It is very difficult to say which method is better as chemotherapy drugs were different, heating methods were different and patients selections were not exactly the same. Nevertheless, The approach which University of Arizona used seem to give better efficacy - 55% vs 33% (Duke) recurrence free after 2 years. I was particularly surprised to see that 55% recurrence free after 2 years for patients BCG did not work is much higher than 25% of recently approved MERCK Keytruda for BCG unresponsive patients.
I have listed a few notable differences in their approaches between Duke University and University of Iowa.
The list is from comparing two published papers. I have listed listed the links to the two papers.
Chemotherapy drug used
Duke : Mitomycin C
Univercity of Arizona : Gemistabine and Docetaxcel
University of Arizona
1. Keep warming bladder by inserting a Foley balloon catheter and fill it with 43–45°C warm water.
2. 200 mg Gemcitabine in 10 mL of warm water is instilled. The patient rotate while the water in the Foley
balloon is exchanged every 20 minutes with warm water.
3. After one hour, the Gemcitabine is emptied and 20 mg of Docetaxel in 10 mL of warm water is instilled,
and the catheter is removed. The patients are instructed to retain the fluid in their bladder for 120
Frequency of the treatment
Duke University For induction, 6 weekly-instillations, followed by monthly for 4 months.
University of Arizona For induction, 6 weekly-instillations, followed by 3 weekly-instillations af 3,6 and 9 mth.
1. 10 (67%) subjects experienced recurrent bladder cancer, with a median time to recurrence of 15.4
months, but none of these recurrences progressed to muscle invasive.
2. Of the 10 subjects that recurred with bladder cancer, six (60%) underwent radical cystectomy at a
median time of 20.1 months from study enrollment. Pathological stage at cystectomy was pTis in five
subjects, pT1 in one subject, and pelvic nodes were negative in all patients (median node count = 15)
University of Arizona 60 patients
1. 60 patients received treatment with a median follow-up of 14.9 months.
55% at 2 years recurrence free.
2. Of the 60 subjects, 3 underwent cystectomy. Of the 60 subjects, 3 has progression.
Several clinical trials have been done including involving US university hospitals. But I do not know which hospitals
provide such therapy in a clinical environment. I tried to call to the chief investigator, an oncology doctor at Duke University in NC who had completed one of the clinical trials which heated bladder using a radiofrequency device and instilled Mitomycin-c chemotherapy drug (Ref.1). Anyway, I have sent an email to Duke university if they can provide us the name of hospitals who are offering such therapy. When and if I will have received their response, I will post it. NIH (National Cancer Institute) states that heperthermia combined with chemotherapy and radiation therapy has been clinically tested on a small scale but no widely used in clinically. (Ref 2).
Anyway, most hyperthermia chemotherapies are used for high risk non muscle invasive bladder cancers patients whose BCG treatment did not work. It is based upon the assumption that heat combined with chemotherapy, i.e. Mitomycin-c will give better efficacy than giving chemotherapy alone.
See Ref 3 for overview and a compilation of other studies
Method of heating
- radiofrequency emitting intravesical catheters (e.g. Synergo, operating at a frequency of 915 MHz,
- externally heated chemotherapy fluid circulation in the bladder,
- intravesical magnetic nanoparticles, and external deep regional radiofrequency transmission with 70–110 MHZ
Assumptions why heating will improve efficacy
1) Tumor cells increase surface expression of several markers (e.g., MHC class I) when exposed to heat.
2) Heat causes the tumor to release HSPs, which in turn activates the host immune response.
3) Heated tumor cells release exosomes that carry tumor antigens to the immune system.
4) Heat alone directly activates the immune system.
5) Heat renders the tumor vasculature more permeable which allows for better trafficking of immune cells.
Additionally, hyperthermia is an interesting topic of research because of the sensitizing effect with chemotherapy and/ or radiotherapy. Hyperthermia has been shown to enhance drug delivery and thermosensitizes cancer cells to certain antineoplastic drugs.
I have noticed that most clinical trials are small scale. The clinical trial of Duke university involved 15 patients.
73% of patients completed induction and maintenance for a dropout rate of 27%. Recurrence-free survival at 24 months was 33%, but this was maintained beyond 3 years. None of the recurrences progressed to muscle invasive disease. Six of the ten patients who experienced recurrence underwent a cystectomy and all were node negative with no greater than T1 disease.