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Purpose: The pathological grade of bladder cancer has an immense impact on patient treatment and prognosis. While most bladder tumors show pure high or low grade patterns, some show a mixed pattern. We explored the incidence and clinical significance of this phenomenon., Materials and Methods: A total of 642 patients with a mean age of 67.5 years underwent transurethral resection of nonmuscle invasive bladder tumors between June 1998 and December 2008, including 156 and 454 with low and high grade lesions, respectively. In 32 patients (5%) mixed grade tumors were found, defined as low grade tumors with 10% or less of a high grade component. All patients were followed a median of 60 months postoperatively., Results: Mean age, the proportion of men and the proportion of stages Ta/T1 in patients with mixed grade tumors were between those of the high and low grade groups. Five-year recurrence-free survival was similar for high, low and mixed grade tumor types (56.9%, 63.8% and 66.4%, respectively, p=0.252). Five-year progression-free survival was significantly lower in patients with high grade disease (73.9%, p<0.0001) but similar in those with high and mixed grade tumors (99% and 96.9%, respectively, p=0.167). Similarly, disease specific survival was significantly worse in patients with high grade tumors (p<0.0001) but similar in those with high and mixed grade lesions (p=0.679)., Conclusions: Mixed grade is found in about 5% of nonmuscle invasive tumors, representing a patient group with unique clinical features. The clinical course of patients with mixed grade tumors parallels that of patients with low grade tumors., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Renal cell carcinoma invading the perinephric fat is classified as a stage T3a tumor in the 2002 TNM version. Based on long-term followup we examined the prognostic significance of this definition., Materials and Methods: We evaluated the outcome in 237 consecutive patients with localized renal cell carcinoma operated on between January 1985 and December 1997. Median followup was 8 years. Disease-free survival was analyzed using univariate and multivariate analyses. Based on this we proposed and tested a new TNM system against the 2002 TNM version., Results: Tumor recurrence was diagnosed in 48 patients (20.2%) at a median of 21.5 months. Diameter based analysis of stage T3a revealed that this was an inhomogeneous group that included patients with small tumors and an excellent prognosis along with patients with large tumors and a poor prognosis. Based on this information we initiated a modified TNM staging system that ignores perinephric fat invasion. In the proposed staging system stage T1a includes tumors 4 cm or less and stage T1b includes tumors more than 4 but 7 cm or less. Stage T2 is divided into T2a-tumors greater than 7 but 10 cm or less and T2b-tumors greater than 10 cm. Stage T3a is reserved for renal vein tumor invasion. The proposed TNM performed better than the 2002 version using the Nagelkerke R(2) test (0.439 vs 0.359), and the Hosmer and Lemeshow test (0.335 vs 0.191)., Conclusions: The current definition of stage T3a renal cell carcinoma embraces an inhomogeneous group of patients with marked differences in prognosis. We believe that tumor invasion into the perinephric fat does not necessarily predict aggressive biological behavior.

We studied 196 radical prostatectomy cases performed for clinical stage B prostate cancer with capsular penetration; in all cases seminal vesicles and lymph nodes were free of tumor. The mean followup in patients who showed no evidence of progression was 5 years. Focal capsular penetration was seen in 93 cases. There was no difference in progression in this group, irrespective of whether margins were negative or positive. High grade tumors (Gleason score 7 or more) had a significantly higher risk of progression compared to lower grade tumors (p = 0.0002). Established capsular penetration was seen in 103 tumors. Cancers with established capsular penetration had a higher risk of progression than those with focal capsular penetration. Established capsular penetration tumors were stratified into 3 groups with increasing risks of progression: 1) margins were negative and grade was low, 2) margins were positive or grade was high yet both adverse features were not present or 3) margins were positive and grade was high. The differences in progression among these 3 groups were statistically significant. Because of the negligible influence of positive margins in patients with focal capsular penetration the status of capsular margins should not influence the decision on whether to administer immediate postoperative adjuvant therapy. To evaluate the efficacy of adjuvant therapy following radical prostatectomy, tumors with capsular penetration should be stratified into groups having similar risks of progression according to the extent of capsular penetration, surgical margins of resection and grade.

Using image cytometry and a video planimetry unit, various deoxyribonucleic acid (DNA) measurements, nuclear size and shape factors, and Gleason grade were correlated with capsular penetration, seminal vesicle invasion and lymph node involvement in 113 radical prostatectomy specimens. Percentage of nondiploid cells was the best DNA measurement and standard deviation of nuclear area was the best size measurement correlating with capsular penetration. However, stepwise regression analysis demonstrated that Gleason grade was the only independent predictor of capsular penetration. The only parameter that independently predicted seminal vesicle invasion in a stepwise regression analysis was percentage of tetraploid cells. The mode of optical density was the best DNA measurement for predicting lymph node involvement, although stepwise regression analysis found that Gleason grade was the only independent predictor. DNA ploidy was not as predictive of pathological stage. In summary, DNA measurements and nuclear morphometry performed on smears offered relatively little additional prediction of pathological stage over that of Gleason grade.