Survival outcome and treatment response of patients with late relapse from renal cell carcinoma in the era of targeted therapy

Eur Urol. 2014 Jun;65(6):1086-92. doi: 10.1016/j.eururo.2013.07.031. Epub 2013 Jul 30.


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.

Keywords: Late recurrence; Renal cell carcinoma; Survival outcome; Targeted therapies; Treatment response.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / secondary*
  • Carcinoma, Renal Cell / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology*
  • Kidney Neoplasms / surgery
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Grading
  • Nephrectomy
  • Retrospective Studies
  • Survival Rate
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Time Factors
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors


  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A
  • MTOR protein, human
  • TOR Serine-Threonine Kinases