Prostate news article, May 2006
FUTURE PROSPECTS FOR MEN WITH PROSTATE CANCER Professor Roger S Kirby Visiting Professor to St George's Hospital, London |
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Prostate cancer is already the commonest cancer in men. This year more than 30,000 individuals will be diagnosed with the disease in the UK. Since prostate cancer is linked to obesity and develops as a result of damage to the genetic material in the gland from a diet high in saturated fats, its prevalence seems certain to rise in the future.
The most appealing strategy of containment would be to prevent the disease from occurring in the first place. As yet there are no chemopreventative agents which are proven to be safe and effective, however the SELECT and REDUCE trials are due to report before too long and will provide important evidence about the role of Selenium/Vitamin E and the 5 alpha-reductase inhibitor dutasteride in this context. In those at especially high risk, such as men with a family history of prostate cancer occurring at a young age (ie <60 years), prevention would be very much preferable to cure.
The efficacy of early detection by prostate specific antigen (PSA) testing is also subject to analysis by on-going randomised controlled trials (RCTs) in Europe and North America. If these confirm a significant mortality reduction there will be intense pressure to introduce screening to the wider population of men. Currently in the USA something like 70% of men are aware of their own PSA value. By contrast only an estimated 4% of men in the UK have had this test. It has been argued that the more proactive approach in the USA is responsible for the recent 25% reduction in mortality from prostate cancer. Other more accurate markers for prostate cancer are certain to be developed. Already the PCA3 test, which is based on the analysis of prostatic epithelial cells derived from prostatic massage, rather than uncomfortable biopsy, is creating some excitement, but is still being evaluated. Since not every prostate cancer is destined to progress and metastasize, a marker, or a battery of markers (a sort of genetic bar code for prostate cancer), that provided accurate prognostic information would be of great value in advising about the necessity for and method of treatment.
Better assessment of how far the cancer has advanced is also likely
to become a future feature. Currently there is often considerable uncertainty
as to whether an individual cancer is truly confined to the prostate
and therefore amenable to surgery, or whether there is extracapsular
extension and/or the development of micrometastases, making other treatment
methods preferable. Magnetic resonance imaging (MRI) seems to hold the
greatest promise, especially with enhancements such as MRI spectroscopy
and the use of iron filing infusions.
Currently, considerable uncertainty surrounds the optimum management
strategy for localised prostate cancer. In the future these uncertainties
will be resolved by RCTs. Low risk small volume well differentiated may
well be best managed by a programme of active surveillance. Moderate
and high risk cancers will usually need treatment and there is currently
a debate as to whether the best strategy is to remove the prostate by
radical prostatectomy or to leave the gland in place and try to eradicate
the tumour by radiotherapy (either external beam or brachytherapy) or
high intensity focused ultrasound (HIFU). Traditional open radical prostatectomy
(RP) is already being replaced by laparoscopic RP and robotically assisted
RP. The advantage of the latter is the 3D visualization and 10x magnification
that the da Vinci robot (Intuitive Surgical Inc. - Figure 1) affords.
Early data from the USA suggests that this technology translates into
improved outcomes in terms of preservation of sexual function, a feature
of obvious importance to both the sufferer and his partner. There is
already a Mark 2 version of the da Vinci robot available and rapid advances
in robotic technology are to be anticipated. In the future we are likely
to look back with incredulity to the times when surgeons actually put
their hands inside their patients!
Radiation technology is also likely to improve. Currently intensity modulated radiation therapy (IMRT) seems to offer some advantages over standard or conformal radiation methods. Brachytherapy with real time adjustment of the dosage regime to conform to the prostate and tumour being treated also looks to be a way forward.
Since prostate cancer is highly dependent on the male hormone testosterone, androgen deprivation therapy is likely to remain a mainstay of treatment, both to enhance the effects of radiation therapy and as a stand alone therapy for men with metastatic disease. Already antiandrogens seem to avoid some of the negative effects on sexuality that are a feature of the chemical castration caused by the luteinising hormone releasing hormone (LHRH) agonists which block the release of testosterone. Unfortunately, after a finite time hormone relapse nearly always occurs, but second responses are now being obtained with chemotherapy using taxotere. Other better tolerated and more effective chemotherapy regimes are very likely to be developed.
More than 100 new compounds are currently being developed and evaluated for their safety and effectiveness in prostate cancer and it is difficult to be certain which of them are going to turn up trumps in the future. Most promising right now appear to be the angiogenesis inhibitors, which stop some prostate cancer metasteses from developing a new blood supply (Figure 2), and growth factor inhibitors but none are licenced for use in patients as yet. Gene therapy also holds considerable promise, however there are safety concerns about the vectors used to deliver the therapy and the potential adverse effects associated with interference with the genome.
It needs to be remembered that prostate cancer does not develop in isolation but is part of the spectrum of “Men’s Health” disorders. Future strategies for dealing with the disease need to be coordinated with a drive to improve not only the quantity but also the quality of life of men beyond middle age. In the past too little attention has been paid to the well-being of this section of male society, and they themselves have done little to lobby for a better deal. This situation contrasts with that of women and breast cancer, where a determined effort has produced in better funding, more trials and several important breakthroughs in therapy. The result is an improvement in survival and a better quality of life for the women that suffer the disease. It is very much to be hoped that these significant advances will be mirrored for men with prostate cancer in the years and decades to come.
Figure 1 Robotic surgical head |
Figure 2 Angiogenesis |