Presentation Authors: Christopher Haiman, Peggy Wan, Alisha Chou, Los Angeles, CA, Emily Vertosick, New York, NY, Lynne Wilkens, Loic Le Marchand, Honolulu, HI, Andrew Vickers*, Hans Lilja, New York, NY
Introduction: The four-kallikrein panel, commercially available as the 4Kscore, has been demonstrated to improve prediction of aggressive prostate cancer compared to prostate-specific antigen (PSA) alone or PSA in combination with free PSA. However, to date, the development and testing of the four-kallikrein panel has been limited primarily to studies conducted in White or African American men. Here we prospectively evaluated the four-kallikrein panel in a nested case-control study among African American (AA), Latino (LA), Japanese (JA), Native Hawaiian (NH) and White (WH) men in the Multiethnic Cohort (MEC).
Methods: Pre-diagnostic blood levels of free, intact, total prostate specific antigen (PSA), human kallikrein-related peptidase 2 (hK2) and microseminoprotein-Î² (MSP) were measured among 2,227 incident prostate cancer cases and 2,189 controls. In statistical models we compared by AUC analysis the discriminative ability of the four-kallikrein panel to PSA for overall prostate cancer, Gleason-Grade Group (GGG) 2 or higher, and aggressive disease (Gleason >7, non-localized disease, or death from prostate cancer) within and across all racial/ethnic groups.
Results: The mean ages of the cases and controls at blood draw were 68 (range: 47-86) and 69 (47-87), respectively, and, for cases, the mean follow-up years was 4.8. For men with elevated PSA (â‰¥2.0 ng/ml; 1,669 cases and 664 controls), the AUC for GGGâ‰¥2 cancer (n=1,077) was 0.78 (95% CI, 0.76-0.80) for the four-kallikrein panel compared to 0.75 (95% C.I. 0.72 - 0.77) for free plus total PSA, and 0.68 (95% CI, 0.66-0.71) for total PSA alone. Discrimination was slightly enhanced for the four-kallikrein panel for aggressive disease (542 cases; 0.79 for panel vs. 0.75 for free plus total PSA vs. 0.68 for total PSA only). This improvement of the four-kallikrein over PSA was observed in each racial/ethnic group for overall prostate cancer (AA, 0.69 vs. 0.64; LA, 0.79 vs. 0.68; JA, 0.77 vs. 0.68; NH, 0.87 vs. 0.78; WH, 0.76 vs. 0.68) as well as for aggressive disease (AA, 0.71 vs 0.67; LA, 0.81 vs. 0.70; JA, 0.81 vs. 0.69; NH, 0.91 vs. 0.73; WH, 0.77 vs. 0.67). The addition of MSP to the four-kallikrein panel did not substantially improve the discrimination for overall prostate cancer or aggressive disease.
Conclusions: In this multiethnic study, the superior predictive ability of the four-kallikrein panel over PSA noted for overall prostate cancer and aggressive disease indicates the four-kallikrein panel has broad clinical applicability.
Source of Funding: This work was supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center [P30 CA008748], a SPORE grant in Prostate Cancer to Dr. H. Scher [P50-CA92629], R01CA160816 to Drs. Lilja and Vickers, the Sidney Kimmel Center for Prostate and Urologic Cancers, David H. Koch through the Prostate Cancer Foundation. This work was also supported in part by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, the Swedish Cancer Society (CAN 2017/559), and the Swedish Research Council (VR-MH project no. 2016-02974). The MEC is supported by NIH/NCI grant U01 CA164973.