Peter E Lonergan1, Emily A Vertosick2, Melissa Assel2, Daniel D Sjoberg2, Alexander Haese3, Markus Graefen3, Stephen A Boorjian4, George G Klee5, Matthew R Cooperberg1,6, Kim Pettersson7, Erica Routila7, Andrew J Vickers2, Hans Lilja8,9. 1. Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA. 2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 4. Department of Urology, Mayo Clinic, Rochester, MN, USA. 5. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 6. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. 7. Departments of Biochemistry/Biotechnology, University of Turku, Turku, Finland. 8. Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 9. Department of Translational Medicine, Lund University, Malmö, Sweden.
Abstract
OBJECTIVES: To prospectively evaluate the performance of a pre-specified statistical model based on four kallikrein markers in blood (total prostate-specific antigen [PSA], free PSA, intact PSA, and human kallikrein-related peptidase 2), commercially available as the 4Kscore, in predicting Gleason Grade Group (GG) ≥2 prostate cancer at biopsy in an international multicentre study at three academic medical centres, and whether microseminoprotein-β (MSP) adds predictive value. PATIENTS AND METHODS: A total of 984 men were prospectively enrolled at three academic centres. The primary outcome was GG ≥2 on prostate biopsy. Three pre-specified statistical models were used: a base model including PSA, age, digital rectal examination and prior negative biopsy; a model that added free PSA to the base model; and the 4Kscore. RESULTS: A total of 947 men were included in the final analysis and 273 (29%) had GG ≥2 on prostate biopsy. The base model area under the receiver operating characteristic curve of 0.775 increased to 0.802 with the addition of free PSA, and to 0.824 for the 4Kscore. Adding MSP to the 4Kscore model yielded an increase (0.014-0.019) in discrimination. In decision-curve analysis of clinical utility, the 4Kscore showed a benefit starting at a 7.5% threshold. CONCLUSION: A prospective multicentre evaluation of a pre-specified model based on four kallikrein markers (4Kscore) with the addition of MSP improves the predictive discrimination for GG ≥2 prostate cancer on biopsy and could be used to inform biopsy decision-making.
OBJECTIVES: To prospectively evaluate the performance of a pre-specified statistical model based on four kallikrein markers in blood (total prostate-specific antigen [PSA], free PSA, intact PSA, and human kallikrein-related peptidase 2), commercially available as the 4Kscore, in predicting Gleason Grade Group (GG) ≥2 prostate cancer at biopsy in an international multicentre study at three academic medical centres, and whether microseminoprotein-β (MSP) adds predictive value. PATIENTS AND METHODS: A total of 984 men were prospectively enrolled at three academic centres. The primary outcome was GG ≥2 on prostate biopsy. Three pre-specified statistical models were used: a base model including PSA, age, digital rectal examination and prior negative biopsy; a model that added free PSA to the base model; and the 4Kscore. RESULTS: A total of 947 men were included in the final analysis and 273 (29%) had GG ≥2 on prostate biopsy. The base model area under the receiver operating characteristic curve of 0.775 increased to 0.802 with the addition of free PSA, and to 0.824 for the 4Kscore. Adding MSP to the 4Kscore model yielded an increase (0.014-0.019) in discrimination. In decision-curve analysis of clinical utility, the 4Kscore showed a benefit starting at a 7.5% threshold. CONCLUSION: A prospective multicentre evaluation of a pre-specified model based on four kallikrein markers (4Kscore) with the addition of MSP improves the predictive discrimination for GG ≥2 prostate cancer on biopsy and could be used to inform biopsy decision-making.
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