Recurrence Of Upper Tract Urothelial Carcinoma Research Articles

1133 - Intravesical BCG instillation is strongly associated with a decreased risk of upper tract urothelial carcinoma recurrence as well as intravesical recurrence in elderly male patients with non-muscle invasive bladder cancer

1133 - Intravesical BCG instillation is strongly associated with a decreased risk of upper tract urothelial carcinoma recurrence as well as intravesical recurrence in elderly male patients with non-muscle invasive bladder cancer

MP82-18 INTRAVESICAL BCG INSTILLATION IS STRONGLY ASSOCIATED WITH A DECREASED RISK OF UPPER TRACT UROTHELIAL CARCINOMA RECURRENCE AS WELL AS INTRAVESICAL RECURRENCE IN ELDERLY MALE PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II (MP82)1 Apr 2020MP82-18 INTRAVESICAL BCG INSTILLATION IS STRONGLY ASSOCIATED WITH A DECREASED RISK OF UPPER TRACT UROTHELIAL CARCINOMA RECURRENCE AS WELL AS INTRAVESICAL RECURRENCE IN ELDERLY MALE PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER Hiroki Ide*, Naoya Niwa, Yuto Baba, and Mototsugu Oya Hiroki Ide*Hiroki Ide* More articles by this author , Naoya NiwaNaoya Niwa More articles by this author , Yuto BabaYuto Baba More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000974.018AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The incidence of elderly males with VUR increases with age, likely to be due to the higher number of men with bladder outlet obstruction. Therefore, intravesical BCG instillation after transurethral resection of bladder tumor (TURBT) may effectively prevent upper tract urothelial carcinoma (UTUC) recurrence as well as bladder recurrence, particularly in elderly males. In the present study, we investigated these relationships in non-muscle invasive bladder cancer (NMIBC) patients. METHODS: Our study population comprised 1128 NMIBC patients without a history of UTUC. Tumor grade and stage were 62.0% low and 38.0% high grade; 68.4% Ta and 31.6% T1 and/or CIS. The mean follow-up period and age were 64 months and 68.2 years old, respectively. We investigated the relationships between clinicopathological factors, including BCG instillation, and UTUC development in NMIBC patients. RESULTS: During the follow-up period, recurrent bladder cancer and UTUC developed in 437 (38.7%) and 38 (3.4%) out of all NMIBC patients, among whom 548 (48.6%) received BCG instillation after surgery. Five-year bladder and UTUC recurrence rates were 33.3 (30.1% in Ta and 37.6% in T1 and/or CIS) and 1.9%, respectively, in patients treated with BCG, which were significantly lower than in those without BCG {47.7 (44.7% in Ta and 47.0% in T1 and/or CIS) and 4.7%, p=0.001 and 0.005, respectively}. A multivariate Cox regression analysis identified BCG instillation as an independent factor for bladder and UTUC recurrence in all NMIBC patients (p=0.001 and 0.001, hazard ratio=0.517 and 0.260, respectively). Furthermore, in male patients, the 5-year UTUC recurrence rate was significantly lower in patients treated with BCG (2.0%) than in those without BCG (4.3%, p=0.022), whereas no significant differences were observed in female patients. In subgroups of older male patients (≥70 years), the 5-year UTUC recurrence rate was significantly lower in patients treated with BCG (1.6%) than in those without BCG (5.9%, p=0.031). In subgroups of younger male patients (<70 years), no significant differences were noted between these two groups. CONCLUSIONS: Intravesical BCG instillation after TURBT may prevent UTUC as well as bladder recurrence, particularly in older male NMIBC patients. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1253-e1254 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroki Ide* More articles by this author Naoya Niwa More articles by this author Yuto Baba More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement PDF downloadLoading ...

The prognostic value of CSN6 expression in upper tract urothelial carcinomas.

CSN6 is a subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN). CSN is involved in cellular and developmental processes such as signal transduction, transcriptional activation, cell cycle control, and tumorigenesis. CSN6 is highly expressed in several human cancers, including colorectal cancer, and breast cancer. However, no previous research has elaborated on the relationship between CSN6 expression and survival in patients with upper tract urothelial carcinoma (UTUC). Therefore, the purpose of this study is to evaluate the clinical significance of CSN6 in UTUC. CSN6 expression in 89 patients with UTUC enrolled in this study was examined using immunohistochemistry. The associations between CSN6 expression and clinicopathological variables were analyzed. CSN6 expression was significantly correlated with patients with high pathological stage (P = .006), male gender (P = .025), and high serum creatinine levels (P = .014). In univariate and multivariable analysis, high CSN6 expression was associated with a higher bladder recurrence (P = .005) and poor cancer-specific survival (P = .001) for UTUC. In conclusion, CSN6 expression is a potential biomarker for predicting cancer recurrence and clinical survival in UTUC. Further research is necessary to investigate its role in the progression of UTUC.

Adjuvant Treatments for Advanced Stage, Non-metastatic Upper Tract Urothelial Carcinoma: A Multicenter Study

We assessed the efficacy of adjuvant treatments in patients with peripelvic/periureteral fat-infiltrating (pT3b), nonmetastatic upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy. The multicenter data of 222 patients with pT3bN0-x disease treated with radical nephroureterectomy were analyzed. The effects of adjuvant radiation therapy and chemotherapy on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS) were evaluated. Adjuvant radiation therapy and chemotherapy were given to 39 (17.6%) and 74 patients (33.3%), respectively. Seventeen patients (7.7%) received concomitant adjuvant radiation therapy and chemotherapy. The median follow-up duration was 34.4months. After adjusting for age, sex, tumor location, multifocality, tumor grade, presence of lymphovascular invasion, surgical margin, execution of node dissection, and other types of concomitant adjuvant treatment (radiation therapy or chemotherapy) through propensity-scored matching, adjuvant radiation therapy significantly reduced the local recurrence (5-year LRFS, 83.9 vs 54.2%; P=.001), distant metastasis (5-year DMFS, 72.1 vs 48.1%; P=.032), and cancer-specific death (5-year CSS, 76.4% vs 55.5%; P=.038) in pT3b UTUC. However, in the same condition, adjuvant chemotherapy did not reduce the local recurrence (5-year LRFS, 69.0% vs 66.2%; P=.786), distant metastasis (5-year DMFS, 65.3% vs 61.1%; P=.436), and cancer-specific death (5-year CSS, 67.9% vs. 67.9%; P=.458) in pT3b UTUC. Our study suggests that adjuvant radiation therapy may be beneficial in patients with T3bN0-x UTUC; however, prospective clinical trials are needed to clarify this issue.

Gradiently degraded electrospun polyester scaffolds with cytostatic for urothelial carcinoma therapy.

Kidney-sparing surgery is the preferred treatment strategy for low-risk upper tract urothelial carcinoma (UTUC). However, after this procedure, prevention of the carcinoma recurrence in the ureter and supporting the ureter with a ureteral stent are necessary. Biodegradable drug-loaded ureteral scaffolds are able to maintain their long-term effective drug concentrations in the lesion sites without the defects of traditional ureteral stents, which may address both issues simultaneously. The purpose of this study was to reveal the possibility of the controlled delivery of epirubicin (EPI) via gradiently degraded electrospun poly(ε-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA) scaffolds to evaluate their antitumor activity against UTUC. The degradable PCL/PLGA scaffolds containing 15.0 and 25.0 wt% PCL and loading of 0, 5.0, and 10.0 wt% EPI were successfully fabricated via electrospinning. In addition, the PCL/PLGA scaffolds showed sustained and controlled degradation and drug release kinetics, that is, their degradation and drug release rates slowed with an increase in the ratio of PCL. The EPI-loaded PCL/PLGA scaffolds showed excellent antitumor activities both in vitro and in vivo without apparent systemic toxicity. Overall, the gradiently-degraded EPI-loaded electrospun polyester scaffolds are potential ureteral stent tubes for the local inhibition of the recurrence of UTUC, where the continued release of EPI can prevent the subsequent proliferation of residual tumor cells, and the gradient degradation is consistent with the repair of the ureter.

Muscle-invasive upper tract urothelial carcinoma predicts invasive bladder recurrence tumor

Objective To evaluate the risk factors and prognosis of high risk bladder recurrence developing after radical nephroureterectomy(RNU) for upper tract urothelial carcinoma (UTUC). Methods The data of 148 UTUC patients who developed bladder tumor after RNU between January 2000 and December 2013 was retrospectively studied. There were 69 males and 79 females, aged from 34 to 82 years old(average 68 years old). 83 patients were accompanied with hydronephrosis. 80 patients were renal pelvic carcinoma. 32 patients had the history of smoking. 24 patients had the history of ureteroscope. 68 patients had the tumor larger than 3 cm. Logistic regression model was used to analyze the risk factors of muscle invasive and high grade bladder recurrence lesions. We compared the clinocopathologic characteristics between primary UTUC and bladder cancer recurrence by using Fisher’s exact test. Cancer specific survival was analyzed using the Kaplan-Meier method, with the log-rank test used to assess significance. A Cox proportional hazard model was used for multivariate analysis. Results Of the 148 patients, non-muscle invasive (Tis、Ta and T1) tumors of primary UTUC and bladder recurrence were 51(34.5%) and 119(80.4%), respectively. High grade (G3) tumors of primary UTUC and bladder recurrence were 41(27.7%) and 53(35.8%), respectively. During follow-up, 94 (63.5%) experienced bladder recurrence once and 54 (36.5%) experienced multiple bladder recurrence. The median follow-up time was 59.5 (rang 8-142) months, 48 (32.4%) patients died of UTUC. The grade of bladder cancer recurrence correlated with the grade (P=0.046), muscle-invasion (P=0.002) and tumor architecture (P=0.034) of the primary UTUC; muscle-invasive bladder cancer recurrence associated with that of the primary UTUC (P=0.009); bladder multiple recurrence related to gender (P=0.007). On multivariate logistic regression analysis, the muscle-invasion of primary UTUC was an independent risk factor for muscle-invasive (HR=5.512, 95%CI 1.654-18.37, P=0.004) and high grade (HR=3.948, 95%CI 1.589-9.813, P=0.004) bladder recurrence tumor. The muscle invasion of primary UTUC (HR=3.498, 95%CI 1.569-7.803, P=0.002) was a prognostic factor for cancer specific survival on multivariate Cox regression analysis. Conclusions Muscle-invasive UTUC tend to predict high risk bladder recurrence tumor, and the female could be more likely to appear multiple recurrence tumor. The muscle invasion of primary UTUC could be an independent prognostic factor for cancer specific survival. Key words: Upper tract urothelial carcinoma (UTUC); Bladder recurrence; Muscle-invasive; Prognosis

Impact of aristolochic acid exposure on oncologic outcomes of upper tract urothelial carcinoma after radical nephroureterectomy

ObjectiveTo investigate the effect of aristolochic acids (AA) exposure, including exposure duration and years since last exposure, on oncologic outcomes of patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).MethodsWe retrospectively collected clinicopathologic and AA exposure variables for 942 UTUC patients treated with RNU between 1999 and 2014 in a high-volume center of China. AA exposure duration was categorized as (>3 vs ≤3 years) and time since last AA exposure to surgery as (>5 vs ≤5 years).ResultsA total of 856 patients (90.9%) had none or possible AA exposure and 86 patients (9.1%) had credible AA exposure history. Among the 86 patients, 57 (66.3%) had AA exposure for ≤3 years and 29 (33.7%) had exposure for >3 years. The median follow-up duration was 60 months. By multivariate analysis, AA exposure history was significantly associated with cancer specific survival (hazard ratio [HR]: 0.43, p=0.02), intravesical recurrence (IVR) (HR: 2.25, p<0.001) and contralateral UTUC recurrence (HR: 2.71, p=0.001). After adjusted for the effects of standard clinicopathologic characteristics, exposure duration was independent risk factor for subsequent IVR (exposure duration ≤3 years vs none/possible AA, HR: 1.87, p=0.009; exposure duration >3 years vs none/possible AA, HR: 3.07, p<0.001), but not for cancer-specific survival (p=0.06). Also, of those patients who had AA exposure, those having exposure within 5 years prior to RNU did not differ from patients having last exposure >5 years ago regarding cancer specific mortality (p=0.67) and IVR (p=0.54).ConclusionAA exposure was associated with worse cancer-specific survival, higher rate of IVR and contralateral UTUC recurrence of UTUC treated with RNU. The association between AA exposure and IVR seems to be time-dependent. Exposure cessation >5 years prior to RNU cannot mitigate the impact of AA on the UTUC prognosis.

Over-expression of Activated Signal Transducer and Activator of Transcription 3 Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma.

Background: Signal transducer and activator of transcription proteins (STATs) play important roles in gene regulation, cell proliferation, and cell differentiation. We aimed to establish the relationship between phosphorylated STAT3 (p-Ser-STAT3) expression and the prognosis of upper tract urothelial carcinoma (UTUC).Methods: This study retrospectively reviewed 100 patients with pathologically confirmed UTUC at Kaohsiung Medical University Hospital. We quantified the expression of p-Ser-STAT3 in cancer cells by immunohistochemistry, and determined the clinicopathological significance of p-Ser-STAT3 expression and prognostic outcomes in patients with UTUC.Results: High p-Ser-STAT3 expression was detected in 52% of UTUC patients. High p-Ser-STAT3 expression was associated with poor recurrence-free survival (p = 0.018) and overall survival (p = 0.026). In advanced cancer samples (stage T3/T4), p-Ser-STAT3 expression is the only independent prognostic factor for recurrence-free survival (hazard ratio = 5.91, p = 0.01) and cancer-specific survival (hazard ratio = 8.83, p = 0.039).Conclusions: The expression of p-Ser-STAT3 can be a potential prognostic marker for cancer recurrence and survival in UTUC, especially in advanced stage cases.

Predictors of recurrence and patterns of failure among patients treated with nephroureterectomy for upper tract urothelial carcinoma.

Recurrence rates following nephroureterectomy (NU) for upper tract urothelial carcinoma (UTUC) remain high. As such, adjuvant therapy directed at high risk sites may improve long term outcomes. We describe patterns and predictors of UTUC recurrence according to patient, disease and treatment-related factors. We reviewed the records of 113 patients treated with NU for UTUC at our institution between 2006 and 2013. Time to locoregional (LR), intravesical (IV), distant recurrence and death were described using the Kaplan-Meier method and compared using the log rank statistic. Cox Proportional Hazards analyses were performed to evaluate the adjusted hazard for LR/IV and LR recurrence. Advanced T stage (T3/4) was present in 41 (36%) patients, 10 (9%) were node-positive and 21 (19%) showed evidence of lymphovascular space invasion (LVSI). Median overall survival and time to any recurrence was 54.6 and 20.7 months, respectively. Disease recurrence was observed in 48 (42%) patients. The location of failure was intravesical in 27 (24%), locoregional in 22 (19%) and distant in 20 (18%). Three-year LR/IV and distant failure rates were 38.7% and 22.2%, respectively. Three-year LR failure was 4.6% in pTa-2 vs. 25.8% in T3-T4 disease. Multivariate analysis identified history of prior bladder disease as a significant predictor of LR/IV recurrence. In this study we demonstrate LR/IV recurrence as the predominant pattern of failure in UTUC patients treated with nephroureterectomy. This systematic description of recurrence patterns and associated factors will guide further investigation of adjuvant therapy to minimize the treatment failures defined herein.

Is Frozen Section Analysis of Ureteral Margins at Time of Radical Cystectomy Useful?

The clinical utility of intraoperative frozen section analysis (FSA) of ureters at the time of radical cystectomy (RC) for urothelial cancer (UC) remains controversial and subject to considerable debate. Potential advantages include intraoperative detection of carcinoma in situ (CIS) or overt malignancy and directed ureteral sectioning to achieve negative margins to reduce anastomotic recurrence. The information gained at the time of FSA may be useful for risk-adapted upper tract surveillance. To critically assess the utility of FSA with respect to these potential advantages, we review the operating characteristics of FSA as a diagnostic test, the relationship between upper tract urothelial carcinoma (UTUC) recurrence and abnormal FSA, and the overall evidence for FSA on oncological end points and cost-effectiveness. Taken together, the weight of evidence suggests that while FSA is a reasonable diagnostic test, its utility has been recently questioned, and prospective study is warranted. There is a need to quantify the risk reduction in anastomotic recurrence in light of the cost-effectiveness of FSA compared to the alternative of only performing permanent analysis of proximal ureteral margins. Given the low rates of UTUC recurrence reported in the literature, the weak association between FSA and these recurrences, and mortality in retrospective studies, the clinical impact of reducing UTUC recurrence by FSA must continue to be critically evaluated.

Prognostic and Predictive Value of Epigenetic Biomarkers and Clinical Factors in Upper Tract Urothelial Carcinoma

We conducted this study to identify gene promoter methylation status and clinical predictors for upper tract urothelial carcinoma (UTUC) patients. Using methylation-sensitive PCR, we examined ten genes promoter methylation status in 687 UTUC patients. A methylated promoter of three genes to predict higher tumor stage (T3 and T4), five genes to predict higher tumor grade (G3) and one gene to predict pN+ were certified in this study. Nine factors were significantly associated with poor cancer-specific survival. Six factors were considered as predictors to develop bladder recurrence after surgery. Methylation occurs commonly in UTUCs, may affect carcinogenic mechanisms, and is a well predictive factor for cancer-specific survival and bladder recurrence in UTUCs.

MP2-01 CONTRALATERAL UPPER TRACT UROTHELIAL CARCINOMA AFTER NEPHROURETERECTOMY: THE PREDICTIVE ROLE OF METHYLATION STATUS

MP2-01 CONTRALATERAL UPPER TRACT UROTHELIAL CARCINOMA AFTER NEPHROURETERECTOMY: THE PREDICTIVE ROLE OF METHYLATION STATUS

Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation.

BackgroundAberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients.MethodsIn a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3–144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.ResultsThirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2–139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P = 0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P = 0.009), history of renal transplantation (P < 0.001), and preoperative renal insufficiency (P = 0.002) are independent risk factors for contralateral UTUC recurrence after RNU.ConclusionsOur data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.

Impact of smoking status at diagnosis on disease recurrence and death in upper tract urothelial carcinoma

Cigarette smoking is the leading cause of urothelial carcinoma; however, the impact of smoking on outcomes after surgery for upper tract urothelial carcinoma is unknown. One study suggests that patients with a smoking history have an increased risk of recurrence in the bladder compared with never smokers but these patients did not differ with respect to time to pelvic recurrence or distant metastasis. We subdivided smokers into current and former smokers and performed multivariate analyses that showed that smoking status was not an independent predictor of recurrence when traditional prognostic factors were taken into account. In addition, competing risks analyses showed that although current smoking did not increase the risk of recurrence, it imparted a significant risk of dying compared with former and never smoking. To evaluate the impact of smoking exposure on oncological outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Patient and disease characteristics from 288 patients with UTUC treated with RNU between 1995 and 2008 were collected from a prospectively maintained database at the Memorial Sloan-Kettering Cancer Center. Disease recurrence was defined as distant metastases, or local failure in the operative site or regional nodes. Factors associated with recurrence and death were determined. The prevalence of current, former and never smoking at diagnosis was 19.1%, 55.2%, and 25.7%, respectively. 71.0% of patients reported a ≥20 pack-year smoking history. With a median follow-up of 4.02 years, disease recurrence occurred in 27% (n = 79) of patients and 41% (n = 117) died during follow-up. While age at diagnosis, American Society of Anesthesiologists score, advanced stage, nodal involvement and high grade adversely affected recurrence-free survival, smoking status was not associated with risk of recurrence or death in multivariate analysis (P = 0.60). Multivariate competing risks regression showed that current smokers faced a significantly higher risk of death than never smokers (hazard ratio 3.64, 95% confidence interval 1.59-8.34). While smoking status at diagnosis and cumulative smoking exposure were not associated with UTUC recurrence, our findings highlight the substantial risk of death in patients with UTUC who are active smokers. Treatment plans to promote smoking cessation are recommended for these patients.