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The decision to treat should be based on the age of the patient and the grade of the cancer
MJA 1998; 169: 11-12
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We know that the incidence of prostate cancer increases with age and that many men "die with, but not from, prostate cancer".1 This has made the medical community concerned that, because of the high prevalence of comorbid illnesses among elderly men, many cancers detected by screening based on prostate-specific antigen (PSA) testing will be clinically insignificant, and that most patients would be overtreated. Unfortunately, we are also faced with the reality that approximately 2500 men succumb to prostate cancer annually, and many, particularly younger men, in fact "die of the disease and not with it".2 Most patients with localised prostate cancer will be given three management options: watchful waiting, radiotherapy, or radical surgery. Watchful waiting is defined as no initial treatment, with regular patient surveillance (which involves frequent consultations, digital rectal examinations and PSA testing) and commencement of androgen ablative therapy when clinical progression occurs. The success of watchful waiting depends on the predicted biological aggression of the cancer (related to the histological grade), as well as on the age and the associated comorbid illnesses of any individual patient. A pooled analysis of 828 patients treated conservatively in six non-randomised studies concluded that histologic grade was an important determinant of outcome. The 10-year cause-specific survival of patients with well or moderately differentiated cancers was 87%, compared with only 36% for those with poorly differentiated disease (who were at high risk of cancer progression and death).3 The cancer had metastasised by 10 years in 19% of men with well differentiated disease and 42% of men with moderately differentiated disease, despite the satisfactory cause-specific survival. Although watchful waiting may be an appropriate treatment choice for men with life expectancy of less than 10 years with well or moderately differentiated cancers, the outcome at 15 years may be less favourable. In another series, among men who survived more than 10 years from their initial diagnosis, prostate cancer was the direct or contributing cause of death in 63%.4 A report from the Connecticut Tumour Registry has shown that in men diagnosed with moderately differentiated cancer there is a modest, but not insignificant, risk of death from prostate cancer (28%) at 15 years with conservative treatment, and a potential loss of 4-5 years of life.5 Both mortality and potential years of life lost were even higher in men diagnosed with poorly differentiated disease. Contemporary radiotherapy offers an alternative to radical surgery for men who prefer not to undergo surgery or who have comorbidities which increase the risks of surgery. It also offers a chance of local tumour control to men with locally advanced cancer deemed unsuitable for curative surgery. There has been debate over the contribution of radiotherapy because surgery achieves higher rates of clinical and biochemical freedom of disease in the long term (although there have been no valid prospective, randomised controlled trials which directly compare these two treatments). However, the apparent advantage of surgery could be a reflection of the use of radiotherapy in patients with more advanced disease than those for whom radical prostatectomy would be contemplated. Success with radiotherapy has been shown to be dependent on both the stage and grade of the cancer. Fifteen-year cause-specific survival rates varied from 84% for low-stage to 52% for high-stage clinically localised cancers, and from 85% for well differentiated to 32% for poorly differentiated cancers.6 Traditional external beam radiotherapy involves a treatment course lasting up to seven or eight weeks. Acute proctitis and cystitis occurs in most patients, and there is a 2%-3% risk of long term rectal morbidity (diarrhoea, rectal bleeding) and a 30%-60% risk of permanent impotence. There are increasingly convincing data to support the hypothesis that local control and disease-free survival rates in patients with apparently localised disease improve with increasing radiation dose.7 Current research strategies are therefore aimed at increasing radiation dose without increasing surrounding normal tissue damage. This may be achieved by three-dimensional conformal therapy or brachytherapy, either alone or in combination with external beam radiotherapy. Another approach is to use androgen ablation to shrink the tumour, and then to deliver radiotherapy to maximise tumour cell kill.8 All these techniques have shown encouraging preliminary results, but follow-up has been relatively short. Improvements in surgical techniques, together with an increased understanding of the anatomy of the prostate, have made radical prostatectomy a popular treatment option for localised prostate cancer since the mid 1980s. A Mayo Clinic review of 3170 men treated by radical prostatectomy for clinically localised disease included 93% of men with clinically palpable disease and 25% with poorly differentiated disease. Cause-specific survival among those with palpable disease at 10 and 15 years was 90% and 82%, respectively, and 82% and 71%, respectively, among those with poorly differentiated cancers.9 The morbidity of radical surgery in an Australian setting has been discussed recently in the Journal.10 Independently administered questionnaires indicated that incontinence requiring daily pads occurred in approximately 10% of men who underwent surgery. Most of those affected required a maximum of one pad per day and the degree of inconvenience was generally low. The nerve-sparing technique may give reasonable postoperative potency rates in selected younger patients,11 but impotence occurs in most older men, and this is the issue that most affects quality of life.10 Nonetheless, men in most series indicated that they would choose to have surgery again,10 suggesting that the patients' desire to be cured of the disease outweighed the disadvantageous side effects.
In a comparison of watchful waiting, radiotherapy and surgery, Surveillance, Epidemiology and End Results (SEER) data from the United States have shown that men with well differentiated cancer treated by watchful waiting have 10-year cause-specific survival rates comparable to those treated actively, while in those with moderately or poorly differentiated cancers treatment provides a survival benefit (Table).12 The gap between these groups is likely to widen further at 15 years as more men treated by watchful waiting live long enough to succumb to the disease. In most watchful waiting series, the mean age of the patients is over 70 years, and therefore few patients (5.9%-8.9%) actually survived 15 years.5,13 A recent study comparing 10-year data with 15-year data for men treated conservatively has shown a 15% reduction in cause-specific survival over the additional five years in men with well or moderately differentiated cancer,14 indicating a cumulative increase in prostate cancer mortality even in this cohort with lower grades of cancer. The hypothesis that death rates are declining as a result of increased diagnosis of localised disease treated at an earlier stage is supported by recent National Cancer Institute data showing that prostate cancer mortality in younger white men had declined by 11.7% this decade.15 It is to be hoped that randomised controlled trials currently under way will provide evidence that this is the case. A preliminary report suggests that this may be so.16 However, until the substantive results of these trials are known, men must be thoroughly counselled about the benefits and risks of early detection and treatment of prostate cancer. Aggressive, early therapy should be recommended for patients who are more likely to benefit from treatment -- those with greater than 10-year life expectancy, especially if diagnosed with a higher histological grade of cancer -- while patients less likely to benefit should be spared the morbidity of treatment. Mark Frydenberg Gillian Duchesne Phillip D Stricker
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©MJA 1998
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