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Published on: November 2, 2013
Comparison Between the Four-kallikrein Panel and Prostate Health Index for Predicting Prostate Cancer
Tobias Nordström1, Andrew Vickers2, Melissa Assel2
1Department of Clinical Sciences, Danderyd's Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Insights
The four-kallikrein panel and Prostate Health Index (PHI) similarly improve prostate cancer (PCa) prediction. These blood tests can help reduce unnecessary biopsies compared to prostate-specific antigen (PSA) screening.
Area of Science:
- Urology
- Oncology
- Biomarker Discovery
Background:
- Prostate cancer (PCa) screening using prostate-specific antigen (PSA) has limitations.
- The four-kallikrein panel and Prostate Health Index (PHI) show promise in improving PCa prediction.
- Direct comparisons between the four-kallikrein panel and PHI are lacking.
Purpose of the Study:
- To compare the predictive performance of the four-kallikrein panel and PHI for PCa in an independent cohort.
- To evaluate the ability of these biomarkers to reduce unnecessary prostate biopsies.
Main Methods:
- Analysis of a population-based cohort of 531 men with PSA levels between 3-15 ng/ml undergoing first-time prostate biopsy.
- Statistical modeling to predict PCa status, including calibration curves and area under the receiver-operating characteristics curve (AUC).
- Decision curve analysis to assess the net benefit and percentage of saved biopsies.
Main Results:
- The four-kallikrein panel and PHI demonstrated similar AUCs for predicting any-grade PCa (69.0% and 70.4%, respectively) and high-grade PCa (71.8% and 71.1%, respectively).
- Both models significantly outperformed a base model using PSA and age (p<0.0001).
- Utilizing a 10% predicted risk cut-off, both biomarkers could save 29% of biopsies, with a 10% risk of delayed diagnosis for high-grade cancers.
Conclusions:
- The four-kallikrein panel and PHI offer comparable improvements in predicting PCa and high-grade PCa.
- These blood tests represent valuable tools to reduce unnecessary prostate biopsies compared to PSA screening alone.
- Both biomarkers provide an important new option for optimizing prostate cancer diagnosis and reducing patient harm.
Background:
The four-kallikrein panel and the Prostate Health Index (PHI) have been shown to improve prediction of prostate cancer (PCa) compared with prostate-specific antigen (PSA). No comparison of the four-kallikrein panel and PHI has been presented.
Objective:
To compare the four-kallikrein panel and PHI for predicting PCa in an independent cohort.
Design, Setting, And Participants:
Participants were from a population-based cohort of PSA-tested men in Stockholm County. We included 531 men with PSA levels between 3 and 15 ng/ml undergoing first-time prostate biopsy during 2010-2012.
Outcome Measurements And Statistical Analysis:
Models were fitted to case status. We computed calibration curves, the area under the receiver-operating characteristics curve (AUC), decision curves, and percentage of saved biopsies.
Results And Limitations:
The four-kallikrein panel showed AUCs of 69.0 when predicting any-grade PCa and 71.8 when predicting high-grade cancer (Gleason score ≥7). Similar values were found for PHI: 70.4 and 71.1, respectively. Both models had higher AUCs than a base model with PSA value and age (p<0.0001 for both); differences between models were not significant. Sensitivity analyses including men with any PSA level or a previous biopsy did not materially affect our findings. Using 10% predicted risk of high-grade PCa by the four-kallikrein panel or PHI of 39 as cut-off for biopsy saved 29% of performed biopsies at a cost of delayed diagnosis for 10% of the men with high-grade cancers. Both models showed limited net benefit in decision analysis. The main study limitation was lack of digital rectal examination data and biopsy decision being based on PSA information.
Conclusions:
The four-kallikrein panel and PHI similarly improved discrimination when predicting PCa and high-grade PCa. Both are simple blood tests that can reduce the number of unnecessary biopsies compared with screening with total PSA, representing an important new option to reduce harm.
Patient Summary:
Prostate-specific antigen screening is controversial due to limitations of the test. We found that two blood tests, the Prostate Health Index and the four-kallikrein panel, performed similarly and could both aid in decision making among Swedish men undergoing a prostate biopsy.
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