@article{3127339,
    title = "Survival outcome and treatment response of patients with late relapse from renal cell carcinoma in the era of targeted therapy",
    author = "Kroeger, N. and Choueiri, T.K. and Lee, J.-L. and Bjarnason, G.A. and Knox, J.J. and Mackenzie, M.J. and Wood, L. and Srinivas, S. and Vaishamayan, U.N. and Rha, S.-Y. and Pal, S.K. and Yuasa, T. and Donskov, F. and Agarwal, N. and Tan, M.-H. and Bamias, A. and Kollmannsberger, C.K. and North, S.A. and Rini, B.I. and Heng, D.Y.C.",
    journal = "European urology oncology",
    year = "2014",
    volume = "65",
    number = "6",
    pages = "1086-1092",
    publisher = "Elsevier",
    doi = "10.1016/j.eururo.2013.07.031",
    keywords = "3' tert butyl 3' n tert butyloxycarbonyl 4 deacetyl 3' n debenzoyl 3' dephenyl 4 o methoxycarbonylpaclitaxel;  ag 117;  ag117;  ags 168mf;  alpha interferon;  antineoplastic agent;  axitinib;  bevacizumab;  cabozantinib;  capecitabine;  crlx 101;  crlx101;  docetaxel;  erlotinib;  everolimus;  foretinib;  gemcitabine;  imcl 1121;  imcL1121;  interleukin 2;  nivolumab;  pazopanib;  perifosine;  rapamycin;  sorafenib;  sunitinib;  temsirolimus;  tivantinib;  tivozanib;  unclassified drug;  unindexed drug;  vorsetuzumab mafodotin;  xl 990;  antineoplastic agent;  MTOR protein, human;  target of rapamycin kinase;  vasculotropin A, adult;  article;  cancer prognosis;  cancer recurrence;  cancer survival;  clinical assessment tool;  demography;  disease free interval;  female;  follow up;  Fuhrman grade;  histology;  human;  kidney carcinoma;  major clinical study;  male;  metastasis;  molecularly targeted therapy;  nephrectomy;  overall survival;  priority journal;  progression free survival;  risk factor;  sarcomatoid carcinoma;  survival time;  treatment outcome;  treatment response;  age;  aged;  antagonists and inhibitors;  cancer grading;  Carcinoma, Renal Cell;  disease free survival;  Kidney Neoplasms;  middle aged;  molecularly targeted therapy;  pathology;  retrospective study;  secondary;  survival rate;  time, Adult;  Age Factors;  Aged;  Antineoplastic Agents;  Carcinoma, Renal Cell;  Disease-Free Survival;  Female;  Humans;  Kidney Neoplasms;  Male;  Middle Aged;  Molecular Targeted Therapy;  Neoplasm Grading;  Nephrectomy;  Retrospective Studies;  Survival Rate;  Time Factors;  TOR Serine-Threonine Kinases;  Vascular Endothelial Growth Factor A",
    abstract = "Background A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence ≤5 yr after initial nephrectomy. Objective To characterize the clinical outcome of patients with late recurrence beyond 5 yr. Design, setting, and participants Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease >3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr. Outcome measurements and statistical analysis Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses. Results and limitations Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5-35 yr) after 5 yr. LRs presented with younger age (p < 0.0001), fewer with sarcomatoid features (p < 0.0001), more clear cell histology (p = 0.001), and lower Fuhrman grade (p < 0.0001). Overall objective response rates to targeted therapy were better in LRs versus ERs (31.8% vs 26.5%; p = 0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5 mo; p = 0.005) and overall survival (OS; 34.0 mo vs 27.4 mo; p = 0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols. Conclusions A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS. © 2013 European Association of Urology."
}