Eric H Kim1, Gerald L Andriole1, E David Crawford2, Daniel D Sjoberg3, Melissa Assel3, Andrew J Vickers3, Hans Lilja4. 1. Division of Urology, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. 2. Division of Urology, Department of Surgery, University of Colorado, Aurora, Colorado. 3. Department of Epidemiology and Biostatistics, Clinical Chemistry Service, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Department of Laboratory Medicine, Urology Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Surgery and Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden. Electronic address: liljah@mskcc.org.
Abstract
PURPOSE: We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). MATERIALS AND METHODS: Levels of free, intact, total prostate specific antigen, human kallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy. RESULTS: The detection of high grade prostate cancer in 94 men (10%) was enhanced by the 4-kallikrein panel with an AUC of 0.79 compared to 0.73 for PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), representing a 0.060 increase (95% CI 0.032-0.088, p <0.01). Additionally, the AUC increased from 0.79 to 0.81 when microseminoprotein-β was added to the 4-kallikrein panel. In African American men, the 4-kallikrein panel model also enhanced high grade prostate cancer detection over that of prostate specific antigen (AUC 0.80 vs 0.67). As an illustration of clinical implications, using 1 cutoff point for biopsy (6% risk of high grade prostate cancer) with the 4-kallikrein panel model would have eliminated unnecessary biopsies in 420 per 1,000 men (42%) while detecting high grade prostate cancer in 83 of 93 (88%). CONCLUSIONS: In a multiethnic United States population, the 4-kallikrein panel demonstrated improved risk discrimination for high grade prostate cancer over conventional clinical variables (age, prostate specific antigen and digital rectal examination) as well as PCPTRC.
PURPOSE: We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). MATERIALS AND METHODS: Levels of free, intact, total prostate specific antigen, humankallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy. RESULTS: The detection of high grade prostate cancer in 94 men (10%) was enhanced by the 4-kallikrein panel with an AUC of 0.79 compared to 0.73 for PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), representing a 0.060 increase (95% CI 0.032-0.088, p <0.01). Additionally, the AUC increased from 0.79 to 0.81 when microseminoprotein-β was added to the 4-kallikrein panel. In African American men, the 4-kallikrein panel model also enhanced high grade prostate cancer detection over that of prostate specific antigen (AUC 0.80 vs 0.67). As an illustration of clinical implications, using 1 cutoff point for biopsy (6% risk of high grade prostate cancer) with the 4-kallikrein panel model would have eliminated unnecessary biopsies in 420 per 1,000 men (42%) while detecting high grade prostate cancer in 83 of 93 (88%). CONCLUSIONS: In a multiethnic United States population, the 4-kallikrein panel demonstrated improved risk discrimination for high grade prostate cancer over conventional clinical variables (age, prostate specific antigen and digital rectal examination) as well as PCPTRC.
Authors: Andrew J Vickers; Angel M Cronin; Gunnar Aus; Carl-Gustav Pihl; Charlotte Becker; Kim Pettersson; Peter T Scardino; Jonas Hugosson; Hans Lilja Journal: Cancer Date: 2010-06-01 Impact factor: 6.860
Authors: Andrew Vickers; Angel Cronin; Monique Roobol; Caroline Savage; Mari Peltola; Kim Pettersson; Peter T Scardino; Fritz Schröder; Hans Lilja Journal: J Clin Oncol Date: 2010-04-26 Impact factor: 44.544
Authors: Jonathan I Epstein; Lars Egevad; Mahul B Amin; Brett Delahunt; John R Srigley; Peter A Humphrey Journal: Am J Surg Pathol Date: 2016-02 Impact factor: 6.394
Authors: Ville Väisänen; Susann Eriksson; Kaisa K Ivaska; Hans Lilja; Martti Nurmi; Kim Pettersson Journal: Clin Chem Date: 2004-07-09 Impact factor: 8.327
Authors: Simpa S Salami; Manish A Vira; Baris Turkbey; Mathew Fakhoury; Oksana Yaskiv; Robert Villani; Eran Ben-Levi; Ardeshir R Rastinehad Journal: Cancer Date: 2014-06-10 Impact factor: 6.860
Authors: William J Catalona; Jerome P Richie; Frederick R Ahmann; M'Liss A Hudson; Peter T Scardino; Robert C Flanigan; Jean B DeKernion; Timothy L Ratliff; Louis R Kavoussi; Bruce L Dalkin; W Bedford Waters; Michael T MacFarlane; Paula C Southwick Journal: J Urol Date: 1994-05 Impact factor: 7.450
Authors: A Gupta; M J Roobol; C J Savage; M Peltola; K Pettersson; P T Scardino; A J Vickers; F H Schröder; H Lilja Journal: Br J Cancer Date: 2010-07-27 Impact factor: 7.640
Authors: Andrew J Vickers; Angel M Cronin; Gunnar Aus; Carl-Gustav Pihl; Charlotte Becker; Kim Pettersson; Peter T Scardino; Jonas Hugosson; Hans Lilja Journal: BMC Med Date: 2008-07-08 Impact factor: 8.775
Authors: Melissa Assel; Liisa Sjöblom; Teemu J Murtola; Kirsi Talala; Paula Kujala; Ulf-Håkan Stenman; Kimmo Taari; Anssi Auvinen; Andrew Vickers; Tapio Visakorpi; Teuvo L Tammela; Hans Lilja Journal: Eur Urol Focus Date: 2017-11-11
Authors: Daniel D Sjoberg; Andrew J Vickers; Melissa Assel; Anders Dahlin; Bing Ying Poon; David Ulmert; Hans Lilja Journal: Eur Urol Date: 2018-03-05 Impact factor: 20.096
Authors: Burcu F Darst; Alisha Chou; Peggy Wan; Loreall Pooler; Xin Sheng; Emily A Vertosick; David V Conti; Lynne R Wilkens; Loïc Le Marchand; Andrew J Vickers; Hans G Lilja; Christopher A Haiman Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-05-08 Impact factor: 4.254
Authors: 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 Journal: BJU Int Date: 2020-12-28 Impact factor: 5.969
Authors: David Eldred-Evans; Henry Tam; Heminder Sokhi; Anwar R Padhani; Mathias Winkler; Hashim U Ahmed Journal: Nat Rev Urol Date: 2020-07-21 Impact factor: 14.432