Prostate news article, February 2006
CHANGING TIMES FOR MEN WITH PROSTATE CANCER Professor Roger S Kirby Visiting Professor to St George's Hospital, London |
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These days prostate cancer is seldom out of the news for very long. Recently a study was published reporting that neither prostate specific antigen (PSA) screening nor digital rectal examination (DRE) appeared to reduce the risk of dying from metastatic prostate cancer (1). However, case control studies are regarded as low level evidence; moreover, during the years of study 1990-1994 knowledge about how to use the PSA test effectively was rather limited, consequently abnormal values (>4.0 ng/ml) were unlikely to have been acted upon appropriately. Current state-of-the-art suggests that it is the rate of change of PSA over time (PSA kinetics) rather than a one off PSA value that is the most helpful. Men with a PSA rise greater than 2 ng/ml/year appear to be at significant risk of harbouring an aggressive, life-threatening form of prostate cancer. Larger randomised trials are underway which will eventually clarify the position.
Although a one-off PSA measurement may not prevent a patient from dying from prostate cancer, sequential tests from which one can calculate a so-called PSA velocity may provide useful prognostic information. This could also identify an at risk group in whom prevention strategies could be deployed. For example, a recent study from the USA suggests that 3 hrs per week of regular, vigorous exercise can cut the risk of developing advanced prostate cancer by a surprising 70% (2). The jury is still out whether selenium or vitamin E are effective as chemopreventive agents, but many patients continue to purchase these supplements, together with lycopenes, from their local health food store or chemist shop.
If PSA is a valuable but imperfect marker for prostate cancer, is there anything more reliable on the horizon? The new urine based PCA3 test looks interesting, but is not approved yet by the regulatory authorities. Cells obtained from the prostate by vigorous massage of the gland are analysed for expression of the PCA3 gene which is over-expressed around 60 times over in men with prostate malignancy. A positive result may be regarded as an indication for transrectal ultrasound guided biopsy of the prostate.
Still the best information about the health or otherwise of the prostate is obtained from the histological analysis of the biopsy specimens. It may seem ironic but Dr Gleason described a scoring system for prostate cancer (Figure 1) that still provides the most valuable prognostic information more than 50 years ago. Newer molecular markers are in the pipeline, however, and almost certainly a tissue-based gene array profile will eventually lead us to the Holy Grail which will allow us to differentiate the so-called “tigers” (aggressive cancers) from the “pussy cats” (cancers that will never progress).
When prostate cancer is detected accurate staging is helpful in determining the best treatment options. Here also we are some way away from achieving perfection. A magnetic resonance image (MRI) provides information about local spread (Figure 2) but not surprisingly, cannot detect microscopic invasion of the prostate capsule. A bone scan is almost only ever positive if the PSA is > 20 ng/ml.
The optimum treatment option for localised prostate cancer is currently the most hotly debated topic in urology. Surgical removal of the gland by radical retropubic prostatectomy (RRP) has been increasingly favoured since Dr Patrick Walsh described his nerve-sparing, anatomical approach in the 1980’s (3). As yet this is the only treatment that has been proven on randomised controlled trials to reduce prostate cancer mortality. Recently laparoscopic RRP has been shown to be feasible, but technically demanding, with a long learning curve . The use of the Intuitive “Da Vinci” robot to achieve RRP has been reported from Detroit (4) (Figures 3a and 3b). The 10x magnification, three D vision and enhanced surgical precision is reported to result in potency rates of 90% one year or more after surgery (5). Currently there are six Da Vinci machines in the UK, but more than 250 operational in the USA. One major advantage of surgery for localised prostate cancer is that radiotherapy can be used as a second-line treatment if local recurrence were to occur.
For men with localised prostate cancer unwilling or unsuitable for surgery radiotherapy offers an attractive treatment option. External beam radiation (EBRT) is delivered over a six and half week period. Conformal targeting has been shown to reduce the incidence of rectal and colonic symptoms. A newer way to achieve curative doses of radiotherapy within the gland is known as brachytherapy. This technique requires a general anaesthetic is involves the ultrasound-guided placement of a hundred or so radioactive seeds within the prostate. Patients with severe bladder outflow obstruction or who have undergone a previous transurethral resection of the prostate (TURP) are usually excluded from this form of treatment. Data up to 12 years after treatment is now available from the USA and seems promising. Failure of either EBRT or brachytherapy usually mandates management by androgen abalation.
For men with locally advanced prostate cancer treatment choices include radiotherapy preceded by androgen ablation or androgen ablation alone. In the absence of metastases radiotherapy can still be curative, but the greater the PSA value is at the time of presentation the greater is the risk of disease is recurrence.
Androgen ablation is now seldom accomplished surgically since medical therapy with luteinising hormone releasing hormone (LHRH) agonists or an antiandrogen, such as bicalutamide, is equally effective and reversible. Men with metastases from prostate cancer almost always respond to endocrine therapy but eventually the PSA level begins to rise. Until recently this situation was regarded as hopeless but new data confirming that the chemotherapy agent taxotere can reduce rising PSA values and prolong survival have offered new hope to men with hormone relapsed prostate cancer (HRPC) (6). Furthermore a randomised, placebo controlled trial of the bisphophonate zoledronic acid has shown a delay in skeletal related events such as spinal cord compression by almost 6 months.
More than 100 promising new wave molecular therapies are also in the pipeline. These include angiogenesis inhibitors, endothelin inhibitors and various growth factor antagonists, as well as a number other agents that target the molecular mechanisms that underlie prostate cancer progression. The outlook for the 30,000 or so men who will be diagnosed with prostate cancer this year is now brighter than ever before. Although the diagnosis, treatment and support of men with this disease lags sadly behind that of women with breast cancer, lobbying from, among others, the Prostate Cancer Charter for Action (a consortium of all the major prostate charities and professional organisations) has at last improved awareness of this disease and highlighted the need greater resources and more research. With so much going on and more and more men affected, prostate cancer seems unlikely stay out of the news for long.
Figure 1 Gleason scale |
Figure 2 MRI image of prostate |
Figure 3a Robotic surgical head |
Figure 3b Surgeon's console |
References:
1. Arch Intern Med 2006;166:38-43 (full ref to follow).
2. Giovannucci EL, Liu Y, Leitzmann MJ et al A prospective study of physical activity and incident and fatal prostate cancer. Arch Int Med 2005,165:1005-10
2. Walsh P, Donker P. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982;128:492-7.
3. Menon M, Hemal A, VIP team. Vattikuti Institute prostatectomy: a technique
of robotic radical prostatectomy: experience in more than 1000 cases. J
Endourol 2004;18:611.
4. Menon M, Kaul S, Bhandari A, et al. Potency following robotic radical
prostatectomy : a questionnaire based analysis of outcomes after conventional
nerve sparing and prostatic fascia sparing techniques. J Urol 2005, 174:2291-96.
5. Petrylak, Daniel P.; Tangen, Catherine M.; Hussain, Maha H.A. Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. New England Journal of Medicine. 2004; 351(15):1513-1520.
6. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L,
Chin JL, Vinholes JJ, Goas JA, Zheng M; Zoledronic Acid Prostate Cancer
Study Group. Long-term efficacy of zoledronic acid for the prevention of
skeletal complications in patients with metastatic hormone-refractory prostate
cancer.
J Natl Cancer Inst. 2004 Jun 2;96(11):879-82