Prostate news article, December 2006
| THE PROSTATE: NEW APPROACHES TO OLD PROBLEMS
Professor Roger S Kirby Visiting Professor to St George's Hospital, London |
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Prostate problems continue to plague of men beyond middle age, and as the population ages and awareness of prostate cancer and benign prostatic hyperplasia (BPH) rises, their impact on family practice and secondary care are bound to increase. Already prostate cancer is the most commonly diagnosed internal malignancy in men and every year almost 10,000 men lose their lives to this disease in the UK. BPH is even more prevalent, with an estimated 43% of men over 65 years of age suffering either symptoms or prostatic enlargement. Symptomatic BPH is strongly associated with a reduction of quality of life, sexual dysfunction and a risk of disease progression.
Differential Diagnosis
From the both the patient and the doctor’s standpoint a test that could reliably differentiate prostate cancer from BPH would be most helpful. Unfortunately a one off prostate specific antigen (PSA) level has somewhat limited utility in this respect, unless it is very significantly elevated. When the most frequently utilised cutpoint of 4.0 ng/ml is employed a significant number of patients with BPH will be identified as false positives. Men with a PSA of between 4.0 and 10 ng/ml have around a one in five chance of harbouring prostate cancer. In those with a PSA of >10.0 ng/ml the chances of a positive biopsy rises to 62%. However the recent Prostate Cancer Prevention Trial (PCPT) demonstrated that 17% of those men who were identified with prostate cancer at the end of the study in fact had a PSA value below 4.0 ng/ml, and some even lower than 2.5 ng/ml. Annual measurements of PSA may improve its performance, although this is still controversial. Several studies have suggested that a PSA rise of >0.75 ng/ml/year (1,2) may be indicative of prostate cancer and D’Amico and colleagues have reported that the rate of PSA rise before diagnosis correlates negatively with survival after treatment for localised disease (3).
In general, an elevated or rising PSA will mandate a transrectal ultrasound (TRUS) guided biopsy of the prostate under local anaesthesia and broad spectrum antibiotic cover. However, the recently developed PCA3 test holds the promise of reducing the number of patients requiring TRUS biopsies. This new test is based on the molecular analysis of prostate epithelial cells obtained from the first 50 ccs of urine passed after a relatively vigorous prostatic massage. The analysis is based on the expression of the UPM3 which is over-expressed by more than 60 times in patients with adenocarcinoma of the prostate.
New Treatment Options for BPH
Traditionally, symptomatic BPH has been managed by either watchful waiting or transurethral resection of the prostate (TURP). The development of effective medical therapy with alpha blockers and/or 5 alpha-reductase inhibitors has changed the scene and resulted in a steady decline in the number of TURPs performed. The 5 year Medical Treatment of Prostate Symptoms (MTOPS) trial confirmed that a combination of these two classes of drug provided the maximum improvement on symptoms as well as preventing disease progression, including the need for surgery. With regard to the latter, the advent of Greenlight laser vaporization and Holmium laser enuceation of the prostate (HoLEP) has altered the situation recently. Laser technology permits the almost bloodless relief of bladder outflow obstruction on a day case or 24hr hospital stay basis. This being the case, some patients may prefer a one-off resolution of the problem to prolonged pharmacotherapy, especially if medical therapy has been tried and found not to be completely effective in resolving symptoms.
Treatment Options for Men with Localised Prostate Cancer
Prostate cancer is increasingly diagnosed at an early stage when still confined to the gland on the basis of PSA testing and TRUS biopsy. While encouraging in some ways, this situation in fact poses a several dilemmas. Firstly, when small foci of well differentiated disease are found, it is not clear whether or not they will pose a threat to the individual within his natural lifespan. In this situation a policy of active surveillance may constitute the base course of action. When more extensive and less well differentiated disease is found which clearly needs treatment, which of the available treatment options should be selected? Surgical removal of the prostate is still the most reliable means of eradicating the disease and achieving an undetectable PSA. It is also the only treatment option that has been demonstrated in a randomised controlled trial to reduce the rate of development of metastases by around 50% and improve overall and prostate cancer specific survival (4).
The disadvantages of surgery however stem from the potential side effects of incontinence and erectile dysfunction, as well as the time required for recovery. Surgical outcomes have been improved by the development of laparoscopic and more recently robotically assisted laparoscopic radical prostatectomy (RALRP). The laparoscopic approach reduces the blood loss because the raised intra-abdominal pressure discourages venous bleeding. The da Vinci robot improves the precision of the dissection and its 10x magnification and 3D visualization allows more precise nerve sparing and a more accurate anastomosis. Early data from the USA where more than 350 robots are in service (compared with only 6 currently in the UK) suggest that these advantages translate into improved recovery of potency after surgery (5).
Radiotherapy to the prostate may be delivered by a 6 week course of external beam radiotherapy (EBRT). The improved accuracy of conformal EBRT technology has been shown to reduce the incidence of side-effects which mainly stem from the inclusion of the anterior rectal wall in the treatment field. Rectal irritation and bleeding are the frequent result, but are usually transient. One way of avoiding the irradiation of the rectum is to employ a technique known as brachytherapy. This involves the implantation of up to 100 radioactive seeds into the prostate under general anaesthesia and TRUS guidance. Satisfactory outcomes from this treatment modality have been reported both in the UK and in the USA in patients who present with lower risk tumours. For men with higher risk disease (T3 tumours and/or Gleason scores >7) EBRT or high dose rate brachytherapy often preceded by androgen ablation with a luteinising hormone releasing hormone (LHRH) analogue is usually more appropriate.
Notwithstanding a more concerted effort to identify and eradicate prostate cancer at an earlier stage, a number of patients still present with metastatic disease, or develop metastases in spite of previous attempts at cure. For these individuals androgen ablation therapy is still the mainstay and responses to LHRH analogues can be sustained for many months as evidenced by prolonged PSA suppression. Eventually however hormone relapsed prostate cancer (HRPC) develops and the PSA begins to rise. Such a scenario is usually premonitory of the development of symptoms from metastases, especially bone pain. Recent data suggests that survival may be prolonged by the judicious use of chemotherapy with taxotere, the intravenously administered bisphosphonate, zolendronic acid has also been shown to delay the development of skeletal related events for up to 6 months but not to improve survival.
Conclusions
Prostate cancer and BPH seem set to impinge on men and on general practice to an ever greater extent. Not only are more and more male members of our rapidly aging society likely to be afflicted by these conditions, but public awareness is also rising fast, driving concerned patients into the surgery. This situation could be construed as an opportunity, as men have traditionally avoided contact with healthcare professionals. Men presenting with lower urinary tract symptoms (LUTS) or anxieties about prostate cancer could be opportunistically evaluated for other comorbidities such as diabetes, hypertension and dyslipidaemia (6). Key health messages about diet, smoking and exercise could also be transmitted (7). Much work remains to be done to improve the evidence base that surrounds prostate disease, but the broader issue of “Men’s Health” is at last beginning to move up the agenda.
Figure 1. A randomised controlled trial comparing watchful waiting to radical prostatectomy in Scandinavia revealed a 50% reduction in the development of metastases and an improvement in survival in the surgically treated cohort (6).
References:
- Goldstraw M, Fitzpatrick JM, Kirby RS, Prostate-specific antigen kinetics and the diagnosis and management of prostate cancer. BJU Int 2006, 98:1141-2.
- Berger A, et al., Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk. Prostate 2005: 64(3):240-245.
- D'Amico A, Chen M, Roehl K, et al. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Eng J Med 2004: 351:125.4.
- Bill-Axelson A, Holmberg L, Ruutu M, et al. Scandinavian prostate cancer group study No 4. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med: 2005;352(19):1977-84.
- Menon M, Kaul S, Bhandari A, Shrivastava A, Tewari A, Hemal A, Potency following robotic prostatectomy: a questionnaire based analysis of outcomes after conventional nerve sparing and prostatic fascia sparing techniques. J Urol 2005: 174:2291-2296.
- Kirby RS, The urologist as an advocate of men’s health. BJUI 2005; 95:929
- Kirby RS, Kirby MG, The urologist as an advocate of men’s health: 10 suggested steps toward helping patient’s achieve better overall health. Urology 2005 66 (suppl 5A) 52-56