134Prognostic impact of tumour stage, grade and angioinvasion in transitional cell carcinoma of the upper urinary tract

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RISK FACTORS FOR BLADDER TUMOUR DEVELOPMENT A F [ E R T R A N S I T I O N A L CELL C A R C I N O M A OF THE UPPER URINARY TRACT

P R O G N O S T I C IMPACT OF T U M O U R STAGE, GRADE AND ANGIOINVASION IN TRANSITIONAL CELL CARCINOMA OF THE UPPER URINARY T R A C T

Zigeuner R.~, Rehak p.2, Langner C.3

Lan~ner C. ~, Rehak p.2, Zigeuner R. s

~Medical University Graz, Urology, Oraz, Austria, aMedical University Graz, Biomedical Engineering and Computing, Graz, Austria, aMedical University Graz, Pathology, Graz, Austria

1Medical University of Graz, Institute of Pathology, Graz, Austria, 2Medical University of Graz, Division of Biomedical Engineering & Computing, Graz, Austria, 3Medical University of Graz, Department of Urology, Graz, Austria

INTRODUCTION & OBJECTIVES: Approximately one third of patients will develop transitional cell carcinoma (TCC) of the bladder after surgery for upper tract TCC. The risk factors for bladder recurrence are not well established.

INTRODUCTION & OBJECTIVES: Initial tumour stage and grade and extent of surgery have been documented as major prognostic factors in patients with upper tract transitional cell carcinoma (TCC). However, data are limited due to small sample size (no studies with more than 86 patients). Therefore, our study aimed to evaluate possible conventional prognostic factors, such as tumour stage and grade as well as angioinvasion, in a large series of consecutive patients.

MATERIAL & M E T H O D S : Surgical specimens of 239 consecutive patients operated for upper tract TCC at our institution were re-evaluated by one pathologist (Ci.). Patients records were reviewed with respect to bladder mmours preceding and/or subsequent to upper tract TCC. Bladder recurrence was investigated considering upper tract TCC location (renal pelvis or ureter), ntmour number (solitary or multifocal), pT-stage, tumour grade, previous bladder tumours and occurrence of metastatic disease using the Fisher's exact test. A multivariate analysis using the Cox regression model was performed. RESULTS: 41 (17%) patients had bladder cancer before upper tract TCC. 142 (59%) had solitary pelvic, 61 (26%) solitary ureteral and 36 (15%) patients had multifocal upper tract TCC. Bladder recurrence was noted in 72/239 (30%) after a median followup of 11 months (range 2-83). Bladder recurrence was noted in: 28/142 (20%) patients with solitary pelvic and 25/61 (41%) patients with solitary ureteral TCCs (p=0.003); 53/203 (26%) solitary vs. 19/36 (53%) multifocal TCCs (p:0.003); 24/41 (59%) patients with and 48/198 (24%) patients without preceding bladder cancer (p<0.0001); 49/122 ((40%) stage pTa/pT1 compared to 23/117 (20%) stage pT2-4 upper tract TCC (p<0.001); 47/128 (37%) low grade and 25/111 (23%) high grade upper tract TCCs (p=0.02); 14/60 (23%) patients developing metastatic disease, compared to 58/151 (38%) available patients with no evidence of metastatic disease (p=0.04). Multivariate analysis proved preceding bladder cancer (p=0.02, risk ratio [RR]=l.88, 95%CI=1.133.14) and ureteral location (p-0.02, RR=l.85, 95%CI=1.09-3.13) independent prognostic factors for bladder recurrence. CONCLUSIONS: In univariate analysis, bladder tumour recurrence after upper tract TCC was significantly higher in patients with ureteral TCC location, multifocal tumours, and preceding bladder cancer, whereas patients with invasive, high grade and metastatic TCCs showed a significantly lower incidence. In multivariate analysis, only ureteral location and preceding bladder tumours were independent risk factors for bladder recurrence.

MATERIAL & METHODS: 239 consecutive patients underwent surgery for upper urinary tract TCC between 1984 and 2004 at our institution. All surgical specimens were systematically re-evaluated by one pathologist (C.L.) regarding pT-stage, tumour grade according to the recent revision of the WHO classification (low grade-LG or high grade-HG) and angioinvasion (venous, lymphatic, or both). Follow-up data were obtained from the electronic documentation system of our institution, study endpoint was diagnosis of metastatic disease. Evaluation of possible prognostic factors included age, gender, pT-stage, tumour grade, angioinvasion, turnout location (pelvic vs. ureteral) and surgical margin status. Subgroups were compared using the Kaplan-Meier method and the log-rank test. For multivariate analysis a Cox's proportional hazards regression model was used. RESULTS: Follow-up data were available from 211/239 (88%) patients. After a mean follow-up of 49 months, metastatic disease was noted in 60/211 (28%) patients. Mean time to progression was 18 months. Significant prognostic factors in univariate analysis were pT-stage > 1 (p<0.0001), high tumour grade (p<0.0001), lymphatic and venous invasion (p<0.0001) and positive surgical margins (p-0.0007). No significant prognostic influence was observed for tumour location, patient age and gender. In multivariate analysis, pT-stage > 1 (Io=0.0001, risk ratio [RR]=9.03, 95% confidence interval [CI]=3.07-26.6) and angioinvasion (p<0.0001, RR=7.25, 95%CI 3.4-15.4) proved to be independent predictors with respect to metastasis-free survival, whereas the other parameters lacked independent influence on patient outcome. CONCLUSIONS: Advanced tumour stage and presence of angioinvasion were independent predictors of metastasis-free survival in upper tract TCCs. No impact was seen for turnout localization (pelvic vs. ureteral), thus supporting the current concept of the TNM system to summarize pelvic and ureteral TCCs in one tumour category.

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UPPER TRACT TRANSITIONAL CELL CARCINOMA IS OF H I G H E R GRADE AND STAGE THAN BLADDER T C C

TRANSABDOMINAL ULTRASONOGRAPHY OF BLADDER T U M O U R S - CONVENTIONAL VERSUS HARMONIC IMAGING

Stewart G.1, Bariol S. ~, Grigor K.2, Tolley D.~, MeRRill A. 1

Belej K., Zatura F., Fiala R., Hrabec M.

aWestem General Hospital, Department of Urology, Edinburgh, United Kingdom, 2Western General Hospital, Department of Pathology, Edinburgh, United Kingdom

University Hospital, Dept. of Urology, Olomouc, Czech Republic

INTRODUCTION & OBJECTIVES: It is perceived that most transitional cell carcinomas (TCC) are low-grade (G1 and G2) and low-stage(pTa and pT1) tumours, even when the upper tract is affected (1). However, it has been observed that upper tract TCC have a greater tendency towards high grade disease (2). This study seeks to clarify the histopathological patterns of upper and lower tract TCC using a large contemporaryseries collated over a tenyear period.

INTRODUCTION & OBJECTIVES: Urinary bladder cancer is a frequently occurring malignancy with a high rate of recurrence and multifocal manifestations, and therefore it requires reliable diagnostic techniques. The aim of this study was to prospectively compare value of harmonic ultrasonography (H-US) and conventional B-mode ultrasonography (US) in patients with suspicion for urinary bladder tumour.

PATIENTS & METHODS: All patients presenting with TCC of bladder or upper tract between February 199l and December 2001 at a single institution were identified. The histological material was reviewed by a single pathologist. Further patient information was obtainedby hospital database and case-notereview. Chi-squaretest was used for analysis. RESULTS: 164 patients with upper tract TCC and 2197 with bladder TCC were identified. Upper tract TCCs were found in the following locations: 97 patients (59.1%) had tumours in the calyces or renal pelvis, 13 (7.9%), 9 (5.5%) and 40 patients (24.3%) had TCC of the upper, mid and lower ureter respectively. Of the upper tract TCCs: 102 patients (62.2%) underwent open nephreuretereetomy, 45 (27.4%) had laparoscopic nephroureterectomies, 5 (3.0%) had ureteroscopic resection of TCC and 12 (7.3%) had other procedures. The majority of patients with bladder TCC underwent a transurethral resection, 214 (9.7%) patients with muscle invasive disease had a cysteetomy. A correlation between grade and stage of both upper tract and bladder TCC was observed (Pearson correlation coefficient, I=0.715). 35.4% of upper tract TCC lesions were classified as grade 2 and 43.9% were grade 3, comparedwith 31.1% and 34.7% respectively for patients with bladder TCC (p-0.003). Thirty-three per cent of upper tract lesions were stage pT2-T4 compared with only 20.0% of bladder TCC (p=0.001). Lmv-grade/superficialTCC occurred in 56.3% patients with bladder TCC and 47.1% patients with upper tract TCC. Highgrade/deeply-invasive TCC occurred in 28.2% of patients with bladder TCC and 39.5% of patients with upper tract TCC (p=0.021). CONCLUSIONS: We demonstrated that upper tract TCC is significantly more aggressive and deeply invasive than TCC affecting the bladder. Although this has been alluded to previously the literature is contradictory and hence this pathological difference has not been well establishedprior to this study. This finding emphasisesthe need for aggressivetreatment of upper tract TCC. If endourological management of upper tract TCC is considered histopathological determination of tumour grade prior to treaanent is essential. References: Messing. Campbell's Urology 2002; Vol. 4, Ch 76 MeRRill SA, et al. BJUI 2000: 86:619-23

European Urology Supplements 4 (2005) No. 3, pp. 36

MATERIAL & M E T H O D S : Between January 2002 and July 2003, 138 consecutive patients were evaluated. Fifty-nine patients had primary evaluation and 79 had at least one positive finding of bladder cancer in medical history. All patients had some clinical sign of having bladder tumour. The patients underwent transabdominal ultrasonography on 2102 Hawk machine (BK Medical, Copenhagen, Denmark) with multifrequency probe (2.7-5 MHz). An experienced urologist performed US by the protocol starting with B-mode imaging and continued with H-US after filling the evaluation form. US imaging was obtained when a patient expressed a normal to strong desire to void. Within a week after performance of US, urologists who were unaware of sonographic findings performed conventional rigid cystoscopy in all patients. All positive findings were proved histologically. RESULTS: Bladder tumour was identified in 94 (68 %) patients, 91 of them had urothelial cancer. Considering conventional cystoscopy to be the gold standard, we found the following diagnostic values for the identification of bladder tumours on B-mode US: sensitivity, 82%; specificity, 74%; positive predictive value, 81%; negative predictive value, 90%. For H-US the sensitivity was 87%; specificity, 83%; positive predictive value, 85%; negative predictive value, 88%. Differences were statistically significant in sensitivity, specificity and positive predictive values respectively. The greatest differences between these two methods appeared in the detection of tumours in bladder neck and at bladder base. CONCLUSIONS: Transabdominal harmonic ultrasonography is a promising imaging modality for bladder evaluation in patients with clinical suspicion for bladder cancer. This non-invasive method, independent of any medication or contrast enhancement, can be of value for primary diagnosis and surveillance of bladder cancer. At present transabdominal US is routine part of our diagnostic algorithm in this group of patients.