Adjuvant Radiotherapy After Cystectomy for Muscle Invasive Bladder Cancer

Adjuvant Radiotherapy After Cystectomy for Patients With Muscle Invasive Bladder Cancer: a Phase II Trial.

A radical cystectomy + extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with ≥pT3 tumors develop a pelvic recurrence. One- and 2-years survival for patients developing a local recurrence after cystectomy is only 8% and 3% respectively, with a median survival of <4 months. For patients with lymph node recurrence prognosis is somewhat better, but nevertheless still disappointing with reported 1- and 2 years survival of 42% and 11% respectively. The investigators hypothesize that an earlier implementation of external beam radiotherapy (EBRT) i.e. in the adjuvant setting, will prevent local and lymph node recurrence and improve disease free- and overall survival as local recurrence is linked to the development of distant metastasis. Adjuvant EBRT was tested in a prospective randomized trial and resulted in a 20% increase in 5-year disease free survival. Despite those impressive results, severe intestinal toxicity rates hampered the enthusiasm to use adjuvant EBRT, till now. In the last decade, great technological advancements in EBRT planning, such as intensity modulated arc therapy (IMAT), and positioning have been realised. This has resulted in a better coverage of the target volume while sparing normal tissue (mainly small bowel) and in a more precise delivery of the EBRT. Therefore, it is desirable to reconsider the use of adjuvant EBRT in selected MIBC patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Toxicity
• Intervention / Treatment: Radiation: Adjuvant EBRT

Detailed Description

The investigators plan to perform a prospective phase 2 study including 76 patients.

Radiation up to a median dose of 50 Gy in 25 fractions will be delivered with IMAT to the pelvic lymph node regions. If there is a positive surgical margin, the operative bladder bed will be included in the radiation field. A simultaneous integrated boost to 64 Gy to the positive lymph nodes will be delivered. Pathological evaluation on cystectomy specimen includes: tumor stage and grade, area of necrosis (absolute and relative), micro vessel density, epidermal growth factor receptor.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Dept of Radiotherapy, University Hospital Ghent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: muscle invasive bladder cancer with:

• ≥ pathological tumor stage (p)T3 stage + presence of lymphovascular invasion on pathological examination
• pT4
• <10 lymph nodes removed
• positive lymph nodes
• positive surgical margins

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjuvant EBRT; Radiation up to a median dose of 50 Gy in 25 fractions will be delivered with IMAT to the pelvic lymph node regions. If there is a positive surgical margin, the operative bladder bed will be included in the radiation field. A simultaneous integrated boost to positive lymph nodes will be delivered.	Radiation: Adjuvant EBRT; Radiation up to a median dose of 50 Gy in 25 fractions will be delivered with IMAT to the pelvic lymph node regions. If there is a positive surgical margin, the operative bladder bed will be included in the radiation field. A simultaneous integrated boost to positive lymph nodes will be delivered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change from baseline in acute Radiation Therapy Oncology Group (RTOG) toxicity	last day of radiotherapy, 1 month and 3 months after last day of EBRT

Secondary Outcome Measures

Outcome Measure	Time Frame
change from baseline in late RTOG toxicity	at 6,9, 12, 18 and 24months after last day of EBRT
change from baseline in local control	at 6,9, 12, 18 and 24months after last day of EBRT
disease free survival	at 6,9, 12, 18 and 24months after last day of EBRT
overall survival	at 6,9, 12, 18 and 24months after last day of EBRT

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Valérie Fonteyne, University Hospital, Ghent

Publications and helpful links

General Publications

• Fonteyne V, Dirix P, Junius S, Rammant E, Ost P, De Meerleer G, Swimberghe M, Decaestecker K. Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer: a phase II trial. BMC Cancer. 2017 May 2;17(1):308. doi: 10.1186/s12885-017-3302-9.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): October 30, 2018
• Study Completion (Estimated): October 30, 2028

Study Registration Dates

• First Submitted: November 19, 2014
• First Submitted That Met QC Criteria: March 24, 2015
• First Posted (Estimated): March 25, 2015

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: assessment of QOL (EORTC QLQ-C30)
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: 2014/0630