Preoperative Urine Cytology Research Articles

Violation of onco-surgical principles is associated with survival outcomes in upper tract urothelial carcinomas after radical nephroureterectomy.

Disease recurrence, particularly intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), is common. We investigated whether violations of onco-surgical principles before or during RNU, collectively referred to as surgical violation (SV), were associated with survival outcomes. Material and methods: Data from a consecutive series of patients who underwent RNU for UTUC 2001-2012 at Skåne University Hospital Lund/Malmö were collected. Preoperative insertion of a nephrostomy tube, opening the urinary tract during surgery or refraining from excising the distal ureter were considered as SVs. Survival outcomes in patients with and without SV (IVR-free [IVRFS], disease-specific [DSS] and overall survival [OS]) were assessed using multivariate Cox regression analyses (adjusted for tumour stage group, prior or concomitant bladder cancer, comorbidity and preoperative urinary cytology). Of 150 patients, 47 (31%) were subjected to at least one SV. Overall, SV was not associated with IVRFS (HR 0.81, 95% CI 0.4-1.6) but with worse DSS (HR 1.9, 95% CI 1.03-3.7) and OS (HR 1.9, 95% CI 1.2-3) in multivariable analysis. Additional analyses with a broader definition of SV including also preoperative instrumentation of the upper urinary tract (ureteroscopy and/or double J stenting) showed similar outcomes for DSS (HR 2.1, 95% CI 1.1-4.3). Worse survival outcomes, despite no difference in IVR, for patients that were subjected to the violation of sound onco-surgical principles before or during RNU for UTUC strengthen the notion that adhering to such principles is a cornerstone in upper tract urothelial cancer surgery.

Comparative assessment of disease recurrence after transurethral resection of non-muscle-invasive bladder cancer with and without a photodynamic diagnosis using 5-aminolevulinic acid: a propensity score-matching analysis.

Among patients with non-muscle-invasive bladder cancer (NMIBC), systematic reviews showed lower recurrence rate in patients treated with photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) than with white-light (WL) TURBT. However, the result is not consistent between clinical trials and the significance of preoperatively available factors in disease recurrence after PDD-TURBT remains unclear. The present study retrospectively analyzed 1174 NMIBC patients who underwent TURBT and were followed up for ≥ 6months. Among 1174 patients, 385 and 789 underwent PDD-TURBT with oral 5-aminolevulinic acid (the PDD group) and WL-TURBT (the WL group), respectively. Recurrence-free survival (RFS) was compared between the PDD and WL groups before and after propensity score matching, and the impact of several baseline parameters on RFS between the 2 groups was investigated after matching. Before propensity score matching, RFS was significantly longer in the PDD group than in the WL group (P = 0.006). After matching, 383 patients were included in both groups, and RFS was significantly longer in the PDD group than in the WL group (P < 0.001). In the cohort after matching, RFS between the two groups was compared in each subgroup classified according to baseline parameters, including age, sex, history of previous or concomitant upper urinary tract urothelial carcinoma, preoperative urinary cytology, tumor multiplicity, and tumor size, and significantly longer RFS was observed in the PDD group in all subgroups, except for the patients with tumors ≥ 30mm (P = 0.21). These results suggest that PDD-TURBT prolongs RFS in NMIBC patients, except for those with tumors ≥ 30mm.

Invasiveness of Upper Tract Urothelial Carcinoma: Clinical Significance and Integrative Diagnostic Strategy.

In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively. Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data. Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001). According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

Urinary bladder recurrences following ureteroscopic biopsies of upper tract urothelial cancers: a multi-centre observational study with genomic assessment for clonality.

Urinary bladder recurrences (UBRs) after radical nephroureterectomy (RNUx) are a known challenge in patients with upper-tract urothelial cancers (UTUCs). We aim to assess factors associated with UBR and clonal-relatedness with resected UTUC. Patients who underwent RNUx for UTUC between 1998 and 2015 in five institutions were identified. Clonal relatedness between primary UTUC and subsequent UBR in a sub-cohort was assessed using next-generation sequencing. A Kaplan-Meier curve was used to assess differences in UBR between two groups (with or without ureteroscopic biopsy). Of 267 patients with complete records, 73 (27.3%) had UBR during follow-up. The five-year UBR-free survival in all patients was 64.7%. The five-year UBR-free-survival was inferior in patients who underwent URS biopsy compared with patients who did not undergo ureteroscopic biopsy (49.9% vs 76.4%, p < 0.001). History of bladder tumour (HR, 95% CI; 2.94, 1.73-5.00, p < 0.001), ureteroscopic biopsy (HR, 95% CI; 2.21, 1.38-3.53, p = 0.001) and preoperative urine cytology ≥C3 (HR, 95% CI; 2.06, 1.24-3.40, p = 0.005) were independently associated with UBR. Patients with ureteroscopic biopsy (n = 3/5) showed identical mutational changes for common genes (TP53 and FGFR3) between primary UTUC and subsequent UBR. Ureteroscopic biopsy of UTUC is a significant risk factor for UBR. Qualitative clonality assessment showed identical mutational signatures between primary UTUC and UBR.

The Paris System for reporting urinary cytology improves the negative predictive value of high-grade urothelial carcinoma

BackgroundThe Paris System (TPS) for reporting urinary cytology differs from conventional systems (CS) in that it focuses on the diagnosis of high-grade urothelial carcinoma (HGUC). This study investigated the impact of TPS implementation on the diagnostic accuracy of HGUC by comparing it with our institutional CS.MethodsA total of 649 patients who underwent transurethral resection of bladder tumor (TURBT) between January 2009 and December 2020 were included in this study. Our institution adopted TPS to report urinary cytology in February 2020. The diagnostic accuracy of HGUC in preoperative urinary cytology was compared with the presence or absence of HGUC in resected specimens of TURBT before and after TPS implementation.ResultsAfter implementing TPS in urinary cytology, 89 patients were reviewed and compared with 560 patients whose urinary cytology was diagnosed by CS. TPS and CS for detecting HGUC had 56.0% and 58.2% sensitivity, 97.8% and 91.2% specificity, and 93.3% and 87.9% positive predictive values, respectively. There were no significant differences between TPS and CS in terms of sensitivity, specificity, and positive predictive value for HGUC (P = 0.83, 0.21, 1.00). On the other hand, the negative predictive value for HGUC using TPS was 80.0%, which was significantly higher than that of CS (66.4%, P = 0.04) The multivariate logistic regression analysis indicated that not using TPS was one of the independent predictive factors associated with false-negative results for HGUC (odds ratio, 2.26; 95% confidence interval, 1.08–4.77; P = 0.03).ConclusionIn instances where urinary cytology is reported as negative for HGUC by TPS, there is a low probability of HGUC, indicating that TPS has a potential diagnostic benefit.

Risk factor analysis of intravesical recurrence after retroperitoneoscopic nephroureterectomy for upper tract urothelial carcinoma

BackgroundOne of the major concerns of patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy is intravesical recurrence (IVR). The purpose of the present study was to investigate the predictive risk factors for IVR after retroperitoneoscopic nephroureterectomy (RNU) for UTUC.MethodsClinicopathological and surgical information were collected from the medical records of 73 patients treated with RNU for non-metastatic UTUC, without a history of or concomitant bladder cancer. The association between IVR after RNU and clinicopathological and surgery-related factors, including preoperative urine cytology and pneumoretroperitoneum time, was analyzed using the Fisher exact test.ResultsDuring the median follow-up time of 39.1 months, 18 (24.7%) patients had subsequent IVR after RNU. The 1- and 3-year IVR-free survival rates were 85.9% and 76.5%, respectively. The Fisher exact test revealed that prolonged pneumoretroperitoneum time of ≥ 210 min was a risk factor for IVR in 1 year after RNU (p = 0.0358) and positive urine cytology was a risk factor for IVR in 3 years after RNU (p = 0.0352).ConclusionsIn UTUC, the occurrences of IVR in 1 and 3 years after RNU are highly probable when the pneumoretroperitoneum time is prolonged (≥ 210 min) and in patients with positive urine cytology, respectively. Strict follow-up after RNU is more probable recommended for these patients.

Predictive Value of Preoperative Positive Urine Cytology for Development of Bladder Cancer After Nephroureterectomy in Patients With Upper Urinary Tract Urothelial Carcinoma: A Prognostic Nomogram Based on a Retrospective Multicenter Cohort Study and Systematic Meta-Analysis.

BackgroundUpper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence (IVR) in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in northeast China are rare.MethodsWe first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 231 UUT-UC patients (training cohort = 142, validation cohort = 89) after radical nephroureterectomy (RNU) by the nomogram model. Subsequently, we quantitatively combined our results with the published data after searching several databases to assess whether preoperative positive urine cytology was associated with poor intravesical recurrence-free survival and a high risk of tumor malignant biological behavior.ResultsFirstly, the multicenter retrospective cohort study demonstrated that preoperative positive urine cytology correlated with poor intravesical recurrence-free survival and can serve as significant independent predictors of IVR by Kaplan–Meier curves and Cox regression analysis. The construction of the nomogram demonstrated that predictive efficacy and accuracy were significantly improved when preoperative urine cytology was combined. Meanwhile, meta-analysis showed that preoperative positive urine cytology was associated with a 49% increased risk of IVR. In the subgroup analysis by region, study type, and sample size, the pooled hazard ratios (HRs) were statistically significant for the Japan subgroup (HR 1.32), China subgroup (HR 1.88), cohort study subgroup (HR 1.45), and the single-arm study subgroup (HR 1.63).ConclusionsPreoperative urine cytology was validated as a potential predictor of intravesical recurrence in patients with UUT-UC after RNU, although these results need to be generalized with caution. Large, prospective trials are required to further confirm its significance in prognosis and tumor malignant biological behavior.

Gain of TPPP as a predictor of progression in patients with bladder cancer.

The present study investigated the role of tubulin polymerization promoting protein (TPPP) in the regulation of bladder cancer (BC) cell proliferation and migration, in addition to the association between TPPP gene copy number amplification and clinicopathological characteristics of BC. TPPP gene amplification was measured in human BC epithelial cells and samples obtained from 52 patients with BC via fluorescence in situ hybridization. TPPP gain was defined as mean TPPP copy number >2.2 per nucleus (cutoff). The neutrophil-to-lymphocyte ratio (NLR) was also obtained from the preoperative data of the patients. For in vitro assays, BC cell lines were transfected with either TPPP small interfering RNAs or scrambled control, following which cell proliferation and migration were determined using Cell Counting Kit-8 and Transwell migration assays, respectively. The percentage of cells with TPPP copy number amplification in the four BC epithelial cell lines (MGH-U1, -U1R, -U3, -U4) examined (86.0-100.0%) was found to be higher compared with that in the normal human uroepithelial cell lines (3.0 and 9.0%). Patients were divided into one- (1.9%), two- (55.8%), three- (7.7%), four- (26.9%) and five-copy (7.7%) types. Results calculated using Fisher's exact test indicated that the gain of TPPP in patients with BC associated significantly with age (P<0.05), advanced histological grade (P<0.001), tumor stage (P<0.05), histological type (P<0.001) and NLR (P<0.05). In MGH-U1R and MGH-U4 cells, cell proliferation and migration were revealed to be significantly lower following TPPP knockdown compared with those in cells transfected with the scrambled control. In conclusion, findings from the present study suggest that TPPP is important for cell proliferation, cell migration and BC progression, such that TPPP copy number assessment would be advised for preoperative urine cytology for urothelial neoplasia diagnosis.

Significance of 5-Aminolevulinic Acid-mediated Photodynamic Diagnosis Following Standard Transurethral Resection in Non-muscle Invasive Bladder Cancer.

Transurethral resection of bladder tumors (TURBT) guided by photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) has been shown to be superior to conventional white light (WL) cystoscopy with regard to diagnostic accuracy, for non-muscle invasive bladder cancer (NMIBC); however, PDD is usually performed prior to WL TURBT. The objective of this study was to investigate the diagnostic significance of 5-ALA-mediated PDD following TUR of NMIBC. In 83 NMIBC patients, all visible tumors were completely resected under the conventional WL guidance followed by additional resection if fluorescent lesions were observed under the blue light (BL) guidance, and random biopsy was further conducted. With the BL source, 39 (47.0%) patients were judged to have fluorescent lesions. Twenty (51.3%) of the 39 patients with positive findings by PDD were diagnosed with residual cancer by additional resection, while random biopsy detected cancers in 2 (4.5%) of the 44 patients with negative findings by PDD. Accordingly, the sensitivity, specificity, positive predictive value and negative predictive value in diagnosing residual cancer by our PDD system were 90.9, 68.9, 51.3 and 95.5%, respectively. Univariate analysis showed that the presence of residual cancers shown by WL TURBT was significantly associated with the preoperative findings of urinary cytology, tumor multiplicity, pathological T stage and tumor grade, of which only the preoperative finding on urinary cytology was shown to have an independent impact on the diagnosis of residual cancer. 5-ALA-mediated PDD following standard WL TURBT could improve the diagnostic accuracy in NMIBC patients, particularly those who are positive for preoperative urinary cytology.

Usefulness of Fluorescent Urine Cytology in the Diagnosis of Urothelial Carcinoma

Five-aminolevulinic acid, an amino acid that is metabolized in the cytoplasm to become protoporphyrin IX, is used in photodynamic diagnosis in various carcinomas because it accumulates in higher concentrations in tumor tissue than in normal tissue. 5-Aminolevulinic acid-induced fluorescent urine cytology is more sensitive than conventional urine cytology only in low grade urothelial carcinoma (UC), but it showed a tendency for higher sensitivity in high grade UC. To increase the number of patients and reconsider our previous findings, we compared the sensitivity and specificity of preoperative urine cytology and fluorescent urine cytology in 343 patients diagnosed as having UCs pathologically (215 bladder cancers, 128 upper tract UCs) and 197 non-cancer patients at Osaka Rosai Hospital from March 2013 to December 2019. The sensitivities of fluorescent urine cytology and conventional urine cytology were 81.1% and 63.3% (p<0.001), respectively, and specificities were 92.9% and 93.9% (p=0.84), respectively. The sensitivity of fluorescent urine cytology was superior to that of conventional urine cytology in both low grade UC (76.8% vs 41.1%, p<0.001) and high grade UC (83.1% vs 74.0%, p=0.023).

Clinical Analysis of the Predictors for Intravesical Recurrence After Laparoscopic Radical Nephroureterectomy in Japanese Patients

Objectives: In this study, we evaluate the clinicopathological independent prognostic factors which to predict IVR in patients who underwent Laparoscopic-assisted radical nephroureterectomy (LRNU) for upper urinary tract carcinoma (UTUC). Methods: Between April 2008 to February 2019, we analyzed 100 japanese patients who were underwent LRNU and 92 patients who were underwent open radical nephroureterectomy (ORNU) at our institutions by retrospectively. The Patients characteristics factors, the clinicopathologic factors were collected. The intravesical recurrence free survival (IVRFS) were analyzed using the Kaplan-Meier method and Univariate and multivariate method by using the Cox proportional hazards regression models were performed to identify independent risk factors for IVR after LRNU. Results: In LRNU group, IVR was observed in 39 cases (39%), and it was not significant difference compare with ORNU (P: 0.36). Tumor location (P=0.002), Tumor size (P=0.001), preoperative urine cytology (P<0.0001), the pneumoperitoneum time (P: 0.0005) and adjuvant chemotherapy (P=0.019) showed significant association with postoperative IVR. In the multivariate Cox hazard models, the tumor location (P=0.0003), positive preoperative urinary cytology (P=0.003), and absence of adjuvant chemotherapy (P=0.003) were independent risk factors for subsequent IVR. There were not associated with smoking, Brinkman index, hydronephrosis and ureterorenoscopy before RNU for IVR. Overal survival (OS) was not significant association for experience IVR (P=0.15). Conclusion: In this study, LRNU was not shown to have a significantly higher IVR compared to ORNU. Patients with ureteral cancer and positive preoperative urinary cytology had a higher risk of IVR after LRNU. The adjuvant chemotherapy was significantly decreased the risk for postoperative IVR.

Impact of Previous, Simultaneous or Subsequent Bladder Cancer on Prognosis after Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma.

We investigated the impact of previous, simultaneous or subsequent bladder cancer on the clinical outcomes of upper urinary tract urothelial carcinoma. We retrospectively collected data on 2,668 patients who underwent radical nephroureterectomy of nonmetastatic upper urinary tract urothelial carcinoma in 1995 to 2009. We evaluated the impact of bladder cancer on overall mortality and the factors predictive of subsequent bladder cancer. A total of 631 patients (23.7%) had previous or simultaneous bladder cancer. Patients with previous or simultaneous bladder cancer had significantly shorter overall survival than patients without previous or simultaneous bladder cancer (HR 1.29, 95% CI 1.09-1.53, p=0.0026). Of the 2,037 patients without previous or simultaneous bladder cancer 683 (33.5%) subsequently had bladder cancer after radical nephroureterectomy. Of patients with pT0-2 disease those with subsequent bladder cancer had significantly shorter overall survival than patients without subsequent bladder cancer (HR 1.81, 95% CI 1.23-2.67, p=0.0025). In patients with pT3-4 disease subsequent bladder cancer was not associated with worse overall survival. On multivariable analyses independent predictors of subsequent bladder cancer were gender, preoperative urine cytology and clinical node status in the preoperative setting, and gender, adjuvant chemotherapy and pathological node status in the postoperative setting. Bladder cancer was significantly associated with worse clinical outcomes after radical nephroureterectomy of upper urinary tract urothelial carcinoma. Preventing subsequent bladder cancer in patients with pT0-2 upper urinary tract urothelial carcinoma may lead to better prognosis in those who undergo radical nephroureterectomy.

Predictors for Intravesical Recurrence Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A National Multicenter Analysis

The purpose of this study was to identify the prognostic impact of intravesical recurrence (IVR) on oncologic outcomes and the clinicopathologic factors that predict IVR in patients who undergo radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. Between January 2000 and December 2015, 760 patients with upper tract urothelial carcinoma underwent RNU at 5 institutions in Korea, and patient data were retrospectively collected. Clinicopathologic factors were analyzed for intravesical recurrence-free survival, cancer-specific survival (CSS), and overall survival (OS). Univariate and multivariate Cox proportional hazards regression models were used to test the clinicopathologic factors on IVR. Of the 760 patients, 231 (30.3%) patients experienced IVR within 10 months of the median interval between RNU and the first IVR. The overall estimated probabilities of 5-year CSS, intravesical recurrence-free survival, and OS were 84.2%, 63.8%, and 79.2%, respectively. No difference was noted in terms of CSS and OS between the patients who did or did not experience IVR. The multivariate Cox analysis showed an association between IVR and positive hydronephrosis, tumor size, positive preoperative urinary cytology, and ureterorenoscopy before RNU (all P< .05). However, a significantly decreased riskof IVR was associated with female gender, laparoscopic RNU, and receipt of adjuvant systemic chemotherapy (allP< .05). The occurrence of IVR following RNU did not affect CSS and OS. Patients with larger tumor size, preoperative hydronephrosis, positive preoperative urinary cytology, and ureterorenoscopy before RNU had a higher risk of IVR following RNU.

The role of urinary cytology when diagnostic workup is suspicious for upper tract urothelial carcinoma but tumour biopsy is nonconfirmatory.

We sought to determine the value of obtaining preoperative urinary cytology when diagnostic workup of an upper tract mass is suspicious for upper tract urothelial carcinoma (UTUC), but biopsy fails to confirm the diagnosis. Using billing code data, 239 patients were identified as having undergone radical nephroureterectomy (RNU) by 16 urologists from September 29, 1998 to July 31, 2015. Of this group, 19 adult patients had a presumed preoperative diagnosis of UTUC in a native kidney, at least three months of followup, no history of concurrent radical cystectomy with RNU, and negative/non-diagnostic tissue biopsy. These patients were divided into three groups: Group A had no urinary cytology taken (n=6); Group B had upper and/or lower tract cytology performed with neither positive nor atypical (n=7); Group C had upper and/or lower tract cytology performed with at least one positive or atypical (n=6). Demographic information and diagnostic workup was similar between the groups, although Group A had more patients with a history of prior radical cystectomy for bladder cancer (p=0.02). One patient in Group B had benign tissue on final pathology. All patients in Groups A and C had malignancy on final pathology and overall, the three groups had similar rates of malignancy. When a composite of clinical findings suggest UTUC, performing urinary cytology may not be necessary. A negative result in this setting should not be used to rule out UTUC, as this is often discordant with final pathology. A positive cytology result may help solidify the diagnosis when other findings are less clear.

Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC). A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH), muscle invasive bladder carcinoma (MIBC), carcinoma in situ (CIS), and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT) and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR). A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior.

Significance of Random Bladder Biopsies in Non-Muscle Invasive Bladder Cancer

Background/Aims: To evaluate retrospectively the clinical outcome of random bladder biopsies in patients with non-muscle invasive bladder cancer (NMIBC) undergoing transurethral resection (TUR). Patients and Method: This study included 234 consecutive patients with NMIBC who underwent random biopsies from normal-appearing urothelium of the bladder, including the anterior wall, posterior wall, right wall, left wall, dome, trigone and/or prostatic urethra, during TUR. Result: Thirty-seven patients (15.8%) were diagnosed by random biopsies as having urothelial cancer. Among several factors available prior to TUR, preoperative urinary cytology appeared to be independently related to the detection of urothelial cancer in random biopsies on multivariate analysis. Urinary cytology prior to TUR gave 50.0% sensitivity, 91.7% specificity, 56.8% positive predictive value and 89.3% negative predictive value for predicting the findings of the random biopsies. Conclusion: Biopsies of normal-appearing urothelium resulted in the additional detection of urothelial cancer in a definite proportion of NMIBC patients, and it remains difficult to find a reliable alternative to random biopsies. Collectively, these findings suggest that it would be beneficial to perform random biopsies as part of the routine management of NMIBC.

The predictive value of positive urine cytology for outcomes following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma: A multi-institutional study

Background and objectiveFew studies have addressed the predictive value of positive urine cytology for prognosis in patients with upper tract urothelial carcinoma (UTUC). We investigated whether the status of preoperative urine cytology could provide additional prognostic information following radical nephroureterectomy (RNU). Materials and methodsThe study included 474 patients with primary nonmetastatic UTUC (pTa-4N0M0) from a retrospective multi-institutional cohort. The median follow-up period was 35 months. Associations between the status of urine cytologic evaluation and outcomes were analyzed using multivariate Cox regression models. Urine cytology was evaluated preoperatively using voided samples. Disease recurrence was defined as any relapse in nonbladder lesions and was coded separately from intravesical recurrence. ResultsPositive urine cytology was detected in 184 patients (38.8%) preoperatively. Disease recurrence occurred in 127 patients, while intravesical recurrence occurred in 219 patients; 83 patients died of UTUC during follow-up. Kaplan-Meier analysis revealed that only the incidence of intravesical recurrence was significantly associated with the status of urine cytologic evaluation (P = 0.024); the intravesical recurrence-free survival rates at 1 and 3 years following RNU were 61.4% and 46.2% in patients with positive urine cytology and 71.1% and 51.6% in their counterparts, respectively. Multivariate analysis showed that gender (hazard ratio [HR] = 1.74, 95% confidence interval [CI]; 1.28–2.43), tumor multifocality in RNU specimens (HR = 1.64, 95% CI; 1.09–2.47), and positive urine cytology (HR = 1.41, 95% CI; 1.08–1.85) were independent risk factors for subsequent intravesical recurrence. ConclusionsThe results showed the prognostic value of positive urine cytology in patients with primary UTUC, and preoperative positive urine cytology may be associated with a significant increase in the prevalence of intravesical recurrence following RNU.

Predictive Factors for Bladder Recurrence after Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma

Introduction: To identify predictive factors for developing subsequent bladder urothelial carcinoma (UC) in patients undergoing radical nephroureterectomy for the treatment of upper urinary tract UC (UUT-UC). Materials and Methods: We retrospectively reviewed the medical records of 78 patients with clinically localized UUT-UC who had undergone operation at our institution between June 1994 and December 2009. Univariate and multivariate analyses were carried out to determine the predictive factors. Results: Out of a total of 78 patients, 14 (17.9%) developed bladder UC after radical nephroureterectomy at a median interval of 10 months (range: 3-46). Of these 14 patients, 11 (78.6%) experienced bladder recurrence within the first 2 years of follow-up. All 14 patients (100%) had non-muscle-invasive bladder UC and 10 patients (71.4%) had high-grade tumors. The univariate analysis identified preoperative voided urine cytology, tumor configuration, and adjuvant systemic chemotherapy as significant predictive factors for bladder recurrence, whereas the multivariate analysis indicated that only preoperative voided urine cytology was an independent predictive factor. Conclusions: Positive preoperative voided urine cytology is an independent predictor for bladder recurrence after radical nephroureterectomy for UUT-UC. Therefore, closer surveillance of the bladder is necessary, especially in patients with positive preoperative urine cytology.

Intravesical Recurrence after Surgical Management of Urothelial Carcinoma of the Upper Urinary Tract

Objectives: To elucidate clinicopathological risk factors for intravesical recurrence (IVR) in patients undergoing nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). Methods: We identified a study population of 151 consecutive patients without previous or concurrent bladder cancer who underwent nephroureterectomy for UUT-UC. IVR was assessed in relation to tumor location, size, and multifocality, operation modality and time, stage, grade, lymphovascular invasion, regional lymph node metastasis, preoperative urinary cytology, and perioperative chemotherapy. The median follow-up time was 24 months. Results: Of 151 patients, 51 (34%) developed IVR after nephroureterectomy, and 50 (98%) of the patients presented with IVR within 2 years. Tumor multifocality and site (located in ureter) were determined as risk factors for IVR by univariate analysis. In a multivariate analysis, only tumor multifocality (relative risk: 4.024, p = 0.001) was an independent predictor of IVR. Ten-year cancer-specific survival rates for the patients with and without IVR were 68 and 52%, respectively (p = 0.06). Conclusions: Tumor multifocality is a significant risk factor in developing IVR after surgery for UUT-UC. These results indicate that despite most IVR occurring within 2 years of treatment, it is necessary to follow such patients more closely using cystoscopy. However, IVR is unlikely to indicate a poorer prognosis.

644 THE IMPACT OF INTRAVESICAL RECURRENCE ON PROGNOSIS AFTER NEPHROURETERECTOMY FOR UPPER URINARY TRACT UROTHELIAL CELL CARCINOMA

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors1 Apr 2012644 THE IMPACT OF INTRAVESICAL RECURRENCE ON PROGNOSIS AFTER NEPHROURETERECTOMY FOR UPPER URINARY TRACT UROTHELIAL CELL CARCINOMA Junichi Inokuchi, Kentaro Kuroiwa, Katsunori Tatsugami, Akira Yokomizo, and Seiji Naito Junichi InokuchiJunichi Inokuchi Fukuoka, Japan More articles by this author , Kentaro KuroiwaKentaro Kuroiwa Fukuoka, Japan More articles by this author , Katsunori TatsugamiKatsunori Tatsugami Fukuoka, Japan More articles by this author , Akira YokomizoAkira Yokomizo Fukuoka, Japan More articles by this author , and Seiji NaitoSeiji Naito Fukuoka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.723AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder tumors have been reported to be found in a range of 15% to 50% after nephroureterectomy (NU) for patients with upper urinary tract urothelial cell carcinoma (UUT-UCC). Although many studies have reported clinicopathological features of UUT-UCC which affect bladder tumor development, these predictive factors are still controversial. Furthermore, the prognostic impact of intravesical recurrence is still contentious. The aim of this study was to identify predictive factors of intravesical recurrence after NU for UUT-UCC and verify prognosis of these patients. METHODS Clinicopathological data from 141 patients who underwent NU for UUT-UCC without distant metastasis between June 1994 and April 2010 in Kyushu University were retrospectively collected. Intravesical recurrence-free survival was analyzed with a log-rank test and a Cox proportional hazard model was used for multivariate analysis. Variables such as prior history of bladder tumor, concurrent bladder tumor, pathological stage, preoperative urine cytology, pathological grade, tumor location, multifocality, presence of CIS and tumor size were assessed. RESULTS The median age and follow-up time after NU were 71 yr (range 32-87) and 35.0 months. For pathological stage, 69 (48.9%) and 72 (51.1%) had non-muscle invasive and muscle invasive diseases, respectively. Of the 141 patients, 63 patients developed intravesical recurrence at a median interval of 8.8 months after NU. Intravesical recurrence-free survival rate at 2 year after NU was 54.0%. 56 (88.9%) of 63 patients had intravesical recurrence within 2 years after NU. Univariate analysis showed concurrent bladder tumor as a predictor for the development of intravesical recurrence. Interestingly patients with intravesical recurrence showed better overall survival rate compared with patients without intravesical recurrence (p=0.023). CONCLUSIONS In this study, patients with intravesical recurrence after NU did not show poor prognosis compared with those without intravesical recurrence, at least. Even though the bladder should be observed in all cases because of high intravesical recurrence rate, intravesical recurrence may not have impact on prognosis. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e262-e263 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Junichi Inokuchi Fukuoka, Japan More articles by this author Kentaro Kuroiwa Fukuoka, Japan More articles by this author Katsunori Tatsugami Fukuoka, Japan More articles by this author Akira Yokomizo Fukuoka, Japan More articles by this author Seiji Naito Fukuoka, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...