Journal of the New Zealand Medical Association, 11-February-2005, Vol 118 No 1209
Prostate cancer screening: is it possible to explain diametrically opposed views?
Prostate cancer screening is controversial.1–3 Clearly, the views of those who support and actively offer prostate cancer screening are very different from the views of those who see no justification for screening at present. How can we understand and explain such opposing views?
It is likely that differences of opinion about prostate cancer screening reflect differences in the way people assess the benefits and risks of screening. By examining each of these in turn, it is possible to understand the controversy, but also determine whether prostate screening is ethical.
Underlying the discrepant views on screening is the extent to which people assume that screening is beneficial. If men and their doctors assume that screening must be beneficial, then irrespective of the outcome of prostate-specific antigen (PSA) testing, both the man and his doctor will be positively reinforced:
A physician is positively reinforced for recommending screening, regardless of the test result, because a negative result makes the patient grateful for reassurance and a positive result makes a patient grateful for early detection. A patient who is impotent and incontinent after a decision for curative treatment may attribute his survival to surgery and be grateful for having his cancer cured. Individual experience provides almost no negative feedback that early detection and aggressive treatment may not work.4
But is prostate cancer screening beneficial? Intuitively it seems obvious; surely picking up disease earlier must be good? Unfortunately we know that screening is not always beneficial. Randomised controlled trials (RCTs) have revealed that some screening procedures (for instance, screening for lung cancer using chest radiography and sputum cytology in high-risk individuals, and screening for breast cancer with breast self-examination), which were previously assumed to be beneficial, are not.5–7
Using methods such as survival comparisons, observational studies, or ecological studies to assess screening is dangerous. These studies are vulnerable to biases, which can cause any benefit of screening to be overestimated, and at worst, can make screening appear beneficial even when it is not (Table 1). Only an appropriately designed and analysed RCT can avoid these biases, and determine whether screening for prostate cancer really is beneficial.
At present, we do not know if there is any benefit from prostate cancer screening, because there is not yet evidence from appropriately designed and analysed randomised controlled trials.8–11 Two large RCTs are presently underway.12
Table 1. Why do we need randomised controlled trials of prostate cancer screening?
Bias is a defect in study design or analysis that causes results to deviate from the truth. The following biases can affect the assessment of prostate cancer screening:
Lead time bias
Screening can detect prostate cancer early, thereby extending the interval between diagnosis and death, even if the time of death is unchanged. Because survival time is measured from time of diagnosis to death, men whose prostate cancer was detected by screening will have longer survival times than men diagnosed clinically, even if screening does not actually extend life.
Fast growing prostate tumours, which tend to have the worst prognosis, are less likely to be detected by screening, because they grow so rapidly that the period when the tumour could be detected by screening before signs or symptoms develop, may be very short. Screening will therefore detect a disproportionate number of slow growing tumours with a good prognosis. Comparisons of outcome between men with screen-detected prostate cancer and men with clinically-diagnosed prostate cancer are likely to be invalid because of this.
Men who take up the offer of screening may differ in their underlying risk of dying from prostate cancer, so that their prognosis would have differed from non-participants even in the absence of screening. Thus, comparing the outcome for men who have been screened with men who have not may be inappropriate. Selection bias can be avoided in a randomised-controlled trial by appropriate (intention to treat) analysis.
Screening may detect abnormalities that are of questionable malignancy and cancers that would not have been diagnosed in the absence of screening. Although some of these abnormalities and cancers may never have been diagnosed, nor affected a man’s life in the absence of screening, they will be counted as ‘screen-detected’ cancers. Because of the inclusion of these cancers, the outcome for a group of screened men with prostate cancer will appear better than the outcome for unscreened men with prostate cancer.
People who are unwell are often prepared to take risks in order to get better. Many patients will accept treatments that carry risks; for instance, drugs that have potential side effects, and radiotherapy or surgery despite their possible complications. Clinicians are used to interacting with people who are unwell and who tolerate potential harm in order to get better. Clinicians may transfer this tolerance of harm to the screening situation, hence urologists may be more likely to support prostate cancer screening than public health physicians.
But people who are well may not share the same tolerance towards potential harm, especially if the benefit is uncertain. If there is no benefit, the net effect of screening will be to harm those who take part. Apart from the obvious harms related to false negative and false positive screening results, overdiagnosis is likely to be a major problem in prostate cancer screening.
Autopsy studies, where prostate biopsies were taken from men who had died of causes other than prostate cancer,13,14 have shown that the histological evidence of prostate cancer in such men is much higher than the lifetime incidence and mortality from prostate cancer. In other words, histological evidence of prostate cancer can be found in far more men than would ever be expected to suffer from or die from the disease.
Further evidence of overdiagnosis comes from the Finasteride Trial,15 which was designed to find out whether the drug Finasteride could prevent prostate cancer. Men aged 55 years and over were randomly allocated to an intervention group (which took Finasteride) and a control group (which took a placebo). All the men had normal digital rectal examinations (DRE) and PSA results at entry to the trial. During the trial, the men underwent annual DRE and PSA tests.
At the end of the trial, all men who had not been diagnosed with prostate cancer during the trial were offered an end-of-study prostate biopsy. Of 4692 men in the control group who had prostate biopsies, nearly a quarter (24.4%) had histological evidence of prostate cancer at the end of the 7 years’ follow-up. The investigators had expected 6.0% of the men to be diagnosed with prostate cancer during the trial, and the expected lifetime prevalence in these men was 16.7%. The trial investigators themselves stated ‘The rate of 24.4% suggests the possibility of overdiagnosis of disease.’15
The results from autopsy studies and the Finasteride trial are a warning. If healthy men have PSA tests, some will be diagnosed with prostate cancer that they would otherwise never have known about, and that would never have threatened their lives. This would be bad enough, but many men who are diagnosed with prostate cancer are offered treatment such as radiotherapy or surgery, and these treatments have significant side effects. The potential side effects include impotence, incontinence, diarrhoea, and death.9
Some of the men who suffer these side effects would never have known they had prostate cancer in the absence of screening, so they will have been directly harmed as a consequence of being screened.
Although it is possible to understand and perhaps explain opposing views on prostate cancer screening, examining the risks and benefits shows that prostate cancer screening is not justified at present. Whether there is any benefit from prostate cancer screening is unknown. It is inappropriate to support screening in the hope that it will be found to be beneficial, since this would be gambling with men’s health.
Prostate cancer screening fails to meet criteria for screening,16,17 and carries potentially serious risks. In the absence of conclusive evidence of benefit, it is entirely possible that prostate cancer screening could cause more harm than good. Therefore, at present, it is unethical to offer prostate cancer screening.18 In the future, screening should only be offered if the randomised controlled trials of prostate screening that are currently underway, demonstrate a benefit.
Author information: Ann K Richardson, Associate Professor, Department of Public Health and General Practice, Christchurch School of Medicine and Health Sciences, University of Otago, PO Box 4345, Christchurch
Correspondence: Dr Ann Richardson, Department of Public Health and General Practice, Christchurch School of Medicine and Health Sciences, University of Otago, PO Box 4345, Christchurch. Fax: (03) 364 3614; email: email@example.com
issue | Search journal |
Archived issues | Classifieds
| Hotline (free ads)
Subscribe | Contribute | Advertise | Contact Us | Copyright | Other Journals