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Prostate cancer: diagnosis, referral and management

Mike G Kirby
MB BS LRCP MRCS FRCP
General Practitioner
Letchworth
Hertfordshire
Director
HertNet
(Hertfordshire primary care research network)
Associate Member
British Association of Urological Surgeons
E:kirbym@globalnet.co.uk

Like many cancers, the cause of prostate cancer remains largely unknown and no single risk factor can explain the majority of cases of the disease. The tumour, however, requires the presence of testosterone to grow, and it is recognised that the overall risk of developing the disease may be affected by hereditary, race, environmental and dietary factors.(1,2)
Favourable treatment outcomes including cure or long-term disease-free survival are more likely if the disease is detected and treated early. Unfortunately, many men do not seek medical attention until the disease has spread beyond the prostate. Increasing awareness of the symptoms of early prostate cancer and the importance of seeking medical attention for these symptoms is a major public health challenge, and those of us working in primary care have an important role to play in this respect. The management of benign prostatic disease has moved from secondary care to primary care with the advent of effective medical therapies for benign prostatic hyperplasia (BPH).(3)
Many men who are at risk of developing prostate cancer are likely to visit their GP for routine health checks or for the treatment of chronic conditions such as hypertension. We are therefore in an ideal position to provide advice about prostate cancer, its prevalence, symptoms and treatment, and to detect the disease in its early stages. One of the problems we face is that there is a surprising lack of consensus regarding the management of the earlier localised lesions.(4) And the problem is further highlighted by statistics on prostate cancer from the USA,(3) which calculate that a man living to 75 years of age has a:

  • 30% change of having microfoci of histological prostate cancer.
  • 10% chance of being diagnosed as suffering from clinical disease.
  • 2.5% lifetime probability of dying from the disease.

Clearly some men die with prostate cancer rather than as a result of it. However, as the death rate for competing mortalities is now falling and the incidence of clinical prostate cancer disease is increasing, the challenge is to identify and treat the life-threatening lesions in the most effective manner. 
Survival rates in patients with prostate cancer vary widely according to the stage and grade of the disease at diagnosis. A prospective population-based study reported by Johansson and colleagues describes the natural history of prostate cancer in patients in one county in Sweden.(5) Fifteen years survival, corrected for causes of death other than prostate cancer, ranged from 81% in patients with localised disease (T0-T2) at diagnosis, to 57% in patients who had locally advanced disease (T3-T4), and 6% in those who had distant metastases at the time of diagnosis.

Should all at-risk patients be screened routinely?
Since prostate cancer may take many years to develop, in some countries, such as the USA, early detection is used in an attempt to identify the disease in its early stages when the chances of survival are greatest. The introduction of a screening programme would have considerable resource and training implications for any healthcare service. To cope with this situation in the UK, the National Screening Committee has recognised that many men are asking GPs for a prostate-specific antigen (PSA) test and that the previous policy did not give clear guidance about how to respond. As a result, ministers made the decision that men who ask for a PSA test are now eligible for a test and any follow-up necessary from the NHS. The National Screening Committee therefore recommended that the first response to a request for a test should be to provide full information to ensure informed choice. A website has been developed for those who wish to explore the subject in depth, and details can be found at www.nelh.nhs.uk/psatesting

Symptoms and methods of detection
Because the tumour is relatively slow-growing, men may live with the disease for many years without experiencing any symptoms. Symptoms occur when the disease has progressed beyond the prostate. Initial symptoms are usually caused by the tumour pressing on the ­urethra and may be similar to those of BPH. Symptoms that occur in the early and advanced prostate cancer are shown in Table 1.

[[NIP07_table1_126]]

A number of techniques can be used to detect the presence of prostate cancer. The four most commonly used methods are:

  • PSA.
  • Digital rectal examination (DRE).
  • Transrectal ultrasonography (TRUS).
  • Prostate biopsy.

PSA measurement is not a definitive test for prostate cancer, and elevated levels may also be found in patients with prostatitis and BPH. Hence the debate regarding the use of the test as a screening tool.(6) The use of age-related PSA, free/total PSA, PSA velocity and PSA density may provide more precise methods to aid diagnosis, but the relative merits of these measures are still subject to debate. PSA measurements are still useful for monitoring response to treatment and can act as an early warning of tumour recurrence.

Referral patterns
Throughout Europe patients will generally report symptoms initially to their GP, but referral practices vary from country to country. For example, in Italy, if a primary care physician suspects that a patient has prostate cancer, he/she will immediately refer the patient to a urologist. However, in the UK, France and Germany, it is likely that the primary care doctor will first request a PSA blood test, and refer if necessary on the basis of the result of the test.
 
Which lesions to treat

Small-volume microscopic foci
Small-volume microscopic foci identified at TURP (transurethral resection of prostate) have little impact on survival, and provided they are not the harbinger of more significant disease in the peripheral zone, or they are not present in older patients or those with significant comorbidity, they may often be left untreated.

Large lesions
Larger lesions (>0.5cm3) are usually more dangerous, as are any histologically less well-differentiated cancers (Gleason grade >3). These tumours are usually but not always associated with:

  • PSA >4ng/ml.
  • Palpable induration of the prostate.
  • An abnormal TRUS image and positive biopsies.

The mortality risk associated with such a lesion must always be balanced against the life expectancy of the individual concerned.

Management of localised prostate cancers
Unhappily in most countries, only about 30% of prostate cancers are diagnosed while still confined within the gland. Those cancers that are detected need to be evaluated by a urologist and carefully staged on the basis of PSA levels, a bone scan and sometimes computed tomography or magnetic resonance imaging scan.

Low-volume lesions
Watchful waiting may be appropriate when the tumour is of low volume and well differentiated (ie, Gleason grade
Radiotherapy
Two radiation modalities are currently in use for patients with a localised prostate cancer: external beam radiation and brachytherapy.

Radical prostatectomy
Radical prostatectomy is the most definitive method of clearing the body of malignant prostate cancer cells, provided that the lesion is still confined within the gland. Agreement is widespread among urologists that patients with localised prostate cancer selected for this operation should have a theoretical life expectancy of at least 10 years and no significant comorbidity.
 
Management of locally invasive prostate cancer
A proportion of patients with prostate cancer present with extraprostatic extension, but no evidence of distant metastases. Radical surgery is inappropriate because of the high local and distant recurrence rates. Radiotherapy is usually the preferred treatment option.

Treatment of metastases
The proportion of patients with localised disease at the time of diagnosis is now rising, probably as a result of PSA testing. Depriving the cancer cells of the androgens necessary for their growth can be accomplished by a variety of means, both medical and surgical.

Antiandrogens
Four antiandrogenic agents have been extensively evaluated clinically for the treatment of metastatic prostate cancer: cyproterone acetate, flutamide, nilutamide and bicalutamide. The addition of such an agent to achieve maximal androgen blockade may possibly increase both the time to disease progression and provide a survival advantage in some patients with good performance status and less advanced metastatic disease, although this is still controversial.

Looking ahead
The optimal management of prostate cancer now requires care to be shared between the urologist and the family practitioner. The initial treatment strategy should be devised by a specialist on the basis of tissue diagnosis and careful staging. Radiotherapy or prostatectomy are obviously the province of the hospital-based team, but the initial diagnosis and follow-up may be the joint responsibility of the urologist and the primary healthcare team. Metastatic disease is increasingly managed by monthly or three-monthly depot injections of luteinising hormone-releasing hormone (LHRH) analogues, and there is now evidence to support the early introduction of endocrine therapy at the time of diagnosis rather than waiting for symptoms to develop.(7)
In the future it may be possible to predict a subgroup of patients in whom total androgen blockade rather than antiandrogen therapy may offer a definite survival advantage. Newer and more effective first- and secondline curative pharmacotherapies also need to be developed. These challenges may be added to the many others that must be overcome to reduce the morbidity and mortality of this prevalent and insidious disease.

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References

  1. Reis LAG, Eisner MP, Kosary CL, et al, editors. Seer Cancer Statistics Review 1973-1998. Bethesda, MD: National Cancer Institute; 2001.
  2. Steinberg GD, Carter BS, Beaty TH, et al. Family history and the risk of prostate cancer. Prostate1990;17:337-47.
  3. Kirby R, Fitzpatrick J, Kirby M, Fitzpatrick A. Shared care for prostatic diseases. 2nd ed. Oxford: Isis Medical Media; 2000.
  4. Kirby RS. Treatment options for early prostate cancer. Urology 1998;52:948-62.
  5. Johansson JE, Holmberg L, Johansson S, Bergstrom R, Adami HO. Fifteen year survival in prostate cancer. A prospective, population based study in Sweden. JAMA 1997;227:467-71.
  6. Kirby RS, Kirby MG. Screening for carcinoma of the prostate: pilot study in general practice. Br J Urol1994;74:64-71.
  7. Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate versus deferred treatment for advanced prostate cancer. Initial results of the medical council trial. Br J Urol 1997;79:235-46.

Resources
National Electronic Library for Health
Prostate Cancer
W:www.nelh.nhs.uk/psatesting
The Prostate Cancer Charity
DuCane Road
London W12 0NN
T:0845 300 8383
W:www.prostate-cancer.org.uk
The Prostate Research Campaign UK
36 The Drive
Northwood
Middlesex
HA16 1HP
T:01923 824278
W:www.prostateresearch.org.uk
Prostatic
Disease Website
W:www.prostatitis. org