High Frequency Ultrasound - A Cancer Miracle?

[ajrmoore]

This morning I read an article in the Times (search Ultrasound on the Times online website and you'll find it immediately). In short, a study of 172 men whose cancer has not progressed beyond the prostate underwent High Frequency Ultrasound (what I shall refer to as HIFU). One year later 92 percent (or 158 men) were completely free of cancer. This struck me as a pretty amazing study. Completely eliminated the cancerous tumour! In the majority of test subjects! Why isn't HIFU being implemented for every cancerous growth from here to Timbaktu. After a moment's consideration however, one or two skeptical thoughts started to niggle at the back of my mind. Firstly, the Times (demonstrating, in my opinion, poor medical and health reporting that is, I believe, of a standard typical in the UK) failed to mention whether the study was controlled, how rigorous it was, and who it was conducted by.

Also, after doing some brief preliminary research online, I not only find a troubling lack of controlled, double-blind studies by independent research groups regarding HIFU available, but also views from prominent Cancer & Health bodies that are glaringly inconsistent with the Times article. I'm not allowed to post links yet, but please visit Cancer Research UK and NHS website respectively for elabouration on the following quotes regarding HIFU:

"If you are invited to go into a trial of HIFU for prostate cancer, your doctors need to make sure you know

What is involved in having the treatment
That we don't know everything about side effects yet
That we don't fully understand how long term effects of HIFU compare to other treatments
What other treatment options they have"

"High intensity focused ultrasound (HIFU) and cryotherapy are not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions."

Aside from my obvious problem with the poor, and I think skewed, reporting by the Times, I have the distinct disadvantage of not having much knowledge or sources with which to approach the subject/procedure from a better informed position. Does anybody else medically savy have other experience or links to further reading. My only frame of reference for ultrasound is the monitoring of the development of the fetus in utero and being aware that they use an Ultrasonic frequency (20Mhz?). If so, what frequency does HIFU operate at?

Would appreciate any feedback or comments! Whether on UK science reporting or HIFU.

[skbuncks]

The NHS take on the article

http://www.nhs.uk/news/2009/07July/Pages/Ultrasoundforprostatecancer.aspx


At present, the main limitation of this particular procedure is that there is little information available on longer-term outcomes... The best-quality evidence would come from randomised controlled trials that compared HIFU to standard options (surgery, radiotherapy or watchful waiting) and other minimally invasive options. Headlines like “Prostate cancer treatment more successful than surgery” are not accurate at present.

Current NICE guidance advises that the evidence supports the safety and efficacy of HIFU for prostate cancer, provided that monitoring, audit and clinical governance of any procedures are carried out. It advises that longer-term effects on survival and quality of life are unknown, and that doctors should therefore ensure that patients understand these uncertainties and the alternative treatment options.


skb

[Pebble]

Nice are not over impressed:

http://www.nice.org.uk/nicemedia/pdf/CG58FullGuideline.pdf

"Qualifying statement: There is insufficient evidence of the clinical and cost effectiveness of cryotherapy and HIFU in comparison to established interventions to recommend their routine use."

There are published clinical trials:

Hinyokika Kiyo. 2005 Oct;51(10):651-8.
Links

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study.
Uchida T, Baba S, Irie A, Soh S, Masumori N, Tsukamoto T, Nakatsu H, Fujimoto H, Kakizoe T, Ueda T, Ichikawa T, Ohta N, Kitamura T, Sumitomo M, Hayakawa M, Aoyagi T, Tachibana M, Ikeda R, Suzuki K, Tsuru N, Suzuki K, Ozono S, Fujimoto K, Hirao Y, Monden K, Nasu Y, Kumon H, Nishi K, Ueda S, Koga H, Naitoh S.
The Department of Urology, Tokai University Hachioji Hospital.
We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.



J Endourol. 2003 Oct;17(8):673-7.
Links

High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study.
Thüroff S, Chaussy C, Vallancien G, Wieland W, Kiel HJ, Le Duc A, Desgrandchamps F, De La Rosette JJ, Gelet A.
Department of Urology, München-Harlaching Krankenhaus, München, Germany.
PURPOSE: To describe the safety and efficacy of high-intensity focused ultrasound (HIFU) for the treatment of prostate cancer as assessed in a Phase II/III prospective multicentric clinical trial. PATIENTS AND METHODS: Patients (N = 402) presenting with localized (stage T(1-2)N(0-x)M(0)) prostate cancer between 1995 and 1999 at six European sites who were not candidates for radical prostatectomy were treated with HIFU under general or spinal anesthesia. Their mean age was 69.3 +/- 7.1 (SD) years, the mean prostate volume 28.0 +/- 13.8 cc, and the mean serum prostate specific antigen (PSA) concentration 10.9 +/- 8.7 ng/mL. Nearly all (92.2%) of the patients had one to four positive biopsy samples at baseline. The Gleason scores were 2 to 4 for 13.2% of the patients, 5 to 7 for 77.5%, and 8 to 10 for 9.3%. During the follow-up, random sextant biopsies and serum PSA measurements were performed. Any positive sample in biopsies performed after the last treatment session resulted in a "HIFU failure" classification. RESULTS: The patients received a mean of 1.4 HIFU sessions. The mean follow-up duration was 407 days (quartile 1 135 days, median 321 days, quartile 3 598 days). The negative biopsy rate observed in the T1-2 primary-care population was 87.2%. These results were also stratified according to the usual disease-related risk classification, and as much as a 92.1% negative biopsy rate was observed in low-risk patients. Nadir PSA results correlated with prostate size and the clinical procedure. CONCLUSION: These short-term results obtained on a large cohort confirm that HIFU is an option to be considered for the primary treatment of localized prostate cancer.

But it is clearly not a cure all

Treatment of patients after failed high intensity focused ultrasound and radiotherapy for localized prostate cancer: salvage laparoscopic extraperitoneal radical prostatectomy.
Liatsikos E, Bynens B, Rabenalt R, Kallidonis P, Do M, Stolzenburg JU.
Department of Urology, University of Patras, Patras, Greece.
INTRODUCTION: To evaluate the feasibility and efficacy of salvage endoscopic extraperitoneal radical prostatectomy (EERPE) in recurrent prostate cancer after failed high intensity focused ultrasound therapy (HIFU), external beam radiotherapy (EBT) and brachytherapy. PATIENTS AND METHODS: Twelve patients with mean age 63.3 years (48-74), mean preoperative PSA 12.7 ng/ml and mean prostate weight 48.8 grams were treated with salvage EERPE with curative intent for biopsy proven locally recurrent prostate cancer. Our group was consisted of four patients who have been treated in the past with HIFU, six with EBT and two with brachytherapy. Operative time, estimated blood loss, conversion to open surgery rate, transfusion rate and transurethral catheter time were recorded. Also functional outcome and short term oncological outcome were reviewed. RESULTS: Average operative time was 153 minutes. Mean blood loss was 238 ml. The procedure was completed in all cases with no difficulty and without intraoperative complications. There was no need for conversion to open surgery or transfusion. Mean total urethral catheterization time was 7.2 days. After mean follow-up of 20 months, 10 patients were completely continent, and 2 needed 1-2 pads per day. Three patients were potent before the surgical treatment, but no one reported potency postoperatively. Biochemical recurrence was observed in only one patient 12 months postoperatively. DISCUSSION: In the initial experience, salvage EERPE in experienced hands has minimal perioperative morbidity. Short term oncological and functional outcomes are encouraging but further studies and longer follow-up are required in order to assess the long-term outcomes.



The logic is fairly straightforward, ultrasound is used to localise the tumour deposits, and then to heat the local tissue causing necrosis, of course this relies on treating only the deposits that can be 'seen' and local damage to surrounding tissues is inevitable, hence the caution in respect of longterm damage. Further the treatment is slow thus expensive to administer and the local swelling results in prolonged catheterisation (approx 2 weeks) so even short-term complications are not unusual

[ajrmoore]

@ Pebble

Thank you for those study summaries (most useful to see excerts from current studies being done) as well as the brief explanation. Quite a lot clearer now. HIFU's action in eliminating tumours through heat-facilitated necrosis makes a lot more sense than just High Frequency waves "massaging the bad away" (what I originally thought when I read the article). The short-term side effects and possible long-term damage is also very interesting. Thanks again.

If I may ask, did you simply Google those studies, or is there an accepted source for that type of information? (Thanks in advance!)

I still feel that the Times article committed a grave error in journalism by failing to report key details in how rigorous the trial was.

[skbuncks]

snip...

If I may ask, did you simply Google those studies, or is there an accepted source for that type of information? (Thanks in advance!)

I still feel that the Times article committed a grave error in journalism by failing to report key details in how rigorous the trial was.

That would be pubmed (http://www.ncbi.nlm.nih.gov/pubmed/) your after

skb

[Pebble]

That would be pubmed (http://www.ncbi.nlm.nih.gov/pubmed/) your after

skb

Thanks SKbuncks. Also helps to check for NICE guidance:

http://guidance.nice.org.uk/

May not agree with their interpretation of the data, but they do present available published, and some unpublished data in a well orgnaised manner.

The final problem is that the abstracts can be remarkably misleading - so except where a quick reply is all that is required need access to a system that houses original articles (e.g. myathens) - usually need to work for a university to have access.