Prognostic Significance of the Controlling Nutritional Status (CONUT) Score in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab after Failure of Prior Tyrosine Kinase Inhibitors.

PURPOSE: The controlling nutritional status (CONUT) score, consisting of albumin, lymphocytes and total cholesterol, is a validated, objective tool for nutritional assessment. Patients with advanced cancer frequently have malnutrition in association with cachexia and chronic inflammation. We explored the prognostic significance of the CONUT score in patients with advanced renal cell carcinoma receiving nivolumab. MATERIALS AND METHODS: This retrospective study included 60 patients with stage IV renal cell carcinoma treated with nivolumab after failure of prior tyrosine kinase inhibitors at 2 cancer centers between 2016 and 2019. Associations of the CONUT score with progression-free survival, cancer specific survival and tumor shrinkage rate were assessed. RESULTS: The median (range) CONUT score was 2 (0-10). During followup periods 29 and 14 patients exhibited disease progression and died of cancer, respectively. Both progression-free survival and cancer specific survival were significantly stratified by CONUT scores of 0 to 1, 2 to 4 and 5 or more (p=0.002). A CONUT score of 5 or more (versus score 0 to 1) was independently associated with unfavorable progression-free survival (HR 5.18, p=0.003) and cancer specific survival (HR 15.34, p=0.014), as was the absence of prior nephrectomy (HR 4.23, p=0.004 and HR 6.57, p=0.001, respectively). C-indices of the CONUT score for predicting progression-free survival and cancer specific survival were 0.694 and 0.737, respectively. The CONUT score was significantly associated with the best response to nivolumab with the median tumor shrinkage rate of -23%, +8% and +24% for CONUT scores of 0 to 1, 2 to 4 and 5 or more, respectively (p=0.021). CONCLUSIONS: The CONUT score may be useful to predict the clinical outcomes and therapeutic response in patients with advanced renal cell carcinoma receiving nivolumab.

Early response of C-reactive protein as a predictor of survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

BACKGROUND: Pretreatment C-reactive protein (CRP) has been shown to be an independent prognostic factor for metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). We further evaluated the early response of CRP after the initiation of TKIs. METHODS: A total of 103 patients (80 men and 23 women) were treated with TKIs for mRCC from 2008-2013. Patients were divided into three groups according to their early CRP kinetics-patients whose baseline CRP levels were <10 mg/L (non-elevated), patients whose baseline CRP levels were ≥10 mg/L and had decreased by >20% at 4 weeks after the initiation of TKIs (early CRP responder), and the remaining patients (non-early CRP responder). The endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up period was 21 (interquartile range 10-34) months. The numbers of patients classified as non-elevated, early CRP responder, and non-early CRP responder were 62, 19, and 22, respectively. The 1-year PFS rates of patients in the non-elevated, early CRP responder, and non-early CRP responder groups were 50, 23, and 9.7%, respectively (p < 0.001). The 1-year OS rates of patients in these three groups were 79, 62, and 36%, respectively (p < 0.001). In multivariate analysis, the early CRP kinetics assessment was a significant independent factor for PFS and OS. CONCLUSIONS: Early CRP response at 4 weeks is predictive of survival for patients with mRCC treated with TKI.

Clinical response to induction chemotherapy predicts improved survival outcome in urothelial carcinoma with clinical lymph nodal metastasis treated by consolidative surgery.

BACKGROUND: To determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC). METHODS: Sixty UC patients with measurable cN+ but without detectable systemic visceral/bone dissemination received induction platinum-based chemotherapy. Consolidative surgery was offered to all patients except for those with progressive disease. We retrospectively analyzed the clinicopathological response to induction chemotherapy and identified prognostic factors for overall survival (OS). RESULTS: The primary cancer site was the urinary bladder in 31 patients (52 %) and upper urinary tract in 29 (48 %). The median number of chemotherapy courses was 4. Forty-five patients (75 %) showed a clinically objective response to the induction chemotherapy. Fifty-one patients (85 %) underwent subsequent consolidative surgery. Histopathological analysis indicated pT0 status in 10 (20 %) and pN0 in 17 (33 %). When all 60 patients were considered, clinical tumor response was found to be significantly correlated with achievement of pathological complete response. At the median follow-up of 22 months, the median progression-free survival and OS periods were excellent: 18.6 and 31.6 months, respectively. In the multivariate analysis, clinical tumor response was found to be an independent pre-surgical prognostic factor for OS, and pathologically negative lymph node, negative resection margin, more LNs removed, and negative lymphovascular invasion were found to be independent post-surgical prognostic parameters for OS. CONCLUSIONS: The median OS in induction chemotherapy followed by consolidative surgery was very encouraging. Our results suggest that achieving a good clinical response to pre-surgical induction chemotherapy is a good indication for subsequent consolidative surgery in UC patients with cN+ to improve OS through a good pathological response.

Clinical efficacy and prognostic factors for overall survival in Japanese patients with metastatic renal cell cancer treated with sunitinib.

UNLABELLED: Study Type--Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? A randomized prospective phase III clinical trial for systemic treatment-naïve metastatic renal cell cancer (RCC) patients demonstrated the superiority of sunitinib over interferon with an acceptable safety profile. However, a commonly asked question is whether patients with RCC in clinical trials are representative of those with this disease being seen in ordinary clinical practice. To our knowledge, this is the first report of sunitinib for the Japanese patients with metastatic RCC in ordinary clinical practice. The estimated median PFS and OS in this study were 9.3 and 32.2 months, respectively. The application of the MSKCC model distinctly separated OS curves (P<0.001), suggesting that MSKCC prognostic factors might be still valid to predict survival in metastatic RCC in the era of molecular targeted therapy. OBJECTIVES: • To report the treatment efficacy and safety profile of sunitinib for patients with metastatic renal cell carcinoma (RCC) in ordinary clinical practice. • In addition, to investigate the prognostic clinicopathological factors in these patients. PATIENTS AND METHODS: • The present study consisted of native Japanese patients with metastatic RCC, comprising 29 pretreated and 34 systemic treatment-naïve patients. • Univariate and multivariate analyses were performed by the log-rank test and the Cox proportional hazards model, respectively. RESULTS: • Estimated median progression-free survival and overall survival (OS) were 9.3 months (95% confidence interval, CI, 5.0-13.7) and 32.2 months (95% CI, 24.4-40.0), respectively. • Among the patients pretreated before sunitinib, two patients were treated with initialized systemic therapy with sorafenib and the remaining 27 were initialized with interferon-α. • The OS from the initial systemic therapy of the patients in pretreated groups was 79.6 months (95% CI, 14.6-144.5). • The application of the Memorial Sloan-Kettering Cancer Center model distinctly separated the OS curves (P < 0.001). • The most common grade 3 adverse events were fatigue (53%), thrombocytopaenia (48%), hand-foot syndrome (16%), anaemia (20%), hypertension (10%) and leucopaenia (9%), although these events were manageable and reversible. CONCLUSIONS: • Sunitinib has a favourable efficacy/safety profile for Japanese metastatic RCC patients in clinical practice. • The estimated median OS was >2 years with acceptable tolerability. • The median OS from the initial systemic therapy of the pretreated patients was >6 years. • Memorial Sloan-Kettering Cancer Center prognostic factors still appear to be valid for predicting survival in metastatic RCC in the era of molecular targeted therapy.

Tumor size is a potential predictor of response to tyrosine kinase inhibitors in renal cell cancer.

OBJECTIVES: To investigate the correlations between the initial tumor size and size reduction rate in patients treated with targeted agents. To select the patients who can benefit the most from treatment with targeted agents, it will be necessary to find a tumor characteristic that predicts their effectiveness. METHODS: The data from 139 metastatic and 16 primary lesions treated with the targeted agents were retrospectively analyzed. They consisted of 86 sunitinib-treated and 69 sorafenib-treated lesions in 54 patients with metastatic renal cell carcinoma who had undergone treatment from April 2008 to July 2010. The relationship between the longest tumor diameter at baseline and the rate of reduction in tumor size was assessed using the Spearmancorrelation test. RESULTS: A linear, moderate to strong association between the initial tumor size and tumor size reduction rate was shown (correlation coefficient -0.441, P < .001). When these tumors were divided into 2 groups at the threshold value (23.95 mm), which was decided by the receiver operating characteristic curve analysis, the smaller tumors demonstrated a significantly greater size reduction than the larger tumors according to the Mann-Whitney U test (P < .001). Both univariate and multivariate linear regression analyses revealed that only the initial tumor size was associated with the rate of reduction in individual tumors (P < .001). CONCLUSIONS: The initial tumor size was a good predictor of the tumor size reduction. This simple observation could be useful for physicians who treat patients with metastatic renal cell carcinoma. In addition, in assessing clinical trials of targeted agents for metastatic renal cell carcinoma using the ResponseEvaluation Criteria in Solid Tumors, perhaps this association should be considered.