Unravelling the prostate-specific antigen controversy: a West of Scotland perspective

Background

Prostate cancer (PCa) is the most common malignancy in males and second commonest cause of death due to cancer in the UK. ¹ The incidence of PCa varies up to fourfold between different European countries, being higher in those countries where testing of asymptomatic men for PCa using serum prostate-specific antigen (PSA) is more common. ² Based upon PSA results, patients may be subjected to prostatic biopsies, which are associated with significant morbidity. Furthermore, a diagnosis of PCa and subsequent radical treatment may not have a significant impact on patient’s overall survival. PCa is common in older men with other co-morbidities and is often slow-growing. Hence, PSA screening in asymptomatic men is hugely controversial and not recommended in the US. ³ The current National Institute of Clinical Excellence (NICE) guidelines recommend PSA testing in men who have (a) lower urinary tract symptoms (LUTS) suggestive of benign prostatic enlargement (BPE) as a marker for disease progression; (b) with an abnormal digital rectal examination (DRE) or (c) in patients concerned about PCa. However, PCa management guidelines ⁴ state that “….serum PSA level alone should not automatically lead to a prostate biopsy. Other factors that should be considered in conjunction with the PSA level are prostate size, DRE findings, age, ethnicity, comorbidities, history of any previous negative biopsy and any previous PSA history”.

The conclusions from two large-scale PCa screening studies^5,6 are controversial: The ‘Prostate, Lung, Colorectal, and Ovarian Cancer’ screening trial (PLCO) suggested that after 13 years of follow-up, there was no evidence of a mortality benefit for organised annual screening compared with opportunistic screening, which forms part of usual care. ⁵ However, the ‘European Randomized study of Screening for Prostate Cancer’ trial (ERSPC) indicated PSA-based screening reduced the rate of death from PCa by 21% but was associated with a high risk of over diagnosis. ⁶ A recent randomised study of radical prostatectomy for PCa suggested that a survival advantage is gained for curative surgery only in patients with ‘high-risk’ disease, ⁷ which cannot be detected by PSA alone.

At present, there is no organised PSA-based population screening programme for PCa in the UK. PSA testing may be used as opportunistic ‘screening’ (casefinding) in asymptomatic men or as part of an assessment for LUTS/BPE. The aim of the present study was to survey the current practice of West of Scotland Urologists in the use of PSA testing.

Materials and methods

An electronic questionnaire (Figure 1) was sent to all Urologists (Consultants and Trainees) in the West of Scotland (n = 105). The survey obtained data on clinician demographics, queried whether the clinician had read the recent PLCO and ERSPC studies and assessed PSA testing practice in both symptomatic and asymptomatic men. There was also a self-assessment question. OPEN IN VIEWER

Results

In total, 47 responses were received (response rate = 45%). We found that 89% of urologists had read the PLCO and ERSPC papers. Amongst the respondents, 55% were Trainees and 45% were Consultants of varying levels of clinical experience (Figure 2). The majority of respondents were less than 40 years of age (Figure 3), reflecting the experientially junior study cohort. We found that 93% would perform PSA testing in patients symptomatic of LUTS/BPE, and only 17% would offer opportunistic PSA screening to patients less than 70 years (Figure 4). In patients over 70 years, 48% of urologists would perform a PSA test in symptomatic patients; none would offer PSA screening. In terms of PSA self-testing, 59% would have a PSA test if symptomatic and 31% would have a PSA test if asymptomatic (Figure 5). OPEN IN VIEWER

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Figure 3.

Age distribution of respondents.

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Figure 4.

Decision making of respondents on PSA testing for asymptomatic and symptomatic men stratified by age.

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Figure 5.

Decision making of respondents on PSA self-testing.

Discussion

Despite two large-scale screening studies, PSA-based screening for PCa remains controversial. The U.S. Preventative Task Force does not recommend PSA-based PCa screening despite wider use of PSA as a tool for opportunistic screening/casefinding in the US than UK. However, this recommendation is based upon incomplete data and studies with a number of methodological flaws. ⁸ For example, there was screening contamination in the PLCO study control group, and the ERSPC study was in fact a collection of trials in different countries with different eligibility criteria, randomisation schemes and strategies for screening and follow-up.

Our survey reflects the ambiguity and inconsistency in UK urological practice that is yet to be clarified by these two large randomised studies and national guidelines. For example, only 17% would offer opportunistic PSA screening in men aged less than 70 years, and contrary to guidelines, only 48% would test for PSA in men with LUTS/BPE over 70 years. However, irrespective of age, more urologists (31%) would self-test for PSA if asymptomatic than offer opportunistic PSA screening to patients (17%). This inconsistency may be driven by other forces such as fear of litigation, misinterpretation of the guideline recommendations, the role of PCa in the public, medical and economic concerns and interests of the urologists.

Irrespective of an individual clinician’s practice, PSA testing should only be offered to patients with full counselling regarding the consequences and risk of a positive test result. Opportunistic screening should probably be avoided in the over 70s where the likely benefit from curative treatment is limited due to co-morbidities and where prior testing at an earlier age places the patient into a low-risk group. ⁹

We believe that PSA testing should be offered, as per UK guidelines, for patients with LUTS/BPE to assess the risk of disease progression and stratify medical treatment or where there is a clinical suspicion of locally advanced/metastatic cancer. Due to heterogeneity of the clinical disease, long-term follow-up from current screening studies and further randomised studies are required to determine whether population-based PSA screening can effectively detect clinically significant PCa.