Overall tPSA seems to have significance as a diagnostic tool. DORs ranged from 0.221 to 4.16. All but two studies gave DORs greater than 1. The SROC curve [Figure ] lies to the left of the diagonal signifying that the PSA test has value. Adequate levels of sensitivity appear to be achieved at the expense of poor specificity, with consequently relatively high numbers of false positive results.
Espana 1998 and Wymenga 2000 had DORs below 1. This suggests that the PSA of more than 4 ng/ml is inversely associated with prostate cancer. Potential sources of bias for Espana 1998 are its age and poor explanation of withdrawn participants. Its small size makes it especially vulnerable to these factors. Wymenga 2000 was a cohort study which did not exclude borderline cases of raised PSA. This gives the appearance of poorer test accuracy, compared to a case-control study.
Unal 2000's isolated position in the top left on the SROC curve produces the most significant results supporting the use of tPSA as a diagnostic test. Its false negative rate of 0 is likely to be due to the small size of the study and its case control design. Despite its outlying results its high methodological quality warrants its inclusion.
In contrast, Aragona 2005 is the largest included study and has the narrowest CI. Its sensitivity and specificity lies within the main cluster of results close to the SROC curve, adding weight to our findings.
Strengths and weaknesses of the review
A large number of abstracts were reviewed. With regards to study design, suitable publications may have been omitted due to the sole use of electronic searches, reviewer error or limited search terms. Further detail could be added to the searches, including the use of limited text terms. Publication bias may occur but there is no consensus on its importance [14
] or how to assess the impact on this on systematic reviews of diagnostic test accuracy [15
]. As the current use of tPSA in clinical practice is debated, it is unclear whether publication bias would exclude papers showing a low test accuracy or high test accuracy.
The populations of our studies were limited to men attending urology clinics because of referral due to clinical evidence in primary or secondary care, such as an abnormal DRE or raised PSA. This means that our results cannot be applied to the screening population. In this setting there would be a lower prevalence of prostate cancer so it is likely that PSA would have less accuracy as a diagnostic test since the specificity has been shown to be low. Also, the populations studied were European men. A more detailed breakdown of the race of the study populations would have provided us with more information on sources of heterogeneity. Overall the results can be applied to symptomatic European men in the primary and secondary healthcare setting.
The subgroup analyses can show valuable results, however there are some limitations. Firstly, there is overlap between case control and cohort studies. It was sometimes difficult to place the studies into these categories. Secondly, for our pre- and post- 1999 analysis there was only 1 study in the pre-1999 group.
Pre-1999 many assays were widely used for the detection of total PSA, for example Tandem-E, Tandem-R, Immulite 2000, ADIVA Centaur and Roche 2. There has been significant difference in the results using the various assays [16
]. Also as mentioned earlier, in 1999 the World Health Organisation established a reference standard for total PSA measurement[5
]. Since then, differences have decreased between the results of different assay methods [6
Ultimately, the lack of large studies on Europeans which were suitable for our analysis was the main limitation of this review.
Applicability of findings to clinical practice and policy
PSA testing is clearly a vital part of the diagnostic pathway. We have previously discussed the limitations of the study populations. However, we can apply our results to patients who are referred for a biopsy. This is useful for general practitioners and urologists to reassure patients with a raised PSA.
We have found that the PSA test had a sensitivity ranging from 0.78 to 1.00, which means it potentially fails to diagnose over 20% of prostate cancers. This is important to consider in patients with continuing symptoms or an isolated, abnormal DRE. Good quality counselling and information needs to be given to patients to ensure they present again if symptoms persist or worsen. The DRE needs to remain a key part in the diagnostic pathway.
PSA is known to have low specificity, however our results show an extremely low range of 0.06 to 0.66. All but Unal 2000 showed a specificity of less than 0.40. This is in contrast to a moderate specificity as stated by NICE in the most recent guidelines on referral practice for suspected cancer in adults and children. Such a low specificity means that in practice many patients are undergoing the invasive procedure of biopsy who do not in fact have prostate cancer. However there is currently no alternative that has been recommended by NICE for use in clinical practice. It might be interesting to sub-analyse the data according to the patients' presenting symptoms, as this would be useful in the assessment of PSA as both a diagnostic test and a screening tool.