Circulating melanoma cells and distant metastasis-free survival in stage III melanoma patients with or without adjuvant interferon treatment (EORTC 18991 side study)

Alberto Fusi, Sandra Collette, Antonia Busse, Stefan Suciu, Anika Rietz, Mario Santinami, Wim H J Kruit, Alessandro Testori, Cornelis J A Punt, Angus G. Dalgleish, Alan Spatz, Alexander M M Eggermont, Ulrich Keilholz

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: To evaluate the prognostic and predictive importance of detection of melanoma cells in peripheral blood using reverse transcriptase polymerase chain reaction (RT-PCR) in stage III cutaneous melanoma patients after sentinel or regional lymph node dissection. Patients and methods: Serial testing for tyrosinase and Mart-1/Melan-A transcripts in peripheral blood was performed every 6 months over a maximum period of 60 months in a subset of patients enrolled in EORTC 18991 phase 3 trial, comparing pegylated interferon-α-2b with observation. Univariate and multivariate analyses were performed to estimate the role of RT-PCR as prognostic and predictive factor for distant metastasis-free survival (DMFS). Results: Among 299 patients who underwent RT-PCR analyses, 109 (36.5%) had at least one positive sample, either at time of randomisation (N = 17) or subsequently (N = 92). The cumulative rate of positive results was similar in the two treatment groups, as the DMFS from first RT-PCR positivity. RT-PCR result, positive versus negative, at a given time point, had no prognostic impact on subsequent DMFS. Cox time-dependent analysis indicated a significantly higher risk of developing distant metastasis in patients with a positive sample as compared to those with a negative one: hazard ratio (HR) of 2.23 (95% confidence interval (CI), 1.40-3.55; p <.001). These results were comparable in the 2 treatment groups, indicating that RT-PCR assessment was not predictive for treatment outcome. Conclusion: Detection of circulating tumour cells by RT-PCR for tyrosinase and Mart-1/Melan-A was a time-dependent moderate prognostic factor for subsequent development of distant metastasis in stage III melanoma patients.

Original languageEnglish
Pages (from-to)3189-3197
Number of pages9
JournalEuropean Journal of Cancer
Volume45
Issue number18
DOIs
Publication statusPublished - Dec 2009

Keywords

  • Circulating melanoma cells
  • EORTC
  • Pegylated interferon α-2b
  • RT-PCR
  • Stage III

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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