13 OUTCOMES OF PATIENTS WITH CLINICAL T1 GRADE 3 BLADDER UROTHELIAL CELL CARCINOMA TREATED WITH RADICAL CYSTECTOMY

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Outcomes of patients with clinical t1 grade 3 bladder urothelial cell carcinoma treated with radical cystectomy

Gupta A.1, Nielsen M.2, Bastian P.2, Palapattu G.2, Vazina A.3, Lerner S.3, Schoenberg M.2, Sagalowsky A.1, Lotan Y.1, Shariat S.1 UT Southwestern, Urology, Dallas, United States of America, 2John Hopkins Univ, Urology, Baltimore, United States of America, 3Baylor College of  Medicine, Urology, Houston, United States of America 1

Introduction & Objectives: Urothelial tumors that invade the lamina propria but not the muscularis propria are a particularly problematic clinical entity. The aim of the present study was to assess the pathologic features and clinical outcomes of patients with clinical T1 grade 3 urothelial cell bladder carcinoma (UCBC) who were treated with radical cystectomy. Material & Methods: The records of 958 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer at three US academic centers were reviewed. 171 of these patients (median age: 66.7 years) underwent radical cystectomy for clinical stage T1 grade 3 UCBC. Patients were categorized into those who were pathologically down-staged (lower pathologic than clinical stage and negative lymph nodes), those who had the same stage (same clinical and pathologic stage and negative lymph nodes), and those who were pathologically up-staged (higher pathologic than clinical stage or positive lymph nodes). Results: Median follow up period was 31.9 months (range: 0.5-177.1). Disease recurred in 48/171 (28.1%) of patients and 17.5% patients died due to bladder cancer. Actuarial recurrence-free estimates were 69.1% (SE: 4.1%) at 3 years, 65.9% (SE: 4.5%) at 5 years, and 57.6% (SE: 6.1%) at 7 years after cystectomy. 17.1% patients had metastases to regional lymph nodes. 51% of patients were pathologically upstaged and 27.5% had extravesical disease. Patients with disease upstaging were more likely to die of bladder cancer. Delay of more than three months between the last trans-urethral resection and radical cystectomy resulted in upstaging of 71% of patients compared to 52% for those in whom radical cystectomy was performed within three months of the last TUR (p=0.07). Pre-cystectomy CIS was associated with a higher risk of bladder cancer recurrence and mortality (p = 0.026 and 0.016 respectively). On pre-operative multivariable analysis, pre-cystectomy CIS was the only independent predictor of disease recurrence (HR: 2.5, 95%CI: 1.2-5.0) and survival (HR:3.0, 95%CI:1.2-7.8).





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Incidence and extent of prostatic urethral involvement in radical cystoprostatectomy specimens: the importance of previous bladder disease and carcinoma in situ of the bladder Arce J., Palou J., Gaya J.M., Huguet J., Rosales A., Algaba F., Villavicencio H. Fundacio Puigvert, Urology, Barcelona, Spain

Introduction & Objectives: Prostatic urethral involvement either as primary or secondary form in urothelial bladder carcinoma in cystoprostatectomy specimens is frequent. Multifocality, carcinoma in situ and other factors have been described as prognostic factors, in an attempt to identify risk group of patients with prostatic involvement. To determine the incidence and extent of prostatic urethral (PU) involvement (non-invasive and stromal invasive) and to evaluate the preoperative tumour characteristics in cystoprostatectomy specimens. Material & Methods: From 1978 to 2002, 717 men underwent radical cystoprostatectomy for urothelial cell carcinoma of the bladder. Indications for radical cystoprostatectomy (RC) were recurrence or progression of superficial bladder cancer to muscle invasive disease or primary muscle invasive bladder cancer. All the patients underwent transurethral resection of the bladder tumour (TURBT) and multiple random biopsies before RC. Patients were classified according to indication for RC. Presence of carcinoma in situ, recurrence and multifocality in previous TUR specimens were analysed. PU involvement was classified as non-invasive and stromal invasive involvement. Univariate and multivariate analysis was performed. Results: PU involvement was present in 19.5% of specimens and 59.3 % had invasive stromal involvement. In univariate analysis, there was not any difference in incidence of PU related to the indication of radical surgery due to primary muscle invasive or superficial recurrence or progression (18.7 to 23.8 %). RC specimens in superficial disease had less invasive disease in the prostate and almost statistically significant (p=0.053). Previous recurrence was not related to PU involvement. Related to multifocality, there was not a difference in the incidence but in the extent of the disease (p=0.02). Carcinoma in situ was a risk factor clearly associated to urothelial PU involvement in univariate and multivariate analysis (p=0.001, OR 1.78 CI 95 % 1.27-2.5).

Conclusions: A large proportion of patients undergoing cystectomy for clinically T1 grade 3 UCBC were upstaged at cystectomy. The recurrence and survival outcomes in this group are sub-optimal. Pre-cystectomy CIS is the best predictor of clinical outcomes after cystectomy and may help in making decisions about early cystectomy in these patients.

Conclusions: The incidence of PU involvement is similar in superficial and muscle invasive RC specimens; but with less invasive stromal pattern in superficial tumours. Only carcinoma in situ in previous TUR is an independent risk factor for prostatic urethral involvement.







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Urothelial recurrence and survival after radical nephroureterectomy in upper tract transitional cell carcinoma: analysis of 145 cases with long-term follow-up Fernández M.1, Bolenz C.1, Trojan L.1, Weiss C.2, Alken P.1, Michel M.S.1

University Hospital Mannheim, Department of Urology, Mannheim, Germany, 2University Hospital Mannheim, Department of Medical Statistics, Mannheim, Germany 1

Introduction & Objectives: Transitional cell carcinomas (TCC) of the upper tract are relatively rare tumors and large series with long-term follow-up are few. Clinicopathological parameters predictive of urothelial recurrence and survival after curative treatment are not well defined. Aim of the study was to identify prognostic factors and analyze outcomes in patients undergoing radical nephroureterectomy in a single center analysis. Material & Methods: Information on 145 patients with upper tract TCC who underwent radical nephroureterectomy from 1983 to 2004 was reviewed retrospectively. Prognostic factors like age, tumor stage, grade, tumor size, location, multifocality and history of previous urothelial carcinoma were analyzed with respect to urothelial and distant recurrence as well as survival. Results: Primary tumor stages pTa and pTis were present in 22 cases (15,2%), pT1 in 31 (21,4%), pT2 in 32 (22,1%), pT3 in 49 (33,8%) and pT4 in 11 patients (7,6%). There was no variation in these proportions throughout the twenty-year evaluation period. There were 10 (6,9%) G1, 93 (64,1%) G2 and 42 (29%) G3 lesions. Multifocality of tumors was present in 28 cases (19,3%). 52 patients had previously been treated for urothelial carcinoma, most of them located in the bladder (78,8%). Urothelial recurrence (bladder or upper tract) occurred in 44 patients, only 5 of them were located in the contralateral upper tract. Mean time for urothelial recurrence was 22,2 months. Multifocality (p=0,1) and history of previous urothelial carcinoma (p=0,08) had a weak correlation with urothelial recurrence on univariate analysis, the latter was however a significant predictor on multivariate analysis (p=0,05). After a mean follow-up of 51,4 months dead of disease was observed in 34/139 (28,2%) patients. 5-year disease-specific survival by tumor stage was 100% for pTa and pTis, 94,7% for pT1, 75% for pT2, 26% for pT3 and 20% for pT4 tumors. Tumor stage and grade correlated significantly with metastasis-free as well as with disease-specific survival on univariate analysis. Grade was the most important predictive factor for disease-specific survival on multivariate analysis (p<0,0001). Conclusions: The present series is the second largest concerning prognostic factors in upper tract TCC after radical surgery. Patients with a previous history of urothelial carcinoma are at higher risk for developing urothelial recurrence after radical surgery and should be considered for more strict surveillance. A significant proportion of upper tract TCCs still present as a locally advanced disease. As survival of patients is determined by tumor stage and grade, further strategies of complementary systemic therapy in addition to new diagnostic methods must be developed in order to improve the outcome of these high-risk tumors.

Eur Urol Suppl 2007;6(2):26



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Transitional cell carcinoma of the ureter: prognostic factors influencing progression and survival Suttmann H., Lehmann J., Kovac I., Hack M., Kamradt J., Siemer S., Wullich B., Zwergel U., Stöckle M. Saarland University Hospital, Urology, Homburg/Saar, Germany Introduction & Objectives: We retrospectively evaluated prognostic factors for progression-free and disease-specific survival in the largest mono-center cohort of patients with transitional cell carcinoma (TCC) of the ureter published so far. Material & Methods: 145 consecutive patients treated with partial resection of the ureter or nephroureterectomy between 1975 and 2004 were evaluated. Median follow-up was 96 months. Routine preoperative laboratory parameters as well as clinical and tumorspecific data were assessed. Univariate and multivariate statistical analyses were performed. Results: 5-year disease-specific survival ranged from 96,1% for stages pTa to 28,6% for pT4. Grade1 tumors were associated with 5-year diseasespecific survival rates of 100% as compared to 84% for G2, and 51,9% for G3 tumors, respectively. Univariate analyses identified pT stage and grade, tumor diameter, cM and pN categories, weight loss, the presence of synchronous tumor in the renal pelvis as well as elevated levels for humoral factors such as serum alkaline phosphatase (AP), white blood cell (WBC) count, platelet count, γ-glutamyl transferase, creatinine and blood urea nitrogen as prognostic factors. In multivariate analyses, tumor grade and WBC counts were predictive for low progression-free survival rates while simultaneous tumor in the renal pelvis, high AP levels and WBC counts were correlated with worse diseasespecific survival. Conclusions: Our retrospective analysis provides clinical factors to identify patients with TCC of the ureter at high risk for progression and death of disease. Interestingly, humoral factors such as elevated serum AP levels and high WBC counts were demonstrated to be of paramount prognostic significance besides tumor stage, grade and multifocality.