22 December 2015
By Dr Wendy Winnall - PCFA Research Team
A recent prostate cancer study from Canada has received a lot of publicity. This study measured the risk of mortality for prostate cancer patients after surgery, compared to radiotherapy. The authors used a technique called "meta-analysis" to combine the data from 19 previous studies of very high quality, measuring the risk of mortality during the study period for patients with localised (lower risk) cancer. They compared patients who received surgery that removed the whole prostate to those who had radiotherapy to treat their cancer. The radiotherapy group either had brachytherapy or external beam radiotherapy (EBRT). Overall, the mortality risk for over 118,000 patients were compared. The mortality risk, within the study period, was greater for those who had radiotherapy compared to those who had surgery. The authors considered mortality from any cause, and, separately, mortality from prostate cancer. Both these mortality risks were higher in the radiotherapy group than the surgery group.
The authors of the Canadian study rightly point out that their data is not sufficient to change clinical guidelines. There are limitations to this study that means we cannot conclude that surgery is always going to be less risky that radiotherapy. The authors describe the potential for bias in their results, that is the result of the study design. An example is the use of some patients that had their radiotherapy or surgery from different clinical centres. The different outcomes for these patients could be in part due to being treated at different centres, or coming from different geographical regions. Regardless of the potential for bias, this study had many strengths, including its vast size and stringent study selection. Due to the size of the study and the long time period, the authors were able to compare mortality between the groups. A smaller study would need to use a "surrogate marker" such as PSA levels, as an indication of which of the two groups had lower mortality risk.
One important reason that clinical guidelines will not rapidly change due to this study is that the data were gathered over long periods of time, starting from the late 1980s. Radiotherapy has seen many improvements over this period, so modern radiotherapy techniques will likely have a different risk of mortality than those used for many of the patients in the Canadian study. This is addressed by a recent Australian study using modern external beam radiotherapy (EBRT) combined with androgen deprivation therapy. The technique is called DE-IG-IMRT; its longer name is modern image-guided dose-escalated intensity-modulated radiotherapy. The Australian study was much smaller and followed patients over a five year period. The authors showed that measures of “disease-free survival” were very good for their patients. 93% of patients were free of a rise in PSA levels for 5 years after therapy, and 97% did not see their cancer spread (metastasis). The authors compared these success rates to other studies in Australia where the same outcomes were measured for surgery and brachytherapy. They concluded that modern EBRT plus androgen deprivation was at least as effective as modern surgery or brachytherapy techniques. Due to its study design, these data also had the potential for bias, because they compared the DE-IG-IMRT patients to those from other studies. The two groups of patients would have many differences between them, that may be affecting the success rates. However this study is useful because it involves the most up-to-date treatments, and is therefore relevant for patients who are currently deciding which path to take in their treatment.
These two studies highlight the need for "gold standard" randomised controlled trials to be performed to compare different treatments for localised prostate cancer. In this trial design, a group of patients would be randomly assigned to different treatments and followed over time. Such trials are not affected by bias, but they are very expensive and time-consuming. One small randomised controlled trial has compared surgery to radiotherapy, but unfortunately did not use enough patients and therefore failed to make significant conclusions. A large randomised controlled trial is finishing soon and the results are eagerly awaited. The ProtecT trial in the UK compares surgery to radiotherapy, to active surveillance for patients with localised prostate cancer. This will only be the first of numerous trials needed to properly address this question, but hopefully the outcomes of these trials will lead to optimal treatment advice for individual patients.
For many men and their families, the prostate cancer journey involves navigating medical advice from a variety of sources. After diagnosis, men and their families are suddenly faced with making sense of varying medical advice from different types of doctors as well as the internet. The Prostate Cancer Foundation of Australia encourages a multidisciplinary approach to treatment, where patients discuss their options with their GP, urologist (surgeon), radiation oncologist, medical oncologist and prostate cancer specialist nurse who work together to establish the best treatment pathway for each patient. There is no one treatment that will be best for everyone, and both modern radiotherapy and surgery have very good outcomes in Australia.