Clinical trial NCT02397434: Adjuvant Radiotherapy After Cystectomy for Muscle Invasive Bladder Cancer
Official title: Adjuvant Radiotherapy After Cystectomy for Patients With Muscle Invasive Bladder Cancer: a Phase II Trial.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Toxicity
Keywords: assessment of QOL (EORTC QLQ-C30)
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2015-03-25
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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:

-

Primary outcomes:
measure: change from baseline in acute Radiation Therapy Oncology Group (RTOG) toxicity
timeFrame: last day of radiotherapy, 1 month and 3 months after last day of EBRT
Secondary outcomes:
measure: change from baseline in late RTOG toxicity
timeFrame: at 6,9, 12, 18 and 24months after last day of EBRT
measure: change from baseline in local control
timeFrame: at 6,9, 12, 18 and 24months after last day of EBRT
measure: disease free survival
timeFrame: at 6,9, 12, 18 and 24months after last day of EBRT
measure: overall survival
timeFrame: at 6,9, 12, 18 and 24months after last day of EBRT
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Dept of Radiotherapy, University Hospital Ghent
Study officials:
affiliation: University Hospital, Ghent
name: Valérie Fonteyne
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.