a phase III randomised trial of intravesical chemotherapy vs thermo-chemotherapy in intermediate risk non-muscle invasive bladder cancer

Standard treatment for non-muscle invasive bladder cancer is transurethral
resection of all visible lesions (TURB). This establishes the diagnosis and
allows pathologic analysis of the resected tumour specimen for tumour grade and
depth of invasion. Despite this resection a recurrence is seen in 50 to 75%
depending on the risk group of the tumour. However, progression into a
muscle-invasive cancer is a much more threatening event and is seen in 20 to
30%. Prognosis of this group of patients is poor with an overall survival of
55% at 5 years.
Last decade, a number of studies have been conducted with intravesical
Mitomycin C in combination with local Hyperthermia to reduce the number of
recurrences with positive results. The combination of loco-regional
hyperthermia and chemotherapy has
proven to have synergistic effects in the treatment of invasive cancer in
pelvic organs. A pilot study of loco-regional thermo-chemotherapy in
non-muscle invasive bladder cancer that was conducted in the AMC 2009-2011
appeared to be feasible and safe.

To compare standard treatment with intravesical chemotherapy with loco-regional
thermo-chemotherapy in patients with an intermediate risk non-muscle invasive
urothelial carcinoma of the bladder after complete transurethral resection of
the tumour(s).

A Phase III randomised trial.

The intervention will be:
Arm 1 (standard arm): Following a complete resection of the bladder tumour(s):
6 weekly courses with intravesical chemotherapy using Mitomycin C 40 mg
followed by a maintenance scheme during 1 year of 1 instillation to be given at
months 3, 6, 9 and 12.

Arm 2 (experimental arm): Following a complete resection of the bladder
tumour(s): 6 weekly courses of intravesical chemotherapy using Mitomycin C 40
mg in combination with loco-regional (70MHz) microwave hyperthermia, followed
by a maintenance scheme during 1 year of 1 instillation to be given at month 3,
6, 9 and 12.

Standard therapy for non-muscle invasive bladder cancer is trans urethral
resection of the tumor followed by Mitomycin C instillations. Patients can go
home after the Mitomycin C is instilled into the bladder and urinate the
contents at home. In arm B, the experimental arm, patients will undergo
directly after the instillation the hyperthermia treatment that takes 2 hours.
During this treatment patients experience heat in the pelvis that can result in
sweating. Most of the time this can easily be solved by cooling with a fan and
/or wet towels. In our fase I study toxicity was limited to grade1 (some
discomfort that can easily be solved) and occasionaly grade 2 toxicity (bladder
spasms).
Hyperthermia treatment will be given 10 times during 1 year. After this period
patient will be in the follow up.
To measure quality of life 2 validated questionary's have to be filled out and
patient have to undergo some additional test to measure the bladder capacity.
These tests are not invasive.
The addition of hyperthermia can reduce the number of recurrences and perhaps
the number of progression. In this case less interventional diagnostics is
needed and in worse cases may even prevend a cystectomy.