Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients

Abstract

Background Prostate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood. Methods A systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression. Results Five hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain. Conclusions Currently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed.

Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank

“…The performance of the integrated risk model is similar to the diagnostic accuracy of PSA as reported in the literature: AUC 0.72 (95% CI 0.68-0.76) [12]. We hypothesise that the optimal predictive model would incorporate PSA, GRS, and other clinical features.…”

“…Only a small proportion of the cohort had a PSA test result on record, and these were abnormal; the AUC for PSA alone was >0.9 which is unrealistic compared to the literature and likely to be the result of ascertainment bias [12]. As PSA is part of the current diagnostic pathway to determine if a patient is investigated for prostate cancer, it has a direct causal effect on whether an individual will be diagnosed with prostate cancer independently of the test's ability to predict that outcome.…”

“…PSA is the only test currently available for detecting prostate cancer in primary care, yet the diagnostic accuracy of PSA in symptomatic men is unclear [9]. The most recent systematic review of the diagnostic accuracy of PSA for prostate cancer in patients with LUTS found that a PSA threshold of 4 ng/mL had a sensitivity of 0.93 (95% CI 0.88, 0.96) and specificity of 0.20 (95% CI 0.12, 0.33), and the area under the curve (AUC) was 0.72 (95% CI 0.68, 0.76) [12]. All included studies for the review were conducted in secondary care patient cohorts, limiting the applicability of the findings to the primary care setting, where cancer incidence is lower, and therefore AUC likely to be lower, due to spectrum bias [13].…”

Prostate cancer in omics era

“…This test is far from ideal, however, because even slightly elevated PSA levels can be associated with confounding factors such as benign prostatic hyperplasia (BPH) or prostatitis [ 9 ]. In addition, more than 25% of men with PCa are found to have normal PSA levels [ 10 , 11 ].…”

Diagnosing prostate cancer in asymptomatic patients

“…The heterogeneous behaviour of prostate cancers, along with the poor performance of prostate specific antigen (PSA) testing in identifying clinically important disease, remain obstacles to implementing beneficial strategies for early diagnosis 34. A systematic review found that PSA screening has little or no effect on prostate cancer mortality (incidence rate ratio 0.96, 95% confidence interval 0.85 to 1.08) and can, at best, prevent one prostate cancer death for every 1000 patients tested over 10 years 5…”