Time Of Transurethral Resection Research Articles

Clinical and biological markers for risk-stratification of T1 high-grade non-muscle invasive bladder cancer.

To summarize the prognostic and predictive role of current clinical and biological markers in patients with T1 high-grade (T1HG) nonmuscle invasive bladder cancer (NMIBC). Classical clinico-pathologic markers such as age, tumor size, focality, and location as well as the presence of concomitant carcinoma in situ, lymphovascular invasion, and histological variants at the time of transurethral resection (TUR) should be used in the risk-stratification of T1HG to improve patients' selection for early aggressive treatment. pathological T1 substaging has shown to predict disease progression and response to intravesical therapy, and should therefore be reported in the pathological assessment to improve clinical decision-making. Urinary inducible cytokines measured at different time points during Bacillus Calmette-Guerin therapy may be used to predict response to treatment, while urinary mRNA-based biomarkers may be of value to select patients for repeated TUR (reTUR). The advent of genomic classification in NMIBC and that of immune markers may improve current risk-stratification tools and pave the way toward personalized treatment. The role of clinico-pathologic variables in the risk-stratification of T1HG NMIBC remains unaltered, despite insufficient. Urinary biomarkers and tissue-based immune markers hold the promise to revolutionize the paradigm of risk-stratification due to their potential role in predicting response to intravesical and systemic immunotherapy. However, to date, none of the investigated biomarkers is used in clinical practice to risk-stratify T1HG patients due to the lack of external and/or prospective validations.

Role of Neoadjuvant Chemotherapy in Squamous Variant Histology in Urothelial Bladder Cancer: Does Presence and Percentage Matter?

The purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT. The records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (< 50% SV vs.≥ 50% SV). The median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P= .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P< .001). The non-organ-confined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P= .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P= .003). In the subgroup analysis, the lower rate of non-organ-confined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival. The effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has< 50% involvement by the variant histology.

Human urothelial bladder cancer generates a clonal immune response: The results of T-cell receptor sequencing

BackgroundHigh T-cell receptor (TCR) repertoire clonality is associated with clinical response to immune checkpoint blockade in bladder cancer. ObjectiveTo determine if TCR repertoire is more clonal in tumors than in benign inflammation. MethodsWe prospectively identified 12 patients with bladder lesions undergoing transurethral resection. Specimens were collected at time of transurethral resection and stored at −80C. DNA was extracted and high throughput DNA sequencing of the CDR3 region of the TCR beta chain using the immunoSEQ assay (Adaptive Biotechnologies) was performed. T-cell fraction, clonal dominance, and maximum frequency of TCR clone were assessed. ResultsOf the 12 bladder lesions resected, 3 of 12 were cT0, 3 of 12 were cTa, 3 of 12 were cT1, and 3 of 12 were cT2 or greater. The median number of T cells in urothelial carcinoma specimens (UC+) and benign (UC−) specimens was 5,569 and 25,872, respectively. The number of unique TCRs sequenced in UC+ and UC− specimens was 3,069 and 9,680, respectively. The median tumor infiltrating lymphocyte percentage in UC+ and UC− specimens was 2% and 12%, respectively. The UC+ specimens demonstrated clonality as evidenced by identification of a specific T-cell clone being present in up to 17% of the total tumor infiltrating lymphocyte pool, in contrast to 2% among UC− specimens. ConclusionsPrimary urothelial tumors contain clonally expanded T-cell populations. These data support the hypothesis that bladder tumors induce an antigen-driven immunogenic host response, in contrast to the benign inflammatory response, which does not appear to demonstrate any T-cell clonal dominance.

The use of blue light flexible cystoscopy with hexaminolevulinate & the diagnosis of bladder cancer.

Blue light cystoscopy improves the detection of bladder cancer at time of transurethral resection of bladder tumor for nonmuscle-invasive bladder cancer. This has translated to decreased tumor recurrence. Given this improvement in rigid cystoscopy, the question remains whether the use of blue light flexible cystoscopy (BLFC) in the surveillance setting provides the same benefits. This review aims to evaluate the recently reported Phase III prospective multicenter study of BLFC which evaluated the detection of bladder cancer during surveillance, which in its earliest reporting demonstrated improved detection of bladder cancer. This study evaluated 304 patients with findings of 63 confirmed malignancies, with 13 (20.6%) only identified by BLFC (p<0.0001). The question still remains whether the improved detection rate will translate to improved clinical outcomes. Further, studies will be necessary to determine which patients will benefit from BLFC, optimal ways to incorporate into surveillance strategies and cost-effectiveness.

MP15-19 IMPROVED RECURRENCE FREE SURVIVAL IN NMIBC PATIENTS TAKING METFORMIN DEMONSTRATES DOSE DEPENDENCE

You have accessJournal of UrologyBladder Cancer: Non-invasive I1 Apr 2017MP15-19 IMPROVED RECURRENCE FREE SURVIVAL IN NMIBC PATIENTS TAKING METFORMIN DEMONSTRATES DOSE DEPENDENCE Timothy Rushmer, Shiva Damodaran, E. Jason Abel, Shi Fangfang, Kyle Richards, David Jarrard, and Tracy Downs Timothy RushmerTimothy Rushmer More articles by this author , Shiva DamodaranShiva Damodaran More articles by this author , E. Jason AbelE. Jason Abel More articles by this author , Shi FangfangShi Fangfang More articles by this author , Kyle RichardsKyle Richards More articles by this author , David JarrardDavid Jarrard More articles by this author , and Tracy DownsTracy Downs More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.504AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous literature has suggested that metformin may affect recurrence of non-muscle invasive bladder cancer (NMIBC), but data could be confounded by differences in cohorts. The purpose of this study was to evaluate the association of metformin among common prognostic factors for bladder cancer recurrence in a multivariate model and evaluate whether Metformin demonstrates a dose dependent effect. METHODS An institutional database identified 503 unique patients treated with transurethral resection (TUR) for NMIBC. These patients were followed longitudinally and had an additional 682 recurrences and subsequent TURs. A total of 1185 TURs were performed on these 503 patients. 144 cases of NMIBC, in 60 unique patients, met inclusion criteria and were taking Metformin at the time of TUR. Cox proportional hazards models were used to evaluate associations with recurrence-free survival (RFS). RESULTS Median time to recurrence was 15 months (IQR 6.18-35.6). Median age was 70.6 years. On univariate analysis, factors associated with statistically significant improved RFS included: metformin use at TUR (p=0.01, HR 0.61, 95% CI 0.42-0.89), metformin dose ≥2000 mg (p=0.03, HR 0.50, 95% CI 0.28-0.90), age, multifocality, tumor size, perioperative Mitomycin-C, bacillus Calmette-Guerin therapy, and intravesical chemotherapy. Multivariate analysis demonstrated improved RFS when comparing diabetic patients on metformin at TUR to diabetic patients not on metformin (p=0.0002, HR 0.51, 95% CI 0.36-0.72) and improved RFS even when comparing diabetic patients on metformin to non-diabetic patients not on metformin (p=0.0001, HR 0.60, 95% CI 0.46-0.77). A separate multivariate analysis, demonstrated improved RFS when comparing patients taking ≥2000 mg of metformin to patients taking <2000 mg at the time of TUR (p=0.0054, HR 0.39, CI 0.20-0.76). The 5-year RFS rate was 42.3% for diabetic patients on metformin, 35.1% for non-diabetics not on metformin, and 9.7% for diabetic patients not treated with metformin (p=0.0001). CONCLUSIONS Metformin use at the time of TUR is associated with improved 5 year RFS in a multivariate model. Metformin dose ≥2000 mg is independently associated with improved RFS. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e178 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Timothy Rushmer More articles by this author Shiva Damodaran More articles by this author E. Jason Abel More articles by this author Shi Fangfang More articles by this author Kyle Richards More articles by this author David Jarrard More articles by this author Tracy Downs More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Assessment of the infiltrative character of bladder cancer at the time of transurethral resection: a single center study.

IntroductionDetermining the clinical stage of bladder carcinoma before radical cystectomy is characterized by a high inaccuracy rate. The discrepancy in some reports reaches up to 48%. Therefore intraoperative clinical staging of bladder carcinoma is not recommended before radical treatment as it is for prostate cancer. However, the accuracy of clinical assessment of the muscle invasive character of the tumors at the time of transurethral resection has not been studied. In our study we estimate the accuracy of clinical staging during endoscopic treatment.Material and methods332 patients who had undergone transurethral resection of bladder cancer were studied in this retrospective analysis. Data such as age, gender, presence of hydronephrosis, operator, the results of bimanual bladder examination, TURB report and pathologic report, were collected from each patient. Intraoperative prediction of the muscle invasive nature of the tumor was compared with pathological reports. A logistic regression analysis was used to evaluate the influence of particular variables on upstaging and downstaging.ResultsOverall accuracy between clinical and histopathology staging was 87.8%. Discrepancy was observed only in 36 patients. Patients with pTa stage were the most numerous group among patients with accurate prediction of the muscle invasiveness character of the tumor. Univariable logistic regression indicated that the presence of a palpable mass in the bimanual examination was a predictor of upstaging, with an OR 11.75 CI95% [2.49–55.32].ConclusionsThe study indicated the high accuracy between clinical and pathological reports. Intraoperative evaluation of tumor character should be an indispensable part of treatment, which can be useful for planning in advance the further stages of treatment.

Concordance in Biomarker Status Between Bladder Tumors at Time of Transurethral Resection and Subsequent Radical Cystectomy: Results of a 5-year Prospective Study.

Purpose:To assess the concordance rate in alterations of molecular markers at the time of transurethral resection (TUR) and subsequent radical cystectomy (RC) among patients with high-grade urothelial carcinoma of the bladder (UCB).Methods:We prospectively performed immunohistochemical staining p53, p21, p27, Ki-67 and cyclin E1 on TUR and on RC specimens from 102 patients treated with RC and bilateral lymphadenectomy for high-grade UCB. We analyzed the concordance rate of individual markers and of the number of altered markers. Concordant and discordant findings were reported in the overall population and according to clinical stage.Results:Median patient age was 74 years (IQR 67–79) and mostly male (86%). Median time from TUR to RC was 1.5 months (IQR 1.0–2.4). Clinical stage at time of RC was cTa/Tis/T1 in 50% , cT2 in 47% , and cT4 in 1% of patients Nine (9%) patients received neoadjuvant chemotherapy. The concordance of biomarkers between TUR and RC specimens was 92.2% , 77.5% , 80.4% , 77.5% , and 83.3% for cyclin E1, p21, p27, p53 and Ki-67, respectively. The concordance between number of altered biomarkers was 51.0%.Conclusions:The rate of individual marker alterations at time of TUR closely approximates that found at RC specimens. However, the correlation of number of altered markers is lower. Molecular marker status at TUR could help predict the marker status at RC and may help guide multimodal therapeutic planning.

MP21-19 BRANCHED EVOLUTION AND INTRATUMOR HETEROGENEITY OF UROTHELIAL CARCINOMA OF THE BLADDER

INTRODUCTION AND OBJECTIVES: Genomic characterization of urothelial carcinoma of the bladder (UCB) has begun to reveal significant intertumor heterogeneity when comparing samples from different subjects. As in other malignancies, intratumor heterogeneity, which may allow for tumor evolution and adaption, poses a significant challenge to personalized-medicine strategies. METHODS: To examine UCB tumor evolution and heterogeneity, we performed next-generation targeted sequencing on multiple temporally and spatially separated bladder tumors obtained at time of transurethral resection (TUR) and radical cystectomy (RC). Specimens were analyzed using a next-generation, targeted sequencing assay designed to identify point mutations, indels, and copy number alterations in 300 cancer-associated genes. RESULTS: Phylogenetic reconstruction revealed evidence of branched evolutionary growth. Evaluation of multiple tumors from individual subjects identified both shared and unique potential driver mutations. Evidence of convergent phenotypic evolution was detected through analysis of multiple distinct tumors from several subjects. For example, three separate tumors in one subject (see Figure) shared a common PIK3CA mutation (E453K) and had unique second mutations in PIK3CA (E542V, E545K, and E545Q, respectively). In another subject, distinct inactivatingmutations of EP300were identified in two temporally separated tumor samples. Macrodissection of single tumors into non-invasive and invasive components revealed significant intratumor heterogeneity; one case illustrates howanalysis of amuscleinvasive TURspecimen could result in undersampling and therebymiss the tumor clone that persisted at time of RC. CONCLUSIONS: We demonstrate branched evolution of UCB through genomic analyses of multiple temporally and spatially distinct bladder tumors from individual subjects. Macrodissection of individual tumor samples identified significant intratumor heterogeneity. These concepts may present major challenges to personalized-medicine approaches that rely on sampling of a single tumor at a specific timepoint in the evolution of a patient’s UCB.

Branched evolution and intratumor heterogeneity of urothelial carcinoma of the bladder.

293 Background: Genomic characterization of urothelial carcinoma of the bladder (UCB) has begun to reveal significant intertumor heterogeneity when comparing samples from different subjects. As in other malignancies, intratumor heterogeneity, which may allow for tumor evolution and adaption, poses a significant challenge to personalized-medicine strategies. Methods: To examine UCB tumor evolution and heterogeneity, we performed next-generation targeted sequencing on multiple temporally and spatially separated bladder tumors obtained at time of transurethral resection (TUR) and radical cystectomy (RC). Specimens were analyzed using a next-generation, targeted sequencing assay designed to identify point mutations, indels, and copy number alterations in 300 cancer-associated genes. Results: Phylogenetic reconstruction revealed evidence of branched evolutionary growth. Evaluation of multiple tumors from individual subjects identified both shared and unique potential driver mutations. Evidence of convergent phenotypic evolution was detected through analysis of multiple distinct tumors from several subjects. For example, three separate tumors in one subject shared a common PIK3CA mutation (E453K) and had unique second mutations in PIK3CA (E542V, E545K, and E545Q, respectively). In another subject, distinct inactivating mutations of EP300 were identified in two temporally separated tumor samples. Macrodissection of single tumors into non-invasive and invasive components revealed significant intratumor heterogeneity; one case illustrates how analysis of a muscle-invasive TUR specimen could result in undersampling and thereby miss the tumor clone that persisted at time of RC. Conclusions: We demonstrate branched evolution of UCB through genomic analyses of multiple temporally and spatially distinct bladder tumors from individual subjects. Macrodissection of individual tumor samples identified significant intratumor heterogeneity. These concepts may present major challenges to personalized-medicine approaches that rely on sampling of a single tumor at a specific timepoint in the evolution of a patient’s UCB.

Preoperative neutrophil-lymphocyte ratio correlates with tumor stage and grade at time of transurethral resection of bladder tumors

Preoperative neutrophil-lymphocyte ratio correlates with tumor stage and grade at time of transurethral resection of bladder tumors

394 CONCORDANCE IN MOLECULAR MARKER STATUS BETWEEN BLADDER TUMORS AT TIME OF TRANSURETHRAL RESECTION AND SUBSEQUENT RADICAL CYSTECTOMY: RESULTS OF A 5-YEAR PROSPECTIVE STUDY

You have accessJournal of UrologyUrothelial Cancer: Natural History, Markers & Pathophysiology1 Apr 2013394 CONCORDANCE IN MOLECULAR MARKER STATUS BETWEEN BLADDER TUMORS AT TIME OF TRANSURETHRAL RESECTION AND SUBSEQUENT RADICAL CYSTECTOMY: RESULTS OF A 5-YEAR PROSPECTIVE STUDY Yair Lotan, Aditya Bagrodia, Niccolo Passoni, Varun Rachakonda, Payal Kapur, Arthur Sagalowsky, and Shahrokh F. Shariat Yair LotanYair Lotan Dallas, TX More articles by this author , Aditya BagrodiaAditya Bagrodia Dallas, TX More articles by this author , Niccolo PassoniNiccolo Passoni Milan, Italy More articles by this author , Varun RachakondaVarun Rachakonda Dallas, TX More articles by this author , Payal KapurPayal Kapur Dallas, TX More articles by this author , Arthur SagalowskyArthur Sagalowsky Dallas, TX More articles by this author , and Shahrokh F. ShariatShahrokh F. Shariat New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1783AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Molecular alterations are common in patients with urothelial carcinoma of the bladder (UCB). In order to make appropriate decisions using molecular alterations, it is important to determine whether marker status at time of transurethral resection (TUR) is concordant with marker status at time of radical cystectomy (RC). This is particularly important to guide decisions regarding neoadjuvant therapies. We performed a 5 year prospective study to evaluate the role of molecular markers in patients with high grade UCB. The goal of the current study was to compare the concordance of molecular marker status of TUR and RC specimens from the same patient. METHODS We prospectively performed p53, p21, p27, Ki67, and cyclin E1 immunohistochemical staining on RC specimens from 243 patients treated with RC and bilateral lymphadenectomy. Of these, 96 patients had staining of the TUR specimen immediately preceding the RC available. RESULTS Median patient age was 70 yr with most being men (78, 81%). Time from TUR to RC was 2 months (IQR 3.5). Clinical stage was cTa/Tis/T1 (52, 54%), cT2 (37, 39%), cT3/T4 (2, 2%), and unknown (5, 5%). High-grade disease was present in 93% of the patients. Pathologic stage was pT0 (6, 6%), pT1 (40, 42%), pT2 (16, 17%), pT3 (27, 28%), and pT4 (7, 7%). Concomitant CIS was seen in 34 patients (35%) and lymphovascular invasion in 21 (22%). The median number of removed lymph nodes was 22 (IQR 16-31) and 20 patients (21%) had lymph node metastasis. Overall, 17 (18%) patients underwent neoadjuvant chemotherapy. The concordance of molecular biomarkers between TUR and RC was 89%, 80%, 88%, 86%, and 82% for cyclin E, p21, p27, p53 and Ki-67, respectively. The likelihood of concordance was not influenced by clinical or pathologic stage, grade, time from TUR to RC and use of neoadjuvant chemotherapy. CONCLUSIONS There is a high rate of concordance in the status of cell-cycle- and proliferation-related markers between the TUR preceding the RC and RC specimens itself. Clinical decision-making regarding neoadjuvant chemotherapy and RC could be guided by molecular marker status of the TUR specimen. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e160 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yair Lotan Dallas, TX More articles by this author Aditya Bagrodia Dallas, TX More articles by this author Niccolo Passoni Milan, Italy More articles by this author Varun Rachakonda Dallas, TX More articles by this author Payal Kapur Dallas, TX More articles by this author Arthur Sagalowsky Dallas, TX More articles by this author Shahrokh F. Shariat New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A Randomized Prospective Trial to Assess the Impact of Transurethral Resection in Narrow Band Imaging Modality on Non–Muscle-Invasive Bladder Cancer Recurrence

BackgroundNarrow band imaging (NBI) is an optical enhancement technology that filters white light into two bandwidths of illumination centered on 415nm (blue) and 540nm (green). NBI cystoscopy can increase bladder cancer (BCa) visualization and detection at the time of transurethral resection (TUR). NBI may therefore reduce subsequent relapse following TUR. ObjectiveAssess the impact of NBI modality on 1-yr non–muscle-invasive BCa (NMIBC) recurrence risk. Design, setting, and participantsConsecutive patients with overt or suspected BCa were included in a prospective study powered to test a 10% difference in 1-yr recurrence risk in favor of cases submitted to NBI TUR. Excluding patients with muscle-invasive BCa, negative pathologic examination, or without follow-up, the study population was composed of 148 subjects randomized from August 2009 to September 2010 to NBI TUR (76 cases) or white light (WL) TUR (72 cases). InterventionTUR was performed in NBI or standard WL modality. MeasurementsThe 1-yr recurrence risks in NBI or WL TUR groups were compared using odds ratio (OR) point and interval estimates derived from logistic regression modeling. Results and limitationsThe 1-yr recurrence-risk was 25 of 76 patients (32.9%) in the NBI and 37 of 72 patients (51.4%) in the WL group (OR=0.62; p=0.0141). Simple and multiple logistic regression analyses provided similar OR points and interval estimates. ConclusionsTUR performed in the NBI modality reduces the recurrence risk of NMIBC by at least 10% at 1 yr.

Using urine microscopy and cytology for early detection of bladder cancer in male patients with lower urinary tract symptoms

Irritative urinary symptoms and micro-hematuria are the common findings in bladder cancer patients. In this study, we investigated the use of urine microscopy and cytological examination for early detection of bladder cancer in patients with lower urinary tract symptoms (LUTS). Male patients presented with LUTS to urology clinic were enrolled. Voiding symptoms were evaluated with international prostate symptoms score, and urine samples were collected for microscopy and cytological examination. Cystoscopy was performed in patients with microscopic hematuria, suspicious/malignant cells in urine or at the time of transurethral resection of prostate. Subjects, who had no indication and did not receive cystoscopy, were followed up in clinic for progress of symptoms, including gross hematuria and occurrence of bladder cancer. Nine hundred and eighty-eight patients were enrolled during the period of 2005-2007. Fifty-two (5.26%) urine samples were documented as atypical, and 936 (94.7%) were negative. There was no suspicious or malignant cytology result in this series. Micro-hematuria was noticed in six patients (0.61%). The mean follow-up time was 29.1 ± 12.5 months. One (0.10%) patient had bladder cancer 44 months after the first visit in the cohort, who had micro-hematuria, atypical urine cytology, but normal cystoscopy before diagnosis. The prevalence rate of bladder cancer in male patients with LUTS is low. This study adds to information that microscopy and cytological examination are not useful to detect bladder cancer. Due to the economic concerns and burden of unnecessary investigations, the routine use of these tests is in doubt.

Quantitative Loss of Heterozygosity Analysis for Urothelial Carcinoma Detection and Prognosis

To evaluate loss of heterozygosity (LOH) using microsatellite polymorphism analysis as a diagnostic and prognostic marker at the time of transurethral resection and as a follow-up marker preceding cystoscopic evidence of recurrence compared with cytology. A total of 127 urothelial carcinoma (UC) patients were included. Tumors were staged and graded according to the International Union Against Cancer-tumor, node, metastases system and to the 2004 World Health Organization classification. LOH urinalysis was performed using 8 markers and marker-specific LOH thresholds. Thirty control samples, obtained from healthy volunteers, were used to determine the positive cut-off for each marker. LOH was significantly more sensitive than cytology in low-grade (64.8% vs 38.5%, P <.001) and low-stage UC (68.6% vs 45.5%, P <.001). The cumulative sensitivity of cytology and LOH reached 74.7% (P <.001) for low-grade and 80.2% (P <.001) for low-stage tumors. Both urinary LOH at TP53 and chromosome 9p markers were associated with an increased risk of recurrence (relative risk = 1.73 [1.30-2.31], P = .0002) and occurred more frequently in the initial urine samples of patients who later relapsed from primary tumors (36.4% vs 0.0%, P <.05 and 57.6% vs 15.8%, P = .0001). Among 32 relapse patients, LOH was positive alongside cystoscopy in 25 of 32 cases and tested positive before cystoscopy detected recurrence in a further 5 of 25 cases. UC diagnosis and monitoring would greatly benefit from supplementing conventional cytology with LOH urinalysis, using a panel of 8 microsatellite markers with specific threshold levels. Given the limitations of both cystoscopy and cytology, novel molecular markers are needed for detection and follow-up of UC.

The role of surveillance in the treatment of patients with muscle‐invasive bladder cancer after chemotherapy

To determine the survival of patients at our institution who were clinically tumour-free (cT0) on re-staging transurethral resection (TUR) after treatment with chemotherapy for muscle-invasive bladder cancer. In all, 55 patients with muscle-invasive, organ-confined transitional cell carcinoma of the bladder were treated with TUR followed by systemic chemotherapy, over a 10-year period. Patients were separated into two groups, those who were clinically T0 and those who showed persistent disease (>cT0) on re-biopsy after chemotherapy. Overall and disease-specific survival rates were calculated for the two groups. The cT0 group was further followed for tumour recurrence and clinical outcomes. Thirty-one patients (56%) were clinically T0 on TUR after chemotherapy; of these patients, 22 (71%) either died from other causes (with no disease recurrence) or are alive and with no evidence of disease at a mean follow-up of 53 months. Twenty of the 31 patients (65%) have retained their bladder with no evidence of cancer recurrence at a mean follow-up of 46 months. Disease-free status (cT0) at the time of TUR after chemotherapy was associated with significantly higher overall and cancer-specific survival (hazard ratio 3.40, P = 0.003; and 8.63, P = 0.001, respectively). Previous studies suggest that surveillance can be a reasonable option for patients with muscle-invasive transitional cell carcinoma of the bladder who show no evidence of disease on TUR after chemotherapy. Patients with persistent bladder cancer on re-biopsy after chemotherapy tend to fare poorly even with immediate cystectomy.

¿Implica el T0 en la pieza de cistectomía encontrarse libre de tumor a largo plazo?

Introduction and objectives The aim of this study was to evaluate the progress of patients with a pT0 radical cystectomy specimen in order to know what factors are helpful in deciding when the bladder can be preserved. Material and methods We reviewed 153 cases of radical cystectomies performed due to bladder tumours without neoadjuvant therapy between 1995 and 2005 and with a minimum of three years of follow-up. Stage pT0 patients were selected. We considered age at time of diagnosis, sex, pathological stage and grade of the tumour at the time of transurethral resection (TUR), number of resections, surgical factors, tumour characteristics (multifocal, papillary or solid), progression-free survival, cancer-specific survival and cause of death. We ran a univariate analysis of the different factors studied along with disease progression. Results 12.8% of cystectomy specimens were pT0N0. Progression occurred in 35% between 6 months and 4 years after the cystectomy. Cancer-specific survival was 75%. Five patients died within an average of 18 months. The cause of death for all of them was tumour progression with distant metastasis . Statistical studies in the univariate analysis were only related to progression and the number of prior TURs, which is probably due to the number of cases, but the tumour multifocality, grade and stage were noteworthy. 15% of the pT0 patients had a papillary phenotype and 33% of them died. Of those with a non-papillary phenotype, 23.5% died. Conclusions A stage pT0N0 cystectomy specimen does not define this surgery as curative, and these cases require the same follow-up as for the rest of the patients. It is of particular interest that out of all of our cases, there was no local recurrence, but there was distant metastasis. This leads us to believe that these patients could have benefitted from systemic chemotherapy with no need for radical surgery. In our study, the number of previous relapses was the only prognostic factor with statistical significance.

Quantitative methylation analysis of BCL2, hTERT, and DAPK promoters in urine sediment for the detection of non-muscle-invasive urothelial carcinoma of the bladder: A prospective, two-center validation study

Objectives Urinary hypermethylation of BCL2, hTERT, and DAPK promoters has been previously demonstrated as an accurate biomarker for the detection of urothelial carcinoma of the bladder (UCB) in patients undergoing radical cystectomy. In the present study, we investigated with a validation intent the frequency and levels of methylation of the same 3 genes in tumor tissue and urine sediment of patients undergoing transurethral resection (TUR) for non-muscle-invasive (NMI) UCB. Materials and methods A total of 108 consecutive patients with NMI UCB and 105 controls with no genitourinary malignancies were enrolled in this prospective study conducted in 2 tertiary referral academic urological departments with an advanced molecular laboratory. The frequency and levels of methylated BCL2, hTERT, and DAPK promoters were evaluated with quantitative methylation-specific real-time polymerase chain reaction in DNA extracted from tumor tissue and paired normal bladder mucosa retrieved at the time of TUR in patients, and from urine in patients and controls. Results In tumor tissue, at least 1 gene was hypermethylated in 91% patients (BCL2 in 62%, hTERT in 53%, DAPK in 48%). Methylation of hTERT was significantly correlated with tumor grade ( P = 0.026). In urine sediment sensitivity and specificity were 76% and 98%, respectively, using BCL2 and hTERT. The number of methylated genes was highly correlated with tumor grade ( P = 0.005). Methylated BCL2 and hTERT in urine sediment were highly correlated with those of the corresponding bladder tumor qualitatively ( P < 0.001), and only BCL2 also quantitatively ( P = 0.005). Methylation levels of BCL2 and hTERT were variably associated with tumor grade and stage, but were significantly correlated with patient age ( P = 0.004 and P = 0.027, respectively). Conclusions These findings suggest that quantitative methylation analysis of BCL2 and hTERT, but not DAPK, in urine sediment may be a useful tool in the diagnosis of NMI UCB, deserving future applicability studies.

Urothelial mucosal concentration of levofloxacin administered before transurethral resection: Is the mucosal concentration predictable?

Although it is an established surgical technique, transurethral resection (TUR) is associated with a certain incidence of postoperative bacteriuria. Assessment was made whether the urothelial mucosal concentration of an antibiotic administered before TUR was high enough to decrease the incidence of urinary tract infection (UTI). Also investigated were factors predicting the organ concentration. Forty-nine patients (45 men and four women aged 51-79 years with a median age of 70 years) who underwent TUR between August 1996 and September 1997 were enrolled in the study. Each patient received 200 mg of levofloxacin (LVFX) about two hours before surgery. Blood and bladder urine were collected and urothelial mucosa was harvested at the time of TUR. Then the LVFX concentration in these samples was measured using high-performance liquid chromatography. The association between drug levels, or the ratio to the serum concentration, and factors likely to affect the vascular system that delivers the drug (age, bodyweight, blood pressure, pulse rate, total cholesterol and diabetes mellitus) were investigated. The mean serum drug level was 2.4 microg/mL, and it was 206.4 microg/mL in the urine and 5.7 microg/mL in the urothelial mucosa. The mean ratio of the mucosal to serum concentrations was 2.6. The urinary drug concentration showed no association with any of the factors assessed, while the serum concentration decreased with increasing bodyweight (P = 0.03). As the diastolic blood pressure increased, both the mucosal drug concentration and the mucosa/serum ratio decreased (P < 0.01). When the relationship between the serum and mucosal concentrations was investigated, no correlation was found. However, the mucosa/serum ratio (indicating the transfer of LVFX from the blood) was positively correlated with the mucosal concentration. Preoperative administration of LVFX was demonstrated to have potential value for the prophylaxis of UTI after TUR. Both the mucosal concentration and the mucosa/serum ratio were correlated with the diastolic blood pressure. As the diastolic blood pressure seems to be an indicator of the tissue concentration of LVFX, it may be possible to set the optimum dose based on the diastolic pressure.

Morbidity of radical retropubic prostatectomy following previous prostate resection

A total of 153 patients with prior prostate surgery underwent a radical retropubic prostatectomy for carcinoma of the prostate. Ninety-seven patients had undergone transurethral resection of the prostate (TURP), and 56 patients had undergone suprapubic transvesical prostatectomy (SPP). In 115 patients, the diagnosis of malignancy was made at the time of transurethral resection or enucleation. No perioperative deaths occurred and no patient suffered rectal injury or ureteral transection. Operative time and blood loss were similar between the TURP and SPP groups and were not different in a group of patients who had not had prior prostate surgery. Early and late complications occurred in eight patients (5.2%), of whom seven had had previous TURP. Complete urinary control was achieved in 96% (147) of the patients; stress incontinence was present in 4% (6 patients); and no patient was totally incontinent. Postoperative complications and the occurrence of stress incontinence were not related to the time elapsed between the previous prostate surgery and the radical prostatectomy. Sexual function was preserved in 32 (71%) of the 45 patients in whom we performed a nerve-sparing radical prostatectomy. Residual cancer was found in the radical prostatectomy specimen in 77 (67%) of the stage A patients. Twenty-nine (25%) of the stage A and 13 (34%) of the stage B patients had pathological evidence of disease extension beyond the confined prostate. Follow-up was 6-92 months, with a mean of 32 months. Four patients died of prostatic cancer, two patients died without cancer, and five have evidence of disease progression; 142 (93%) are alive without evidence of disease. Although radical prostatectomy sometimes is more difficult after previous prostate surgery, operative complication rates, patient morbidity, and the opportunity for surgical cure are not different from those seen in patients with no history of previous prostate operations.

Flow cytometric determination of ploidy in prostatic adenocarcinoma and its relation to clinical outcome

Flow cytometry was used to measure the DNA content in paraffin-embedded archival specimens of prostatic adenocarcinoma. The specimens were from 49 patients who were found to have adenocarcinoma of the prostate at the time of transurethral resection of the prostate for bladder outlet obstruction. At initial presentation, 34 of these patients had clinically localized disease and 15 had metastatic disease. The authors studied the relationship of DNA ploidy to clinical stage, histologic grade, disease progression, and duration of survival. Their results indicate that regardless of the clinical stage at presentation, the mean time to disease progression is longer in a patient with a DNA diploid tumor when compared with that in a patient with a DNA aneuploid tumor (18.1 months vs 6.5 months, respectively). Additionally, mean time of survival was longer in a patient with a diploid tumor than in a patient with an aneuploid tumor (31.6 months vs 9.6 months, respectively).