Safety Analysis and Oncological Outcomes in HoLERT vs TURBT

NCT ID: NCT05833997

Last Updated: 2023-04-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-10
• Study Completion Date: 2025-12-31

Brief 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.

Detailed 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.

Conditions

Bladder Urothelial Carcinoma; Bladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Holmium Laser En-bloc Resection of Bladder Tumors (HoLERBT) arm

Patients randomized to HoLERBT group will have their tumor resected using the Megapulse 70w (Richard Wolf).

Group Type: EXPERIMENTAL

Holmium Laser resection of bladder tumor (HoLEBT)

Intervention Type: PROCEDURE

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.

Control arm

Patients randomized to control arm will undergo a monopolar transurethral resection of bladder tumor.

Group Type: ACTIVE_COMPARATOR

Monopolar Transurethral resection of bladder tumor

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto do Cancer do Estado de São Paulo

OTHER

Sponsor Role: lead

Responsible Party

Alexandre Iscaife

Md, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William Nahas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto do Cancer do Estado de São Paulo

Locations

Instituto do Cancer do Estado de São Paulo (ICESP)

São Paulo, , Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Alexandre Iscaife, MD, PhD

Role: CONTACT

alexandre.iscaife@hc.fm.usp.br

+5511976280082

Facility Contacts

Alexandre Iscaife, MD, PhD

Role: primary

alexandre.iscaife@hc.fm.usp.br

References

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.

Reference Type: BACKGROUND

PMID: 23335087 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12600426 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19271220 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24472711 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23906669 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22285403 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25910478 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24935098 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24284200 (View on PubMed)

Other Identifiers

NP1537/2019

Identifier Type: -

Identifier Source: org_study_id