Impact of Positron Emission Tomography (PET) Imaging in Muscle-invasive Urothelial Carcinoma of the Bladder Staging (PET MUSE)

Bladder cancer is the fifth most common cancer in Canada and there has been relatively little progress in altering its clinical course over the last three decades. One of the major problems identified in the management of this disease, is under staging of muscle invasive disease which can lead to suboptimal treatment and outcomes. PET-CT has the potential to more accurately stage MIBC than standard CT by detecting pelvic adenopathy and/or distant sites of disease that may not be found on standard imaging. In the former situation, more aggressive therapy with extended lymph node dissection and/or neoadjuvant chemotherapy prior to cystectomy can be offered. While in the latter situation patients can be spared the morbidity of a cystectomy performed in a setting of metastatic disease. This study will address whether PET-CT adds a clinically meaningful difference in care.

Study Overview

• Status: Active, not recruiting
• Conditions: Muscle-invasive Bladder Cancer
• Intervention / Treatment: Other: Whole-body FDG PET-CT

Detailed Description

A multicenter randomized controlled trial will be performed. Patients usually present with symptoms (e.g., painless hematuria). The urologist will perform cystoscopy and if urothelial cancer of the bladder is suspected, the patient is taken to the operating room for an examination under anesthesia (EUA) and a TURBT. If this shows muscle invasion then conventional staging with CT chest, abdomen, and pelvis is performed. The patient who has TNM Stage T2a-T4a N0-3 M0 is eligible to be enrolled in the trial. Eligible consenting patients will be randomized 2:1 to PET-CT or none (Control). The actual treatment received by the patient will be documented. The primary outcome measure is treatment received.

• Study Type: Interventional
• Enrollment (Actual): 292
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Regional Cancer Centre
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women with newly diagnosed muscle-invasive high grade urothelial carcinoma of the bladder (TNM stage T2a-T4a, N0-3, M0), who are eligible for either radical cystectomy or radiotherapy-based bladder conservation.
• Being considered for treatment of curative intent.

Exclusion Criteria:

• Age < 18 years.
• ECOG performance status >2.
• Predominant histology (>50% of specimen) involves non-urothelial cell carcinoma.
• Prior partial cystectomy.
• Prior pelvis surgery that obviates a completed extended lymphadenectomy (e.g., aorto-femoral/iliac bypass) or for whom the surgeon feels that their ability to perform a standard or extended pelvic node dissection would be compromised.
• Contraindications to FDG PET-CT.
• Inability to lie supine for imaging with PET-CT.

• Inadequate hepatic function:

  (i) Bilirubin >1.5 X ULN and (ii) SGOT and Alkaline phosphatase >3 X ULN

• History of another invasive malignancy within the previous 5 years with the exception of non-melanoma skin cancer.
• Known pregnancy or lactating female.
• Inability to complete the study or required follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Whole-body FDG PET-CT; Whole-body FDG PET-CT (Experimental arm)	Other: Whole-body FDG PET-CT; Other Names: PET-CT imaging
No Intervention: No PET-CT; No PET-CT (Control arm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment received	For patients with planned cystectomy, treatment received includes: avoidance of planned cystectomy and node dissection, an extended (vs standard) node dissection (or standard dissection when extended is the surgeon's usual practice), use of neoadjuvant chemotherapy (vs no neoadjuvant chemotherapy). For patients with planned bladder conservation, treatment received includes: avoidance of bladder and nodal radiation (vs bladder only or no radiation) and use of neoadjuvant chemotherapy (or not).	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Disease-free survival defined as objectively defined (RECIST criteria, version 1.1.) local or distant recurrence or death.	5 years
Overall survival	Overall survival defined by all-cause mortality.	5 years
Quality of life analysis	Overall QOL assessed using the EORTC QLQ-C30 version 3.	5 years
Health economic analysis	Health economic analysis assessed using EQ-5D health utility questionnaire and total healthcare costs.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in planned management	Assess change in planned management with actual treatment delivered in both pre-operative PET-CT versus no PET-CT (control) patients.	5 years
Clinical and pathology response to chemotherapy using interim response of FDG PET-CT after 2 cycles of chemotherapy	Explore if interim response on FDG PET-CT after 2 cycles of chemotherapy is associated with clinical and pathology response to chemotherapy and if early interim metabolic response correlates with other outcome measures including DFS and OS.	5 years

Collaborators and Investigators

• Sponsor: Ontario Clinical Oncology Group (OCOG)
• Collaborators: Cancer Care Ontario
• Investigators: Principal Investigator: Srikala Sridhar, MD, Princess Margaret Hospital, Canada; Principal Investigator: Nicholas Power, MD, LHSC-Victoria Hospital; Principal Investigator: Som Mukherjee, MD, Juravinski Cancer Centre; Principal Investigator: Ur Metser, MD, Princess Margaret Hospital, Canada; Study Director: Mark Levine, MD, Ontario Clinical Oncology Group (OCOG)

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2016
• Primary Completion (Actual): March 31, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: May 27, 2015
• First Submitted That Met QC Criteria: June 1, 2015
• First Posted (Estimated): June 4, 2015

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Bladder cancer; Muscle-invasive bladder cancer; PET imaging; FDG
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell
• Other Study ID Numbers: OCOG-2013-PETMUSE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No