Prostate cancer is the third cause of cancer deaths among men. A growing number of cases are now being detected at a localized stage, i.e. before metastatic spread, meaning that treatment with radiotherapy or surgery can be started early. Ablatherm, a technological innovation based on the use of ultrasound waves, could offer an interesting alternative for some patients who do not qualify for surgery (mainly men over 70).
The ultrasound technique, developed by Jean-Yves Chapelon's team at INSERM U281 in Lyon (directed by Dominique Cathignol) and transformed into a practical medical application by the French company EDAP Technomed, has a number of appreciable advantages, such as being minimally invasive, cutting the time spent in hospital, and limiting adverse effects. And if the first treatment course is inadequate, the procedure can be repeated (unlike radiotherapy). Initial clinical evidence of Ablatherm's effectiveness, published in the Journal of Urology, was obtained in collaboration with Dr Albert Gelet at the Urology and Transplant Surgery Department of Edouard Herriot hospital in Lyon (directed by Professor Jean Michel Dubernard).
The Ablatherm device destroys tumor tissue by delivering High-Intensity Focused Ultrasound (HIFU) via an endorectal probe. The delivered ultrasound causes an abrupt rise in temperature that leads to local tissue necrosis. The same endorectal probe is also used to visualize the prostate. Using a computer, the physician advances the probe through the rectum until the target prostate tissue is reached, and then triggers shots ultrasound waves. The chosen volume of prostate tissue is destroyed by multiple shots (an average of 500), the beam being moved slightly between each shot. The control software defines the precise target volume and ensures that neighboring healthy tissues are respected (no energy is delivered to non target tissues).
Ablatherm is already being tested in the clinical setting. Preliminary treatment results for 50 patients have just been published. The trial, authorized by the Lyon Ethics Committee in 1992, involved patients over 67 (mean age 71 years) who had localized prostate cancer and did not qualify for radical prostatectomy (i.e. removal of the prostate). The results of the ultrasound treatment were assessed by monitoring changes in the PSA level in blood and biopsy specimens obtained at regular intervals. The patients underwent a thorough investigation within the year following treatment to check for metastatic spread to other parts of the body. The results were analyzed with a mean follow-up period of 340 days.
Local disease control in 80% of cases
- The treatment was considered a success in 28 of the 50 patients, i.e. those
who had a complete response (the control biopsies showed no residual cancer
cells, and the mean PSA level fell significantly then stabilized ).
- 12 patients had a partial response to treatment: residual cancer cells were
detected in 9 patients although their mean PSA level had normalized, while the
other 3 patients had no residual cancer cells but a slightly elevated PSA level.
- Finally, treatment was considered to have failed in the remaining 10 patients, 3 of whom required hormone therapy and 7 external radiation therapy.
These results show that treatment with the Ablatherm device can provide local disease control in approximately 80% of cases (complete control in 56% and partial control in 24%).
As regards adverse effects, 14 (31%) of the patients in this study had one or several complications, but an improved prototype has been found to give a far lower rate of complications (17%). The risk of incontinence is low (18%), and the impact on sexual function is not yet known.
It's too early to say how useful this device will be in the treatment of localized prostate cancer. Only 13 patients have more than three years' follow-up since treatment, and the promising initial results must be confirmed in trials with larger numbers of patients. A European multicenter phase II trial is underway in Lyon (Edouard Herriot hospital), Paris (Montsouris Institute and Saint-Louis hospital), Germany (Munich and Regensburg), and the Netherlands (Nijmegen). Phase III trials are being planned to assess the efficacy, adverse effects and cost of this new approach relative to existing alternatives.
Four major sets of patents with international extensions have been applied for jointly by INSERM and EDAP Technomed, and Ablatherm could become commercially available as early as June 1999. EDAP Technomed have just obtained US Food and Drug Administration (FDA) approval for a multicenter study in the United States.
An example of successful technology transfer, against the odds
Ablatherm is the latest fruit of close collaboration between INSERM U281 (a
group working on tumor diagnosis and treatment by physical agents such as shock
waves and ultrasound), the urology department of Edouard Herriot hospital, and
EDAP Technomed (formerly Technomed).
It took 10 years to develop Ablatherm, from fundamental research by the INSERM group through to prototype development and the first clinical trials. The development process was not helped by the fact that Technomed ran into financial difficulties, leading to its takeover by Edap, a direct competitor. However, the tenacity of the company's director and medical staff, together with active support from by INSERM's service de valorisation, saw the Ablatherm project through to fruition, under the auspices of a new company, EDAP Technomed.
Cooperation between the various actors in the Ablatherm project is long-standing: in 1985 it gave rise to Sonolith, the first French-made device designed to break up kidney stones by the use of shock waves (it was this application that led to the creation of Technomed).
INSERM makes a major contribution to human health, and to French economic development, by promoting active partnerships with private enterprise. This partnership policy ensures that INSERM's fundamental and applied research finds applications in innovative products and services. A few data on INSERM collaboration with the private sector:
- 689 contracts with industry
- partnerships with more than 200 private enterprises worldwide
- a portfolio of 346 primary patents is managed by INSERM.
EDAP Technomed develops, manufactures and markets high-tech noninvasive
therapeutic equipment. It is a world leader in extracorporeal shock-wave
lithotripsy (destruction of kidney stones), and in microwave heat treatment of
prostatic adenoma.
EDAP Technomed:
- 170 personnel, 100 of whom work in France
- Cumulative worldwide sales of more than 150 lithotripsy devices based on INSERM research