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Multicenter Study
. 2013 Nov 15;119(22):3992-4002.
doi: 10.1002/cncr.28303. Epub 2013 Sep 4.

Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer

Matthew Truong  1 , Jon A Slezak, Chee Paul Lin, Viacheslav Iremashvili, Martins Sado, Aria A Razmaria, Glen Leverson, Mark S Soloway, Scott E Eggener, E Jason Abel, Tracy M Downs, David F Jarrard
Affiliations
Multicenter Study

Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer

Matthew Truong et al. Cancer. .

Abstract

Background: Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC.

Methods: More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis.

Results: On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals.

Conclusions: A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance.

Keywords: active surveillance; low-risk prostate cancer; prostate-specific antigen.

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURE

Dr. Jarrard has been a consultant for Dendreon and Johnson & Johnson, and has grants from National Institutes of Health. Mr. Slezak has received grants from the National Institutes of Health and University of Wisconsin School of Medicine and Public Health. Dr. Eggener has been a consultant for Myriad Genetics and Genomic Health, has received grants from Myriad Genetics, and has received travel/meeting expenses from Myriad Genetics and Genomic Health. Dr. Downs has been a consultant for Photocure. Dr. Soloway has received travel/meeting expenses from Photocure, Astellas, and Sanofi Aventis. All other authors made no disclosure.

Figures

Figure 1
Figure 1
Receiver operating characteristic curves are shown for the Biopsy-Integrated Algorithm for Determining Gleason 6 Upgrading Risk (BADGR). BADGR discriminated with areas under the curve (AUCs) of 0.753, 0.677, and 0.672 at University of Wisconsin (UW), University of Chicago (UC), and University of Miami (UM), respectively (all P <0.0001).
Figure 2
Figure 2
Calibration and decision curves for the Biopsy-Integrated Algorithm for Determining Gleason 6 Upgrading Risk (BADGR) are shown. (A) Calibration demonstrated virtually no departure from ideal predictions in all cohorts across all probabilities of upgrading from Gleason 6 prostate cancer. (B) Decision analysis demonstrated high net benefit across a wide range of threshold probabilities. PSAD indicates prostate-specific antigen density.
Figure 2
Figure 2
Calibration and decision curves for the Biopsy-Integrated Algorithm for Determining Gleason 6 Upgrading Risk (BADGR) are shown. (A) Calibration demonstrated virtually no departure from ideal predictions in all cohorts across all probabilities of upgrading from Gleason 6 prostate cancer. (B) Decision analysis demonstrated high net benefit across a wide range of threshold probabilities. PSAD indicates prostate-specific antigen density.
Figure 3
Figure 3
Graphical representation of the Biopsy-Integrated Algorithm for Determining Gleason 6 Upgrading Risk (BADGR). BADGR is validated and calibrated for use in predicting upgrading in patients with Gleason 6 PC with least 10 cores on transrectal ultrasound-guided biopsy and no history of neoadjuvant therapy. Each individual variable is assigned points using the top scale. The total points score is then converted to the predicted probability of Gleason upgrading using the bottom scale. Abbreviations: BMI, body mass index; PSAD, prostate-specific antigen density.
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