Prostate cancer patients should be treated with “radiotherapy as well as hormones” according to The Daily Telegraph . It reports that scientists recommend that using both treatments should be the standard for tackling the cancer, instead of the current practice prescribing long-term hormone treatment only.
This story is based on new research in men with locally advanced prostate cancer, meaning it has spread to tissues surrounding the prostate, but not to other areas of the body. Researchers randomly split 875 men into two groups. One group had treatment with standard hormone therapy, while the other group had the same treatment plus a course of radiotherapy. Researchers found the men given the combined treatment were 56% less likely to die from prostate cancer within 10 years.
The newspaper reports that a combination of hormones and radiotherapy should be the new standard treatment. Current NICE guidance already recommends a curative prostate removal, or combined radiotherapy and hormone therapy to treat men with locally advanced or high-risk localised cancer and a good prognosis. This well-conducted study provides further evidence on this existing treatment.
Where did the story come from?
This research was carried out by Professor Anders Widmark of Department of Radiation Sciences, Umeå University, Sweden, and colleagues.
It was funded by Schering-Plough Inc, Abbot Scandinavia Inc, Nordic Cancer Union, Swedish Cancer Society, Norwegian Cancer Society, Lions Cancer Foundation and Umeå University. The study was published in the peer-reviewed medical journal The Lancet .
What kind of scientific study was this?
This was a randomised controlled trial designed to compare the effect of combined local radiotherapy and endocrine (hormone) therapy with hormone therapy alone in treating locally advanced prostate cancer.
It reports that trials had previously demonstrated hormone therapy to be the optimal treatment for cases of locally advanced prostate cancer that had not spread to the rest of the body (non-metastatic) but were too advanced for curative treatment.
The study included 875 men from Norway, Sweden and Denmark who had been diagnosed with non-metastatic prostate cancer. Only men considered to have a good outlook and a life expectancy of more than 10 years were included in this study. Participants were recruited between February 1996 and December 2002.
The men were randomised to receive either just hormone treatment (439 men) or a combination of hormone treatment and radiotherapy targeting the prostate (436 men). Disease characteristics (e.g. tumour stage and markers for possible prostate problems) were equally balanced between the two groups of men.
The hormone treatment used was a slow-release injection of the drug leuprorelin, administered over three months. At the same time a course a drug called flutamide was taken orally each day until death or progression of the disease.
The men allocated to receive radiotherapy had this same hormone therapy plus a course of radiotherapy three months into drug treatment. Medical ‘removal of the testes’ was performed if there was evidence of disease progression.
The main objective of the study was to see whether the addition of radiotherapy would improve cancer survival at seven years compared to hormone treatment alone. This was done by looking at time from entry into the study to death. All men were linked to nationwide population registries to ensure no loss to follow-up.
All deaths were classified as either being due to prostate cancer, due to another cause but with prostate cancer a significantly contributing factor, due to cancer treatments, due to an unrelated cause, or unknown cause.
What were the results of the study?
Average duration of follow-up was 7.6 years, and 100% of those randomised were followed up.
The total deaths from prostate cancer at study completion were 116 (18.0% of the hormone only group and 8.5% of the combined treatment group), which included 28 deaths from a cause other than prostate cancer where prostate cancer was a significantly contributing factor.
A measure called cumulative incidence (occurrence during a specified period of time) was used to calculate prostate mortality: at seven years was 9.9% in the hormone alone group and 6.3% in the combined group.
At the 10-year mark this increased to 23.9% and 11.9% respectively, meaning there was a significant difference of 12% between the two groups. Therefore the combined treatment of hormone treatment plus radiotherapy was found to reduce the risk of death from prostate cancer by 56% compared to hormone treatment alone (relative risk 0.44, 95% confidence interval 0.30 to 0.66).
In general, adverse effects of treatment did not significantly differ between the two groups, with the exception of urinary problems (urgency, incontinence and stricture of the urethra) and erectile dysfunction, which were significantly more common in the combined treatment group. Diarrhoea four years after treatment was also reported significantly more often in the combined treatment group.
What interpretations did the researchers draw from these results?
The authors conclude that the addition of local radiotherapy to hormone treatment halved the 10-year prostate-specific cancer mortality rate for locally advanced high-risk prostate cancer. They suggest that in light of these findings, combined treatment should be the new standard for this group of people.
What does the NHS Knowledge Service make of this study?
This was a high-quality randomised controlled trial that had several strengths, including a large sample size and a seven-year follow-up of 100% of the men in the study. It has demonstrated that combined hormone and radiotherapy treatment halved the death rate due of men with locally advanced prostate cancer, compared to hormone treatment alone.
The study has a few limitations, which were acknowledged by the researchers:
- The study was conducted in parts of Scandinavia and treatment protocols may differ elsewhere. The authors mention that surgical or medical castration may be the preferred treatment for locally advanced prostate cancer in other countries (although the use of hormone therapy is well established in Europe).
- The study used lower radiation doses than are now possible, so the survival benefit of combined treatment may actually be higher than estimated: a standard dose in this study was 70Gy, while NICE guidance in the UK recommends a minimum dose of 74Gy.
- Adverse effects need to be considered. There was a significant increase in urinary problems, sexual dysfunction and diarrhoea in the combined treatment group.
- Combined radiotherapy and hormone therapy can not be compared to surgical removal of the prostate (prostatectomy). Previous research has shown that the addition of hormone therapy to prostatectomy does not improve survival.
Current NICE guidance advises that those men with high-risk localised prostate cancer and a good prognosis, or those with locally advanced prostate cancer (such as in this study) are offered either curative prostatectomy, or curative radiotherapy combined with hormone therapy.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 16 December 2008
The Independent, 16 December 2008
The Mail on Sunday, 14 December 2008
Links to the science
The Lancet, 2008 16 Nov [early online publication]