Oriontime-Widget-Sviluppo e validazione di un test sulle urine per il cancro alla prostata di alto g

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Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer

Background Background

Benefits of prostate cancer (PCa) screening with prostate-specific antigen (PSA) alone are largely offset by excess negative biopsies and overdetection of indolent cancers resulting from the poor specificity of PSA for high-grade PCa (ie, grade group [GG] 2 or greater).

Objectives

To develop a multiplex urinary panel for high-grade PCa and validate its external performance relative to current guideline-endorsed biomarkers.

Development of the optimal 18-gene model for high-grade cancer

Decision curve analysis plots illustrating the net reduction in biopsies

legenda

PHI Prostate Health Index -MPSMyProstateScore 2 gene-MPS2 MyProstateScore 18 geneMPS2+ MyProstateScore 18 gene+ prostate volume

• A new 18-gene PCa test had higher diagnostic accuracy for high-grade PCa relative to existing biomarker tests.

• Clinically, use of this test would have meaningfully reduced unnecessary biopsies performed while maintaining highly sensitive detection of high-grade cancers.

• These data support use of this new PCa biomarker test in patients with elevated PSA levels to reduce the potential harms of PCa screening while preserving its long-term benefits

Conclusion: Development cohort Validation cohort 761 men Mediam age 63 (58-68) median PSA level 5,6(4,6-7,2) ng/ml 1 7 2 6 3 5 4 743 men Mediam age 62 (57-68) median PSA level 5,6(4,1-8,0)ng/ml 1 62 68 57 63 68 58 7 2 6 3 5 4
Participant
761 Participants included in the development cohort 18 Markers TMPRSS2-ERG SCHLAP1 OR51E2 APOC1 PCAT14 CAMKK2 PCA3 NKAIN1 B3GNT6 TFF3 SPON2 PCGEM1 TRGV9 TMSB15A ERG KLK4 HOXC6 KLK3(reference) Marker priority ranked by frequency of model inclusion and summed importance among 40 models Marker and clinical variable model coefficients determined inoverall cohort Calibration with re-estimation of model intercept and slope 10-Fold internal cross-validation Locked models provided for blinded external validation and performance assessment Model 1 (+4n) Model 2 (+4n) Model 3 (+4n) Model 4 (+4n) Partition 1 Partition 2 Partition 3 Partition 4 Repeated ×10
Net reduction in biopsies per 100 patients 100 75 50 25 0 Threshold probability, % 0 5 10 15 20 25 PSA Risk calculator PHI 2-Gene model 3-Gene model MPS MPS2 MPS2+
REF:https://pubmed.ncbi.nlm.nih.gov/38635241/

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