Diagnostic Ureteroscopy in CT Urography-Diagnosed Upper Tract Urothelial Carcinoma: Delay in Definitive Treatment and Increased Intravesical Recurrence.

Purpose To investigate the effect of diagnostic ureteroscopy (URS) on the delay to surgical treatment of upper tract urothelial carcinoma (UTUC) detected by imaging and the risk of intravesical recurrence. Materials and methods We undertook a retrospective case-note analysis of all patients who underwent radical nephroureterectomy (NUU) from November 2012 to July 2019. We identified those who underwent diagnostic ureteroscopy prior to NUU as Group 1 and those who did not undergo diagnostic URS as Group 2. Perioperative and pathological parameters were compared between both groups. Kaplan-Meier and Log-Rank analyses were used to compare delay to NUU and the intravesical recurrence (IVR) free survival. Cox regression models were employed to analyze the risk factors of intravesical recurrence. Results Out of 69 patients with a mean age of 71.3 years and a mean follow-up of 48.5 months, 49 (71%) underwent URS while 20 (29%) did not. The mean time between the computerized tomography urography (CTU) and surgery was 86 days with URS and 59 days in the control groups(p=0.007). Intravesical recurrence in year one postoperatively was 28.2 % in the URS group vs 5.9% in the control group (p=0.04). The Kaplan-Meier curve showed improved, yet insignificant, IVR-free survival for the control group (Log-Rank p-value=0.21). In multivariate Cox regression analysis, concomitant bladder carcinoma was an independent risk factor for IVR (HR, 15.01; 95%CI, 3.311 - 68.07; p=0.0004). Intravesical mitomycin-c was a protective factor (HR 0.154; 95%CI 0.025 - 0.922; p=0.040). Conclusion In our retrospective single-unit study, diagnostic ureteroscopy for CTU-detected upper tract urothelial carcinoma delayed definitive surgical treatment. Furthermore, it was associated with a significantly increased risk of early intravesical recurrence. URS can provide useful information and reassurance prior to major surgery but must be used with caution in light of these findings.

Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder.

BACKGROUND: Meta-analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose-intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway. METHODS: Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro-oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m(2) , vinblastine 3 mg/m(2) , doxorubicin 30 mg/m(2) , and cisplatin 70 mg/m(2) ) were given at 2-week intervals, with granulocyte colony-stimulating factor support, prior to either radical surgery or radical radiotherapy. RESULTS: All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two-year disease-free and overall survival were 65% and 77%, respectively. CONCLUSIONS: AMVAC is safe and appears to be a well-tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials.

Radiotherapy in localized bladder cancer: what is the evidence?

PURPOSE OF REVIEW: Bladder-sparing bladder treatments have recently been rejuvenated with the introduction of concomitant chemotherapy usually as part of multimodality therapy including endoscopic resection and radiotherapy. This article reviews recent evidence for the role of radiotherapy in the treatment of localized bladder cancer. RECENT FINDINGS: Several single institution series of multimodality radiochemotherapy have shown consistently fair disease-specific survival and local control in those who show a complete response after endoscopic resection. Developments in radiotherapy fractionation, adaptive planning and chemotherapy delivery are clearly in progress. SUMMARY: Much of the evidence is retrospective and involves treating locally advanced poor-risk patients. It would seem right to attempt to prospectively evaluate these treatments for truly localized (T1/2) bladder cancer.

Outcomes from Gleason 7, intermediate risk, localized prostate cancer treated with Iodine-125 monotherapy over 10 years.

BACKGROUND AND PURPOSE: The effect of predominating Gleason grade (3+4 versus 4+3) in Gleason sum score (GS) 7 prostate cancer (PCa) on brachytherapy outcomes is unclear. The 10 year experience of permanent brachytherapy monotherapy at a single UK centre for GS 7, intermediate risk (Memorial Sloan-Kettering model), PSA < or = 10 ng/ml, localised PCa is reported. MATERIALS AND METHODS: Between 1995 and 2004, the outcomes of 187 patients with GS 7 PCa (PSA < or = 10 ng/ml) were analysed from a cohort of 1298 men treated with permanent Iodine-125 prostate brachytherapy, including PSA relapse-free survival (PSA-RFS). RESULTS: Median follow-up was 5.0 years (range 2.0-10.1 years). One patient has died of PCa. At 10 years, PSA-RFS was 82.4%/78% (ASTRO consensus and nadir +2 definitions). For GS 3+4, 5 year PSA-RFS was 86.7%/87.9% and for GS 4+3: 85.2%/96.6% respectively, with no significant difference between groups. Five year PSA-RFS (ASTRO) of 92.6% was seen for D(90) > or = 140 Gy (50% total), compared with 77.0% below 140 Gy (p=0.08). CONCLUSIONS: Iodine-125 brachytherapy monotherapy achieved good rates of medium term biochemical control in GS 7, intermediate risk localised PCa patients. There was a trend to improved outcomes in men with a D90 in excess of 140 Gy.

A 10-year retrospective review of a nonrandomized cohort of 458 patients undergoing radical radiotherapy or cystectomy in Yorkshire, UK.

PURPOSE: We have previously reported on the mortality, morbidity, and 5-year survival of 458 patients who underwent radical radiotherapy or surgery for invasive bladder cancer in Yorkshire from 1993 to 1996. We aim to present the 10-year outcomes of these patients and to reassess factors predicting survival. METHODS AND MATERIALS: The Northern and Yorkshire Cancer Registry identified 458 patients whose cases were subjected to Kaplan-Meier all-cause survival analyses, and a retrospective casenote analysis was undertaken on 398 (87%) for univariate and multivariate Cox proportional hazards modeling. Additional proportional hazards regression modeling was used to assess the statistical significance of variables on overall survival. RESULTS: The ratio of radiotherapy to cystectomy was 3:1. There was no significant difference in overall 10-year survival between those who underwent radiotherapy (22%) and radical cystectomy (24%). Univariate analyses suggested that female sex, performance status, hydronephrosis and clinical T stage, were associated with an inferior outcome at 10 years. Patient age, tumor grade, treatment delay, and caseload factors were not significant. Multivariate analysis models were created for 0-2 and 2-10 years after treatment. There were no significant differences in treatment for 0-2 years; however, after 2 years follow-up there was some evidence of increased survival for patients receiving surgery compared with radiotherapy (hazard ratio 0.66, 95% confidence interval: 0.44-1.01, p = 0.06). CONCLUSIONS: a 10-year minimum follow-up has rarely been reported after radical treatment for invasive bladder cancer. At 10 years, there was no statistical difference in all-cause survival between surgery and radiotherapy treatment modalities.

Fulguration of the lumen does not improve vasectomy sterilization rates.

OBJECTIVES: To assess the effect of adding lumen diathermy fulguration to our standard technique of vas ligation with polyglactin 910 (Vicryl(TM), Ethicon, Sommerville, NJ, USA) excision and fascial interposition, in an attempt to improve our sterilization rates. We previously reported the effect of changing suture material on vasectomy success rates; 3005 post-vasectomy semen analyses (PVSA) revealed a decrease in sterilization rates after surgery on changing from chromic catgut to polyglactin 910. PATIENTS AND METHODS: We retrospectively reviewed PVSA undertaken for vasectomies performed by urological surgeons at the Mid-Yorkshire NHS Trust for 18 months from September 2005 to February 2007. RESULTS: There were 592 vasectomies in all; the age distribution of patients between the groups treated with the standard and new method was similar. Overall, 166 patients (28%) failed to provide two semen samples as instructed, and so were excluded from further analyses. Sterility was achieved in 367 patients (86%); a further 28 (7%) have indeterminate analyses to date, with one of the last two PVSAs showing sperm, with the PVSA of 32 (7%) patients showing persisting sperm. For the eight surgeons reviewed the sterility rates were broadly similar. CONCLUSIONS: The introduction of diathermy fulguration of the lumen has not improved vasectomy sterilization rates, with up to 14% having sperm on PVSA.

Y-V preputioplasty for adult phimosis: a review of 89 cases.

OBJECTIVES: Numerous surgical techniques have been proposed for preputial relief to avoid circumcision. We aimed to review the indications, techniques, and outcomes of Y-V preputioplasty for men with phimosis treated at our institution between 1995 and the present. METHODS: We retrospectively examined the case notes of 89 patients who underwent Y-V preputioplasty since 1995. Indication, technique, and immediate outcomes were recorded. We have subsequently attempted to contact these patients for the completion of a satisfaction questionnaire. RESULTS: All case notes were retrieved; 87 of 89 procedures were undertaken by a single surgeon (I.A.). The median age at operation was 29 years (range, 18-84 years) and median follow-up was 4 years. Seven patients required revision surgery (3: Y-V preputioplasties; 2: circumcisions; 1: adhesion division; and 1: frenuloplasty), whereas 2 patients reported unresolved symptoms but have not undergone additional procedures. Currently, we have successfully contacted 31 of 89 (35%) patients by telephone. These cases appear to have similar demographic features to the whole group. All agreed to complete a satisfaction questionnaire, and 30 replies were received. Overall, 12 patients (40%) were very satisfied and 10 (33%) were satisfied, whereas 4 (13%) were indifferent and 4 (13%) were dissatisfied. Two patients have subsequently undergone circumcision. Twenty-one (70%) patients described their cosmetic result as very good or good, and 22 (73%) patients would recommend the operation to a friend. Dissatisfaction with the procedure seemed to be associated with pre-existing erectile dysfunction, and not retracting the foreskin postoperatively. CONCLUSIONS: Y-V preputioplasty would seem a good alternative to circumcision for men with phimosis who wish to preserve their foreskin.

Urinary biomarker profiling in transitional cell carcinoma.

Urinary biomarkers or profiles that allow noninvasive detection of recurrent transitional cell carcinoma (TCC) of the bladder are urgently needed. We obtained duplicate proteomic (SELDI) profiles from 227 subjects (118 TCC, 77 healthy controls and 32 controls with benign urological conditions) and used linear mixed effects models to identify peaks that are differentially expressed between TCC and controls and within TCC subgroups. A Random Forest classifier was trained on 130 profiles to develop an algorithm to predict the presence of TCC in a randomly selected initial test set (n = 54) and an independent validation set (n = 43) several months later. Twenty two peaks were differentially expressed between all TCC and controls (p < 10(-7)). However potential confounding effects of age, sex and analytical run were identified. In an age-matched sub-set, 23 peaks were differentially expressed between TCC and combined benign and healthy controls at the 0.005 significance level. Using the Random Forest classifier, TCC was predicted with 71.7% sensitivity and 62.5% specificity in the initial set and with 78.3% sensitivity and 65.0% specificity in the validation set after 6 months, compared with controls. Several peaks of importance were also identified in the linear mixed effects model. We conclude that SELDI profiling of urine samples can identify patients with TCC with comparable sensitivities and specificities to current tumor marker tests. This is the first time that reproducibility has been demonstrated on an independent test set analyzed several months later. Identification of the relevant peaks may facilitate multiplex marker assay development for detection of recurrent disease.

Proteomic profiling of urinary proteins in renal cancer by surface enhanced laser desorption ionization and neural-network analysis: identification of key issues affecting potential clinical utility.

Recent advances in proteomic profiling technologies, such as surface enhanced laser desorption ionization mass spectrometry, have allowed preliminary profiling and identification of tumor markers in biological fluids in several cancer types and establishment of clinically useful diagnostic computational models. There are currently no routinely used circulating tumor markers for renal cancer, which is often detected incidentally and is frequently advanced at the time of presentation with over half of patients having local or distant tumor spread. We have investigated the clinical utility of surface enhanced laser desorption ionization profiling of urine samples in conjunction with neural-network analysis to either detect renal cancer or to identify proteins of potential use as markers, using samples from a total of 218 individuals, and examined critical technical factors affecting the potential utility of this approach. Samples from patients before undergoing nephrectomy for clear cell renal cell carcinoma (RCC; n = 48), normal volunteers (n = 38), and outpatients attending with benign diseases of the urogenital tract (n = 20) were used to successfully train neural-network models based on either presence/absence of peaks or peak intensity values, resulting in sensitivity and specificity values of 98.3-100%. Using an initial "blind" group of samples from 12 patients with RCC, 11 healthy controls, and 9 patients with benign diseases to test the models, sensitivities and specificities of 81.8-83.3% were achieved. The robustness of the approach was subsequently evaluated with a group of 80 samples analyzed "blind" 10 months later, (36 patients with RCC, 31 healthy volunteers, and 13 patients with benign urological conditions). However, sensitivities and specificities declined markedly, ranging from 41.0% to 76.6%. Possible contributing factors including sample stability, changing laser performance, and chip variability were examined, which may be important for the long-term robustness of such approaches, and this study highlights the need for rigorous evaluation of such factors in future studies.

Fibroblast growth factors and their receptors in transitional cell carcinoma.

PURPOSE: The recent identification in transitional cell carcinoma of mutations in a fibroblast growth factor (FGF) receptor, namely FGF receptor-3, has provoked great interest in the potential usefulness of FGF receptors and their ligands as molecular markers and as targets for bladder cancer therapy. We examined these possibilities in light of the published literature. MATERIALS AND METHODS: We reviewed the world literature on FGFs and their receptors from 1966 to January 2002 using PubMed. RESULTS: The recent identification in transitional cell carcinoma of a high frequency of mutations in FGF receptor-3 predicted to activate kinase activity of the receptor indicate a likely role as an oncogene in the urothelium. The finding of FGF receptor-3 mutations only rarely in other tumor types to date indicates surprising urothelial specificity that requires tissue specific approaches for evaluation and exploitation. In contrast, FGF receptor-2 expression is down-regulated in bladder tumors, suggesting a possible tumor suppressor role. Information is available on the expression of FGF receptors-1 and 2 in normal bladder and urine, and in bladder tumors. These angiogenic factors represent potential urine markers of bladder neoplasia, although as single markers they lack sufficient sensitivity and specificity. Some interesting insights into the potential role of these factors have come from studies using in vitro model systems. However, there is little information on the numerous other members of this family of growth factors in the bladder and, therefore, much scope for future studies. CONCLUSIONS: It is clear that the FGFs and their receptors have important roles in the development of transitional cell carcinoma. Undoubtedly it will be a focus for much future research. It can be anticipated that members of these protein families would represent useful clinical markers and potential targets for bladder cancer therapy.