Survival In Transitional Cell Carcinoma Research Articles

Incidence, mortality and survival of transitional cell carcinoma in the urinary system: A population-based analysis.

The goal of this study is exploring the disparity of incidence, mortality and survival outcome among transitional cell carcinomas (TCCs) in the 4 parts of urinary system. This study comprehensively evaluates these disparities using the Surveillance, Epidemiology, and End Results (SEER) (2000-2018) database. According to the SEER database, the urinary tract is divided into 4 parts: urinary bladder, renal pelvis, ureter, and urethra. The joinpoint regression was used to analyze the secular trend of incidence and incidence-based mortality (IBM). The Kaplan-Meier method with the log-rank test is performed to evaluate survival outcomes. The bladder TCC has the highest age-adjusted incidence and mortality rate compared with TCC in other 3 locations. A slight decrease in incidence is shown in the both bladder and urethra TCCs during 2000-2018. The age-adjusted mortality rate similarly presents an initial increase among 4 locations TCCs at the beginning of study period. The survival curves demonstrate that patients with bladder TCCs have better overall survival (OS) and cancer-specific survival (CSS), whereas those with renal pelvis TCCs have the worse OS and CSS. In addition, patients with bladder TCC have the highest 1-year, 3-year, 5-year relative survival rate, and those with renal pelvis TCC have the lowest. These disparities are especially essential when we explore tumor characteristics and treatment, extrapolated from the literature on bladder TCC for upper tract urothelial carcinoma (UTUC). Notably, patients with bladder TCC especially for localized stage have better survival outcomes than those with UTUC.

Crosstalk between autophagy and bladder transitional cell carcinoma by autophagy-related lncRNAs.

The aim of this study was to investigate the crosstalk between autophagy and bladder transitional cell carcinoma (TCC) by autophagy-related long noncoding RNAs (lncRNAs). A total of 400 TCC patients from The Cancer Genome Atlas were enrolled in this study. We identified the autophagy-related lncRNA expression profile of the TCC patients and then constructed a prognostic signature using the least absolute shrinkage and selection operation and Cox regression. Risk, survival, and independent prognostic analyses were carried out. Receiver operating characteristic curve, nomogram, and calibration curves were explored. Gene Set Enrichment Analysis was employed to verify the enhanced autophagy-related functions. Finally, we compared the signature with several other lncRNA-based signatures. A 9-autophagy-related lncRNA signature was established by least absolute shrinkage and selection operation-Cox regression that was significantly associated with overall survival in TCC. Among them, 8 of the 9 lncRNAs were protective factors while the remaining was a risk factor. The risk scores calculated by the signature showed significant prognostic value in survival analysis between the high- or low-risk groups. The 5-year survival rate for the high-risk group was 26.0% while the rate for the low-risk group was 56.0% (P < .05). Risk score was the only significant risk factor in the multivariate Cox regression survival analysis (P < .001). A nomogram connecting this signature with clinicopathologic characteristics was assembled. To assess the performance of the nomogram, a C-index (0.71) was calculated, which showed great convergence with an ideal model. The Gene Set Enrichment Analysis results demonstrated 2 major autophagy-related pathways were significantly enhanced in TCC. And this signature performed a similar predictive effect as other publications. The crosstalk between autophagy and TCC is significant, and this 9 autophagy-related lncRNA signature is a great predictor of TCC.

The impact of marital status on the survival of transitional cell carcinoma of the bladder.

578 Background: Marital status is one of the multiple lifestyle factors that affect the survival of several malignancies. Prior literature has demonstrated that married individuals have better survival in cases of transitional cell carcinoma (TCC). In this study, we aim to demonstrate the association in a large cohort of patients. Methods: Data of TCC patients with known marital status who were diagnosed between 1973 and 2015 in the US was obtained using the Surveillance Epidemiology and End Results (SEER) database. We compared the overall and cancer-specific survival of patients according to their marital status using Kaplan-Meier test and multivariable covariate-adjusted Cox models. Results: We reviewed 204,862 TCC patients, of which 64.26%, 10.64%, 1.01%, 7.31%, and 16.78% were married, single, separated, divorced, and widowed, respectively. Married patients had the highest overall survival (median 123 months), followed by single patients (median 111 months), divorced (median 102 months), separated (median 60 months), and widowed (median 43 months). Bladder cancer-specific survival followed relatively similar trends with married patients having significantly better survival when compared to other groups. When we adjusted for age, sex, race, stage, grade, and undergoing cancer-targeted surgery, married patients had better survival outcomes when compared to single patients (HR = 1.322, p-value &lt; 0.001), separated patients (HR = 1.409, p-value &lt; 0.001), divorced patients (HR = 1.358, p-value &lt; 0.001), and widowed patients (HR = 1.242, p-value &lt; 0.001). Conclusions: Our results demonstrate a clear survival advantage in cases of transitional cell carcinoma of the bladder with married individuals having the highest overall and cancer-specific median survival. These results shed the light on the lifestyle and the psychosocial factors, including the social support that married patients may have comparing to unmarried patients, and their effect on the disease prognosis and survival. Understanding the social and psychological factors associated with the observed disparity may help enhance management plans for affected patients.

O2-3-3 - Does a prior malignancy impact the survival of transitional cell carcinoma of the bladder?

O2-3-3 - Does a prior malignancy impact the survival of transitional cell carcinoma of the bladder?

O2-3-2 - Survival of transitional cell carcinoma of the bladder for Japanese patients residing in the United States

O2-3-2 - Survival of transitional cell carcinoma of the bladder for Japanese patients residing in the United States

Impact of BCL2 polymorphisms on survival in transitional cell carcinoma of the bladder.

To evaluate the impact of three BCL2 single-nucleotide polymorphisms, i.e., c.-938C>A (rs2279115), c.21G>A (rs1801018), and c.*2203A>G (rs4987853) on survival in patients with transitional cell carcinoma of the bladder. We analyzed 179 patients who underwent surgical treatment for bladder cancer at the Clinic of Urology, University Hospital Essen, Germany. Genomic DNA was extracted and genotyped for the polymorphisms. For all polymorphisms, linkage analysis was performed. Kaplan-Meier and Cox regression analyses were used to determine the putative impact of the three polymorphisms on outcome. c.-938C>A and c.21G>A, but not c.*2203A>G, are in strong linkage disequilibrium (D' 0.96). We found a significant association between c.-938C>A and relapse-free survival (p = 0.024) with an allele dose effect. In the same way, c.21G>A had a significant impact on both relapse-free survival (p = 0.009) and progression-free survival (p = 0.012), as well as a pronounced allele dose effect. Regression analysis proved c.21G>A and c.-938C>A, to be an independent risk factor in univariate and multivariable analyses. In our cohort, both c.-938C>A and c.21G>A showed a significant impact on outcome with TCC of the bladder. Due to the linkage disequilibrium of both SNPs, maybe, only one of them could mediate this effect. In multivariable analysis, however, both proved to be independently associated with overall survival. Contrary to other findings which found the c.-938C>A mainly influencing outcome, our data may suggest that the main effect on TCC could be due to the c.21G>A polymorphism.

Association of glutathione transferase omega polymorphisms with risk and survival in transitional cell carcinoma of urinary bladder

Exposure to chemical carcinogens, especially smoking and occupational exposure, is an etiologic factor for transitional cell carcinoma (TCC) of the urinary bladder. Cytosolic glutathione transferases (GSTs) are a superfamily of enzymes that protect normal cells by catalyzing conjugation reactions of electrophilic compounds, including carcinogens, to glutathione. Several types of allelic variations have been identified within GSTO class, with GSTO1*A140D (NCBI SNP ID: rs4925, 419 C to A) and GSTO2*N142D (NCBI SNP ID: rs156697, 424 A to G) being the most common. Individuals with the GSTO2*G/G genotype carry a higher risk for TCC. Our results indicate that GSTO1*C/GSTO2*G haplotype is associated with increased TCC risk, which is more pronounced in carriers of variant GSTO2*G/G combined with smoking. Furthermore, GSTO1*A/A and GSTO2*G/G genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive TCC. Newly discovered deglutathionylase activity of GSTO1 suggests its potential important role in redox perturbations present in TCC, which might contribute to progression of TCC.

Squamous Cell Malignancies of the Upper Urinary Tract: A Survival Study and a Systematic Review of the Literature

Background: Carcinomas of the renal pelvis and ureter are rare diseases. Previous reports suggest that squamous cell histology is associated with inferior survival. We present one of the largest population based analysis to date of survival in patients with upper urinary tract malignancies and a systematic review of the subject. Methods: We analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2004 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis. Results: We identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 3.7 (95% CI 3.0-4.5) for SCC when compared to TCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (p = 0.84) and for patients with clear lymph nodes (p = 0.92). Conclusions: SCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage.

Renal Function and Oncologic Outcomes of Parenchymal Sparing Ureteral Resection Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

We compared renal function and oncologic outcomes of parenchymal sparing ureteral resection with radical nephroureterectomy for the treatment of upper tract urothelial carcinoma confined to the ureter. Review of a large institutional database identified 367 patients treated for primary upper tract urothelial carcinoma with radical nephroureterectomy or parenchymal sparing ureteral resection from 1994 to 2009. Patients with known renal pelvis tumors, muscle invasive urothelial carcinoma, prior cystectomy, contralateral upper tract urothelial carcinoma, metastatic disease or chemotherapy were excluded, leaving 120 patients for analysis. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Recurrence-free, cancer specific and overall survival were estimated using Kaplan-Meier analysis. Radical nephroureterectomy was performed in 87 patients and parenchymal sparing ureteral resection in 33. Median age at surgery was 73 years in the radical nephroureterectomy group (IQR 64-76) vs 70 years (IQR 59-77) in the parenchymal sparing ureteral resection group (p = 0.5). The radical nephroureterectomy and parenchymal sparing ureteral resection cohorts had several disparate clinicopathological variables including preoperative hydronephrosis (80% vs 45%, p = 0.0006), stage (pT3 or greater 26% vs 9%, p = 0.01) and baseline estimated glomerular filtration rate (51 vs 63 ml/minute/1.73 m(2), p = 0.009). Patients who underwent radical nephroureterectomy experienced a significantly greater decrease in estimated glomerular filtration rate after surgery (median -7 vs 0 ml/minute/1.73 m(2), p <0.001). Median followup was 4.2 years. Of the patients 79 experienced cancer recurrence and 44 died (28 of upper tract urothelial carcinoma). There were no obvious differences in the rates of recurrence, cancer specific death or overall death by procedure type. However, due to the limited number of events we cannot exclude the possibility that there are large differences in oncologic outcomes by procedure type. Parenchymal sparing ureteral resection is associated with superior postoperative renal function. However, the impact on cancer control cannot be determined conclusively due to the small sample size and putative selection bias.

Survival of Patients with Squamous Cell Malignancies of the Upper Urinary Tract

BackgroundCarcinomas of the renal pelvis and ureter are rare diseases, accounting for only about 1% of all urogenital malignancies. Previous reports suggest that squamous cell histology is associated with inferior survival. We present the largest population based analysis to date of survival in patients with upper urinary tract malignancies.MethodsWe analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis.ResultsWe identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 3.7 (95% CI 3.0–4.5) for SCC when compared to TCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (P = 0.84) and for patients with clear lymph nodes (P = 0.92).ConclusionsSCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage.

Prognostic Value of Cyclooxygenase-2 Expression in Squamous Cell Carcinoma of the Bladder

Inflammation is associated with the pathogenesis of carcinoma, including squamous cell carcinoma of the bladder. Cyclooxygenase-2 is an enzyme that is induced at inflammation sites. We assessed the expression pattern of cyclooxygenase-2 in patients with squamous cell carcinoma of the bladder and determined whether cyclooxygenase-2 expression is associated with clinical outcomes after radical cystectomy. Immunohistochemical staining for cyclooxygenase-2 was done on archival bladder specimens from 152 patients treated with radical cystectomy for squamous cell carcinoma on the Autostainer (DakoCytomation, Carpinteria, California). Bright field microscopy imaging coupled with advanced color detection software was used. Cyclooxygenase-2 was defined as over expressed when greater than 20% cells were positive. We assessed the relationship of cyclooxygenase-2 expression with pathological parameters and clinical outcome. The study included 99 male and 53 female patients with a mean age of 52 years who had squamous cell carcinoma, including 80.9% with bilharziasis. Presenting stage was T2 or greater and presenting grade was GII or less in 93.4% of patients. Median followup was 63.2 months. Cyclooxygenase-2 was over expressed in 74 cystectomy specimens (48.7%) and associated with higher pathological stage (p=0.003) and grade (p=0.049). On multivariate Cox proportional hazards regression analysis cyclooxygenase-2 over expression was associated with disease recurrence (p=0.031) and bladder cancer specific mortality (p=0.046). Cyclooxygenase-2 over expression is associated with pathological stage, grade and worse outcomes after radical cystectomy, suggesting a role in bladder squamous cell carcinoma progression. Our findings support the need for further evaluation of cyclooxygenase-2 and inflammatory signaling pathways, and cyclooxygenase-2 targeted prevention or therapy in patients with bladder squamous cell carcinoma.

Editorial Comment

Patients with invasive upper tract transitional cell carcinoma (UTTCC) pose a difficult management problem with prognosis dependent on the degree of invasion, the relationship, if any, to previous superficial or invasive bladder cancer, and the presence of metastatic nodes. Similar to invasive bladder cancer, preoperative staging can often be inaccurate and distinguishing superficial invasion from deep invasion may not always be possible. Unlike invasive bladder cancer, strategies to improve survival rates using neoadjuvant systemic chemotherapy before nephroureterectomy have not been subjected to clinical trials. However, many urological and medical oncologists advocate systemic platinum-based chemotherapy before nephroureterectomy with the expectations of improving survival rates of 40%-70% for T2-T3 tumors. 1 Hall C.M. Womack S. Sagalowsky A.I. et al. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30 year experience in 252 patients. Cancer. 1998; 52: 594-601 Google Scholar , 2 Balaji K.C. McGuire M. Grotas J. et al. Upper tract recurrences following radical cystectomy: an analysis of prognostic factors, recurrence pattern, and stage of presentation. J Urol. 1999; 162: 1603-1606 Abstract Full Text Full Text PDF Scopus (87) Google Scholar , 3 Mullerad M. Russo P. Golijanin D. et al. Bladder cancer as a prognostic factor for upper tract transitional cell carcinoma. J Urol. 2004; 172: 2177-2181 Abstract Full Text Full Text PDF Scopus (83) Google Scholar , 4 Novara G. De Marco V. Gottardp F. et al. Independent predictors of cancer specific survival in transitional cell carcinoma of the upper urinary tract. Cancer. 2007; 110: 1715-1722 Crossref Scopus (165) Google Scholar The need for a complete, meticulous, full, bilateral pelvic lymphadenectomy has been established for invasive bladder cancer with a therapeutic advantage achieved for micrometastatic disease as well as critical information for decision-making regarding adjuvant systemic therapies. 5 Herr H.W. Bochner B.H. Dalbagni G. et al. Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol. 2002; 167: 1295-1298 Abstract Full Text Full Text PDF Scopus (508) Google Scholar Still, for reasons not clear, the concept of meticulous retroperitoneal node dissection for invasive UTTCC has not been adopted by urologists worldwide despite reports for a similar therapeutic and staging advantage as reported in invasive bladder cancer. 6 Brausi M.A. Gavioli M. De Luca G. et al. Retroperitoneal lymph node dissection in conjunction with nephroureterectomy in the treatment of infiltrative transitional cell carcinoma of the upper urinary tract: impact on survival. Eur Urol. 2007; 52: 1414-1420 Abstract Full Text Full Text PDF Scopus (106) Google Scholar , 7 Roscigno M. Cozzarini C. Bertini R. et al. Prognostic value of lymph node dissection in patients with muscle-invasive transitional cell carcinoma of the upper urinary tract. Eur Urol. 2008; 53: 794-802 Abstract Full Text Full Text PDF Scopus (135) Google Scholar Assessment of the Minimum Number of Lymph Nodes Needed to Detect Lymph Node Invasion at Radical Nephroureterectomy in Patients With Upper Tract Urothelial CancerUrologyVol. 74Issue 5PreviewTo determine whether a minimum number of lymph nodes (LNs) exist to detect lymph node invasion (LNI) in patients undergoing radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. Full-Text PDF Editorial CommentUrologyVol. 74Issue 5PreviewThis is a well-conducted retrospective review of a large cohort of patients with upper tract urothelial carcinoma. I commend the authors on their efforts in establishing the minimum extent of nodal dissection in this patient population. To date, there is increasing evidence on both the prognostic and therapeutic effects of lymphadenectomy in patients with urothelial carcinoma of the bladder undergoing cystectomy. Furthermore, numerous studies have examined the limits and extent of lymph node dissection in patients with bladder cancer. Full-Text PDF ReplyUrologyVol. 74Issue 5PreviewDespite the prognostic and predictive effect of lymph node (LN) metastases, the benefit of lymphadenectomy (LND) in patients treated with radical nephroureterectomy (RNU) for urinary tract urothelial cancer (UTUC) remains debatable, and the procedure is still not widely performed.1,2 Even in our retrospective study, the low median number of nodes removed reflects a significant problem of quality of care when performing LND in patients with upper tract disease. Full-Text PDF ReplyUrologyVol. 74Issue 5PreviewA maximum of 30% of patients with muscle-invasive UTUC show nodal metastases at the time of surgery, which represents a well established poor prognostic factor.1 Despite the prognostic and predictive effect of LN metastases, the benefit of lymphadenectomy (LND) in patients treated with radical nephroureterectomy (RNU) for UTUC remains debatable, and the procedure is not widely performed.2,3 Full-Text PDF

Editorial Comment

Even representing a small percentage of all urothelial carcinomas, upper urinary tract transitional cell cancer (UUT-TCC) has, interestingly, a much greater incidence in Taiwan than worldwide. 1 Yang M.H. Chen K.K. Yen C.C. et al. Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan. Urology. 2002; 59: 681-687 Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar The tumor stage has been widely recognized as an important prognostic factor 2 Hall M.C. Womack S. Sagalowsky A.I. et al. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology. 1998; 52: 594-601 Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar ; however, to date, the definite risk factors for recurrence and survival for patients after radical nephroureterectomy remains unclear. This group of investigators had already reported on the potential of urine prothymosin-α (PTMA) as a specific tumor marker for the detection and monitoring of urothelial bladder cancer. 3 Tzai T. Tsai Y. Shiau A. et al. Urine prothymosin-alpha as novel tumor marker for detection and follow-up of bladder cancer. Urology. 2006; 67: 294-299 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar The same tumor marker has been also investigated by others in prostate cancer. 4 Suzuki S. Takahashi S. Takahashi S. et al. Expression of prothymosin alpha is correlated with development and progression in human prostate cancers. Prostate. 2005; 66: 463-469 Crossref Scopus (37) Google Scholar Duplicating their previous findings in bladder cancerous tissue, 5 Tsai Y. Jou Y. Lee G. et al. Aberrant prothymosin-alpha expression in human bladder cancer. Urology. 2009; 73: 188-192 Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Tzai et al. 3 Tzai T. Tsai Y. Shiau A. et al. Urine prothymosin-alpha as novel tumor marker for detection and follow-up of bladder cancer. Urology. 2006; 67: 294-299 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar report on the tissue expression of PTMA in UUT-TCC samples and its correlation with other variables and patient outcome. Despite the rather short follow-up and limited sample size, this study provides some intriguing information. First, PTMA is overexpressed in UUT-TCC cells. Second, no significant association was found between the intensity of PTMA expression and tumor stage or grade. Third, cytoplasmic PTMA-expressing tumors have a more advanced stage compared with nuclear PTMA-expressing tumors. Finally, cytoplasmic PTMA has an independent clinical significance in predicting for tumor recurrence in the residual urinary tract, mostly bladder cancer. How these findings will affect the current treatment of patients with UUT-TCC remains to be established. Additional clinical and translational research in this area is warranted. The role of PTMA in transitional cell carcinogenesis needs to be elucidated further and its potential role as a prognostic marker needs to be validated within larger samples with longer oncologic follow-up. Prognostic Relevance of Prothymosin-α Expression in Human Upper Urinary Tract Transitional Cell CarcinomaUrologyVol. 74Issue 4PreviewTo investigate the prognostic role of prothymosin-α (PTMA) expression in human upper urinary tract transitional cell carcinoma (UUT-TCC). Full-Text PDF

The Protective Role of Renal Parenchyma as a Barrier to Local Tumor Spread of Upper Tract Transitional Cell Carcinoma and its Impact on Patient Survival

We investigated whether tumor location has independent prognostic significance in upper tract transitional cell carcinoma cases and which factor determines it. We reviewed data on 122 renal pelvis and 102 ureteral tumor cases, including the recurrence pattern. Tumor location and other clinicopathological variables were evaluated regarding cancer specific and recurrence-free survival. Stage pT3 tumors were stratified into those invading renal parenchyma or peripelvic/periureteral fat. Overall 5-year cancer specific survival and recurrence-free survival rates were 77.0% and 71.6%, respectively, at a mean followup of 60.7 months. Of the clinicopathological parameters T stage was the most significant prognosticator of the survival rate, while nodal involvement, high grade and ureteral tumor location were also significant for lower survival rates. Stratification analysis for matching pathological stage revealed that, while survival rates were similar in the renal pelvis and ureteral tumor groups at stage pT2 or less, renal pelvic tumors were associated with significantly higher survival rates than ureteral tumors for stage pT3. Specifically renal pelvic tumors invading the renal parenchyma were associated with a lower local failure rate, and higher cancer specific and recurrence-free survival rates than tumors invading peripelvic or periureteral fat, ie 77.5% vs 49.7% 5-year cancer specific survival and 75.6% vs 32.0% 5-year recurrence-free survival (p = 0.014 and 0.003, respectively). Tumor location is an independent prognostic factor for pT3 upper tract transitional cell carcinoma. The overall better prognosis of renal pelvic tumors was mainly attributable to pT3 tumor outcomes, specifically lesions invading the renal parenchyma. These findings may be due to the protective role of thick renal parenchyma against local tumor spread.

Adjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma: Results From the Upper Tract Urothelial Carcinoma Collaboration

There is relatively little literature on adjuvant chemotherapy after radical nephroureterectomy in patients with upper tract urothelial carcinoma. We determined the incidence of adjuvant chemotherapy in high risk patients and the ensuing effect on overall and cancer specific survival. Using an international collaborative database we identified 1,390 patients who underwent nephroureterectomy for nonmetastatic upper tract urothelial carcinoma between 1992 and 2006. Of these cases 542 (39%) were classified as high risk (pT3N0, pT4N0 and/or lymph node positive). These patients were divided into 2 groups, including those who did and did not receive adjuvant chemotherapy, and stratified by gender, age group, performance status, and tumor grade and stage. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall and cancer specific survival in the cohorts. Of high risk patients 121 (22%) received adjuvant chemotherapy. Adjuvant chemotherapy was more commonly administered in the context of increased tumor grade and stage (p <0.001). Median survival in the entire cohort was 24 months (range 0 to 231). There was no significant difference in overall or cancer specific survival between patients who did and did not receive adjuvant chemotherapy. However, age, performance status, and tumor grade and stage were significant predictors of overall and cancer specific survival. Adjuvant chemotherapy is infrequently used to treat high risk upper tract urothelial carcinoma after nephroureterectomy. Despite this finding it appears that adjuvant chemotherapy confers minimal impact on overall or cancer specific survival in this group.

The Prognostic Predictors of Primary Ureteral Transitional Cell Carcinoma After Radical Nephroureterectomy

We studied the long-term prognosis, and evaluated the predictors of disease specific and recurrence-free survival in a large cohort of patients who had undergone radical nephroureterectomy for primary transitional cell carcinoma of the ureter. From January 1990 to December 2006, 145 patients with primary ureteral transitional cell carcinoma treated with nephroureterectomy and bladder cuff removal at our institution were included in the study. The medical records of these patients were reviewed retrospectively. The clinical and histopathological data were analyzed to evaluate the prognostic predictive factors. Univariate and multivariate statistical analyses were performed. The 5-year disease specific survival rates of stage pTa/Tis/T1, pT2, pT3 and pT4 were 94.6%, 81.8%, 47.4% and 0%, respectively. The 5-year recurrence-free survival rates according to tumor grade were 68.4% for low grade and 35.7% for high grade disease. Of the 145 patients subsequent bladder tumors developed in 38 (26.2%), local recurrence developed in 11 (7.6%) and metachronous contralateral upper urinary tract tumor developed in 3 (2.1%). Most patients had subsequent tumor recurrence within the first year after radical surgery. On univariate and multivariate analyses tumor stage, tumor grade, severity of chronic renal disease, synchronous bladder tumor and hematuria were the significant prognostic variables predicting disease specific and recurrence-free survival. Advanced tumor and chronic renal disease stages were significantly associated with a worse prognosis in patients with primary ureteral transitional cell carcinoma who had undergone radical nephroureterectomy. With regard to tumor recurrence, advanced tumor stage, high tumor grade and synchronous bladder tumor were independent risk factors.

Is squamous cell histology an adverse prognosticator for survival of malignancies of the upper urinary tract?

6617 Background: Carcinomas of the renal pelvis and ureter are rare diseases, accounting for only about 1% of all urogenital malignancies. Previous reports suggest that squamous cell histology is associated with inferior survival. We present the largest population based analysis to date of survival in patients with upper urinary tract malignancies. Methods: We analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis. Results: We identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 0.42 (95% CI 0.36–0.47) for TCC when compared to SCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (p = 0.84) and for patients with clear lymph nodes (p = 0.92). Conclusions: SCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage. No significant financial relationships to disclose.

The Role of Lymphovascular Invasion in Predicting the Prognosis of Clinically Localized Upper Tract Urothelial Carcinoma (pT1-3cN0M0)

We assessed the impact of lymphovascular invasion on the prognosis of patients treated for clinically localized (pT1-3N0M0) upper tract urothelial carcinoma. From January 1998 to December 2004, 106 patients treated surgically for clinically localized upper tract urothelial carcinoma (pT1-3cN0M0) were recruited for analysis retrospectively. We assessed the impact of multiple prognostic factors including age, sex, smoking, tumor multiplicity, pathological stage, grading, squamous differentiation, subsequent bladder tumor recurrence, tumor site and lymphovascular invasion on the recurrence-free survival rate. We clarified the role of lymphovascular invasion in predicting cancer specific survival in these patients. Mean patient age was 67.2 +/- 11.1 years and median followup was 47.5 months (range 40 to 115). Lymphovascular invasion was present in 32 of 106 (30.2%) patients. The 5-year recurrence-free survival rate in patients with and without lymphovascular invasion was 65.3% and 91.9%, respectively (p <0.001). On multivariate analysis lymphovascular invasion status, pT3 and ureteral involvement were significant predictors of patient recurrence-free survival. The positivity of lymphovascular invasion was also significantly associated with the risk of higher stage disease (OR 7.49). Patients with lymphovascular invasion had a higher risk of greater pathological stage disease. Lymphovascular invasion and high stage disease with ureteral involvement led to a greater risk of disease recurrence and, in turn, recurrence caused a higher mortality rate. This finding could help identify patients at greater risk for disease recurrence who would benefit from close followup and early adjuvant therapy.

Implications of p53 gene mutations on patient survival in transitional cell carcinoma of the bladder: A long-term study

Objective To determine the prognostic value of p53 gene mutations and P53 overexpression for predicting the incidence of recurrence, progression and long-term survival of patients with transitional cell carcinoma (TCC) of the bladder. Methods Prospective cohort study with 94 consecutive patients diagnosed and treated for TCC. DNA was obtained from tumor tissue to perform PCR-SSCP of p53 exons 5–9, with automatic sequencing of any mutated samples. Immunohistochemistry using anti-human P53 monoclonal antibody was also performed. Survival was analyzed and the survival curves compared (Mantel-Haenszel). Lastly, a Cox proportional hazards model was constructed. Results Mutations were found in 46.8% of samples, with 61.8% in infiltrating tumors. Exon 8 was involved in 42.3%. P53 overexpression (cutoff ≥20%) was found in 52.1%. Mean follow-up was 44.1 months; 43.6% had died by the end of this period. Mean survival was lower in patients with exon 8 mutations (38.4 months), compared with patients without this exon mutated ( P = 0.016). There were no differences in patient survival based on positive or negative immunohistochemistry (cutoff ≥20%), although survival was lower in patients with a percentage higher than 50% of antibody-stained cells ( P = 0.02). In the Cox analysis, tumor stage, pM stage, and interaction between stage ≥pT2 and mutated p53 gene were independent risk factors, with a 6.13-fold risk of death in these patients ( P = 0.019). The number of tumors, nuclear grade, pTa stage, and the interaction between GI degree and nonmutated p53 gene remained in the Cox model for superficial tumors, such that these patients had a lower risk of recurrence or progression ( P = 0.008). Conclusions Alterations in the p53 gene may be indicative of poorer prognosis and greater recurrence in patients with urothelial bladder tumor, in particular, the presence of mutations in exon 8 and a greater percentage of stained cells in the immunohistochemistry. Nevertheless, the classic prognostic factors (primarily, pTNM stage) should still be considered the most useful factors for follow-up of these patients.

Independent predictors of cancer‐specific survival in transitional cell carcinoma of the upper urinary tract

The objective of the current study was to identify variables that were predictive of cancer-specific survival in patients with nonmetastatic transitional cell carcinoma of the upper urinary tract (UUT-TCC). Clinical and pathologic data from 269 patients who underwent nephroureterectomy for UUT-TCC from 1989 to 2005 in 3 urologic European centers were collected retrospectively. Log-rank tests and Cox proportional-hazards regression models were used for univariate and multivariate analyses. Two hundred fifty patients underwent nephroureterectomy, and 19 patients underwent concomitant cystectomy for synchronous muscle-invasive bladder cancer. The median follow-up of the whole cohort was 34 months, and the median follow-up of the patients who remained alive and disease-free was 52 months. At follow-up, 57 cancer-related deaths (21.2%) were censored, and 169 patients (62.8%) were alive and disease-free. On univariate analysis, a history of previous bladder cancer, pathologic stage of the primary tumor and lymph nodes, tumor grade, the presence of lymphovascular invasion, tumor site, synchronous muscle-invasive bladder TCC, and tumor multifocality were associated with cancer-specific survival probabilities. On multivariate analysis, pathologic stage of the primary tumor and lymph nodes, tumor multifocality within the UUT, synchronous muscle-invasive bladder TCC, and a history of bladder TCC before the diagnosis of UUT-TCC were independent predictors of cancer-specific survival probabilities. In a multi-institutional dataset of patients who had undergone nephroureterectomy for UUT-TCC, the current results indicated that pathologic stage of the primary tumor and lymph nodes, a history of prior bladder TCC, the presence of synchronous muscle-invasive bladder cancer, and tumor multifocality within the UUT were independent predictors of cancer-specific survival probabilities.