Molecular Biomarkers for the Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis

Tasmania Del Pino-Sedeño; Diego Infante-Ventura; Aythami de Armas Castellano; Pedro de Pablos-Rodríguez; Antonio Rueda-Domínguez; Pedro Serrano-Aguilar; María M Trujillo-Martín

doi:10.1016/j.euros.2022.10.017

Molecular Biomarkers for the Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis

Eur Urol Open Sci. 2022 Nov 10:46:105-127. doi: 10.1016/j.euros.2022.10.017. eCollection 2022 Dec.

Authors

Tasmania Del Pino-Sedeño^{1

2

3

4}, Diego Infante-Ventura^{1

2}, Aythami de Armas Castellano^{1

2}, Pedro de Pablos-Rodríguez^{5

6

7}, Antonio Rueda-Domínguez^{8

9}, Pedro Serrano-Aguilar^{2

4

9

10

11}, María M Trujillo-Martín^{1

2

4

9

10}

Affiliations

¹ Canary Islands Health Research Institute Foundation (FIISC), Tenerife, Spain.
² The Spanish Network of Agencies for Health Technology Assessment and Services of the National Health System (RedETS), Madrid, Spain.
³ European University of the Canary Islands (UEC), Santa Cruz de Tenerife, Spain.
⁴ Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Tenerife, Spain.
⁵ Department of Urology, Valencian Institute of Oncology Foundation, Valencia, Spain.
⁶ Doctoral School of University of Las Palmas de Gran Canaria, Las Palmas, Spain.
⁷ Research Institute of Biochemical and Health Sciences, Barcelona, Spain.
⁸ Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain.
⁹ Research Network on Health Services in Chronic Diseases (REDISSEC), Madrid, Spain.
¹⁰ Institute of Biomedical Technologies (ITB). University of La Laguna, Tenerife, Spain.
¹¹ Evaluation Unit (SESCS), Canary Islands Health Service (SCS), Tenerife, Spain.

Abstract

Context: Prostate cancer (PCa) is the second most common type of cancer in men. Individualized risk stratification is crucial to adjust decision-making. A variety of molecular biomarkers have been developed in order to identify patients at risk of clinically significant PCa (csPCa) defined by the most common PCa risk stratification systems.

Objective: The present study aims to examine the effectiveness (diagnostic accuracy) of blood or urine-based PCa biomarkers to identify patients at high risk of csPCa.

Evidence acquisition: A systematic review of the literature was conducted. Medline and EMBASE were searched from inception to March 2021. Randomized or nonrandomized clinical trials, and cohort and case-control studies were eligible for inclusion. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Pooled estimates of sensitivity, specificity, and area under the curve were obtained.

Evidence synthesis: Sixty-five studies (N = 34 287) were included. Not all studies included prostate-specific antigen-selected patients. The pooled data showed that the Prostate Health Index (PHI), with any cutoff point between 15 and 30, had sensitivity of 0.95-1.00 and specificity of 0.14-0.33 for csPCa detection. The pooled estimates for SelectMDx test sensitivity and specificity were 0.84 and 0.49, respectively.

Conclusions: The PHI test has a high diagnostic accuracy rate for csPCa detection, and its incorporation in the diagnostic process could reduce unnecessary biopsies. However, there is a lack of evidence on patient-important outcomes and thus more research is needed.

Patient summary: It has been possible to verify that the application of biomarkers could help detect prostate cancer (PCa) patients with a higher risk of poorer evolution. The Prostate Health Index shows an ability to identify 95-100 for every 100 patients suffering from clinically significant PCa who take the test, preventing unnecessary biopsies in 14-33% of men without PCa or insignificant PCa.

Keywords: Clinically significant cancer; Meta-analysis; Molecular markers; Prostatic neoplasms; Systematic review.

Publication types

Review