Vesical Imaging-Reporting and Data System (VI-RADS) Followed by Photodynamic Trans-urethral Resection of Bladder Tumours (PDD-TURBT) to Avoid Secondary Resections (Re-TURBT) in Non-Muscle Invasive Bladder Cancers (NMIBCs)

NCT05962541 | Recruiting Phase 4

• 1 other identifier: N764J-20022023
• Study Type: interventional
• Target: 327
• Locations: 1 country
• Sites: 1

Brief Summary

Background: In European Association of Urology (EAU) Guidelines, the vast majority of non-muscle-invasive bladder cancers (NMIBCs) undergo a primary transurethral resection of the bladder tumor (TURBT) followed by a repeat TURBT (Re-TURBT). The Re-TURBT is recommended due to the possibility of residual bladder cancer but is unnecessary in many cases by constituting overtreatment. Currently, no diagnostic strategy or predictive tools have been implemented to further stratify who does or does not benefit from Re-TURBT. Recently, an MRI-based Vesical Imaging Reporting and Data System (VI-RADS) score has been developed to stage as to the preoperative probability of muscle invasion, which could potentially exclude those who do not require a Re-TURBT when a primary high-quality resection is delivered. As such, performing TURBT with standard white light (WL) cystoscopy is known to miss many bladder tumours, which may be poorly visible, and a technique known as with photodynamic diagnosis (PDD) results in lower residual tumor and lower early intravesical recurrence rates. PDD is performed using violet light to improve the detection of these lesions not easily visible with WL cystoscopy. Methods/Aims: The investigators propose an Italian, single-center, phase IV, open-label, non-inferiority, randomized controlled trial, in which participants (n=112) who had already received a mpMRI/VI-RADS score, are randomized to receive PDD-TURBT, no Re-TURBT versus standard of care represented by conventional WL-TURBT followed by WL-Re-TURBT. The primary outcome is proportions of early recurrence in the urinary bladder. Secondary outcomes will include proportions of late BCa recurrence, late disease-free interval, time to progression to MIBC, patient's quality of life assessment, and cost-analysis. Perspective: The CUT-less trial aims to respond to this unmet need through a non-inferiority randomized clinical study potentially shaping the perspective for a paradigm shift towards a more personalized, socially, and economically sustainable updated NMIBC therapeutic pathway. Implications: The current clinical trial proposal is aiming to achieve a paradigm shift in the oncological and socio-economical management of urothelial malignancies of the urinary bladder. Our first concern is indeed to guarantee a safe and ground-breaking strategy to manage the pathway of such patients in order to guarantee the non-inferior oncologic safety (and possibly superiority) when compared to the current standard of care. Additionally, if our hypotheses are confirmed, the investigators will be able to significantly relieve these patients from the oncologic burden of an already invasive and arduous bladder cancer care path. Finally, safely avoiding an unnecessary, expensive surgical procedure will bring significant social and economic benefits to the EU healthcare system and possibly worldwide.

Conditions

Non-muscle-invasive Bladder Cancer; Non-Muscle Invasive Bladder Urothelial Carcinoma; High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of EARLY Bladder Cancer (BCa) recurrences

  The proportion of early BCa recurrences (i.e., within 4.5 months follow-up) in those non-muscle invasive bladder cancer (NMIBC) treated by standard of care (i.e., TURBT followed by Re-TURBT) compared to our novel algorithm proposal (i.e., primary PDD-TURBT followed by no Re-TURBT).

  within 4.5 months following primary intervention

Secondary Outcomes (6)

• Proportion of LATE BCa recurrences

  after 4.5 months following primary intervention

• Proportion of progression from NMIBC to MIBC

  over 3 years follow-up

• Changes in health-related quality of life (HRQoL)

  over 3 years follow-up

• Changes in health-related quality of life (HRQoL)

  over 3 years follow-up

• Changes in health-related quality of life (HRQoL)

  over 3 years follow-up

Study Arms (2)

PPD-TURBT (no Re-TURBT)

EXPERIMENTAL

Primary PDD-TURBT, not followed by Re-TURBT

Drug: PDD-TURBT with hexaminolevulinate (Hexvix®); Device: Power Led Saphira (TM)

WL TURBT plus Re-TURBT (Standard of Care)

NO INTERVENTION

Standard of care consisting in primary WL TURBT followed by WL Re-TURBT within 2 - 6 weeks from initial WL TURBT

Interventions

PDD-TURBT with hexaminolevulinate (Hexvix®) DRUG

In order to undergo PDD-TURBT, all eligible patients in the experimental arm will be administered the photosensitizer hexaminolevulinate (85 mg in 50 ml of phosphate buffered saline, Hexvix®) on an inpatient setting through a urethral catheterization of the participant's bladder. During the PDD-TURBT surgery, the bladder will be illuminated with blue light (wavelength 380-450 nm). The operating rooms of the participant institutions will therefore need to have the specialized equipment consisting in the blue-light source (POWER LED SAPHIRA \[TM\]).

Also known as: Hexvix®

PPD-TURBT (no Re-TURBT)

Power Led Saphira (TM) DEVICE

This is a light source based on LED technology. It can be used for both White Light (WL) and fluorescence applications in blue light (i.e., Photodynamic diagnosis PDD) for visualizing tumor lesions during trans-urethral resection of bladder tumors (PPD- TURBT).

PPD-TURBT (no Re-TURBT)

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 at least 18 years old referred for clinical suspicion of primary or recurrent BCa who have been advised to undergo TURBT.
• Patients with a TUR-confirmed diagnosis of NMIBC and candidate for second look and resection (Re-TURBT) according to EAU Guidelines \[6\].
• No imaging evidence (i.e., mpMRI/VI-RADS score 1 or 2) of muscle-invasive, locally advanced, or metastatic BCa (i.e., only confirmed CIS, Ta, T1, N0, M0 will be considered eligible).
• Patients who did or did not receive previous BCG immunotherapy (i.e., BCG naïve and non-naïve patients).
• Fit to undergo all procedures listed in protocol.
• Able to provide written informed consent.

You may not qualify if:

• Contraindication to TURBT and/or Re-TURBT.
• Initial TURBT diagnosis of MIBC (i.e., T2) or locally advanced BCa (i.e., T3-T4).
• Preoperative evidence of metastatic disease (i.e., cN1 - N3 and/or cM1).
• Visual evidence of low-risk NMIBC (solitary tumor, \< 1 cm) before initial TURBT.
• Visual evidence of MIBC on preliminary cystoscopy (i.e., non-papillary or sessile mass attached directly by its base without a stalk).
• TURBT diagnosis of NMIBCs not eligible for Re-TURBT according to EAU Guidelines (i.e., Ta-LG; Ta-HG with detrusor muscle in the specimen; primary CIS) \[6\].
• Concomitant Upper tract (kidney or ureteric) tumours on imaging.
• Contraindication to adjuvant intravesical BCG immunotherapy.
• Unfit to undergo any procedures listed in protocol.

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

AOU Policlinico Umberto I Hospital, UOC Urologia SMUC05, Rome, Italy

Rome, Lazio, 00161, Italy

RECRUITING

Related Publications (21)

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MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

5-aminolevulinic acid hexyl ester

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Francesco Del Giudice, MD

CONTACT

+39 3395382464; francesco.delgiudice@uniroma1.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator, MD, PhD, Assistant Professor, Consultant Urologic Surgeon

Model Details: Italian, single-center, phase IV, open-label, randomized controlled trial, with patients randomized in a 1:1 ratio to one of two arms

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: July 27, 2023
• Study Start: December 22, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2031
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)