Sten Holmäng

A retrospective study was done on 176 patients with primary stages Ta and T1 bladder cancer treated between 1963 and 1972. One patient was lost to followup after 6 years, while the remainder were followed to death or for at least 20 years. In 1993, 13 patients had no evidence of disease, 39 died of bladder cancer and 123 died of intercurrent disease. Of 77 patients with a primary noninfiltrating tumor and 99 with a primary lamina propria invasive tumor 9 (11%) and 30 (30%), respectively, died of bladder cancer. Recurrences were noted on 10 or more cystoscopic studies in 16 patients and 10 died of bladder cancer 3.5 to 19 years after the primary transurethral resection. A total of 14 patients received repeated thiotepa instillations, all continued to have recurrences and 10 subsequently died of bladder cancer. Only 1 upper tract tumor was diagnosed on routine followup excretory urography. Invasive transitional cell carcinoma of the bladder developed in only 1 of 59 patients who had been tumor-free for 5 years. The results indicate that patients with recurrences on 10 or more cystoscopic studies will continue to have recurrences until death or cystectomy. Recurrence more than 4 years after the primary tumor operation is another ominous sign. Repeated thiotepa instillations did not influence the course of the disease in patients with a history of multiple recurrences. Followup cystoscopy may be discontinued 5 to 10 years after the last recurrence, at least in patients with a solitary low grade primary tumor. Routine followup urographic studies are neither cost-effective, clinically indicated nor justified in patients with superficial bladder cancer.

PURPOSE: We studied 363 patients with stage Ta bladder tumors during long-term followup who were classified according to the 1998 WHO and International Society of Urological Pathology consensus classifications. We determine whether various immunohistochemical and molecular markers could predict tumor progression. MATERIALS AND METHODS: A total of 680 patients in western Sweden with a first diagnosis of bladder carcinoma in 1987 and 1988 were registered and followed for at least 5 years. There were 363 (53%) tumors that were papillary stage pTa. The tumors were classified as papillary urothelial neoplasm of low malignant potential in 95 patients, low grade papillary urothelial carcinoma in 160 and high grade carcinoma in 108. Of the patients in the latter group 95 were subdivided into WHO grade 2 and 13 into WHO grade 3. Tissue from the primary tumors that progressed in stage during followup was further analyzed with immunohistochemical methods (p21, p53, Ki67 and pRb), DNA ploidy and mitotic frequency. The results were compared with those in matched controls (nonprogressors). RESULTS: Recurrence developed in 35% of patients with papillary urothelial neoplasm of low malignant potential compared to 71% with low grade urothelial carcinoma and 73% with high grade carcinoma (p <0.0001). No papillary urothelial neoplasm of low malignant potential progressed in stage. Disease progressed in 4% of patients with low grade compared to 23% with high grade carcinoma (p <0.0001). Of the patients with WHO grade 3 disease progressed in 45% compared to grade 2 in 20% (p <0.0011). At first diagnosis p53 score was significantly higher (p <0.0022) among patients with WHO grade 2 carcinoma which later progressed compared to that in matched controls but there was no significant difference regarding the other markers. In contrast to grade 2 most grade 3 carcinoma was aneuploid, had high mitosis frequency, high p53 and Ki67 scores as well as loss of retinoblastoma gene expression. CONCLUSIONS: The 1988 WHO and International Society of Urological Pathology consensus classifications divide noninvasive papillary bladder tumors into 3 subgroups with different clinical behavior, which seems to be an advantage compared with the 1973 WHO classification. A disadvantage is that the high grade carcinoma group contains 2 subgroups with different progression rates and immunohistochemical marker profiles, corresponding to the 1999 WHO grades 2 and 3. Grade 2 tumors in patients that progressed in stage years later seem to have different immunohistochemical and molecular marker profiles compared to those in matched controls.

PURPOSE: We report long-term followup data on patients with World Health Organization (WHO) grade I bladder tumors, and determine whether histopathological subgrouping as papillary neoplasm of low malignant potential and low grade papillary carcinoma is of clinical value. MATERIALS AND METHODS: All 680 patients in western Sweden with first diagnosis of bladder carcinoma in 1987 to 1988 were registered and followed for at least 5 years. Of the tumors 255 (37.5%) were stage Ta, WHO grade I. Tumors were further classified as papillary neoplasm of low malignant potential in 95 patients and low grade papillary carcinoma in 160 according to WHO and the International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the bladder. RESULTS: Mean age of patients at first diagnosis of low grade papillary carcinoma was 69.2 years, which was 4.6 years higher than those with papillary neoplasm of low malignant potential (p<0.005). During a mean observation time of 60 months our 255 patients underwent 577 operations for recurrences and had 1,858 negative cystoscopies. The risk of recurrence was significantly lower in patients with papillary neoplasm of low malignant potential compared to those with low grade papillary carcinoma (35 versus 71%, p<0.001). The risk of recurrence was higher in patients with multiple tumors at first diagnosis as well as those with recurrence at the first followup after 3 to 4 months. Stage progressed in 6 patients (2.4%), all with low grade papillary carcinoma at diagnosis. CONCLUSIONS: More than 90% of patients with stage Ta, WHO grade I have a benign form of bladder neoplasm, and few have truly malignant tumors. Future research should focus on reducing the number of recurrences and followup cystoscopies, and finding methods to identify malignant tumors so that pertinent treatment can be instituted. Subgrouping of WHO grade I bladder tumors as papillary neoplasm of low malignant potential and low grade papillary carcinoma seems to add valuable prognostic information.