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Abstract: Background and objective: Few 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 methods: The 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. Results: Positive 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. Conclusions: The 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. [Copyright &y& Elsevier]

Purpose: The objective of this study was to develop a novel prognostication model in patients with treatment-naïve metastatic renal cell carcinoma (mRCC).Methods: This study included 325 consecutive mRCC patients receiving first-line molecular-targeted therapy at 4 institutions. Potential parameters associated with overall survival (OS) in these patients were investigated to develop a novel stratification model.Results: Median OS of the 325 patients was 38 months. A multivariable analysis of several factors identified independent predictors associated with unfavorable OS as follows: no previous nephrectomy, Karnofsky performance status <80%, albumin (Alb) ≤3.5 g/dl, C-reactive protein (CRP) >0.5 mg/dl and neutrophil-to-lymphocyte ratio (NLR) >3. Of these 5 independent OS predictors, 3 numeric factors were used to develop the ACN (Alb, CRP, and NLR) model by dividing patients into 3 groups according to the positive numbers of these 3 numeric risk factors. Median OS durations were 63, 37, and 11 months in the favorable (n = 105, 32.3%, without risk factors), intermediate (n = 88, 27.1%, with a single risk factor), and poor (n = 132, 40.6%, with multiple risk factors) risk groups, respectively. The ACN model as a prognostication tool was shown to be superior to the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models by both the concordance index and decision curve analysis.Conclusions: The ACN model could stratify the prognostic risk of mRCC patients receiving first-line targeted therapy more accurately than the MSKCC and IMDC models. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the impact of discontinuation of first-line (1L) molecular-targeted therapy on prognostic outcomes among patients with metastatic renal cell carcinoma (mRCC).Methods: Study patients with mRCC were treated with 1L molecular-targeted agents at 4 separate institutions. Prognostic outcomes in this patient cohort were analyzed retrospectively based on whether discontinuation of 1L therapy was related to adverse events (AEs) or progression of disease (PD).Results: Of the 201 patients enrolled, 117 patients (58%) and 84 patients (42%) discontinued 1L targeted therapy due to PD and AEs, respectively. Second-line therapy was subsequently provided to 101 (86%) and 66 (79%) of the patients who discontinued 1L therapy secondary to PD or AEs, respectively. Patients who discontinued 1L therapy due to AEs were significantly older than those with PD. The progression-free survival and overall survival from the initiation of 1L targeted therapy were significantly longer in patients who discontinued 1L therapy due to AE than in those who discontinued 1L therapy due to PD. The OS from the initiation of second-line targeted therapy was significantly longer in patients who discontinued 1L therapy due to AE than those with PD. Furthermore, AE as a reason for discontinuation of 1L targeted therapy as opposed to PD was independently associated with longer progression-free survival and OS as determined by multivariate analysis.Conclusions: Our findings suggest that mRCC patients who discontinue 1L therapy due to AEs have a more favorable prognosis than those who discontinue therapy due to PD. [ABSTRACT FROM AUTHOR]

Purpose: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model has been designed for prognostification in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. One factor is neutrophil count; however, increasing evidence has suggested the superiority of neutrophil-to-lymphocyte ratio (NLR) for predicting outcome. In this study, we evaluate the prognostic effect of NLR levels on patients with mRCC treated with targeted therapy, and then we compare the predictive accuracy of the IMDC risk model and its modified one by using NLR, instead of neutrophil count.Patients and Method: A total of 277 patients are included for the analysis. All patients underwent targeted therapies and associated outcome are assessed using multivariate analysis.Results: Pretreatment NLR levels are elevated in 30.3% and 23.1% of patients in the first-line and subsequent second-line setting, respectively. Kaplan-Meier curves reveal that elevated pretreatment NLR is significantly associated with poor overall survival (OS) since first-line (P<0.001) and second-line targeted therapy administration (P<0.001). Also, multivariate analyses show that elevated pretreatment NLR is an independent predictor for poor OS since first-line and second-line targeted therapy administration. The addition of NLR to the IMDC risk model, instead of neutrophil count, significantly improves the predictive accuracy for OS, and estimated gain is 1.7% and 6.2% in first-line and second-line targeted therapy, respectively.Conclusion: Changes in NLR levels could be predictive for prognosis in patients with mRCC treated with first-line and second-line targeted therapy. The addition of NLR significantly improves the predictive accuracy of the IMDC risk model in the first-line and subsequent second-line setting. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prognostic effect of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model reclassification after targeted therapy administration in metastatic renal cell carcinoma (mRCC).Patients and Method: A total of 245 mRCC patients treated with targeted therapy are included. The IMDC model reclassification is performed at 1 month after treatment induction of both first-line and second-line targeted therapy.Results: Of the 245 patients, 74 (30.2%) are divided into different risk groups by the IMDC model reclassification after first-line targeted therapy, and patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.018). Of the 119 patients treated with subsequent second-line targeted therapy, 25 (21.0%) are divided into different risk groups by the IMDC model reclassification after second-line targeted therapy, and patients newly classified with poor risk tend to have increased all-cause mortality compared with those remaining in the primary intermediate-risk group (P = 0.007), whereas patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.034).Conclusion: Approximately a quarter of the mRCC patients are classified into different risk groups of the IMDC model following targeted therapy administration in the first-line and second-line settings. There is a significant difference in overall survival of subgroups after the IMDC model reclassifications. [ABSTRACT FROM AUTHOR]