To prospectively evaluate the performance of a prespecified statistical model based on four kallikrein markers in blood (total prostate-specific antigen [PSA], free PSA, intact PSA, and human kallikrein-related peptidase 2[hK2]), commercially available as the 4Kscore, in predicting Gleason grade group (GG) ≥2 prostate cancer at biopsy in an international multi-center study at three academic medical centers, and whether microseminoprotein-β (MSP) adds predictive value.
984 men were prospectively enrolled at three academic centers. The primary outcome was GG ≥ 2 on prostate biopsy. Three prespecified 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.
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 (AUC) 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.
A prospective multi-center evaluation of a prespecified 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.
BJU international. 2020 Dec 11 [Epub ahead of print]
Peter E Lonergan, Emily A Vertosick, Melissa Assel, Daniel D Sjoberg, Alexander Haese, Markus Graefen, Stephen A Boorjian, George G Klee, Matthew R Cooperberg, Kim Pettersson, Erica Routila, Andrew J Vickers, Hans Lilja
Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA., Departments of Biochemistry/Biotechnology, University of Turku, Turku, Finland., Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.