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Prediction of Prostate-Specific Antigen Recurrence in Men with Long-term Follow-up Postprostatectomy Using Quantitative Nuclear Morphometry

¹ The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland and ² Quakertown, Pennsylvania

Requests for reprints: Robert W. Veltri, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287. Phone: 410-614-6380; Fax: 410-614-3695. E-mail: rveltri1{at}jhmi.edu

Background: Nuclear morphometric signatures can be calculated using nuclear size, shape, DNA content, and chromatin texture descriptors [nuclear morphometric descriptor (NMD)]. We evaluated the use of a patient-specific quantitative nuclear grade (QNG) alone and in combination with routine pathologic features to predict biochemical [prostate-specific antigen (PSA)] recurrence-free survival in patients with prostate cancer.

Methods: The National Cancer Institute Cooperative Prostate Cancer Tissue Resource (NCI-CPCTR) tissue microarray was prepared from radical prostatectomy cases treated in 1991 to 1992. We assessed 112 cases (72 nonrecurrences and 40 PSA recurrences) with long-term follow-up. Images of Feulgen DNA–stained nuclei were captured and the NMDs were calculated using the AutoCyte system. Multivariate logistic regression was used to calculate QNG and pathology-based solutions for prediction of PSA recurrence. Kaplan-Meier survival curves and predictive probability graphs were generated.

Results: A QNG signature using the variance of 14 NMDs yielded an area under the receiver operator characteristic curve (AUC-ROC) of 80% with a sensitivity, specificity, and accuracy of 75% at a predictive probability threshold of 0.39. A pathology model using the pathologic stage and Gleason score yielded an AUC-ROC of 67% with a sensitivity, specificity, and accuracy of 70%, 50%, and 57%, respectively, at a predictive probability threshold of 0.35. Combining QNG, pathologic stage, and Gleason score yielded a model with an AUC-ROC of 81% with a sensitivity, specificity, and accuracy of 75%, 78%, and 77%, respectively, at a predictive probability threshold of 0.34.

Conclusions: PSA recurrence is more accurately predicted using the QNG signature compared with routine pathology information alone. Inclusion of a morphometry signature, routine pathology, and new biomarkers should improve the prognostic value of information collected at surgery. (Cancer Epidemiol Biomarkers Prev 2008;17(1):102–10)