder Tumor Resection With Laser Holmium Compared With Transurethral Resection: a Prospective and Randomized Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05833997
• Other study ID #: NP1537/2019
• Status: Recruiting
• Phase: N/A
• Start date: December 10, 2020
• Est. completion date: December 2025

Study information

• Verified date: April 2023
• Source: Instituto do Cancer do Estado de São Paulo
• Contact: Alexandre Iscaife, MD, PhD
• Phone: +5511976280082
• Email: alexandre.iscaife[@]hc.fm.usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Bladder urothelial cancer is the second most common urologic tumor and represents a worldwide public health problem. Most cases are diagnosed as non-muscle invasive tumors, and can be treated with transurethral resection of bladder tumor (TURBT). However, the electrical energy-based TURBT fragments the tumor, burning it to its own muscular layer leading to artifacts that may spoil the histopathological analysis, resulting in understaging after the first TURBT ranging from 30-64%, depending on the presence of detrusor muscle. Modern laser technologies have been emerging as an alternative to classical TURB using en bloc tumor resection technique (ERBT). Therefore, the laser is applied on tumor's pedicle to resect the whole and intact tumor without fragmentation or fulguration as occurs in TURBT. The purpose of using laser if to improve the resection quality, decrease intra and perioperative complications, avoid re-TURBT and reduce recurrence rates at the resection site and in distant sites. Thus, the purpose of this study is to evaluate Laser Holmium use for large tumors resection (>3cm), reducing complications, costs, and the need for new approaches, and improving the muscle layers samples.

Description:

This is a single-institution, randomized, single-blinded, prospective, controlled study, with 2 groups - 50 patients in Holmium Laser En-bloc Resection of Bladder Tumors (HoLERBT) arm and 50 patients in TURBT arm. All the patients will undergo a new procedure between 30-60 days after the first one (monopolar re-TURBT). The laser group will be operated by an experienced surgeon with more than 50 cases of prostate resection. The monopolar TURBT group will be operated by institutions´s surgeons assistants, urologists with more than 2 years of experience in the area and more than 50 surgeries performed. Pathological samples will be analyzed in the FMUSP Urology Laboratory by a pathologist with huge experience in analysis of bladder tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients aged between 18 and 80 years old;

• Presence of bladder tumor > 3cm without signals of MIBC or advanced disease (US, CT scan or MRI 3 months before surgery)

• Able to understand and willing to sign a written informed consent document

• Satisfactory clinical pre operatory conditions for surgery with regional or general anesthesia.

Exclusion Criteria:

• Previous diagnosis of muscle-invasive bladder cancer;

• Tumor's Invasive aspect (T2 or more) on image (US, TC or RNM);

• Previous TURBT in the last 5 years;

• Urethral stenosis;

• Previous intra-vesical os systemic chemotherapy or radiotherapy;

• Previous treatment with intravesical BCG

• No clinical conditions for regional or general anesthesia;

• Any other significant disease or disorder which, in the opinion of the investigator may either put the participant at risk because of trial participation or may influence the trial result, or the participant's ability ti participate in the trial.

Related Conditions & MeSH terms

• Bladder Cancer
• Bladder Urothelial Carcinoma
• Urinary Bladder Neoplasms

Intervention

Procedure:
• Monopolar Transurethral resection of bladder tumor
Patients randomized to Monopolar TURBT will be operated using a 26F continuous-flow resectoscope sheaths and a single-pole working element to exclusive use of the resection. The power will be set to cut in 80w and 60w. The technique that will be performed will be the classic endoscopic resection from the top of the tumor until reaching the base, taking a sample from the base of the lesion (muscle layer). Fragments will be removed through an Ellik evacuator, and the solution used will be 3% glycine. After the procedure, the patient will will be catheterized with a silicon catheter number 22F with three ways and continuous irrigation. After 30-60 days of the first procedure, all patients diagnosed with a lamina propria invasion in the uro-pathology analysis (T1) will be submitted to a new monopolar TURBT.
• Holmium Laser resection of bladder tumor (HoLEBT)
It will be used a 24-26F continuous-flow resectoscope sheath with a specific working element to use with a 600µm fiber to Laser Holmium. Patients will be operated with the Megapulse 70w (Richard Wolf) and laser will be set to deliver the energy of 0,5J and 30-40Hz frequency, 15-20W of final energy. The solution used will be 0,9% saline solution. The resection will start from the base of the lesion, reaching the muscle layer to obtain a sample and resection of the whole tumor, without fragmentation. After this, the morcellation will be performed in the apex of tumor sparing the base with a long nephroscope, and the patient will will be catheterized with a silicon catheter number 22F with three ways and continuous irrigation. The morcellated product will be sent to the pathology lab for detailed analysis.

Locations

Country	Name	City	State
Brazil	Instituto do Cancer do Estado de São Paulo (ICESP)	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Instituto do Cancer do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (9)

De Nunzio C, Franco G, Cindolo L, Autorino R, Cicione A, Perdona S, Falsaperla M, Gacci M, Leonardo C, Damiano R, De Sio M, Tubaro A. Transuretral resection of the bladder (TURB): analysis of complications using a modified Clavien system in an Italian real life cohort. Eur J Surg Oncol. 2014 Jan;40(1):90-5. doi: 10.1016/j.ejso.2013.11.003. Epub 2013 Nov 12. — View Citation

Herrmann TR, Liatsikos EN, Nagele U, Traxer O, Merseburger AS; EAU Guidelines Panel on Lasers, Technologies. EAU guidelines on laser technologies. Eur Urol. 2012 Apr;61(4):783-95. doi: 10.1016/j.eururo.2012.01.010. Epub 2012 Jan 17. — View Citation

Kramer MW, Rassweiler JJ, Klein J, Martov A, Baykov N, Lusuardi L, Janetschek G, Hurle R, Wolters M, Abbas M, von Klot CA, Leitenberger A, Riedl M, Nagele U, Merseburger AS, Kuczyk MA, Babjuk M, Herrmann TR. En bloc resection of urothelium carcinoma of the bladder (EBRUC): a European multicenter study to compare safety, efficacy, and outcome of laser and electrical en bloc transurethral resection of bladder tumor. World J Urol. 2015 Dec;33(12):1937-43. doi: 10.1007/s00345-015-1568-6. Epub 2015 Apr 25. — View Citation

Kramer MW, Wolters M, Cash H, Jutzi S, Imkamp F, Kuczyk MA, Merseburger AS, Herrmann TR. Current evidence of transurethral Ho:YAG and Tm:YAG treatment of bladder cancer: update 2014. World J Urol. 2015 Apr;33(4):571-9. doi: 10.1007/s00345-014-1337-y. Epub 2014 Jun 17. — View Citation

Miladi M, Peyromaure M, Zerbib M, Saighi D, Debre B. The value of a second transurethral resection in evaluating patients with bladder tumours. Eur Urol. 2003 Mar;43(3):241-5. doi: 10.1016/s0302-2838(03)00040-x. — View Citation

Rink M, Babjuk M, Catto JW, Jichlinski P, Shariat SF, Stenzl A, Stepp H, Zaak D, Witjes JA. Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature. Eur Urol. 2013 Oct;64(4):624-38. doi: 10.1016/j.eururo.2013.07.007. Epub 2013 Jul 19. — View Citation

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17. — View Citation

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. — View Citation

Svatek RS, Hollenbeck BK, Holmang S, Lee R, Kim SP, Stenzl A, Lotan Y. The economics of bladder cancer: costs and considerations of caring for this disease. Eur Urol. 2014 Aug;66(2):253-62. doi: 10.1016/j.eururo.2014.01.006. Epub 2014 Jan 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of Detrusor Muscle (DM) on histopathological analysis of morcellated tumor from HoLERBT and TRUBT	Evaluate the presence of muscle layer in the samples of tumor resection	Up to 1 month after the first surgery
Secondary	Compare intraoperative an peri-operative complications	Evaluate intra and peri-operative complications (according to Clavien-Dindo scale) between the two groups	During surgery
Secondary	Clinical recurrence-free survival	Clinical recurrence-free survival at 3, 6, 9, 12, 15, 18 and 24 months follow-up (US, CT-scan, MRI, cystoscopy, TURBT)	Until 2 years after surgery
Secondary	Clinical progression-free survival	Clinical progression-free survival at 3, 6, 9, 12, 15, 18 and 24 months follow-up (US, CT-scan, MRI, TURBT)	Until 2 years of surgery
Secondary	Overall and cancer-specific survival	Overall and cancer-specific survival at 13, 6, 9, 12, 15, 18 and 24 months follow-up	Until 2 years of surgery