The impact of lymph node status and features on oncological outcomes in urothelial carcinoma of the upper urinary tract (UTUC) treated by nephroureterectomy.

PURPOSE: Prognostic impact of lymphadenectomy during radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UTUC) is controversial. Our aim was to assess the impact of lymph node status (LNS) on survival in patients treated by RNU. METHODS: In our multi-institutional, retrospective database, 714 patients with non-metastatic UTUC had undergone RNU between 1995 and 2010. LNS was tested as prognostic factor for survivals through univariate and multivariable Cox regression analysis. RESULTS: Median age was 70 years [interquartile range (IQR), 60-75] with median follow-up of 27 months (IQR, 10-50). Overall, lymphadenectomy was performed in 254 patients (35.5 %). Among these patients, 204 (80 %) had negative lymph nodes (pN0) and 50 (20 %) had positive lymph nodes (pN1/2). The 5-year cancer-specific survival (CSS) was 81 % [95 % confidence interval (CI), 73-88 %] for pN0 patients, 85 % (95 % CI, 80-90 %) for pNx patients and 47 % (95 % CI, 24-69 %) for pN1/2 patients (p < 0.001). Metastasis-free survival (MFS) and overall survival (OS) rates were significantly lower in pN1/2 patients than in pN0 and pNx patients (p < 0.05). On multivariable analysis, LNS did not appear as an independent prognostic factor for CSS, OS or MFS (p > 0.05). In case of lymph node involvement, extra-nodal extension was marginally associated with worse CSS (log rank p = 0.07). The retrospective design was the main limitation. CONCLUSION: LNS is helpful for survival stratification in patients treated with RNU for UTUC. However, LNS did not appear as an independent predictor of survival in this retrospective series and needs to be investigated in a large multicentre, prospective evaluation.

Six years' experience with high-intensity focused ultrasonography for prostate cancer: oncological outcomes using the new 'Stuttgart' definition for biochemical failure.

OBJECTIVE: • To determine oncological outcomes after high-intensity focused ultrasonography (HIFU) treatment in patients with localized prostate cancer using a new, more accurate, definition ('Stuttgart' definition) of biochemical failure. PATIENTS AND METHODS: • We performed a retrospective review of all patients in our centre who received first-line treatment with a second-generation Ablatherm™ device (EDAP-TMS, Lyon, France). • Oncological failure was given either by biochemical failure (prostate-specific antigen, PSA, nadir plus 1.2 g/mL) (Stuttgart definition) or the start of salvage therapy because of a persistently positive biopsy after the HIFU procedure. • The 5-year biochemical-free survival rate and 5-year disease-free survival rate were calculated. RESULTS: • In total, 53 patients were included (mean age, 72.5 ± 4.5 years, range 60-79 years; 28 low risk and 25 intermediate risk). None had undergone previous hormonal therapy. Mean ±sd follow-up was 45.4 ± 15.5 months (range 16-71 years). Mean (range) pre-treatment PSA was 8.5 ± 4 (0.29-18) ng/mL. The median (range) PSA nadir value was 1 (0.01-14) ng/mL and occurred after a mean (range) of 5.09 (3-24) months. • Overall, 36 patients (67.9%) experienced oncological failure. • These included 33 cases (62.2%) of biochemical failure. A PSA nadir of ≤0.2, 0.21-1.0 and >1 ng/mL was reached in 20.8%, 30.2% and 49% of patients, respectively, and was associated with biochemical failure in 9.1%, 30.3% and 60.6%, respectively. • The 5-year biochemical-free survival rate and disease-free survival rate were 21.7% and 13.5%, respectively. In multivariate analysis, a PSA nadir of >1 ng/mL was significantly associated with a risk of biochemical and oncological failure (P= 0.002 and P < 0.001). • Oncological failure was not associated with any risk group. • No patient died from prostate cancer. CONCLUSIONS: • In our experience, Ablatherm™ treatment for clinically localized prostate cancer was associated with a high rate of biochemical failure as determined by the 'Stuttgart' definition, and did not achieve effective cancer control. • The PSA nadir value after HIFU treatment was a significant predictor of treatment failure.

Endothelin-1: a predictor of extracapsular extension in clinically localized prostate cancer?

OBJECTIVE: To assess the value of endothelin-1 (ET-1) expression in predicting extracapsular extension (ECE) in clinically localized prostate cancer (PCa). PATIENTS AND METHODS: ET-1 expression was determined by immunohistochemistry on archival needle biopsies (NBs) from 94 patients (49 pT2 and 45 pT3a) who underwent radical prostatectomy (RP) for clinical T1-T2 PCa. Each sample was analysed independently by two pathologists blinded to the clinical data. RESULTS: In univariate analysis, high ET-1 expression in NBs, pre-operative prostate-specific antigen (PSA) level >10 ng/ml, percentage of positive biopsy cores and NB Gleason score ≥7 were significantly associated with ECE as determined on subsequent RP. No significant association was found between clinical stage and ECE. In multivariate analysis, there was a significant association with high ET-1 expression in NBs (p = 0.006), pre-operative PSA level >10 ng/ml (p = 0.049), and NB Gleason score ≥7 (p = 0.002). These three pre-operative factors combined provided the best model for predicting ECE with 93.3% sensitivity, 49% specificity, 62.5% positive predictive value, 88.9% negative predictive value. The combination yielded a higher concordance index (0.760 vs 0.720) and offered a higher log partial likelihood than the same model without ET1 (112.8 vs 105.7, p = 0.01). CONCLUSIONS: ET-1 expression was strongly associated with ECE and, when combined with pre-operative PSA level and Gleason score, improved the predictive accuracy of pre-operative NBs. Its assessment in patients with localized PCa might be useful when making treatment decisions. Further studies with standardisation of immunohistochemical staining and multi-institutional validation are now needed to establish the appropriate use of ET-1 staining in PCa staging and to evaluate inter-observer reproducibility.

Salvage radiotherapy after high-intensity focused ultrasound treatment for localized prostate cancer: feasibility, tolerance and efficacy.

BACKGROUND: The objective of this study is to evaluate the feasibility, tolerance and efficacy of salvage external beam radiotherapy (EBRT) in persistent or recurrent prostate cancer after failed high intensity focused ultrasound (HIFU) therapy. METHODS: We reviewed data on tolerance and oncologic outcomes for all patients with biopsy-proven locally recurrent or persistent prostate cancer who underwent salvage EBRT in our department between April 2004 and June 2008. Minimum follow-up for inclusion was 2 years. Failure with EBRT was defined as biochemical relapse (Phoenix definition) or introduction of androgen deprivation therapy (ADT). Gastrointestinal and urinary toxicity and urinary stress incontinence were scored at 12 and 24 months (Radiation Therapy Oncology Group and Ingelman Sundberg rating, respectively). RESULTS: The mean age of the patients was 68.8 years (range: 60-79). Mean prostate-specific antigen (PSA) before EBRT was 5.57 ng/mL (range: 2.5-14.8). Median follow-up was 36.5 ± 10.9 months (range: 24-54). No patient received adjunctive ADT. The EBRT course was well-tolerated and completed by all patients. The mean PSA nadir was 0.62 ng/mL (range: 0.03-2.4) and occurred after a median of 22 months (range: 12-36). One patient experienced biochemical failure and was prescribed ADT 30 months after EBRT. The disease-free survival rate was 83.3% at 36.5 months. There was no major EBRT-related toxicity at 12 or 24 months. CONCLUSIONS: Our early clinical results confirm the feasibility and good tolerance of salvage radiotherapy after HIFU failure. Oncological outcomes were promising. A prospective study with longer follow-up is needed to identify factors predictive of success for salvage EBRT therapy after HIFU failure.

Bladder recurrence after surgery for upper urinary tract urothelial cell carcinoma: frequency, risk factors, and surveillance.

OBJECTIVE: To highlight the main risk factors for metachronous bladder recurrence after treatment of an upper urinary tract urothelial cell carcinomas (UUT-UCCs) based on the recent literature. MATERIALS AND METHODS: Data on urothelial malignancies after UUT-UCCs management in the literature were searched using MEDLINE and by matching the following key words: urinary tract cancer; bladder carcinomas, urothelial carcinomas, upper urinary tract, renal pelvis, ureter prognosis, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, cystectomy, nephroureterectomy, minimally invasive surgery, recurrence, and survival. RESULTS: No evidence level 1 information from prospective randomized trials was available. A range of 15% to 50% of patients with a UUT-UCC will subsequently develop a metachronous bladder UCC. Intraluminal tumor seeding and pan-urothelial field change effect have both been proposed to explain intravesical recurrences. In most cases, bladder cancer arises in the first 2 years after UUT-UCC management. However the risk is lifelong and repeat episodes are common. The identification of variables that allow accurate risk stratification of UUT-UCC patients with regards to future bladder relapse is disappointing. No factors have been identified to date that can reliably predict bladder recurrences. A history of bladder cancer prior to UUT-UCC management and upper tract tumor multifocality are the only frequently reported clinical risk factors among current literature. CONCLUSION: Prior histories of bladder cancer and upper tract tumor multifocality are the most frequently reported risk factors for bladder tumors following UUT-UCCs. Surveillance regimen is based on cystoscopy and on urinary cytology for at least 5 years.

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.

Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE: Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS: Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION: All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS: Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS: RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.