Prediction Medicine: Biomarkers, Risk Calculators and Magnetic Resonance Imaging as Risk Stratification Tools in Prostate Cancer Diagnosis

Osses, Daniël F.; Roobol, Monique J.; Schoots, Ivo G.

doi:10.3390/ijms20071637

Cited by 85 publications

(89 citation statements)

References 107 publications

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“…EUR 100) to select suitable patients prior to mpMRI (cost: several hundreds of euros) will be of great interest in the future. In this context, in 2019, Osses et al [16] suggest a triage prior to mpMRI in their current review. This means that in patients with clinical suspicion of PCa (suspicious progression and/or elevated t-PSA and/or abnormal DRE findings), RC could be applied first.…”

Section: Color Version Available Onlinementioning

confidence: 98%

Use of the Prostate Health Index and Density in 3 Outpatient Centers to Avoid Unnecessary Prostate Biopsies

Schulze¹,

Christoph²,

Sachs³

et al. 2020

Urol Int

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Objectives: We investigated the diagnostic efficacy of the prostate health index (PHI) and PHI density (PHID) to avoid unnecessary prostate biopsies in 3 urological practices. Methods: In 122 patients, total prostate-specific antigen (PSA), free PSA (f-PSA), the quotient from total PSA and f-PSA (f-PSA%), and [-2]pro-PSA were measured in the serum; PHI, PHID, and PSA density (PSAD) were calculated prior to prostate biopsy. Tissue sampling via transrectal biopsy was indicated in case of suspicious PSA (progression and/or elevation of PSA) and/or suspicious digital rectal examination. PSAD, PHI, and PHID were not used for biopsy indication. The diagnostic efficacy was determined with receiver-operating characteristic (ROC) and decision curve analyses. Results:Based on prostate biopsies, 38% (n = 46) of the cases had no prostate carcinoma (PCa), 21% (n = 26) no clinically significant (insignificant) PCa, and 41% (n = 50) had clinically significant PCa. ROC analyses of the PSA parameters showed higher diagnostic efficacy for PHI and PHID (AUC 0.722 and 0.739) than for f-PSA%, PSA, and PSAD (AUC 0.612, 0.595, and 0.698, respectively) regarding carcinoma diagnosis. With a combined use of PHI and PHID (cutoff > 40 and > 0.9, respectively), only 1 clinically significant PCa would have been missed (sensitivity 98%); in 24 (20%) patients, biopsy could have been avoided. Conclusion: The integration of PHI and PHID could improve the diagnostic efficacy of risk calculators to avoid unnecessary prostate biopsies. However, as a prerequisite, validation of cutoff values in prospective studies is urgently required.

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Section: Color Version Available Onlinementioning

confidence: 98%

Use of the Prostate Health Index and Density in 3 Outpatient Centers to Avoid Unnecessary Prostate Biopsies

Schulze¹,

Christoph²,

Sachs³

et al. 2020

Urol Int

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“…The phi is one of many biomarkers reported in the last 10 years that have shown stronger predictive accuracy compared to PSA in detecting prostate cancer [20,21]. Early studies compared these biomarkers head to head against mpMRI, but inevitably mpMRI proved superior as not only does it improve detection but also helps guide biopsies [28][29][30]. Subsequent studies have sought to combine biomarkers with mpMRI with all showing consistently better results than biomarkers alone but often in a retrospective setting.…”

Section: Discussionmentioning

confidence: 99%

Clinical utility and cost modelling of the phi test to triage referrals into image-based diagnostic services for suspected prostate cancer: the PRIM (Phi to RefIne Mri) study

Kim

Boxall

George

et al. 2020

BMC Med

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Background: The 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. Methods: A 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. Results: A 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 cutoffs 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. Conclusion: phi as a triaging test may be an effective way to reduce mpMRI and biopsies without compromising detection of significant prostate cancers.

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“…Many of them have great potential as diagnostic/prognostic markers and therapeutic targets. A great example is the lncRNA prostate cancer antigen 3 (PCA3), already used as a molecular marker in prostate cancer [58,59]. PCA3 is a prostate-specific lncRNA overexpressed in 95% of prostate cancer cases.…”

Section: Clinical Application For Lncrnasmentioning

confidence: 99%

“…PCA3 has a high expression in prostate cancer without any correlation to prostatic volume and other prostatic diseases. This feature makes a PCA3 an attractive biomarker [61], but some recent studies question the use of this isolated biomarker and propose that the test should be carried out in association with another test, like TMPRSS2:ERG quantification [58].…”

Section: Clinical Application For Lncrnasmentioning

confidence: 99%

lncRNAs in Hallmarks of Cancer and Clinical Applications

Garcia¹,

Zambalde²,

Mathias³

et al. 2020

Non-Coding RNAs

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Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides in length that, in general, do not appear to have protein-coding potential. lncRNAs act in gene regulation involved with several biological processes. Furthermore, lncRNAs have been associated with a significant number of cancers, suggesting a potential role in tumorigenesis and progression. For example, HOTAIR regulates proliferation processes and other lncRNAs like highly upregulated in liver cancer (HULC), H19, PTENP1, HEIH, and antisense noncoding RNA in the INK4 locus (ANRIL). Other lncRNAs as AFAP1-AS1 and lincRNA-p21 can interact with BCL-2 and TP53, acting in apoptosis. Moreover, NORAD plays a vital role in genomic stability. Additionally, due to deregulated expression and high tissue specificity level, lncRNAs exhibit great potential as prognostic markers. In this chapter, we review the most highlighted lncRNAs acting in hallmarks of cancer and clinical application.

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Prediction Medicine: Biomarkers, Risk Calculators and Magnetic Resonance Imaging as Risk Stratification Tools in Prostate Cancer Diagnosis

Cited by 85 publications

References 107 publications

Use of the Prostate Health Index and Density in 3 Outpatient Centers to Avoid Unnecessary Prostate Biopsies

Use of the Prostate Health Index and Density in 3 Outpatient Centers to Avoid Unnecessary Prostate Biopsies

Clinical utility and cost modelling of the phi test to triage referrals into image-based diagnostic services for suspected prostate cancer: the PRIM (Phi to RefIne Mri) study

lncRNAs in Hallmarks of Cancer and Clinical Applications

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