Comparative outcomes following endoscopic ureteral detachment and formal bladder cuff excision in open nephroureterectomy for upper urinary tract transitional cell carcinoma.

PURPOSE: The introduction of laparoscopic nephroureterectomy highlights the need for the critical appraisal of approaches to the distal ureter at surgery for upper tract transitional cell carcinoma. We compared differences after endoscopic ureteral detachment and open bladder cuff excision in nephroureterectomy. MATERIALS AND METHODS: A total of 138 patients underwent open nephroureterectomy for upper urinary tract transitional cell carcinoma from 1982 to 2005 with a median followup of 43 months. Of these patients 90 underwent endoscopic ureteral detachment and 48 underwent bladder cuff excision. Demographic, perioperative and oncological outcome data were collected in all cases. Statistical analyses were performed using the Student t test, chi-square and log rank tests, and logistic and Cox regression. RESULTS: Mean operative duration was significantly lower in the endoscopic detachment group than in the bladder cuff group (p <0.01). There were 49 (54.4%) bladder recurrences in the endoscopic detachment group, of which 8 (16.3%) were muscle invasive and 3 (3.3%) developed at the resection site. There were 23 (47.9%) bladder recurrences in the bladder cuff group, of which 3 (13.0%) were muscle invasive and 2 (4.2%) developed at the resection site. All 5 resection site tumors occurred after excision of muscle invasive distal ureteral tumors and 4 of these had positive margins. There were no differences in recurrence-free survival or disease specific survival between the groups. Operation subtype did not predict oncological outcome on univariate or multivariate analysis. CONCLUSIONS: Endoscopic ureteral detachment reduces operative duration and is associated with equivalent oncological outcomes compared with open bladder cuff excision in nephroureterectomy. Caution should be exercised in patients with low ureteral tumors.

Carbonic anhydrase IX expression and outcome after radiotherapy for muscle-invasive bladder cancer.

AIMS: Carbonic anhydrase IX (CA IX) expression has been described as an endogenous marker of hypoxia in solid neoplasms. Furthermore, CA IX expression has been associated with an aggressive phenotype and resistance to radiotherapy. We assessed the prognostic significance of CA IX expression in patients with muscle-invasive bladder cancer treated with radiotherapy. MATERIALS AND METHODS: A standard immunohistochemistry technique was used to show CA IX expression in 110 muscle-invasive bladder tumours treated with radiotherapy. Clinicopathological data were obtained from medical case notes. RESULTS: CA IX immunostaining was detected in 89 ( approximately 81%) patients. Staining was predominantly membranous, with areas of concurrent cytoplasmic and nuclear staining and was abundant in luminal and perinecrotic areas. No significant correlation was shown between the overall CA IX status and the initial response to radiotherapy, 5-year bladder cancer-specific survival or the time to local recurrence. CONCLUSIONS: The distribution of CA IX expression in paraffin-embedded tissue sections seen in this series is consistent with previous studies in bladder cancer, but does not provide significant prognostic information with respect to the response to radiotherapy at 3 months and disease-specific survival after radical radiotherapy.

Concomitant chemoradiotherapy for muscle-invasive bladder cancer: the way forward for bladder preservation?

Muscle-invasive bladder cancer is a common malignancy with a high mortality rate. Despite ongoing debates about the optimal primary intervention, radical cystectomy remains the cornerstone of first-line therapy in many institutions. Over the past decade, bladder-preserving strategies involving transurethral resection (TUR), chemotherapy and radiotherapy have evolved. However, the advantage of these approaches over radiation treatment as monotherapy has yet to be fully evaluated. In other tumour models, most notably cervical and anal cancer, radiation and chemotherapy delivered concomitantly have resulted in significant survival advantages. Here, we consider the potential value of this approach in the treatment of invasive bladder cancer. Concomitant chemoradiotherapy is currently the mainstay of several bladder-preserving programmes reported in the medical literature. Overall, local control and survival rates compare favourably with contemporary cystectomy series; however, difficulties in drawing valid conclusions are highlighted. Concomitant chemoradiotherapy may have a role in the management of certain patient subgroups, and the debate should remain open. Further large-scale randomised trials are needed, and information regarding bladder function and quality of life after treatment is lacking at present. The importance of close follow-up and prompt salvage cystectomy is emphasised.

Measurements using the alkaline comet assay predict bladder cancer cell radiosensitivity.

In the UK, the two main treatments of invasive bladder cancer are radiotherapy or cystectomy. However, approximately 50% of patients undergoing radiotherapy fail to respond. If tumour radiosensitivity could be predicted in advance, it may be possible to improve control rates significantly by selecting for radiotherapy those patients whose tumours are radiosensitive. Additionally, patients who would benefit from surgery would be identified earlier. The alkaline comet assay (ACA) is a sensitive method for the detection of DNA strand break damage in cells. In the present study, using six bladder cancer cell lines of differing radiosensitivities, cell survival was compared to the manifestation of radiogenic DNA damage as assessed by ACA. For all the cell lines, the extent of comet formation strongly correlates with cell killing (R2>0.96), with a greater response being noted in radiosensitive cells. In repair studies, measures of residual damage correlate with survival fraction at 2 Gy (R2>0.96), but for only five of the cell lines. Finally, cells from human bladder tumour biopsies reveal a wide range of predicted radiosensitivies as determined by ACA. Overall, these studies demonstrate ACA to be a good predictive measure of bladder cancer cell radiosensitivity at low dose, with potential clinical application.