Abstract
BackgroundThe clinical pathway to detect and diagnose prostate cancer has been revolutionised by the use of multiparametric MRI (mpMRI pre-biopsy). mpMRI however remains a resource-intensive test and is highly operator dependent with variable effectiveness with regard to its negative predictive value. Here we tested the use of the phi assay in standard clinical practice to pre-select men at the highest risk of harbouring significant cancer and hence refine the use of mpMRI and biopsies.MethodsA prospective five-centre study recruited men being investigated through an mpMRI-based prostate cancer diagnostic pathway. Test statistics for PSA, PSA density (PSAd) and phi were assessed for detecting significant cancers using 2 definitions: ≥ Grade Group (GG2) and ≥ Cambridge Prognostic Groups (CPG) 3. Cost modelling and decision curve analysis (DCA) was simultaneously performed.ResultsA total of 545 men were recruited and studied with a median age, PSA and phi of 66 years, 8.0 ng/ml and 44 respectively. Overall, ≥ GG2 and ≥ CPG3 cancer detection rates were 64% (349/545), 47% (256/545) and 32% (174/545) respectively. There was no difference across centres for patient demographics or cancer detection rates. The overall area under the curve (AUC) for predicting ≥ GG2 cancers was 0.70 for PSA and 0.82 for phi. AUCs for ≥ CPG3 cancers were 0.81 and 0.87 for PSA and phi respectively. AUC values for phi did not differ between centres suggesting reliability of the test in different diagnostic settings. Pre-referral phi cut-offs between 20 and 30 had NPVs of 0.85–0.90 for ≥ GG2 cancers and 0.94–1.0 for ≥ CPG3 cancers. A strategy of mpMRI in all and biopsy only positive lesions reduced unnecessary biopsies by 35% but missed 9% of ≥ GG2 and 5% of ≥ CPG3 cancers. Using PH ≥ 30 to rule out referrals missed 8% and 5% of ≥ GG2 and ≥ CPG3 cancers (and reduced unnecessary biopsies by 40%). This was achieved however with 25% fewer mpMRI. Pathways incorporating PSAd missed fewer cancers but necessitated more unnecessary biopsies. The phi strategy had the lowest mean costs with DCA demonstrating net clinical benefit over a range of thresholds.Conclusionphi as a triaging test may be an effective way to reduce mpMRI and biopsies without compromising detection of significant prostate cancers.
Highlights
The clinical pathway to detect and diagnose prostate cancer has been revolutionised by the use of multiparametric MRI. multiparametric magnetic resonance imaging (mpMRI) remains a resource-intensive test and is highly operator dependent with variable effectiveness with regard to its negative predictive value
Men were excluded if they had (i) a previous biopsy, (ii) pelvic metalwork interfering with mpMRI quality or no mpMRI and (iii) if no biopsy was done after mpMRI
prostatespecific antigen (PSA) and phi assay was taken before biopsy and PSA density (PSAd) calculated using mpMRI-defined prostate volumes
Summary
The clinical pathway to detect and diagnose prostate cancer has been revolutionised by the use of multiparametric MRI (mpMRI pre-biopsy). mpMRI remains a resource-intensive test and is highly operator dependent with variable effectiveness with regard to its negative predictive value. The clinical pathway to detect and diagnose prostate cancer has been revolutionised by the use of multiparametric MRI (mpMRI pre-biopsy). The use of multiparametric magnetic resonance imaging (mpMRI) pre-biopsy is firmly embedded in the prostate cancer diagnostic pathway as a method to try and address this [1,2,3,4,5]. This enables targeting of positive lesions and in the case of negative imaging, avoiding biopsy all together in a proportion of referrals [5]. Few have considered how biomarker-imaging combinations might work to refine the use of tests and cost-effectiveness
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