Taking hormone treatment early during radiotherapy slows the spread of prostate cancer by up to eight years, The Times and other newspapers have reported. The reports are based on a study that looked at a treatment that lowers testosterone levels in the blood. They reported that although the therapy is already established in the treatment of prostate cancer, it is generally used later in the course of the disease and for longer periods.
The reports are based on the 10 year follow-up of a study of men with locally advanced prostate cancer. This research supplies further information on the benefits of combining treatments for prostate cancer. It applies to a specific group of patients with this common form of cancer and provides good evidence for the effectiveness of this treatment option. It should be noted that not all of the patients delayed their spread of prostate cancer by eight years.
Where did the story come from?
Dr Mack Roach and colleagues from the Departments of Radiation, Oncology and Urology at the University of California and other cancer treatment centres around the US conducted the research. The study was supported by grants from the National Cancer Institute and the authors fully disclosed any potential conflicting interests. The study was published in the peer-reviewed Journal of Clinical Oncology.
What kind of scientific study was this?
The journal article reported the long-term follow-up data from a randomised controlled trial of patients with locally advanced prostate cancer.
From 1987 to 1991 the authors enrolled 456 patients who were an average 70 years old with locally advanced prostate cancer. The researchers included men who had large tumours (more than 2in/5cm across), regardless of whether their prostate cancer had spread to the pelvic lymph nodes. Men with more advanced distant spread or smaller tumours (such as those only detected by blood tests) were not included in the study.
Participants were randomised to receive either short term androgen deprivation therapy (ADT) plus conventional radiotherapy or conventional radiotherapy alone.
ADT consisted of two hormonal type treatments, goserelin and flutamide, and began two months before any radiotherapy and continued for a total of four months.
Every four weeks the men in the ADT group were given injections of goserelin - a treatment that blocks the production of the male sex hormone, testosterone. The men also took another anti-androgen drug, flutamide, as a tablet three times a day. This drug has a similar structure to testosterone and blocks the action of the patients’ own testosterone (which can encourage the tumour to grow).
The researchers looked at several outcomes including overall survival, survival without the disease, mortality due to prostate cancer, and the rates of spread of prostate cancer, either locally or to other parts of the body.
What were the results of the study?
After ten years there was no significant difference in overall survival from the date the men were originally randomly allocated to each group to their death from any cause or the last follow-up date.
However, there were significant improvements in measures related specifically to the prostate. Almost four times as many men survived free of any prostate disease for 10 years in the ADT and radiotherapy treated group compared to the group that received radiotherapy alone (11% compared to 3%).
The researchers found no significant difference in the risk of death from cardiac (heart) events between the groups.
What interpretations did the researchers draw from these results?
The researchers conclude that the addition of four months of androgen deprivation therapy to conventional radiotherapy for men with advanced prostate disease “appears to have a dramatic impact on clinically meaningful endpoints”, without any impact on the risk of fatal cardiac events.
What does the NHS Knowledge Service make of this study?
This well conducted study shows there are important benefits for this type of short therapy used in conjunction with radiotherapy in men with advanced prostate cancer.
The claim in the newspaper reports that prostate cancer spread was delayed for eight years originates from the finding that it took eight years longer for 40% of the men treated with ADT and radiotherapy to develop bone metastases than it did for 40% of men treated with radiotherapy alone. However, this does not mean that all men receiving ADT will survive for an additional eight years as around half of the men in the study had died within eight years of entering the study.
When interpreting these studies it is worth noting that the expected lifespan of men in their 70s is close to the length of this study and that therefore, not surprisingly, less than 20% of the men were still alive 15 years after enrolment.
Death from other causes not related to prostate cancer had a large effect on the overall survival rates of the men. Of those enrolled, about 30 to 40% were still alive at the 10 year follow up. Most men at this age die from other diseases rather than from their prostate cancer. Only a small proportion of men remained alive and free of any prostate disease recurrence at 10 years (between 3 and 11%) either with or without ADT treatment.
Despite this, eight years of improved quality of life at this age, free of prostate cancer, is certainly a potential advantage for men with good life expectancy who meet the same criteria as those enrolled in this trial.
Sir Muir Gray adds...
This is one of the most difficult decisions for cancer patients because of the side effects. The balance between the benefits and the harms of longer treatment with antiandrogens is based on evidence, but has to take into account the values of the individual and their spouse.