Daniel D Sjoberg1, Andrew J Vickers1, Melissa Assel1, Anders Dahlin2, Bing Ying Poon1, David Ulmert3, Hans Lilja4. 1. Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Department of Clinical Microbiology, Lund University, Skåne University Hospital, Malmö, Sweden. 3. Molecular Pharmacology Program, Sloan Kettering Institute, New York, NY, USA; Division of Urological Research, Department of Clinical Sciences, Lund University, Malmö, Sweden. 4. Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Translational Medicine, Lund University, Malmö, Sweden. Electronic address: liljah@mskcc.org.
Abstract
BACKGROUND: Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. OBJECTIVE: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. DESIGN, SETTING, PARTICIPANTS: Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. RESULTS AND LIMITATIONS: Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. CONCLUSIONS: A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. PATIENT SUMMARY: Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy.
BACKGROUND:Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. OBJECTIVE: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. DESIGN, SETTING, PARTICIPANTS: Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. RESULTS AND LIMITATIONS: Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. CONCLUSIONS: A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. PATIENT SUMMARY:Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy.
Authors: H Ballentine Carter; Peter C Albertsen; Michael J Barry; Ruth Etzioni; Stephen J Freedland; Kirsten Lynn Greene; Lars Holmberg; Philip Kantoff; Badrinath R Konety; Mohammad Hassan Murad; David F Penson; Anthony L Zietman Journal: J Urol Date: 2013-05-06 Impact factor: 7.450
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: Andrew J Vickers; Cathee Till; Catherine M Tangen; Hans Lilja; Ian M Thompson Journal: J Natl Cancer Inst Date: 2011-02-24 Impact factor: 13.506
Authors: Dipen J Parekh; Sanoj Punnen; Daniel D Sjoberg; Scott W Asroff; James L Bailen; James S Cochran; Raoul Concepcion; Richard D David; Kenneth B Deck; Igor Dumbadze; Michael Gambla; Michael S Grable; Ralph J Henderson; Lawrence Karsh; Evan B Krisch; Timothy D Langford; Daniel W Lin; Shawn M McGee; John J Munoz; Christopher M Pieczonka; Kimberley Rieger-Christ; Daniel R Saltzstein; John W Scott; Neal D Shore; Paul R Sieber; Todd M Waldmann; Fredrick N Wolk; Stephen M Zappala Journal: Eur Urol Date: 2014-10-27 Impact factor: 20.096
Authors: Andrew J Vickers; Angel M Cronin; Thomas Björk; Jonas Manjer; Peter M Nilsson; Anders Dahlin; Anders Bjartell; Peter T Scardino; David Ulmert; Hans Lilja Journal: BMJ Date: 2010-09-14
Authors: Mieke Van Hemelrijck; Annette Wigertz; Fredrik Sandin; Hans Garmo; Karin Hellström; Per Fransson; Anders Widmark; Mats Lambe; Jan Adolfsson; Eberhard Varenhorst; Jan-Erik Johansson; Pär Stattin Journal: Int J Epidemiol Date: 2012-05-04 Impact factor: 7.196
Authors: Andrew J Vickers; David Ulmert; Daniel D Sjoberg; Caroline J Bennette; Thomas Björk; Axel Gerdtsson; Jonas Manjer; Peter M Nilsson; Anders Dahlin; Anders Bjartell; Peter T Scardino; Hans Lilja Journal: BMJ Date: 2013-04-15
Authors: Melissa J Assel; Hans David Ulmert; R Jeffery Karnes; Stephen A Boorjian; David W Hillman; Andrew J Vickers; George G Klee; Hans Lilja Journal: Prostate Date: 2019-10-11 Impact factor: 4.104
Authors: Emily A Vertosick; Stephen Zappala; Sanoj Punnen; Jonas Hugosson; Stephen A Boorjian; Alexander Haese; Peter Carroll; Matthew Cooperberg; Anders Bjartell; Hans Lilja; Andrew J Vickers Journal: Urology Date: 2021-08-24 Impact factor: 2.649
Authors: Weiqiang Li; Mesude Bicak; Daniel D Sjoberg; Emily Vertosick; Anders Dahlin; Olle Melander; David Ulmert; Hans Lilja; Robert J Klein Journal: Prostate Date: 2020-09-11 Impact factor: 4.104
Authors: Evan Kovac; Sigrid V Carlsson; Hans Lilja; Jonas Hugosson; Michael W Kattan; Erik Holmberg; Andrew J Stephenson Journal: JAMA Netw Open Date: 2020-01-03
Authors: Ingrid J Guldvik; Verena Zuber; Peder R Braadland; Helene H Grytli; Håkon Ramberg; Wolfgang Lilleby; Bernd Thiede; Manuela Zucknick; Fahri Saatcioglu; Randi Gislefoss; Rune Kvåle; Anne George; Henrik Grönberg; Fredrik Wiklund; David E Neal; Vincent J Gnanapragasam; Kristin A Taskén; Ian G Mills Journal: Eur Urol Open Sci Date: 2020-10-13