Véronique Phé

Ureteral and Multifocal Tumours Have Worse Prognosis than Renal Pelvic Tumours in Urothelial Carcinoma of the Upper Urinary Tract Treated by Nephroureterectomy

BACKGROUND It is not known whether the primary tumour location of upper urinary tract urothelial carcinoma (UUT-UC) is associated with prognosis. OBJECTIVE To evaluate the impact of initial primary tumour location on survival in patients who had undergone radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS Using a multi-institutional, retrospective database, we identified 609 patients with UUT-UC who had undergone RNU between 1995 and 2010. Tumour location was categorised as renal pelvis, ureter, or multifocal. INTERVENTION All patients had undergone RNU. MEASUREMENTS Tumour location was tested as a prognostic factor for survival through univariate and multivariable Cox regression analysis. RESULTS AND LIMITATIONS Tumour location was renal pelvis in 317 cases (52%), ureter in 185 cases (30%), and multifocal in 107 cases (18%). Compared to renal pelvic and ureteral tumours, multifocal tumours were more likely to be associated with advanced stages (pT3/pT4; 39%, 30%, and 54%, respectively; p<0.001) and high-grade disease (53%, 56%, and 76%, respectively; p<0.001). On multivariable analysis, tumour location was an independent prognostic factor for cancer-specific death, disease recurrence, and metastasis (p<0.05). The 5-yr cancer-specific death-free survival probability was 86.8% for renal pelvic tumours, 68.9% for ureteral tumours, and 56.8% for multifocal tumours (p<0.001). The retrospective design of this study was its main limitation. CONCLUSIONS Ureteral and multifocal tumours had a worse prognosis than renal pelvic tumours. These findings are not in line with recently published data and should be investigated in a prospective assessment to obtain a definitive statement regarding this matter.

Methylated genes as potential biomarkers in prostate cancer.

Prostate cancer is the most common malignancy of the urogenital tract. Although controversial, prostate‐specific antigen (PSA) testing is widely used for screening and follow‐up of prostate cancer, but because of its limited specificity and sensitivity, PSA is not an ideal test. We currently lack the necessary tools to differentiate between latent disease with little likelihood of clinical manifestation and aggressive tumours that are likely to metastasize and lead to potentially lethal disease. DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumour initiation and progression. Currently, aberrant promoter hypermethylation has been investigated in specific genes from the following groups: tumour‐suppressor genes, proto‐oncogenes, genes involved in cell adhesion, and genes involved in cell‐cycle regulation. Glutathione S‐transferase P1 (GSTP1) has been shown to be a biomarker for prostate cancer. Other genes, e.g. CD44, PTGS2, E‐cadherin, CDH13, and cyclin D2 have been found to be prognostic markers for prostate cancer. In cell samples derived from the urine, the presence of the hypermethylation of either GSTP1 or RASS1a has been shown to be both sensitive and specific for detecting prostate cancer. Several studies have found that analysis of hypermethylation using a panel of tumour‐suppressor genes yielded better results for detecting prostate cancer than the analysis of single‐gene methylation. Hence, these different panels (e.g. GSTP1, APC, PTGS2, T1G1 and EDNRB) are of interest for detecting prostate cancer. Also, the methylation profile of multiple regulatory genes might be altered at the time of cancer relapse. Thus, preliminary results on the use of the methylation status of specific genes as potential tumour biomarkers for the early diagnosis and the risk stratification of patients with prostate cancer are promising.

Long‐term functional outcomes after artificial urinary sphincter implantation in men with stress urinary incontinence

To evaluate long‐term functional outcomes of artificial urinary sphincters (AUSs) and to determine how many men required explantation because of stress urinary incontinence (SUI) caused by sphincter deficiency after prostate surgery.

Interest of methylated genes as biomarkers in urothelial cell carcinomas of the urinary tract.

Urothelial cell carcinomas (UCC), including bladder cancer and upper urinary tract cancer, are the second most common malignancy of the urogenital tract after prostate cancer. It is a critical issue to differentiate accurately those patients whose tumour will recur and/or progress after initial treatment from those without recurrence and/or progression because tumours with a similar morphology behave differently. Patients undergo lifelong cystoscopic and cytology surveillance to detect subsequent tumour recurrence. New noninvasive methods for the diagnosis and surveillance of UCCs are required. DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumour initiation and progression. Currently, aberrant promoter hypermethylation has been investigated in specific genes, i.e. tumour‐suppressor genes, proto‐oncogenes, genes involved in cell adhesion, and genes of cell cycle regulation. E‐cadherin has been shown to be an independent marker of prognosis. Other genes, e.g. APC, RASSF1a, TNFRSF25, EDNRB, and p14, are implicated in tumour progression. IGFBP3 and APAF‐1 are independent markers of recurrence. APAF‐1 is also correlated with tumour stage and grade. In urine, hypermethylation of DAPK, RARβ, E‐cadherin and p16 has been shown to have a good sensitivity and specificity for bladder cancer detection. Several studies found that analysis of hypermethylation using a panel of tumour‐suppressor genes yielded superior results to cytology in the detection of bladder cancer and its progression. Hence, the different panels (e.g. RASSF1a/APC/p14, RAR_/DAPK/E‐cadh/p16, p16/p14/MGMT/GSTP1, and RASSF1a/E‐cadh/APC) are of interest in the detection of bladder cancer. The last panel and RASSF1a/E‐cadh/APC/TNFRSF25/EDNRB are also interesting for tumour progression. There is evidence that the extent of the mutator and methylator phenotypes in UCCs differs with tumour location, perhaps suggesting that carcinogens affect the urinary tract in different ways. For all loci studied except DAPK, there was more frequent methylation in UUT‐UCCs than in the bladder cancers; this difference was statistically significant for hMLH1, RARB, E‐cadherin, p16 and MINT31. In contrast to UUT‐UCCs, hMLH1 and MINT31 were rarely methylated in bladder tumours, suggesting that they play a role in UUT carcinogenesis but not bladder cancer.

Does the surgical technique for management of the distal ureter influence the outcome after nephroureterectomy

Study Type – Therapy (case series) 
Level of Evidence 4

A proportion of hereditary upper urinary tract urothelial carcinomas are misclassified as sporadic according to a multi-institutional database analysis: proposal of patient-specific risk identification tool.

Study Type – Diagnostic (exploratory cohort)

Is there a contemporary role for percutaneous needle biopsy in the era of small renal masses

Study Type – Diagnostic (case series)

Influence of previous or synchronous bladder cancer on oncologic outcomes after radical nephroureterectomy for upper urinary tract urothelial carcinoma

OBJECTIVE The objective of the study was to evaluate the effect of a history of bladder cancer (BC) or synchronous BC on the prognosis and survival of patients who have undergone radical nephroureterectomy (RNU). METHODS AND MATERIALS Using a multi-institutional, retrospective database, we identified 662 patients with upper urinary tract urothelial carcinoma (UUT-UC) treated by radical nephroureterectomy, between 1995 and 2010. We analyzed clinicopathologic characteristics and outcomes according to the history of BC or concomitant BC or both, at the time of diagnosis. BC was evaluated as a prognostic factor for bladder recurrence and survival. RESULTS Overall, 83 (12.5%) patients had previous BC, 62 (9.4%) exhibited concomitant BC, and 75 (11.3%) presented with both previous and current BC. A history of BC was less seen in women and nonsmokers (P<0.0001 and P = 0.013, respectively). The patients with associated BC had more tumors located in the ureter (P<0.0001), as well as more multiple locations in the upper tract (P<0.0001). The tumors without concomitant BC were more likely to be associated with locally advanced stages (P = 0.024). At a median follow-up time of 37.3 months, 31.4% of patients experienced BC recurrence and 2.9% developed contralateral upper tract tumor. Using multivariate analyses, the previous or synchronous BC (P = 0.01) and positive surgical margins (P = 0.03) are independent prognostic factors for BC recurrence. The metastasis-free survival and cancer-specific survival rates did not significantly differ according to the associated BC status. CONCLUSIONS In patients without previous or concomitant BC, the upper tract tumors are more frequently localized in the renal pelvis and are associated with a more invasive status at the time of diagnosis. Nevertheless, the presence of UUT-UC without previous or synchronous BC did not significantly affect the survival rates after nephroureterectomy.

Robot-assisted laparoscopic artificial urinary sphincter insertion in men with neurogenic stress urinary incontinence.

To describe for the first time the technique of robot‐assisted artificial urinary sphincter (R‐AUS) insertion in male patients with neurogenic incontinence.

Long-term functional outcomes after artificial urinary sphincter implantation in women with stress urinary incontinence: Long-term functional outcomes of AUS in women with SUI

To assess the long‐term outcomes obtained after artificial urinary sphincter (AUS) implantation in women with stress urinary incontinence (SUI).