PREDICTORS OF GLEASON PATTERN 4/5 PROSTATE CANCER ON PROSTATECTOMY SPECIMENS: CAN HIGH GRADE TUMOR BE PREDICTED PREOPERATIVELY?

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Abstract
Radical prostatectomy provides excellent cancer control in men with clinically localized prostate carcinoma. However, to our knowledge preoperative parameters for distinguishing indolent from clinically significant cancer are not well characterized. In fact, recent evidence suggests that the percent of Gleason pattern 4/5 carcinoma in the complete radical prostatectomy specimen is one of the strongest predictors of prostate cancer progression and a valid measure of cancer severity. However, it is unclear whether preoperative parameters, including biopsy Gleason pattern 4/5 carcinoma, may predict radical prostatectomy Gleason pattern 4/5 disease and, thereby, distinguish indolent from clinically significant cancer. We prospectively obtained 101 consecutive radical prostatectomy specimens and processed them in whole mount fashion. In addition to total tumor volume, we determined tumor volume for each Gleason pattern. Biopsy tumor area was measured in a similar fashion. Univariate and multivariate analyses were performed to identify preoperative clinical and pathology parameters for predicting Gleason pattern 4/5 carcinoma on prostatectomy specimens. Biopsy Gleason score 7 or greater, Gleason pattern 4/5 carcinoma, perineural invasion and biopsy tumor area had statistically significant associations for identifying Gleason pattern 4/5 carcinoma on prostatectomy specimens. Logistic regression models for predicting any or greater than 10% Gleason pattern 4/5 carcinoma on prostatectomy specimens revealed that an area of pattern 4/5 disease of greater than 0.01 cm.2 on biopsy was the best single predictor with odds ratios of 15.0 (95% confidence interval 3.3 to 69.0, p = 0.0005) and 3.9 (95% confidence interval 1.4 to 10.9, p = 0.009), respectively. For predicting any pattern 4/5 carcinoma on prostatectomy specimens a biopsy area of pattern 4/5 disease of greater than 0.01 cm.2 had only 38% sensitivity but 96% specificity. Similarly for predicting significant pattern 4/5 disease on prostatectomy specimens, defined as 10% or greater pattern 4/5, sensitivity and specificity for a biopsy area of greater than 0.01 cm.2 were 34% and 88%, respectively. Therefore, due to high false-negative rates these models had limited predictive value on an individual basis. Biopsy parameters such as Gleason pattern 4/5 carcinoma may provide adequate specificity for predicting clinically significant cancer, as defined by high grade Gleason patterns in the corresponding radical prostatectomy specimen. However, the accuracy of these parameters for predicting indolent cancer is limited by a prohibitive rate of false-negative findings.