@article{3104092,
    title = "Synchronous Versus Metachronous Metastatic Disease: Impact of Time to Metastasis on Patient Outcome-Results from the International Metastatic Renal Cell Carcinoma Database Consortium",
    author = "Donskov, F. and Xie, W. and Overby, A. and Wells, J.C. and Fraccon, A.P. and Sacco, C.S. and Porta, C. and Stukalin, I. and Lee, J.-L. and Koutsoukos, K. and Yuasa, T. and Davis, I.D. and Pezaro, C. and Kanesvaran, R. and Bjarnason, G.A. and Sim, H.-W. and Rathi, N. and Kollmannsberger, C.K. and Canil, C.M. and Choueiri, T.K. and Heng, D.Y.C.",
    journal = "European urology oncology",
    year = "2020",
    volume = "3",
    number = "4",
    pages = "530-539",
    publisher = "NLM (Medline)",
    doi = "10.1016/j.euo.2020.01.001",
    keywords = "aged;  comparative study;  factual database;  female;  human;  international cooperation;  kidney tumor;  male;  middle aged;  mortality;  pathology;  renal cell carcinoma;  retrospective study;  survival rate;  time factor, Aged;  Carcinoma, Renal Cell;  Databases, Factual;  Female;  Humans;  International Cooperation;  Kidney Neoplasms;  Male;  Middle Aged;  Retrospective Studies;  Survival Rate;  Time Factors",
    abstract = "BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) may present with primary metastases (synchronous disease) or develop metastases during follow-up (metachronous disease). The impact of time to metastasis on patient outcome is poorly characterised. OBJECTIVE: To characterise overall survival (OS) and time to treatment failure (TTF) based on time to metastasis in mRCC patients treated with targeted therapy (tyrosine kinase inhibitors [TKIs]). DESIGN, SETTING, AND PARTICIPANTS: We used the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare synchronous (metastases within ≤3 mo of initial diagnosis of cancer) versus metachronous disease (evaluated by >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr intervals). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS and TFF were assessed using Kaplan-Meier curves. Cox multivariable regressions analyses (MVAs) were adjusted for baseline factors. RESULTS AND LIMITATIONS: Of 7386 patients with mRCC treated with first-line TKIs, 3906 (53%) and 3480 (47%) had synchronous and metachronous metastasis, respectively. More patients with synchronous versus metachronous disease had higher T stage (T1-2: 19% vs 34%), N1 disease (21% vs 6%), presence of sarcomatoid differentiation (15.8% vs 7.9%), Karnofsky performance status <80 (25.9% vs 15.1%), anaemia (62.5% vs 42.3%), elevated neutrophils (18.9% vs 10.9%), elevated platelets (21.6% vs 11.4%), bone metastases (40.4% vs 29.8%), and IMDC poor risk (40.6% vs 11.3%). Synchronous versus metachronous disease by intervals >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr correlated with poor TTF (5.6 mo vs 7.3, 8.0, 10.8, and 13.3 mo, p <  0.0001) and poor OS (median 16.7 mo vs 23.8, 30.2, 34.8, and 41.7 mo, p <  0.0001). In MVAs, the adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.98 (0.90-1.06), 0.81 (0.73-0.91), 0.74 (0.68-0.81), and 0.60 (0.54-0.67), respectively, for OS (p <  0.0001), and 1.00 (reference), 0.99 (0.92-1.06), 0.98 (0.90-1.07), 0.83 (0.77-0.89), and 0.66 (0.60-0.72), respectively, for TTF (p <  0.0001). Data were collected retrospectively. CONCLUSIONS: Timing of metastases after initial RCC diagnosis may impact the outcomes from targeted therapy in mRCC. PATIENT SUMMARY: We looked at the impact of the timing of metastatic outbreak on survival outcomes in kidney cancer patients treated with targeted therapy. We found that the longer time to metastatic development was associated with improved outcome. Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved."
}