Re-evaluating the diagnostic efficacy of PSA as a referral test to detect clinically significant prostate cancer in contemporary MRI-based image-guided biopsy pathways

Abstract

Introduction: Modern image-guided biopsy pathways at diagnostic centres have greatly refined the investigations of men referred with suspected prostate cancer. However, the referral criteria from primary care are still based on historical prostate-specific antigen (PSA) cut-offs and age-referenced thresholds. Here, we tested whether better contemporary pathways and biopsy methods had improved the predictive utility value of PSA referral thresholds. Methods: PSA referral thresholds, age-referenced ranges and PSA density (PSAd) were assessed for positive predictive value (PPV) in detection of clinically significant prostate cancer (csPCa – histological ⩾ Grade Group 2). Data were analysed from men referred to three diagnostics centres who used multi-parametric magnetic resonance imaging (mpMRI)-guided prostate biopsies for disease characterisation. Findings were validated in a separate multicentre cohort. Results: Data from 2767 men were included in this study. The median age, PSA and PSAd were 66.4 years, 7.3 ng/mL and 0.1 ng/mL2, respectively. Biopsy detected csPCa was found in 38.7%. The overall area under the curve (AUC) for PSA was 0.68 which is similar to historical performance. A PSA threshold of ⩾ 3 ng/mL had a PPV of 40.3%, but this was age dependent (PPV: 24.8%, 32.7% and 56.8% in men 50–59 years, 60–69 years and ⩾ 70 years, respectively). Different PSA cut-offs and age-reference ranges failed to demonstrate better performance. PSAd demonstrated improved AUC (0.78 vs 0.68, p < 0.0001) and improved PPV compared to PSA. A PSAd of ⩾ 0.10 had a PPV of 48.2% and similar negative predictive value (NPV) to PSA ⩾ 3 ng/mL and out-performed PSA age-reference ranges. This improved performance was recapitulated in a separate multi-centre cohort ( n = 541). Conclusion: The introduction of MRI-based image-guided biopsy pathways does not appear to have altered PSA diagnostic test characteristics to positively detect csPCa. We find no added value to PSA age-referenced ranges, while PSAd offers better PPV and the potential for a single clinically useful threshold (⩾0.10) for all age groups. Level of evidence: IV

Urinary symptoms and prostate cancer—the misconception that may be preventing earlier presentation and better survival outcomes

“…One caveat is that many of these studies were done before pre-biopsy MRI imaging to target biopsies (as in modern pathways) and tumours may have been harder to find in larger prostates. However, a recent study from our own unit has identified that size-cancer relationship remained the same (inverse) in men investigated by MRI-guided biopsies [19].…”

Alternatives for MRI in Prostate Cancer Diagnostics—Review of Current Ultrasound-Based Techniques

“…This indicates that large prostates may be protective of PCa when compared to smaller prostates, which is favorable for the limited wave penetration of MicroUS. This finding is supported by the study of Lophatananon et al, who enrolled 2767 men suspected of PCa and found mean gland volume higher in men with a benign diagnosis (68.1 mL, SD = 35.5, p < 0.0001) compared to any PCa (52.5 mL, SD = 29.0, p < 0.0001) or csPCa (51.9 mL, SD = 30.0, p < 0.0001) diagnosis [48]. However, the same small PCa lesion is easier to be hit by a biopsy needle in a small prostate than in a much larger prostate.…”

Editorial Commentary

“…Systematic review and meta-analysis studies on transrectal ultrasound and MRI have shown a highly significant negative association between prostate/BPH size and incidence of biopsy-proven PCa; no study was found showing the contrary. 1–3 Since this phenomenon and possible causes are controversially discussed, this should encourage researchers and clinicians to further investigate the dynamic interactions between the different prostatic zones in aging men with growing prostates. A better understanding of the cancer risks in the PZ and TZ could significantly influence future clinical management of both diseases, BPH and PCa alike.…”