Thursday July 2 2009
Scan of a prostate with a non-cancerous tumour (pink)
“A pioneering treatment for the UK's most common male cancer is more successful than surgery or radiotherapy,” The Daily Telegraph reported. The newspaper said that new research shows that intensive ultrasound therapy is as effective as traditional treatments (surgery or radiotherapy) but that side effects are dramatically reduced.
This research found reasonably favourable results from high-intensity focused ultrasound (HIFU) treatment in 172 men with localised prostate cancer (cancer that had not spread). It also found that there were relatively low rates of urinary incontinence and erectile dysfunction following treatment.
At present, treatment for localised prostate cancer is normally either radical (surgery or radiotherapy) or involves ‘watchful waiting’, where the cancer is monitored but not treated unless it develops. As such, minimally invasive alternatives like HIFU may be a preferable alternative. However, as with other newer alternative treatments for prostate cancer, available evidence is from small case series only and information on long-term outcomes is lacking. Further follow-up of men treated with HIFU and randomised controlled trials to directly compare the new treatment with surgery are needed.
Where did the story come from?
The research was carried out by Dr HU Ahmed and colleagues from University College London. Funding was provided by the Prostate Research Campaign UK and Prostate Cancer Research Centre UK. One of the authors received funding from and is a consultant for Negma Lerads, a manufacturer of a photodynamic agent used in prostate cancer therapy. The study was published in the peer-reviewed British Journal of Cancer.
What kind of scientific study was this?
This research examined the effectiveness of high-intensity focused ultrasound (HIFU) at treating men with localised prostate cancer. Men with localised prostate cancer normally have the options of radical treatment, such as surgery or radiotherapy, or monitoring, a process known as active surveillance or watchful waiting. However, the decision between doing nothing or having radical treatment is not an easy one.
HIFU is known as a minimally invasive therapy and, along with other alternatives such as radiofrequency ablation, cryosurgery and photodynamic therapy, offers a middle-ground approach. It has a potentially reduced risk of adverse effects compared to radical treatment and is more proactive than watchful waiting. However, these therapies are in various stages of research and development and their use in clinical practice is limited.
HIFU involves focussing high-energy ultrasound waves on the target cancerous tissues, which causes them to coagulate and die. The probe that emits the ultrasound waves is inserted into the rectum and a cooling balloon around the probe protects the surrounding healthy tissue. After the procedure, catheterisation is required for a period of time.
This case series reported on 172 men (average age 64 years) who received HIFU at two London centres between February 2005 and May 2007. The men had rejected surveillance and were either unable or did not wish to undergo surgery or radiotherapy. The men understood that HIFU was not a standard procedure and that knowledge of short- and medium-term outcomes was restricted to a few case series. Men were excluded if they had any specific symptoms that made HIFU inadvisable (contraindications), including a prostate volume greater than 40ml, calcification of the prostate or significant anorectal disease preventing probe insertion (for example, previous haemorrhoid removal or inflammatory bowel disease).
Some of the men who were included were pre-treated for three months with low-dose anti-androgen (anti-male hormone) treatment to reduce the size of their prostate. In procedures carried out earlier in the case series, standard urethral catheters were inserted for one to two weeks following HIFU. In later procedures, this was replaced with a suprapubic catheter.
Follow-up of the men was the same as that used for standard radical treatment. Serum PSA (prostate specific antigen, a prostate cancer marker that indicates disease activity) measurements were taken at six weeks and then every three months for the first year and every six months during subsequent years of follow-up. At one of the centres, patients also completed questionnaires that assessed any adverse effects they had experienced.
What were the results of the study?
Of the 172 men treated with HIFU, analysis was only possible in 136 cases as there was not complete data for risk stratification in the other 36 men. Of the 136 men analysed, 27.8% (38 men) were considered to have low-risk disease, 37.5% (51) had intermediate-risk disease and 34.6% (47) had high-risk disease. Following treatment, 78% of the men were discharged after an average of five hours. Average duration of follow-up was 346 days (range 135–759 days).
Adverse effects of HIFU were given as:
- Men who received post-treatment suprapubic catheterisation were significantly less likely to experience urethral stricture (narrowing of the urethra causing difficulty in passing urine) than men who received urethral catheterisation (19.4% against 40.4%).
- Antibiotics for suspected urinary tract infection were given to 23.8% of men.
- Epididymitis (infection and inflammation of a structure at the back of the testicle where sperm is stored) developed in 7.6% of men.
- Mild urinary incontinence occurred in 7% (12 out of 172) and one man needed to use pads for more severe incontinence.
- After one year, the majority of men (70%) were still able to achieve erection.
- There was no report of rectal problems following the procedure.
Overall, 78.3% of the men achieved a low PSA level one year after treatment (0.5 micrograms/ml or lower, and below 0.2 micrograms/ml in 57.8% of men) and 92.4% of men (159 out of 172) either achieved a low PSA level or had negative biopsy results, demonstrating no residual disease. Of the 13 men who were candidates for further treatment, eight received further HIFU, one had salvage radiotherapy and four were managed with active surveillance for low-risk disease.
What interpretations did the researchers draw from these results?
The authors concluded that, in the short term, good outcomes can be achieved following HIFU, with reasonably low levels of erectile dysfunction and urinary incontinence. However, longer-term outcomes need to be assessed.
What does the NHS Knowledge Service make of this study?
This case series has found reasonably favourable outcomes following HIFU treatment in 172 men with localised prostate cancer. This minimally invasive technique is an alternative for men who would otherwise only have the options of radical treatment (and its associated risks and adverse effects) or watchful waiting. However, as with most new techniques, it should be remembered that the evidence is limited to small case series only.
At present, the main limitation of this particular procedure is that there is little information available on longer-term outcomes. As the authors say, an international registry of all cases treated with HIFU would be helpful to document its success. However, it will be some time before this could become a standard treatment option and the outcomes of much larger numbers of men who have had this treatment are needed. 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.