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


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-alpha-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.


CONCLUSIONS
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.
Fusi
Alberto
A
Charité - Campus Benjamin Franklin, Berlin, Germany.
Collette
Sandra
S
Busse
Antonia
A
Suciu
Stefan
S
Rietz
Anika
A
Santinami
Mario
M
Kruit
Wim H J
WH
Testori
Alessandro
A
Punt
Cornelis J A
CJ
Dalgleish
Angus G
AG
Spatz
Alan
A
Eggermont
Alexander M M
AM
Keilholz
Ulrich
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008197:Lymph Node Excision; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000097:blood*; D009363:Neoplasm Proteins / Q000097:blood*; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D013223:Statistics as Topic; D055815:Young Adult
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D014442:Monophenol Monooxygenase; C417083:peginterferon alfa-2b