Individual patient data meta-analysis of discrimination of the four kallikrein panel associated with the inclusion of prostate volume.

To assess whether adding prostate volume to the kallikrein panel improves discrimination for ISUP Grade Group 2 or higher (GG2+) disease, as some men may have volume measurements available at the time of blood draw. While prostate volume predicts biopsy outcome, it requires an imaging procedure for measurement. The four kallikrein panel - commercially available as the 4Kscore - predicts risk of GG2+ disease and requires only a blood draw.

9,131 patients with available prostate volume and total PSA ≤25 ng/ml from 5 historical (sextant biopsy, pre-ISUP 2005 grading) and 4 contemporary cohorts (10+ cores, ISUP 2005 grading). Previously published kallikrein panel models were used to predict risk of GG2+. Volume was added to the model in each cohort and change in discrimination was meta-analyzed.

Increased prostate volume was associated with decreased risk of GG2+ disease after controlling for the kallikrein panel in 7/9 cohorts. However, kallikrein panel discrimination (0.817, 95% CI 0.802, 0.831) was not improved after including volume (AUC difference 0.002, 95% CI -0.003, 0.006). Heterogeneity (p<0.0001) was driven by an AUC increase in one cohort of academic cancer centers (0.044, 95% CI 0.025, 0.064), with no evidence of heterogeneity after excluding this cohort (p=0.15).

The kallikrein panel provides a non-invasive approach to assess the risk of high-grade prostate cancer. Our results do not justify the inclusion of prostate volume in the four kallikrein panel. There is some evidence that the predictive value of prostate volume is provider dependent: further research is needed to address this question.

Urology. 2021 Aug 24 [Epub ahead of print]

Emily A Vertosick, Stephen Zappala, Sanoj Punnen, Jonas Hugosson, Stephen A Boorjian, Alexander Haese, Peter Carroll, Matthew Cooperberg, Anders Bjartell, Hans Lilja, Andrew Vickers

Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Andover Urology, Andover, MA, Tufts University School of Medicine, Boston, MA, USA., Department of Urology, University of Miami and Sylvester Comprehensive Cancer Center, Miami, FL, USA., Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Göteborg, Göteborg, Sweden., Department of Urology, Mayo Clinic, Rochester, MN, USA., Martini-Clinic Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA., Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; Department of Epidemiology and Statistics, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA., Department of Urology, Skåne University Hospital Malmö, Lund University, Sweden., Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Department of Translational Medicine, Lund University, Malmö, Sweden., Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address: .