Prediction of pathological stage in patients with clinical stage T1c prostate cancer: The new challenge

Purpose: We developed an algorithm for predicting the likelihood of organ confined disease in patients with clinical stage T1c prostate cancer using biopsy pathology, computer assisted image analysis and serum prostate specific antigen (PSA). Materials and Methods: Of the 557 consecutive men enrolled in this study between October 1998 and January 2000 scheduled for radical prostatectomy at a single institution 386 (69%) presented with clinical stage T1c disease. Study exclusion criteria included neoadjuvant hormonal treatment with luteinizing hormone-releasing hormone, antiandrogen or 5alpha-reductase inhibitors. Preoperative serum, biopsy histology slides, clinical demographic information, prostatectomy pathology and prostate weight data were obtained. Biomarkers assessed included total PSA, complexed PSA, free PSA, the free-to-total PSA ratio, quantitative nuclear grade determined by image analysis, complexed PSA density, and biopsy Gleason grade and score. To determine patient specific quantitative nuclear grade values, images from approximately 125 cancer nuclei were captured per patient from the area of the biopsy section with the highest Gleason score. The variance in 60 nuclear size, shape and chromatin texture descriptors was calculated for each gallery of nuclei. Logistic regression was done to determine the most accurate combination of variables for predicting organ confined prostate cancer. Results: Complete results and data were available on 255 of the 386 men (66%) with an average age plus or minus standard deviation of 58.8 +/- 6 years who had stage T1c disease, including 49 (19%) with pathologically nonorgan confined disease. Logistic regression analysis revealed that quantitative nuclear grade, biopsy Gleason score, total PSA, the calculated free-to-total PSA ratio, complexed PSA and complexed PSA density were univariately significant for predicting organ confined disease (p < 0.05). On backward stepwise logistic regression only quantitative nuclear grade, complexed PSA density and Gleason score remained in a model yielding an area under the receiver operating characteristics curve of 82.4%. Conclusions: The quantitative nuclear grade biomarker was the strongest independent predictor of pathological stage in men with clinical stage T1c prostate cancer when combined with biopsy Gleason score and complexed PSA density data.