Men with prostate cancer face a bewildering array of treatment options, including watchful waiting, active surveillance, radiotherapy and surgery. Deciding what to do is difficult, not just because there are so many options, but because they vary so widely.
For the most part, men must make their choice without the help of information from good quality trials to guide them. That’s why the results of the Prostate cancer Intervention Versus Observation Trial (PIVOT) are extremely welcome.
PIVOT randomly allocated 731 men with localised prostate cancer between surgery and watchful waiting. Those allocated to surgery had a radical prostatectomy to remove the prostate gland. Watchful waiting involved observation, with no attempt at cure.
Whereas one might have expected a big benefit from surgery, in fact, 12 years later there was no significant difference in the survival of the two groups. However, surgery was associated with a 60 per cent reduction in deaths from prostate cancer in patients with intermediate or high-risk disease. In my view, this suggests that surgery should still be a standard treatment for younger, fitter men with intermediate and high-risk cancer.
The key challenge is to identify which men need treatment and which can be safely watched without it
Where PIVOT really challenges current practice is in the management of low-risk prostate cancer. In the low-risk sub-group, the risk of death from prostate cancer was less than 3 per cent at 12 years, with no benefit for surgery. Indeed, if anything, the survival rates favoured watchful waiting rather than surgery. So PIVOT has shown both the value of surgery for high-risk prostate cancer and the excellent outcome of low-risk prostate cancer even without treatment.
These results provide some of the most important information currently available for men with localised prostate cancer faced with deciding on their treatment. The ongoing ProtecT trial is addressing a similar question. It is comparing surgery, radiotherapy and active monitoring, but the results will not be available for several years.
So the key challenge is to identify which men need treatment and which can be safely watched without it. Active surveillance offers men with favorable-risk prostate cancer the hope of avoiding unnecessary treatment and any attendant side effects, such as incontinence and impotence. At the moment, men on active surveillance are monitored using prostate-specific antigen (PSA) blood tests, repeat prostate biopsies and magnetic resonance imaging (MRI). Those with signs of disease progression are advised to have treatment, while those in whom the cancer appears stable continue on observation.
However, monitoring the change in PSA level over time is not as useful as we once thought. Repeat biopsies can be painful and cause bleeding or infection. Furthermore, significant cancers may be missed on biopsy and disease progression may go undetected. MRI appears to be a useful indicator of disease progression, but this requires confirmation in large studies.
In the future, our aim should be to tailor treatment to the individual. If we could accurately predict how each individual cancer was going to behave and distinguish the harmless prostate cancers from the lethal ones, then we would be able to advise each individual man whether or not he needs treatment.
Dr Chris Parker is senior lecturer and honorary consultant in clinical oncology and prostate cancer translational research at The Royal Marsden, London. His special interests include active surveillance of low-risk prostate cancer, the role of post-operative adjuvant therapy and of bone-targeted therapy for advanced disease.