Optimisation of the size variation threshold for imaging evaluation of response in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium treated with vinflunine

Eur J Cancer. 2012 Jul;48(10):1495-502. doi: 10.1016/j.ejca.2011.11.018. Epub 2011 Dec 14.

Abstract

Background: Vinflunine (VFL) has been approved in the European Union for second-line treatment of advanced transitional cell carcinoma of the urothelial tract (TCCU) in patients who progress after a platinum based regimen. However, very few patients achieve response by response evaluation criteria in solid tumours (RECIST). Therefore, another 'response' threshold may be more useful than RECIST 1.0 in this setting.

Methods: One hundred and seventy nine patients with advanced TCCU treated with second-line VFL therapy had chest Computed Tomography (CT) and abdominal/pelvic CT or MRI performed at baseline and at first follow-up (6 weeks ± 3 days) after therapy initiation. Tumour measurements and response by RECIST 1.0 were correlated with overall survival (OS). Kaplan-Meier and receiver operating characteristic (ROC) analysis were then used to determine the optimal size threshold to define 'responders'. Impact of adverse prognostic factors including Eastern Cooperative Oncology Group Performance Status (ECOG PS) >0, Hb <10 g/dL, and liver metastases was analysed.

Results: Tumour response included 13 partial responses (PR) by RECIST 1.0 and 52 patients with ≥ 10% decrease in the sum of longest diameters. Responders by RECIST 1.0 did not have a statistically significant improvement in OS, while patients with sum long axis diameter (SLD) reduction of ≥ 10% had a longer OS than those with SLD reduction of <10%: 11.3 versus 6.9 months (log rank p=0.0224). ROC analysis yielded ≥ 10% decrease in SLD as the optimal size change correlating with OS. These results persisted on multivariate analysis.

Conclusion: In the study population, a ≥ 10% reduction in SLD at first follow-up imaging is a better early predictor of outcome than RECIST.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Transitional Cell / drug therapy*
  • Diagnostic Imaging / methods*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Liver Neoplasms / pathology
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • ROC Curve
  • Time Factors
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urothelium / pathology*
  • Vinblastine / analogs & derivatives*
  • Vinblastine / therapeutic use

Substances

  • vinflunine
  • Vinblastine