Survival of patients receiving systematic therapy for metachronous or synchronous metastatic renal cell carcinoma: a retrospective analysis.
ABSTRACT: BACKGROUND:The differences in progression-free survival (PFS) and cancer-specific survival (CSS) of metastatic renal cell carcinoma (mRCC) patients according to treatment, type of metastasis, and Heng criteria risk are unclear. In this study, we compared survival according to various such parameters. METHODS:Between 2000 to 2014, 214 mRCC patients, of whom 171 (79.9%) were intermediate-risk and 43 (20.1%) were poor-risk, were retrospectively selected; 126 (58.9%) patients were treated with immunotherapy (IT) and 88 (41.1%) with targeted therapy (TT). Moreover, 144 patients had synchronous mRCCs (67.3%, SM) and 70 had metachronous mRCCs (32.7%, MM). The Kaplan-Meier method and log-rank test were used to compare progression-free survival (PFS) and CSS. RESULTS:During a median 4.2 (1.0-70.4) months of systemic treatment and 98.3 (4.8-147.6) months of follow-up, the median PFS and CSS were 4.7 (95% confidence interval [CI]: 3.8-5.5) and 13.8 (95% CI, 9.8-18.3) months, respectively. The PFS and CSS were significantly better in the MM (5.9 and 21.3 months) and intermediate-risk groups (5.2 and 18.3 months) than those in the SM (4.4 and 9.6 months) and poor-risk groups (2.7 and 5.8 months), respectively (p < 0.05). Further stratification showed that TT produced significantly better PFS than IT in intermediate-risk patients with SM and a treatment-free interval (TFI) < 1 year, and in those with MM with a TFI ≥1 year (p < 0.05). There were no differences in survival outcomes according to various other subgroup stratifications (p > 0.05). CONCLUSION:Dividing patients into specific subcategories helps to better predict therapeutic outcomes.
Project description:Purpose:This study aimed to compare progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) in Heng intermediate-risk patients with metastatic renal cell carcinoma (mRCC) treated with first-line immunotherapy (IT) or targeted therapy (TT). Materials and Methods:From 2000 to 2017, a total of 186 intermediate-risk mRCC patients treated with first-line IT (n=64, 34.4%) or TT (n=122, 65.6%) were retrospectively evaluated for PFS, OS, and CSS using the Kaplan-Meier method with log-rank test and Cox proportional hazards models for their risk factors with a p-value for significance of <0.05. Results:During a median 5.08-month of systemic treatment and 92.22 months of follow-up, the median PFS, OS, and CSS were 5.16, 18.44, and 19.04 months, respectively. The comparison of baseline characteristics between the two groups showed a significantly higher rate of T3-4 stages, a lower rate of high nuclear grades, shorter follow-up, longer treatment durations, lesser rates of cytoreductive nephrectomy, a lower objective response rate, and no cases of complete response in the TT group compared with the IT group (p<0.05). The survival comparisons between the two groups showed that PFS was significantly different, whereas OS and CSS were not significantly different. The multivariate analyses showed that synchronous metastatic type(hazard ratio [HR], 2.285), IT (HR, 1.746), and treatment-free interval <1 year (HR, 1.926) were significant factors for PFS, whereas none of the risk factors were significant for OS or CSS. Conclusions:TT significantly prolonged PFS compared with IT, whereas long-term survival was not significantly different in intermediate-risk mRCC patients.
Project description:<h4>Purpose</h4>The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and the Memorial Sloan Kettering Cancer Center (MSKCC) risk models were developed predominantly with clear cell renal cell carcinoma (RCC). Accordingly, whether these two models could be applied to metastatic non-clear cell RCC (mNCCRCC) as well has not been well-known and was investigated herein.<h4>Materials and methods</h4>From the Korean metastatic RCC registry, a total of 156 patients (8.1%) with mNCCRCC among the entire cohort of 1,922 patients were analyzed. Both models were applied to predict first-line progression-free survival (PFS), total PFS, and cancer-specific survival (CSS).<h4>Results</h4>The median first-line PFS, total PFS, and CSS were 5, 6, and 24 months, respectively. The IMDC risk model reliably discriminated three risk groups to predict survival: the median firstline PFS, total PFS, and CSS for the favorable, intermediate, and poor risk groups were 9, 5, and, 2 months (p=0.001); 14, 7, and 2 months (p < 0.001); and 41, 21, and 8 months (p < 0.001), all respectively. The MSKCC risk model also reliably differentiated three risk groups: 9, 5, and, 2 months (p=0.005); 10, 7, and 3 months (p=0.002); and 50, 21, and 8 months (p < 0.001), also all respectively. The concordance indices were 0.632 with the IMDC model and 0.643 with the MSKCC model for first-line PFS: 0.748 and 0.655 for CSS.<h4>Conclusion</h4>The current IMDC and MSKCC risk models reliably predict first-line PFS, total PFS, and CSS in mNCCRCC.
Project description: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.
Project description:We compared progression-free survival (PFS) and overall survival (OS) among 292 metastatic renal cell carcinoma (mRCC) patients either undergoing nephrectomy (Nx, 61.6%) or not (non-Nx, 38.4%), stratified according to the MSKCC and Heng risk models, treated with either immunotherapy (IT, 45.2%) or targeted therapy (TT, 54.8%) between 2000 and 2015. During the follow-up duration of 16.6 months, PFS/OS of the Nx (6.0/30 months) and non-Nx (3.0/6.0 months) groups were significantly different despite differences among baseline parameters (p?<?0.05). The intermediate- and poor-risk patients defined using either model showed significantly longer PFS and OS in the Nx group than in the non-Nx group (p?<?0.05). After stratifying groups by systemic therapy and risk models, both the Nx and non-Nx groups showed no significant differences in intermediate and poor-risk models (p?>?0.05). In both synchronous and metachronous mRCC patients, both PFS and OS showed similar survivals; the Nx group had significantly longer PFS and OS than the non-Nx group, even after considering each systemic therapy and prognostic model. Nx showed a significant positive benefit in PFS and OS compared to no Nx upon patient stratification according to the MSKCC and Heng risk models. The metastatic type did not significantly affect survival between the two groups.
Project description:Sunitinib is the currently standard treatment for metastatic renal cell carcinoma (mRCC). Multiple candidate predictive biomarkers for sunitinib response have been evaluated but none of them has been implemented in the clinic yet. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) in genes linked to mode of action of sunitinib and immune response as biomarkers for mRCC. This is a multicenter, prospective and observational study involving 20 hospitals. Seventy-five mRCC patients treated with sunitinib as first line were used to assess the impact of 63 SNPs in 31 candidate genes on clinical outcome. rs2243250 (IL4) and rs5275 (PTGS2) were found to be significantly associated with shorter cancer-specific survival (CSS). Moreover, allele C (rs5275) was associated with higher PTGS2 expression level confirming its functional role. Combination of rs5275 and rs7651265 or rs2243250 for progression free survival (PFS) or CSS, respectively, was a more valuable predictive biomarker remaining significant after correction for multiple testing. It is the first time that association of rs5275 with survival in mRCC patients is described. Two-SNP models containing this functional variant may serve as more predictive biomarkers for sunitinib and could suppose a clinically relevant tool to improve the mRCC patient management.
Project description:Eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) is phosphorylated and activated by mammalian target of rapamycin complex 1, which serves as a regulator of cell growth, cell survival, metastasis and angiogenesis in many types of cancer. The aim of this study was to evaluate the role of phosphorylated 4EBP1 (p4EBP1) in primary renal cell carcinoma (RCC) as a biomarker in metastatic RCC (mRCC) and non-mRCC cohorts. Primary tumor tissue from 254 non-mRCC and 60 mRCC patients were immunohistochemically stained for t4EBP1 and p4EBP1. The disease-free interval (DFI) categorized by the expressions and clinical parameters were assessed by univariate and multivariate analysis in the non-mRCC cohort. Then, the cause-specific survival (CSS) was assessed in the mRCC cohort by the same methods as used in the non-mRCC cohort. In the non-mRCC cohort, patients with t4EBP1 expression had no RCC recurrence. Patients with p4EBP1 expression had the shorter DFI in univariate analysis (P=0.037). p4EBP1 and pT1b-4 expression levels were independent predictors for de novo metastasis. In the mRCC cohort, intermediate/poor MSKCC risk, non-clear cell RCC, and no p4EBP1 expression were correlated with poor CSS on multivariate analysis. Expression of p4EBP1 could be a predictive biomarker for de novo metastasis in non-mRCC patient cohort. By contrast, mRCC patients showing no p4EBP1 expression had shorter CSS than patients with p4EBP1 expression.
Project description:Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design.Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria.In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months.Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials.
Project description:This study evaluated the effects of metastasectomy on overall survival (OS) and progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC) according to metastatic organs. The medical records (2005-2017) of 273 patients with mRCC were analyzed retrospectively to evaluate OS and PFS according to metastatic organs and their metastasectomy states. The Cox proportional hazard model was used to determine the prognostic significance of metastasectomy. The Kaplan-Meier curve and log-rank test were used to compare groups with different modalities and metastatic organs at a statistical significance of p < 0.05. The overall median age was 57 years; 175 (64.3%) and 83 (30.4%) patients received cytoreductive nephrectomy and metastasectomy, respectively. The metastasectomy group was significantly younger and had a lower clinical T stage with significantly better PFS/OS (20.2/32.0 vs. 9.7/12.8 months) than that in the non-metastasectomy group (N = 190, p < 0.05). Liver with lung metastases were the worst metastatic combination for survivals in which liver metastasis was the only significant unfavorable risk factor for both PFS (HR 1.67) and OS (HR 1.74) (p < 0.05). Multivariable analysis confirmed that metastasectomy was a significant favorable risk factor for PFS (HR 0.70) and OS (HR 0.56) (p < 0.05) along with non-clear cell type (HR 0.61 for PFS), whereas the nuclear grade and poor Heng risk group were unfavorable risk factors (HR > 2.0) for both PFS and OS (p < 0.05). Metastasectomy and the affected metastatic organs significantly influenced prognostic survival in mRCC.
Project description:Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer in ccRCC patients and the hazard ratio of death was 0.71 for ccRCC patients. No differences in PFS or ORR were detected between type I and II PRCC in this limited dataset. The median OS for type I pRCC was 20.0 months while the median OS for type II was 12.6 months (P = 0.096). The IMDC prognostic model was able to stratify pRCC patients into favorable risk (OS = 34.1 months), intermediate risk (OS = 17.0 months), and poor-risk groups (OS = 6.0 months). pRCC patient outcomes were inferior to ccRCC, even after controlling for IMDC prognostic factors. The IMDC prognostic model was able to effectively stratify pRCC patients.
Project description:The aim of the present study was to investigate the association between clinical parameters and the overall survival (OS) of Japanese patients with metastatic renal cell carcinoma (mRCC). The medical records of 59 consecutive mRCC patients receiving molecular-targeted therapy were retrospectively assessed. Kaplan-Meier and log-rank analyses were used to evaluate the progression-free survival (PFS) and OS, and a multivariate Cox proportional hazard model was used to analyze the clinical parameters for their prognostic relevance. The median OS for all patients was 23.7 months [95% confidence interval (CI): 17.9-30 months], and the median OS stratified by the Memorial Sloan Kettering Cancer Center risk classification was 28.5, 20.9 and 8.1 months for the favorable-, intermediate- and poor-risk groups, respectively (P=0.137; degree of freedom: 2). Univariate analyses identified prior nephrectomy, number of metastatic sites, anemia, best response to first-line treatment and PFS with first-line treatment as prognostic variables. Multivariate analyses identified number of metastatic sites [2: hazard ratio (HR)=3.351, 95% CI: 1.460-8.201, P=0.004; ≥3: HR=6.397, 95% CI: 1.939-20.209, P=0.003], time from diagnosis to therapy (≥1 year: HR=0.334, 95% CI: 0.137-0.755, P=0.008), PFS with first-line treatment (≥5.1 months: HR=0.353, 95% CI: 0.156-0.766, P=0.008) and number of lines of molecular-targeted agents (≥3: HR=0.248, 95% CI: 0.091-0.664, P=0.006) as independent prognostic factors. The results indicated that the PFS of first-line treatment may be a meaningful intermediate endpoint for OS in patients with mRCC who received treatment with molecular-targeted therapy.