Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma

Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26.


Background: The predictive role of objective remission remains undefined for targeted agents in metastatic renal cell carcinoma (mRCC); however, early tumour shrinkage (eTS) was shown to be predictive and/or prognostic for overall survival (OS) and progression-free survival (PFS) in mRCC in several small studies.

Objective: To evaluate the degree of eTS following systemic therapy that may predict survival in mRCC.

Design, setting, and participants: Data from 4334 patients with mRCC in phase 2 and 3 clinical trials between 2003 and 2013 were pooled for analyses. Early tumour shrinkage was assessed based on percentage change in sum of the longest diameters of target lesions at first postbaseline scan. Patients were categorised by a more or equal versus less optimal threshold of eTS, assessed using receiver operating characteristic (ROC) analysis. OS and PFS in patients with eTS were summarised using the Kaplan-Meier method.

Intervention: Axitinib, bevacizumab, interferon α, sorafenib, sunitinib, or temsirolimus.

Outcome measurements and statistical analysis: We measured optimal thresholds of eTS and eTS as a predictor of OS or PFS.

Results and limitations: Optimal threshold of eTS for the prediction of OS and PFS was determined to be approximately 10%. In Cox proportional hazards models, compared with patients without eTS, those with eTS had significantly longer OS (hazard ratio [HR]: 0.615; p<0.0001; median: 28.5 vs 16.0 mo) and PFS (HR: 0.628; p<0.0001; median: 10.5 vs 5.3 mo). The major limitation was the retrospective nature of our analysis, including different lines and types of therapy, although subset analyses detected a similar predictive pattern for eTS across all lines and types of therapy.

Conclusions: Early tumour shrinkage ≥10% at first postbaseline assessment could serve as a putative early end point in patients with mRCC. A prospective evaluation of eTS in clinical trials is warranted.

Patient summary: Early tumour shrinkage may be used to identify patients with metastatic renal cell carcinoma who would benefit from treatment with antitumour agents.

Trial registration: The clinical trials are registered on ClinicalTrials.gov (NCT00267748, NCT00338884, NCT00835978, NCT00065468, NCT00083889, NCT00631371, NCT00920816, NCT00077974, NCT00137423, NCT00054886, NCT00678392, and NCT00474786).

Keywords: Early tumour shrinkage; Overall survival; Predictive factor; Prognostic factor; Progression-free survival; Renal cell carcinoma.

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Axitinib
  • Bevacizumab / administration & dosage
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / secondary
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Disease-Free Survival
  • Humans
  • Imidazoles / therapeutic use
  • Indazoles / therapeutic use
  • Indoles / therapeutic use
  • Interferon-alpha / therapeutic use
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Prognosis
  • Proportional Hazards Models
  • Pyrroles / therapeutic use
  • Remission Induction
  • Retrospective Studies
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives
  • Sorafenib
  • Sunitinib
  • Survival Rate
  • Treatment Outcome
  • Tumor Burden


  • Antineoplastic Agents
  • Imidazoles
  • Indazoles
  • Indoles
  • Interferon-alpha
  • Phenylurea Compounds
  • Pyrroles
  • Niacinamide
  • Bevacizumab
  • temsirolimus
  • Sorafenib
  • Axitinib
  • Sunitinib
  • Sirolimus

Associated data

  • ClinicalTrials.gov/NCT00267748
  • ClinicalTrials.gov/NCT00338884
  • ClinicalTrials.gov/NCT00054886
  • ClinicalTrials.gov/NCT00065468
  • ClinicalTrials.gov/NCT00083889
  • ClinicalTrials.gov/NCT00835978
  • ClinicalTrials.gov/NCT00077974
  • ClinicalTrials.gov/NCT00474786
  • ClinicalTrials.gov/NCT00631371
  • ClinicalTrials.gov/NCT00920816
  • ClinicalTrials.gov/NCT00678392
  • ClinicalTrials.gov/NCT00137423