A Multi-institutional Prospective Trial in the USA Confirms that the 4Kscore Accurately Identifies Men with High-grade Prostate Cancer

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 & 8 others Kimberley Rieger-Christ, Daniel R. Saltzstein, John W. Scott, Neal D. Shore, Paul R. Sieber, Todd M. Waldmann, Fredrick N. Wolk, Stephen M. Zappala

Research output: Contribution to journalArticle

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Abstract

Background: The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy. Objective: To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA. Design, setting, and participants: Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014. Intervention: The 4Kscore. Outcome measurements and statistical analysis: The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis. Results and limitations: Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58% in the number biopsies was identified with delayed diagnosis in only 1.3-4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review. Conclusion: The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer. Patient summary: The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy. The 4Kscore accurately predicts the probability of significant cancer on prostate biopsy. The test showed excellent calibration and discrimination for Gleason ≥7 cancer and is helpful for shared decision-making regarding the need for prostate biopsy.

Original languageEnglish
JournalEuropean Urology
DOIs
StateAccepted/In press - Jan 1 2014

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Prostatic Neoplasms
Biopsy
Prostate
Calibration
Decision Support Techniques
Standard of Care
Neoplasms
Decision Making
Kallikreins
Delayed Diagnosis
Urology
Prostate-Specific Antigen
ROC Curve
Area Under Curve

Keywords

  • Biomarkers
  • Biopsy
  • Prostate cancer
  • Screening

Cite this

A Multi-institutional Prospective Trial in the USA Confirms that the 4Kscore Accurately Identifies Men with High-grade Prostate Cancer. / Parekh, Dipen J; Punnen, Sanoj; Sjoberg, Daniel D.; Asroff, Scott W.; Bailen, James L.; Cochran, James S.; Concepcion, Raoul; David, Richard D.; Deck, Kenneth B.; Dumbadze, Igor; Gambla, Michael; Grable, Michael S.; Henderson, Ralph J.; Karsh, Lawrence; Krisch, Evan B.; Langford, Timothy D.; Lin, Daniel W.; McGee, Shawn M.; Munoz, John J.; Pieczonka, Christopher M.; Rieger-Christ, Kimberley; Saltzstein, Daniel R.; Scott, John W.; Shore, Neal D.; Sieber, Paul R.; Waldmann, Todd M.; Wolk, Fredrick N.; Zappala, Stephen M.

In: European Urology, 01.01.2014.

Research output: Contribution to journalArticle

Parekh, DJ, Punnen, S, Sjoberg, DD, Asroff, SW, Bailen, JL, Cochran, JS, Concepcion, R, David, RD, Deck, KB, Dumbadze, I, Gambla, M, Grable, MS, Henderson, RJ, Karsh, L, Krisch, EB, Langford, TD, Lin, DW, McGee, SM, Munoz, JJ, Pieczonka, CM, Rieger-Christ, K, Saltzstein, DR, Scott, JW, Shore, ND, Sieber, PR, Waldmann, TM, Wolk, FN & Zappala, SM 2014, 'A Multi-institutional Prospective Trial in the USA Confirms that the 4Kscore Accurately Identifies Men with High-grade Prostate Cancer', European Urology. https://doi.org/10.1016/j.eururo.2014.10.021
Parekh, Dipen J ; Punnen, Sanoj ; Sjoberg, Daniel D. ; Asroff, Scott W. ; Bailen, James L. ; Cochran, James S. ; Concepcion, Raoul ; David, Richard D. ; Deck, Kenneth B. ; Dumbadze, Igor ; Gambla, Michael ; Grable, Michael S. ; Henderson, Ralph J. ; Karsh, Lawrence ; Krisch, Evan B. ; Langford, Timothy D. ; Lin, Daniel W. ; McGee, Shawn M. ; Munoz, John J. ; Pieczonka, Christopher M. ; Rieger-Christ, Kimberley ; Saltzstein, Daniel R. ; Scott, John W. ; Shore, Neal D. ; Sieber, Paul R. ; Waldmann, Todd M. ; Wolk, Fredrick N. ; Zappala, Stephen M. / A Multi-institutional Prospective Trial in the USA Confirms that the 4Kscore Accurately Identifies Men with High-grade Prostate Cancer. In: European Urology. 2014.
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abstract = "Background: The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy. Objective: To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA. Design, setting, and participants: Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014. Intervention: The 4Kscore. Outcome measurements and statistical analysis: The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis. Results and limitations: Gleason ≥7 PCa was found in 231 (23{\%}) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58{\%} in the number biopsies was identified with delayed diagnosis in only 1.3-4.7{\%} of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review. Conclusion: The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer. Patient summary: The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy. The 4Kscore accurately predicts the probability of significant cancer on prostate biopsy. The test showed excellent calibration and discrimination for Gleason ≥7 cancer and is helpful for shared decision-making regarding the need for prostate biopsy.",
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TY - JOUR

T1 - A Multi-institutional Prospective Trial in the USA Confirms that the 4Kscore Accurately Identifies Men with High-grade Prostate Cancer

AU - Parekh, Dipen J

AU - Punnen, Sanoj

AU - Sjoberg, Daniel D.

AU - Asroff, Scott W.

AU - Bailen, James L.

AU - Cochran, James S.

AU - Concepcion, Raoul

AU - David, Richard D.

AU - Deck, Kenneth B.

AU - Dumbadze, Igor

AU - Gambla, Michael

AU - Grable, Michael S.

AU - Henderson, Ralph J.

AU - Karsh, Lawrence

AU - Krisch, Evan B.

AU - Langford, Timothy D.

AU - Lin, Daniel W.

AU - McGee, Shawn M.

AU - Munoz, John J.

AU - Pieczonka, Christopher M.

AU - Rieger-Christ, Kimberley

AU - Saltzstein, Daniel R.

AU - Scott, John W.

AU - Shore, Neal D.

AU - Sieber, Paul R.

AU - Waldmann, Todd M.

AU - Wolk, Fredrick N.

AU - Zappala, Stephen M.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy. Objective: To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA. Design, setting, and participants: Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014. Intervention: The 4Kscore. Outcome measurements and statistical analysis: The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis. Results and limitations: Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58% in the number biopsies was identified with delayed diagnosis in only 1.3-4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review. Conclusion: The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer. Patient summary: The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy. The 4Kscore accurately predicts the probability of significant cancer on prostate biopsy. The test showed excellent calibration and discrimination for Gleason ≥7 cancer and is helpful for shared decision-making regarding the need for prostate biopsy.

AB - Background: The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy. Objective: To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA. Design, setting, and participants: Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014. Intervention: The 4Kscore. Outcome measurements and statistical analysis: The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis. Results and limitations: Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58% in the number biopsies was identified with delayed diagnosis in only 1.3-4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review. Conclusion: The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer. Patient summary: The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy. The 4Kscore accurately predicts the probability of significant cancer on prostate biopsy. The test showed excellent calibration and discrimination for Gleason ≥7 cancer and is helpful for shared decision-making regarding the need for prostate biopsy.

KW - Biomarkers

KW - Biopsy

KW - Prostate cancer

KW - Screening

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