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Inherent characteristics of metachronous metastatic renal cell carcinoma in the era of targeted agents.

ABSTRACT: To assess the prognostic and predictive factors of time to treatment failure (TTF) and overall survival (OS), respectively, in patients with metachronous metastatic renal cell carcinoma (mRCC) who were treated with targeted agents.We retrospectively reviewed metachronous mRCC patients, defined as individuals diagnosed with metastatic disease >3 months after initial nephrectomy, treated at an institute since 2005. Cox proportional hazard regression analysis was performed to discover the most determinant variables associated with TTF and OS.Sarcomatoid features, absence of metastasectomy, multiple site metastasis, time to metastasis <1.5 year, and increased corrected calcium were independent prognostic factors of OS. The low risk group (0-1 risk factors) did not reach the median OS, whereas the OS for the intermediate (2 risk factors) and high risk groups (3-5 risk factors) were 58.6 and 23.6 months, respectively (p<0.001). When a death event was considered the dependent factor, the area under the receiver operating characteristic curve was significantly higher than in the existing International mRCC Database Consortium (IMDC; p=0.010) and Memorial Sloan Kettering Cancer Center (MSKCC; p=0.010) risk criteria models.Initial tumor size or T stage did not affect TTF or OS. Patients who could not undergo metastasectomy and rapidly developed multiple metastases with higher corrected calcium and initial tumors with sarcomatoid features were less likely to benefit from targeted therapy; thus, the new agents under development or clinical trials could be more helpful than the use of standard targeted agents.

SUBMITTER: Han JH

PROVIDER: S-EPMC5668001 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Inherent characteristics of metachronous metastatic renal cell carcinoma in the era of targeted agents.

Han Jang Hee JH Lee Seung Hwan SH Ham Won Sik WS Han Woong Kyu WK Rha Koon Ho KH Choi Young Deuk YD Hong Sung Joon SJ Yoon Young Eun YE

Oncotarget 20170812 45

<h4>Background</h4>To assess the prognostic and predictive factors of time to treatment failure (TTF) and overall survival (OS), respectively, in patients with metachronous metastatic renal cell carcinoma (mRCC) who were treated with targeted agents.<h4>Materials and methods</h4>We retrospectively reviewed metachronous mRCC patients, defined as individuals diagnosed with metastatic disease >3 months after initial nephrectomy, treated at an institute since 2005. Cox proportional hazard regression ...[more]

PMID: 29108268

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Project description:Recent phase III studies of targeted agents for metastatic renal cell carcinoma (mRCC) have generated median survival estimates that far exceed those observed during the cytokine era. However, substantial population-based data does not exist to confirm this trend. We sought to determine whether survival has improved for patients with mRCC diagnosed in the era of targeted therapies, as compared to the era of immunotherapy.The Surveillance, Epidemiology, and End Results (SEER) Registry was used to identify patients aged 18 and older diagnosed stage IV RCC between 1992 and 2009. Patients had documented clear cell, papillary or chromophobe histology. The Kaplan Meier method and log-rank test were used to compare disease-specific survival (DSS) for patients diagnosed from 1992-2004 (i.e., the cytokine era) and 2005-2009 (i.e., the targeted therapy era). Univariate and multivariate analyses of relevant clinicopathologic characteristics were also performed.Of 5,176 patients identified using the above characteristics, 2,392 patients were diagnosed from 1992-2004 and 2,784 from 2005-2009. Median DSS was improved in those patients diagnosed from 2005-2009 (16 months vs 13 months; P<0.0001). A similar temporal trend towards improving survival was noted in patients with clear cell (P = 0.0006), but not in patients with non-clear cell disease (P = 0.32). Notable findings on multivariate analysis include an association between shorter DSS and the following characteristics: (1) diagnosis from 1992-2004, (2) advanced age (80+), and (3) absence of cytoreductive nephrectomy.These data reflect progress in the management of mRCC, specifically in the era of targeted therapies. Notably, it was inferred that certain treatment strategies were employed during pre-specified time periods, representing a major caveat of the current analysis. Further studies related to the influence of age and race/ethnicity are warranted, as are studies exploring the role of cytoreductive nephrectomy and novel treatments for non-clear cell disease.

Project description:BackgroundAlthough commonly observed, malnutrition is poorly characterized and frequently underdiagnosed in patients with metastatic renal cell carcinoma (RCC). The ability of nutritional screening tools to predict overall survival (OS) in patients with RCC has not been adequately validated. The objective of this study was to investigate the performance of nutritional screening tools and their additional prognostic value in patients with metastatic RCC treated with targeted therapies.MethodsPatients were prospectively recruited from three tertiary hospitals between 2009 and 2013. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI) and the Mini Nutritional Assessment-Short Form (MNA-SF). Their OS and early grade 3/4 adverse events were recorded as outcomes of interest, and their associations with nutritional status were assessed using Cox regression and logistic regression, respectively. The incremental value in prognostication was evaluated using concordance index and decision curve analyses.ResultsOf the 300 enrolled patients, 95 (31.7%) and 64 (21.3%) were classified as being at risk of malnutrition according to the GNRI and MNA-SF, respectively. Both GNRI and MNA-SF were independent predictors of OS in multivariate analyses and provided significant added benefit to Heng risk classification. Compared with the MNA-SF, the GNRI contributed a higher increment to the concordance index (0.041 vs. 0.016). Nutritional screening, however, was not associated with early grade 3/4 adverse events in multivariate analyses. Further investigations are needed using more comprehensive and accurate assessment tools.ConclusionsThis prospective study confirmed the importance of nutritional screening tools in survival prognostication in patients with metastatic RCC. The standardized and objective measurements would allow clinicians to identify metastatic RCC patients at risk of poor survival outcomes. Individualized nutritional assessment and intervention strategies may be included in the multidisciplinary treatment.

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Inherent characteristics of metachronous metastatic renal cell carcinoma in the era of targeted agents.

Publications

Inherent characteristics of metachronous metastatic renal cell carcinoma in the era of targeted agents.

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