Predicting cancer progression in patients with stage T1 bladder carcinoma.

PURPOSE: A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS: The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS: The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P =.037). The 5-year progression-free survival rate for patients with depth of invasion of >/= 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P =.009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION: The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.

Natural history of urothelial dysplasia of the bladder.

Urothelial dysplasia is the putative precursor of urothelial carcinoma in situ (CIS) and invasive urothelial carcinoma of the urinary tract. Urothelial dysplasia is frequently identified in patients with urothelial CIS and cancer. However, very little is known about the clinical presentation and natural history of urothelial dysplasia in the absence of urothelial CIS or invasive cancer. The authors studied 36 patients with isolated urothelial dysplasia at the Mayo Clinic between 1969 and 1984. None of these patients had previous or concurrent urothelial CIS or invasive cancer, and none received treatment for dysplasia. The histopathologic features of urothelial dysplasia were examined, and long-term clinical follow-up was obtained. Progression was defined as the development of urothelial CIS or carcinoma. The male-to-female ratio was 2.6:1, and the mean patient age at the time of diagnosis was 60 years (range 25-79). Urothelial dysplasia has a predilection for the posterior wall. Eleven patients had urinary irritative symptoms, 10 had hematuria, 3 had both irritative symptoms and hematuria, and 12 were found to have dysplasia incidentally. The mean follow-up was 8.2 years (range 0.1-25.5). Seven (19%) of 36 patients developed biopsy-proven progression, including 4 with CIS and 3 with invasive cancer, and 1 of them died of bladder cancer. The intervals from diagnosis to progression ranged from 6 months to 8 years (mean 2.5 years). One of the remaining 29 patients had positive cytologic results 2.5 years after the initial diagnosis of dysplasia. The authors conclude that urothelial dysplasia is a significant risk for the development of CIS and invasive urothelial carcinoma, and patients with urothelial dysplasia should be followed up closely.

Prevalence and distribution of prostatic intraepithelial neoplasia in salvage radical prostatectomy specimens after radiation therapy.

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer. The effect of radiation therapy (RT) on the prevalence of PIN is uncertain. We studied 86 patients who underwent salvage radical prostatectomy after irradiation failure at the Mayo Clinic. The prevalence, volume, multicentricity, spatial proximity to cancer, and architectural patterns of PIN were evaluated. High-grade PIN was identified in 53 (62%) of 86 prostatectomy specimens. Multiple architectural patterns were usually observed, including tufting in 87%, micropapillary in 66%, cribriform in 38%, and flat in 17%. The mean volume of PIN was 0.12 cm3 (range, 0.05-1.20 cm3). PIN was usually multicentric (70%), with a mean number of PIN foci of 2.5 (range, 1-10). Ninety-four percent of PIN foci were located within 2 mm of invasive cancer. There was no correlation between PIN and pathologic stage, surgical margin, tumor size, DNA ploidy, post-RT Gleason score, time interval from RT to biopsy-proven recurrence, postoperative prostate-specific antigen level, distant metastasis-free survival, or cancer-specific survival. Our examination of salvage radical prostatectomy specimens indicated that the prevalence and extent of PIN appeared to be reduced after RT compared to published studies of prostatectomies without prior RT.

Grading and staging of bladder carcinoma in transurethral resection specimens. Correlation with 105 matched cystectomy specimens.

We compared the grading and staging of transurethral resection of the bladder (TURB) and cystectomy specimens for 105 patients who underwent radical cystectomy for urothelial carcinoma between 1980 and 1984. Of 105 patients, 96% underwent cystectomy within 100 days of TURB (median interval, 10 days). Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system and staging according to the 1997 TNM classification. Histologic grade was low-grade, 13; high-grade, 92 in TURB specimens; low-grade, 17; high-grade, 88 in cystectomy specimens. Pathologic stage was Ta, 15; T1, 55; and T2, 35 in TURB specimens; Ta, 5; T1, 19; T2, 19; T3, 46; and T4, 16 in cystectomy specimens. Histologic grade at TURB was associated with pathologic stage at cystectomy (P < .001). When all advanced-stage (muscle-invasive) carcinomas (pT2 or more) were considered together, 55 patients were understaged by TURB, 4 had higher stage in TURB than in cystectomy, and 46 were the same stage as by cystectomy. Forty-three of 55 patients with stage T1 carcinoma at TURB had advanced-stage carcinoma at cystectomy, including 34 who had extravesicular extension (pT3 or more). We found pathologic understanding by TURB occurs in a significant number of patients with bladder cancer; the newly proposed grading system predicted final pathologic stage.

Papillary urothelial neoplasms of low malignant potential. Clinical and biologic implications.

BACKGROUND: Knowledge of the long term outcomes of patients with papillary urothelial neoplasms of low malignant potential (LMP) is limited. METHODS: The authors studied 112 consecutive patients who were diagnosed with papillary urothelial neoplasms of LMP (formerly Ta, World Health Organization Grade 1 of 3 papillary urothelial carcinoma) at the Mayo Clinic between 1958 and 1963. All histologic slides were reviewed and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system. RESULTS: Patient age at diagnosis ranged from 33 to 99 years (mean, 65 years). The male-to-female ratio was 3:1. The mean follow-up was 12.8 years (range, 0.1-35 years; median, 11.7 years). Twelve patients had biopsy-proven, noninvasive urothelial carcinoma; 17 patients had cystoscopically detected recurrences (all were treated by fulguration without biopsy); and 4 patients developed invasive urothelial carcinoma (including 2 with muscle-invasive carcinoma). Twelve (75%) of 16 patients with biopsy-proven recurrence or progression had cancer dedifferentiation, which resulted in a diagnosis of higher grade cancer than was indicated on initial biopsies. The mean interval from initial diagnosis to development of invasive carcinoma was 13.3 years (range, 10-14 years). Three patients died of bladder cancer. CONCLUSIONS: Patients with papillary urothelial neoplasms of LMP have increased risks of local recurrence, progression, and death from bladder carcinoma. Long term clinical follow-up may be indicated for patient management.

Flat intraepithelial lesions of the urinary bladder.

BACKGROUND: In the 1998 World Health Organization and International Society of Urologic Pathology (WHO/ISUP) classification system for bladder neoplasms, flat intraepithelial lesions of the urinary bladder were categorized as reactive atypia, atypia of unknown significance, dysplasia, and carcinoma in situ. The clinical outcomes of patients diagnosed with these atypical urothelial proliferations are uncertain. METHODS: The authors studied a series of patients who were diagnosed with reactive atypia of the urinary bladder (25 patients), urothelial atypia of unknown significance (35), or urothelial dysplasia (26) between 1985 and 1993. All histologic slides were reviewed and classified according to the 1998 World Health Organization and International Society of Urologic Pathology classification system. Patients with a concomitant or prior history of carcinoma in situ or urothelial carcinoma were excluded. RESULTS: Patient age at diagnosis ranged from 24 to 88 years (mean, 65 years). The male-to-female ratio was 3:1. The mean follow-up was 3.9 years (range, 0.1-13.4 years; median, 3.5 years). None of the patients with reactive atypia or atypia of unknown significance developed dysplasia, carcinoma in situ, or urothelial carcinoma. Four patients (15%) with urothelial dysplasia developed biopsy-proven cancer, including 3 patients with muscle-invasive cancer. The mean interval from the diagnosis of urothelial dysplasia to the development of cancer was 4.5 years. CONCLUSIONS: Patients with a diagnosis of urothelial atypia of unknown significance or reactive atypia do not have adverse clinical outcomes, whereas patients with urothelial dysplasia of the bladder have an increased risk for the development of carcinoma in situ and urothelial carcinoma.

Substaging of T1 bladder carcinoma based on the depth of invasion as measured by micrometer: A new proposal.

BACKGROUND: A significant number of T1 bladder carcinoma patients are understaged by transurethral resection of the bladder (TURB), indicating a substantial need for more accurate staging. METHODS: The authors studied 55 patients with T1 bladder carcinoma detected by TURB at the Mayo Clinic between December 1979 and July 1984. The mean age of the patients was 66 years (range, 50-78 years). All patients were treated by cystectomy. The median interval from TURB to cystectomy was 10 days. Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system. The 1997 TNM classification was used for pathologic staging. In addition, the depth of invasion was measured from the mucosal basement membrane by micrometer. Receiver operating characteristic (ROC) analysis was used to evaluate the usefulness of depth of invasion as a marker for advanced stage bladder carcinoma (>/= T2). RESULTS: The final pathologic stages were Ta (2 patients), T1 (10 patients), T2a (9 patients), T2b (13 patients), T3 (11 patients), and T4 (10 patients) at cystectomy. There was a significant correlation between the depth of invasion at TURB and the final pathologic stage (Spearman correlation coefficient = 0.63; P < 0.001). The overall accuracy for the prediction of advanced stage (>/= T2) bladder carcinoma as measured by the area under the ROC curve was 0.89 (standard error, 0.05). Using 1.5 mm as a threshold (with >1.5 mm indicating advanced stage disease), the sensitivity, specificity, and positive and negative predictive values were 81%, 83%, 95%, and 56%, respectively. Histologic grade at the time of TURB also was associated significantly with final pathologic stage at cystectomy (P = 0.03) whereas stratification of patients according to invasion above or below the muscularis mucosae at TURB was not a significant predictor of final pathologic stage. CONCLUSIONS: The results of the current study show that substaging of T1 bladder carcinoma according to the depth of invasion (as measured by micrometer) provides significant prognostic information. Therefore the authors recommend that it be reported in specimens obtained by TURB.

Cancer heterogeneity and its biologic implications in the grading of urothelial carcinoma.

BACKGROUND: Urothelial carcinoma of the bladder often contains areas with different histologic grades. The influence of cancer heterogeneity on grading and its relation to patient outcome is uncertain. METHODS: The study group consisted of 164 patients with Ta urothelial carcinoma diagnosed at the Mayo Clinic between 1985 and 1986. None had previous or coexistent urothelial carcinoma in situ or invasive carcinoma. The primary (most common) and secondary (second most common if at least 5% of the cancer) patterns of cancer growth were graded by the newly proposed World Health Organization and International Society of Urological Pathology (WHO/ISUP) grading system. Scores of 1, 2, and 3 were assigned to urothelial neoplasms of low malignant potential (LMP), low grade urothelial carcinoma, and high grade urothelial carcinoma, respectively. The mean follow-up was 7.7 years (range, 0-13.3 years; median, 9.2 years). Progression was defined as the development of invasive carcinoma, distant metastasis, or death due to bladder carcinoma. RESULTS: Patient ages ranged from 36 to 96 years (mean, 69 years), and the male-to-female ratio was 4:1. Disease progression developed in 32 patients during a mean follow-up of 7.7 years. The mean interval from diagnosis to progression was 3.1 years (range, 0.01-8.7 years). Progression free survival was 82%, 77%, and 76% at 5, 7, and 10 years, respectively. Primary and secondary grades were different for 52 patients (32%). Based on the worst grade, 19 patients (12%) had urothelial neoplasms of low malignant potential (LMP), 92 (56%) had low grade carcinoma, and 53 (32%) had high grade carcinoma. Histologic grades based on worst, primary, secondary, and combined primary and secondary grades were all significant for predicting progression (P = 0.0009, 0.0004, 0.001, and 0.0001, respectively). Seven-year progression free survival rates for patients with LMP, low grade, and high grade carcinoma (based on worst grade) were 93%, 82%, and 61%, respectively; for patients with combined scores of 2, 3, 4, 5, and 6, survival rates were 93%, 80%, 82%, 68%, and 40%, respectively. The difference between patients with combined scores of 5 or 6 was statistically significant (P = 0.02). CONCLUSIONS: Histologic grade of urothelial carcinoma based on the newly proposed WHO/ISUP grading system stratifies patients into prognostically significant groups. Grading should also take cancer heterogeneity into consideration, and prognostic accuracy appears to be increased when the combined primary and secondary grades are applied. [See editorial counterpoint on pages 1509-12 and reply to counterpoint on pages 1513-6, this issue.]

Urothelial papilloma of the bladder. Clinical and biologic implications.

BACKGROUND: An international consensus has been reached regarding diagnostic criteria for papilloma of the urinary bladder. However, the incidences of recurrence and progression in patients with urothelial papilloma are uncertain. METHODS: The population for this study consisted of 52 patients who were diagnosed with urothelial papilloma of the bladder at the Mayo Clinic between 1914 and 1998. All histologic slides were reviewed and fulfilled the diagnostic criteria of urothelial papilloma from the 1998 World Health Organization/International Society of Urological Pathology classification system. No patients had previous or coexistent urothelial carcinoma, and none were treated after biopsy. RESULTS: The mean patient age at diagnosis was 57 years (range, 22-89 years). The male-to-female ratio was 1.9:1. The mean follow-up was 9.8 years (range, 0.1-58 years). Four patients developed recurrent papilloma (mean interval from diagnosis to recurrence, 3.3 years); 1 other patient developed papillary neoplasm of low malignant potential (Ta WHO Grade 1 papillary urothelial carcinoma) 6 years after the initial diagnosis of papilloma. None of these patients developed dysplasia, carcinoma in situ, or invasive urothelial carcinoma or died of bladder cancer. CONCLUSIONS: Patients with urothelial papilloma have a low incidence of recurrence and rarely, if ever, develop urothelial carcinoma.

Predicting the survival of bladder carcinoma patients treated with radical cystectomy.

BACKGROUND: Clinical outcomes vary for patients treated with radical cystectomy. The authors sought to identify factors associated with the survival of patients treated with radical cystectomy for urothelial carcinoma of the urinary bladder. METHODS: The authors studied 218 patients treated with radical cystectomy for urothelial carcinoma between 1980 to 1984. Patient ages ranged from 41 to 78 years (mean, 64 years). Using the 1997 TNM system, T classifications were Ta (17 patients), T1 (44), T2 (71), T3a (42), T3b (14), T4a (28), and T4b (2). Thirty-two patients had lymph node metastasis at the time of surgery. Histologic grade was determined according to the newly proposed World Health Organization and International Society of Urological Pathology grading system; tumor was low grade in 43 patients and high grade in 175. The male-to-female ratio was 4.9 to 1. The mean follow-up of patients still alive was 13.1 years (median, 13.8 years; range, 30 days to 18 years). Cox proportional hazards models were used to determine the impact of numerous clinical and pathologic findings on survival. RESULTS: Ten-year local recurrence free, distant metastasis free, cancer specific, and all-cause survival were 71%, 73%, 67%, and 41%, respectively. In univariate analysis, cancer size, T classification, and lymph node status were associated with distant metastasis free, cancer specific, and all-cause survival. Histologic grade and surgical margin status were significantly associated with worse cancer specific and all-cause survival, but not with distant metastasis free survival. In multivariate analysis, cancer size, margin status, T classification, and lymph node status were identified as significantly associated with cancer specific survival after adjustment for age and gender. CONCLUSIONS: Long term survival is achieved in a significant number of patients treated with radical cystectomy. In this study, patients with organ-confined (< or = pT2) and small size (< or = 3 cm) cancer had favorable 10-year distant metastasis free (93%) and cancer specific survival (88%) after cystectomy. Tumor size, margin status, extravesical involvement, and lymph node metastasis are important pathologic factors and should be considered as stratification variables in identifying patients for whom adjuvant chemotherapy should be evaluated in clinical trials.

Paraganglioma of the urinary bladder: can biologic potential be predicted?

BACKGROUND: Paraganglioma of the urinary bladder is rarely encountered and its biologic behavior is uncertain. The authors sought to determine the prognostic factors that would predict patient outcome. METHODS: The Mayo Clinic experience over 53 years with paraganglioma of the bladder was reviewed. All histologic slides from 16 patients were reviewed by the authors. Eight cases were examined immunohistochemically with cytokeratin (AE1/3, cytokeratin 7, and cytokeratin 20), vimentin, S-100 protein, neuroendocrine markers (chromogranin, synaptophysin, and neuron specific enolase), p53 protein, and MIB-1. DNA ploidy was determined by digital image analysis in formalin fixed, paraffin embedded tissue. The mean follow-up was 6.3 years (range, 0.4-16.4 years). RESULTS: Paraganglioma usually occurred in young adult women (mean age, 45 years; range, 16-74 years). The male-to-female ratio was 1 to 3. The common symptoms and signs were hypertension and hematuria. The tumors were usually located intramurally in the lateral and posterior wall of the bladder and were multifocal in 3 cases (18%). Seven patients were treated by transurethral resection, eight by partial cystectomy, and one by radical cystectomy. T classification was T1 (1 patient), T2 (9 patients), T3 (2 patients), and T4b (4 patients). At the time of diagnosis, one patient had distant metastasis and one had regional lymph node metastasis. One patient developed metastasis 1 year after diagnosis and died of the disease 1.5 years later. None of the patients with T1 or T2 tumors had recurrence or tumor progression. All tumors were aneuploid. The mean MIB-1 labeling index was 1.5% (range, 0.03-7.0%). The tumor cells displayed immunoreactivity for S-100 protein and neuroendocrine markers and were negative for p53 (except 1 case) and cytokeratin. CONCLUSIONS: Paraganglioma of the urinary bladder occurs mostly in young adult women. Patients with tumor of advanced classification (>/=T3) are at risk of recurrence, metastasis, and dying of the disease, whereas patients in this study with T1 or T2 disease had favorable outcomes after complete tumor resection.

Survival of patients with carcinoma in situ of the urinary bladder.

BACKGROUND: To the authors' knowledge, the long term follow-up of patients with carcinoma in situ of the urinary bladder is limited. METHODS: The authors studied 138 patients diagnosed with urothelial carcinoma in situ of the bladder at the Mayo Clinic between 1972-1979. All the histologic slides were reviewed and fulfilled the diagnostic criteria for carcinoma in situ according to the newly proposed World Health Organization and International Society of Urologic Pathology classification system. None of these patients had previous or coexisting invasive urothelial carcinoma at the time of diagnosis. Cox proportional hazards models were used to determine the prognostic significance of numerous clinical and pathologic findings using progression free, cancer specific, and all-cause survival as the endpoints for analysis. Progression was defined as the development of invasive carcinoma, distant metastases, or death from bladder carcinoma. RESULTS: The patients ages at the time of diagnosis ranged from 32-90 years (mean, 65.6 years). The male to female ratio was 7:1. Carcinoma in situ usually was multifocal (50%) with a predilection for the trigone, lateral wall, and dome. The mean follow-up after surgery was 11.0 years (range, 0.7-25 years). Actuarial progression free, cancer specific, and all-cause survival rates were 63%, 79%, and 55%, respectively, at 10 years, and 59%, 74%, and 40%, respectively, at 15 years. The mean interval from the time of diagnosis to cancer progression was 5 years. Patient age at diagnosis was significant in predicting progression free (P = 0.01) and all-cause survival (P = 0.002). Cystectomy performed within 3 months after the initial diagnosis was associated with improved all-cause survival (P = 0.03). After controlling for age, there was no difference in survival between patients who received immediate cystectomy and those did not (P = 0.16). CONCLUSIONS: Patients with carcinoma in situ of the bladder are at significant risk of cancer progression and death from bladder carcinoma. Cystectomy does not appear to offer a significant survival advantage in patients with carcinoma in situ of the bladder after adjusting for age.

Tumor size predicts the survival of patients with pathologic stage T2 bladder carcinoma: a critical evaluation of the depth of muscle invasion.

BACKGROUND: Accurate examination of radical cystectomy specimens is critical for stratifying patients into prognostically important groups and determining the need for adjuvant treatment. Evidence has accumulated that cancers invading the superficial muscle wall (T2a) behave similarly to those invading the deep muscle wall (T2b). Quantitative analysis of the depth of invasion in relation to patient outcome is needed. METHODS: The authors systematically evaluated the depth of invasion by micrometer measurement and its relation to the survival of 64 patients with bladder carcinoma pathologic classification as pT2 who had long term follow-up after radical cystectomy. Numerous clinical and pathologic variables were analyzed with univariate and multivariate Cox proportional hazards models. The mean age of patients was 64 years, and their mean follow-up was 8.3 years. RESULTS: There was no significant difference in clinical outcome between patients with T2a carcinoma and those with T2b. Lymph node metastasis and tumor size were each significantly associated with distant metastasis free and cancer specific survival. Ten-year distant metastasis free and cancer specific survival were 100% and 94%, respectively, for patients with tumors <3 cm (P = 0.006) and 68% and 73%, respectively, for patients with tumors > or = 3 cm (P = 0.005). After adjustment for lymph node status, tumor size maintained significance in predicting distant metastasis free survival (risk ratio, 1.5; 95% confidence interval, 1.1-2.0; P = 0.009) and cancer specific survival (risk ratio, 1.5; 95% confidence interval, 1.1-1.9; P = 0.01). Age was associated with recurrence free survival and all-cause survival. None of the other variables, including gender, vascular invasion, presence of carcinoma in situ, pathologic classification (T2a vs. T2b), depth of invasion, depth of muscle invasion, ratio of depth of invasion to bladder wall thickness, and percentage of muscle wall invasion, were significantly associated with patient outcome. CONCLUSIONS: The findings of this study indicate that the subclassification of T2 bladder carcinoma by depth of muscle invasion is of no prognostic value; conversely, tumor size, an easily measured factor, is predictive of distant metastasis free and cancer specific survival.

Predictors of cancer progression in T1a prostate adenocarcinoma.

BACKGROUND: The biologic behavior of T1a prostate adenocarcinoma is variable. A critical issue in the management of patients with T1a prostate adenocarcinoma is to distinguish those who will develop cancer progression from those who will not. Predictive factors that identify those at high risk of cancer progression are needed to stratify patients for treatment. In the current study the authors attempted to identify such predictors of cancer progression in a large series of untreated patients with lengthy follow-up. METHODS: The authors studied 102 patients who were diagnosed with T1a prostate adenocarcinoma (incidental tumor involving < or = 5% of the resected prostatic tissue) at the time they underwent transurethral resection of the prostate (TURP) at the Mayo Clinic between 1960-1970. None of these patients were treated. Patient ages ranged from 48-91 years (mean +/- standard deviation, 69 +/- 7 years). The average weight of the resected prostate tissue was 24 +/- 18 g (range, 3-115 g; median, 18 g). Tumor volume was measured by the grid method. Cox proportional hazards models were used to identify factors associated with cancer progression. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Five-year and 10-year progression free survival rates were 93% and 87%, respectively. During the mean follow-up of 9.5 +/- 6.8 years (range, 0.3-31 years; median, 9.0 years), 14 patients developed clinical cancer progression, including 5 patients with systemic progression (1 with distant metastases and 4 who died of prostate adenocarcinoma). The interval from diagnosis to clinical cancer progression ranged from 1-23 years (mean, 7.3 years). The amount of resected prostate tissue (TURP weight) was associated with progression (P = 0.04). Patients with a TURP weight > or = 30 g had 100% progression free survival at 10 years compared with a progression free survival rate of 73% in patients with a TURP weight < 12 g. Gleason score, tumor volume, number of chips involved by tumor, number of tumor foci, and the presence of high grade prostatic intraepithelial neoplasia were not significant in predicting cancer progression. There was a trend toward a worse prognosis with the increasing number of chips involved by cancer (P = 0.16). Patients with < 3 chips involved by cancer had a 88% 10-year progression free survival rate compared with 73% in patients with > or = 3 chips involved by cancer. CONCLUSIONS: The clinical course of T1a prostate adenocarcinoma is variable. If left untreated, a small but significant proportion of patients are at risk for disease progression and death. However, the current study found that patients with a TURP weight > or = 30 g have an excellent prognosis and can be managed conservatively.

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy.

BACKGROUND: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS: Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS: Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy.

Hemangioma of the urinary bladder.

BACKGROUND: Hemangioma of the urinary bladder is rare and the long term outcome of patients is unknown. METHODS: The authors evaluated the clinical and pathologic findings in 19 patients with a vesical hemangioma. All patients were treated at the Mayo Clinic between 1932-1998 and had histologic confirmation of the diagnosis. Hemangioma was classified into cavernous, capillary, or arteriovenous types based on conventional criteria from other sites. Clinical information was obtained from chart review. The mean follow-up of the patients was 6.9 years (range, 0.3-25 years). RESULTS: The mean patient age at the time of diagnosis was 58 years (range, 19-76 years) and the male-to-female ratio was 3.7:1. Patients typically presented with macroscopic hematuria and endoscopic findings usually were nonspecific. The diagnosis of hemangioma was suspected in 3 patients (16%) prior to biopsy. There was a predilection for the posterior and lateral walls and the tumor usually was small (range, 0.2-3 cm; median, 0.7 cm) and solitary. The histologic types of hemangioma were cavernous (15 cases), capillary (2 cases), and arteriovenous (2 cases). All patients were treated with biopsy with or without fulguration, except for one patient who was treated with a partial cystectomy. No patients developed a recurrence during a mean follow-up of 6.9 years. CONCLUSIONS: Patients with hemangioma of the urinary bladder have a favorable outcome. Biopsy and fulguration are effective for hemangioma of the bladder when the lesion is small.

p53 protein overexpression is associated with increased cell proliferation in patients with locally recurrent prostate carcinoma after radiation therapy.

BACKGROUND: The biologic changes in recurrent prostate carcinoma following radiation therapy are not fully understood. The authors sought to determine the level of p53 protein overexpression and its association with cellular proliferation (Ki-67 labeling index), glutathione S-transferase-pi (GST-pi) expression, and other clinical pathologic findings in patients with locally persistent prostate carcinoma after radiation therapy. METHODS: The authors investigated p53 nuclear accumulation, cellular proliferation activity (Ki-67 labeling index by digital image analysis), and GST-pi expression in 55 patients with persistent or recurrent prostate carcinoma after radiation therapy. All patients underwent salvage radical prostatectomy and bilateral pelvic lymphadenectomy following irradiation failure. The interval from radiation therapy to cancer recurrence ranged from 6 months to 17 years (mean, 3.8 years). Age at surgery ranged from 51 to 78 years (mean, 65 years). Mean follow-up after surgery was 5.7 years (range, 1-13 years). RESULTS: p53 protein overexpression was associated with increased cell proliferation (Spearman rank correlation coefficient = 0.29, P = 0.03). A substantial proportion (62%) of recurrent cancer also showed GST-pi immunoreactivity. No apparent correlation was observed between p53 protein overexpression, cellular proliferation (Ki-67 labeling index), or GST-pi expression and Gleason score, pathologic stage, DNA ploidy, or patient outcome. There was an inverse correlation between GST-pi expression and Gleason score (P = 0.06). The majority of prostate carcinomas (95%) were proliferative (mean Ki-67 labeling index, 7.0; range, 0-20), whereas concurrent prostatic intraepithelial neoplasia (PIN) had a lower Ki-67 labeling index (mean, 3.1; range, 0-11.5). Nineteen of 28 (68%) concurrent PIN demonstrated p53 immunoreactivity. A trend toward adverse clinical outcome was observed in patients with a higher Ki-67 labeling index in recurrent cancer. CONCLUSIONS: In this study cohort selected for salvage prostatectomy, recurrent cancers were biologically aggressive following radiation therapy. Whether this represents selective persistence and regrowth of prognostically unfavorable tumor clonogens or stepwise clonogenic progression is uncertain. Further investigation is needed to elucidate the correlation between p53 overexpression and the presence of other biologic changes after radiation therapy.