Post by Deleted on Nov 25, 2016 17:37:04 GMT
Evaluating the Four Kallikrein Panel of the 4Kscore for Prediction of High-grade Prostate Cancer in Men in the Canary Prostate Active Surveillance Study
Abstract
Background
Diagnosis of Gleason 6 prostate cancer can leave uncertainty about the presence of undetected aggressive disease.
Objective
To evaluate the utility of a four kallikrein (4K) panel in predicting the presence of high-grade cancer in men on active surveillance.
Design, setting, and participants
Plasma collected before the first and subsequent surveillance biopsies was assessed for 718 men prospectively enrolled in the multi-institutional Canary PASS trial. Biopsy data were split 2:1 into training and test sets. We developed statistical models that included clinical information and either the 4Kpanel or serum prostate-specific antigen (PSA).
Outcome measurements and statistical analysis
The endpoint was reclassification to Gleason ≥7. We used receiver operating characteristic (ROC) curve analyses and area under the curve (AUC) to assess discriminatory capacity, and decision curve analysis (DCA) to report clinical net benefit.
Results and limitations
Significant predictors for reclassification were 4Kpanel (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.31–1.81) or PSA (OR 2.11, 95% CI 1.53–2.91), ≥20% cores positive (OR 2.10, 95% CI 1.33–3.32), two or more prior negative biopsies (OR 0.19, 95% CI 0.04–0.85), prostate volume (OR 0.47, 95% CI 0.31–0.70), and body mass index (OR 1.09, 95% CI 1.04–1.14). ROC curve analysis comparing 4K and base models indicated that the 4Kpanel improved accuracy for predicting reclassification (AUC 0.78 vs 0.74) at the first surveillance biopsy. Both models performed comparably for prediction of reclassification at subsequent biopsies (AUC 0.75 vs 0.76). In DCA, both models showed higher net benefit compared to biopsy-all and biopsy-none strategies. Limitations include the single cohort nature of the study and the small numbers; results should be validated in another cohort before clinical use.
Conclusions
The 4Kpanel provided incremental value over routine clinical information in predicting high-grade cancer in the first biopsy after diagnosis. The 4Kpanel did not add predictive value to the base model at subsequent surveillance biopsies.
Patient summary
Active surveillance is a management strategy for many low-grade prostate cancers. Repeat biopsies monitor for previously undetected high-grade cancer. We show that a model with clinical variables, including a panel of four kallikreins, indicates the presence of high-grade cancer before a biopsy is performed.
Take Home Message
In men undergoing active surveillance, the Four Kallikrein panel provides incremental value over routine clinical information for prediction of high-grade cancer in the first biopsy after diagnosis. These data support incorporation of emerging biomarkers in models that aid in patient decision-making.
www.europeanurology.com/article/S0302-2838(16)30850-8/abstract/evaluating-the-four-kallikrein-panel-of-the-4kscore-for-prediction-of-high-grade-prostate-cancer-in-men-in-the-canary-prostate-active-surveillance-study
Abstract
Background
Diagnosis of Gleason 6 prostate cancer can leave uncertainty about the presence of undetected aggressive disease.
Objective
To evaluate the utility of a four kallikrein (4K) panel in predicting the presence of high-grade cancer in men on active surveillance.
Design, setting, and participants
Plasma collected before the first and subsequent surveillance biopsies was assessed for 718 men prospectively enrolled in the multi-institutional Canary PASS trial. Biopsy data were split 2:1 into training and test sets. We developed statistical models that included clinical information and either the 4Kpanel or serum prostate-specific antigen (PSA).
Outcome measurements and statistical analysis
The endpoint was reclassification to Gleason ≥7. We used receiver operating characteristic (ROC) curve analyses and area under the curve (AUC) to assess discriminatory capacity, and decision curve analysis (DCA) to report clinical net benefit.
Results and limitations
Significant predictors for reclassification were 4Kpanel (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.31–1.81) or PSA (OR 2.11, 95% CI 1.53–2.91), ≥20% cores positive (OR 2.10, 95% CI 1.33–3.32), two or more prior negative biopsies (OR 0.19, 95% CI 0.04–0.85), prostate volume (OR 0.47, 95% CI 0.31–0.70), and body mass index (OR 1.09, 95% CI 1.04–1.14). ROC curve analysis comparing 4K and base models indicated that the 4Kpanel improved accuracy for predicting reclassification (AUC 0.78 vs 0.74) at the first surveillance biopsy. Both models performed comparably for prediction of reclassification at subsequent biopsies (AUC 0.75 vs 0.76). In DCA, both models showed higher net benefit compared to biopsy-all and biopsy-none strategies. Limitations include the single cohort nature of the study and the small numbers; results should be validated in another cohort before clinical use.
Conclusions
The 4Kpanel provided incremental value over routine clinical information in predicting high-grade cancer in the first biopsy after diagnosis. The 4Kpanel did not add predictive value to the base model at subsequent surveillance biopsies.
Patient summary
Active surveillance is a management strategy for many low-grade prostate cancers. Repeat biopsies monitor for previously undetected high-grade cancer. We show that a model with clinical variables, including a panel of four kallikreins, indicates the presence of high-grade cancer before a biopsy is performed.
Take Home Message
In men undergoing active surveillance, the Four Kallikrein panel provides incremental value over routine clinical information for prediction of high-grade cancer in the first biopsy after diagnosis. These data support incorporation of emerging biomarkers in models that aid in patient decision-making.
www.europeanurology.com/article/S0302-2838(16)30850-8/abstract/evaluating-the-four-kallikrein-panel-of-the-4kscore-for-prediction-of-high-grade-prostate-cancer-in-men-in-the-canary-prostate-active-surveillance-study