Effectiveness of adjuvant chemotherapy after radical nephroureterectomy for locally advanced and/or positive regional lymph node upper tract urothelial carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 305-305
Author(s):  
Ross Erik Krasnow ◽  
Thomas Seisen ◽  
Joaquim Bellmunt ◽  
Morgan Roupret ◽  
Jeffrey J. Leow ◽  
...  
Keyword(s):  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Treatment Effect ◽  
Cox Regression ◽  
Regional Lymph Node ◽  
Locally Advanced ◽  
Upper Tract Urothelial Carcinoma ◽  
Radical Nephroureterectomy ◽  
Kaplan Meier

305 Background: There is limited evidence supporting the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with an overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Methods: Within the National Cancer Data Base (2004-2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients in the two treatment groups. Additionally, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathological stage (pT3/T4N0, pT3/T4Nx and pTanyN+) and surgical margin status. Results: Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation after RNU, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC vs. observation (47.41 [IQR, 19.88-112.39] vs. 35.78 [IQR, 14.09-99.22] months; P< 0.001). The 5-year IPTW-adjusted rates of OS for AC vs. observation were 43.90% vs. 35.85%, respectively. In IPTW-adjusted Cox regression analysis, AC was associated with a significant OS benefit (HR = 0.77; 95% CI = [0.68-0.88]; P< 0.001). This benefit was consistent across all subgroups examined (all P< 0.05) and no significant heterogeneity of treatment effect was observed (all Pinteraction> 0.05). The 3-month conditional landmark IPTW-adjusted analysis demonstrated little impact of immortal time bias (HR = 0.79; 95% CI = [0.70-0.91]; P = 0.001). Conclusions: We report an OS benefit in patients who received AC vs. observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.

Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial Carcinoma

2017 ◽  
Vol 35 (8) ◽  
pp. 852-860 ◽  
Author(s):  
Thomas Seisen ◽  
Ross E. Krasnow ◽  
Joaquim Bellmunt ◽  
Morgan Rouprêt ◽  
Jeffrey J. Leow ◽  
...  
Keyword(s):  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Proportional Hazards ◽  
Regional Lymph Node ◽  
Locally Advanced ◽  
Cox Proportional Hazards ◽  
Radical Nephroureterectomy ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier

Purpose There is limited evidence to support the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Patients and Methods Within the National Cancer Database (2004 to 2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW) –adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare OS of patients in the two treatment groups. In addition, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathologic stage (pT3/T4N0, pT3/T4Nx and pTanyN+), and surgical margin status. Results Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation, respectively, after RNU. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation (47.41 [interquartile range,19.88 to 112.39] v 35.78 [interquartile range, 14.09 to 99.22] months; P < .001). The 5-year IPTW-adjusted rates of OS for AC versus observation were 43.90% and 35.85%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit (hazard ratio, 0.77 [95% CI, 0.68 to 0.88]; P < .001). This benefit was consistent across all subgroups examined (all P < .05), and no significant heterogeneity of treatment effect was observed (all Pinteraction > .05). Conclusion We report an OS benefit in patients who received AC versus observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.

scholarly journals Adjuvant chemotherapy after radical nephroureterectomy improves the survival outcome of high-risk upper tract urothelial carcinoma patients with cardiovascular comorbidity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yong Luo ◽  
Bingfu Feng ◽  
Dechao Wei ◽  
Yili Han ◽  
Mingchuan Li ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Urothelial Carcinoma ◽  
Survival Outcome ◽  
Upper Tract Urothelial Carcinoma ◽  
Radical Nephroureterectomy ◽  
Cardiovascular Comorbidity ◽  
Kaplan Meier

Abstract This prospective randomized comparative trial study aimed to evaluate the therapeutic outcomes of radical nephroureterectomy and adjuvant chemotherapy (ACT) used in combination in high risk upper tract urothelial carcinoma (UTUC) patients with cardiovascular comorbidity. Based on the inclusion criteria of high-risk UTUC in EAU guidelines (updated in 2014), all eligible patients treated in our hospital from January 2014 to March 2018 were included, and cases with late disease, renal dysfunction, severe cardiopulmonary disease or other malignant tumors were excluded. The cases were randomized into two groups based on treatment regimen. Multivariate analyses were performed to analyze the influencing factors of survival outcome in the enrolled patients. The Cox proportional-hazards model and the Kaplan–Meier method were employed to assess progression free survival (PFS), overall survival (OS) and cancer specific survival (CSS). In addition, the potential adverse effects of chemotherapy were actively monitored. A total of 176 high-risk UTUC individuals with cardiovascular comorbidity were enrolled and evaluated in this study. Median follow-up durations were 30 months (range 6–54) in the RNU (n = 82) group and 36 months (range 6–54) in the RNU + ACT (n = 94) group. Multivariable analysis indicated that peri-operative cardiovascular events risk grade was independent prognostic factor for OS. Tumor size was independent prognostic factor for PFS and CSS. BMI and lymphovacular invasion were significant predictors of PFS. Clinical stage, lymph node involvement, and tumor grade were significant predictors of PFS, OS and CSS in these patients. Especially, chemotherapy was helpful in improving PFS [P < 0.001, HR = 6.327 (5.115–7.793)], OS [P = 0.013, HR = 2.336 (1.956–2.883)] and CSS [P = 0.008, HR = 3.073 (2.533–3.738)]. Kaplan–Meier analysis demonstrated that the oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT, including PFS [P = 0.0033, HR = 3.78 (3.13–4.55)], OS [P = 0.0397, HR = 1.39 (1.01–1.75)] and CSS [P = 0.0255, HR = 1.26 (1.07–1.45)]. Further analysis of the lymph node positive subgroup showed that the median time of oncologic events was enhanced in RNU + ACT treated individuals in comparison with the RNU group, including PFS (11.4 months vs. 31.9 months, P = 0.0018), OS (26.8 months vs. 36.3 months, P = 0.0255) and CSS (28.2 months vs. 39.3 months, P = 0.0197). In the T3/4 cohort, significantly increased median PFS (13.9 months vs. 36.3 months, P = 0.0217), OS (20.6 months vs. 32.2 months, P = 0.0183) and CSS (21.9 months vs. 38.4 months, P = 0.0226) were obtained in the combination group. Additionally, no severe adverse events (over grade 4) associated with chemotherapy were detected in the RNU + ACT group. In conclusion, ACT after radical surgery has statistically significant therapeutic effects on PFS, OS and CSS in high-risk UTUC patients with cardiovascular comorbidity.

Prognostic assessments in patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy and systematic regional lymph node dissection

2021 ◽  
pp. 039156032110349
Author(s):  
Ryo Sato ◽  
Kyohei Watanabe ◽  
Yuto Matsushita ◽  
Hiromitsu Watanabe ◽  
Daisuke Motoyama ◽  
...  
Keyword(s):  
Lymph Node ◽  
Urothelial Carcinoma ◽  
Lymph Node Dissection ◽  
Regional Lymph Node ◽  
Upper Tract Urothelial Carcinoma ◽  
Radical Nephroureterectomy ◽  
Node Dissection ◽  
Upper Tract ◽  
Regional Lymph Node Dissection ◽  
Univariate Analyses

Objectives: Systematic regional lymph node dissection (LND) combined with radical nephroureterectomy (RNU) has been reported to improve the outcomes of upper tract urothelial carcinoma (UTUC) patients. The objective of the present study was to assess the prognostic outcomes of UTUC patients undergoing systematic regional LND combined with RNU. Patients and methods: We conducted a retrospective evaluation of prognostic outcomes of 68 consecutive UTUC patients treated with RUN and systematic regional LND. Results: The median durations of recurrence-free survival (RFS) and overall survival (OS) were 45 and 166 months, respectively. Univariate analyses of several parameters showed that despite the lack of a significant predictor for RFS, the presence of lymph node metastasis correlated with poor OS. Conclusion: These results suggest that comparatively favorable outcomes are achievable in UTUC patients by RNU and systematic regional LND; however, special attention is needed for patients with nodal involvement even after systematic regional LND due to the adverse impact of this factor on OS.

scholarly journals The hemoglobin, albumin, lymphocyte, and platelet (HALP) score as a prognostic marker for patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy: a retrospective study from two centers

2022 ◽  
Author(s):  
Xiaomin Gao ◽  
Binwei Lin ◽  
Qi Lin ◽  
Tingyu Ye ◽  
Tao Zhou ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Upper Tract Urothelial Carcinoma ◽  
Youden Index ◽  
Rank Test ◽  
Radical Nephroureterectomy ◽  
Cutoff Value ◽  
Cox Regression Analysis ◽  
Upper Tract ◽  
Kaplan Meier

The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP<28.67 group and HALP≥28.67 group. Kaplan-Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (P<0.001) and progression-free survival (PFS) (P<0.001). Multivariate analysis demonstrated that lower HALP score was an independent risk factor for OS (HR=1.54, 95%CI, 1.14-2.01, P=0.006) and PFS (HR=1.44, 95%CI, 1.07-1.93, P=0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without. In the subgroup analysis, the HALP score could also stratify patients with respect to survival under different pathologic T stages. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients

2021 ◽  
Author(s):  
Shicong Lai ◽  
Xingbo Long ◽  
Pengjie Wu ◽  
Jianyong Liu ◽  
Samuel Seery ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Upper Tract Urothelial Carcinoma ◽  
Chinese Patients ◽  
Clinicopathological Parameters ◽  
Radical Nephroureterectomy ◽  
Ki 67 ◽  
Data Set ◽  
Mainland Chinese ◽  
Upper Tract

Abstract Objective To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. Methods This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. Results With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P &lt; 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas’ model in terms of discriminative capacity (all P &lt; 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients’ net benefit. Conclusions This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

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