Personalised Prostate Cancer Diagnosis: Evaluating Biomarker-based Approaches to Reduce Unnecessary Magnetic Resonance Imaging and Biopsy Procedures

Abstract

Background and objective: Efforts made over the last decade for the detection of prostate cancer (PCa) have revolutionised disease diagnostics, and implementation of prebiopsy magnetic resonance imaging (MRI) has received widespread acceptance. However, universal adoption of prebiopsy MRI and the benefits achieved have been limited by availability and equivocal MRI findings. This review aims to evaluate the latest evidence on the role of existing PCa risk calculators (RCs), and blood and urinary biomarkers as part of the diagnostic algorithm to improve the diagnosis of clinically significant PCa (csPCa) and reduce unnecessary MRI procedures and biopsies. We will also evaluate the potential of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) to enhance sensitivity and specificity for PCa diagnosis, complement MRI, and refine biopsy strategies within the diagnostic pathway.

Methods: We performed a narrative review using the PubMed/MEDLINE database, which included papers published between January 2014 and June 2024. The outcome measures included rates of reduced diagnoses of nonsignificant PCa (defined as International Society of Urological Pathology [ISUP] grade group 1) cases, diagnoses of csPCa (defined as ISUP grade group ≥2) cases missed, and MRI scans and prostate biopsies avoided.

Key findings and limitations: In men with abnormal prostate-specific antigen (PSA) levels, further risk stratification using RCs, or blood or urine biomarkers can reduce up to 16-51% MRI scans, while missing 1-16% csPCa cases. In case of equivocal MRI results or Prostate Imaging Reporting and Data System 3 lesions, RCs or biomarkers could reduce up to 72% of biopsies, while missing only 3-13% csPCa cases. PSMA PET has emerging potential to improve csPCa prediction in combination with MRI and may further reduce unnecessary biopsies. A limitation of this study is that this is a narrative but not a systematic review.

Conclusions and clinical implications: RCs and biomarkers have been demonstrated to enhance the performance and efficiency of MRI in detecting csPCa in men with elevated PSA levels. PSMA PET shows promise in detecting csPCa, complementing MRI and refining biopsy indications.

Patient summary: In men with a suspicion of prostate cancer, magnetic resonance imaging prostate scans are effective in predicting clinically relevant cancer, but challenges including availability and equivocal scans exist. A personalised approach by adding one or more of clinical risk calculators, blood or urine biomarkers, or even novel imaging techniques such as positron emission tomography scans may improve cancer prediction further and reduce unnecessary scans and biopsies.

Keywords: Biopsy; Diagnostic pathway; Magnetic resonance imaging; Prostate cancer; Screening.

Fig. 1

Diagnostic algorithm incorporating various biomarkers and imaging for biopsy-naïve men with elevated PSA. csPCa = clinically significant prostate cancer; EAU = European Association of Urology; MRI = magnetic resonance imaging; PET = positron emission tomography; PI-RADS = Prostate Imaging Reporting and Data System; PSA = prostate-specific antigen; PSMA = prostate-specific membrane antigen; RC = risk calculator. ^a Risks related to PSA density and MRI PI-RADS score classification in EAU guidelines: low: 5–10%, intermediate low: 10–20%, Intermediate high: 20–30%, high: 30%, and very high: >40%.