Assessment of prognostic circulating tumor cells in a phase III trial of adjuvant immunotherapy after complete resection of stage IV melanoma.
OBJECTIVE
To verify circulating tumor cell (CTC) prognostic utility in stage IV resected melanoma patients in a prospective international phase III clinical trial.


BACKGROUND
Our studies of melanoma patients in phase II clinical trials demonstrated prognostic significance for CTCs in patients with AJCC stage IV melanoma. CTCs were assessed to determine prognostic utility in follow-up of disease-free stage IV patients pre- and during treatment.


METHODS
After complete metastasectomy, patients were prospectively enrolled in a randomized trial of adjuvant therapy with a whole-cell melanoma vaccine, Canvaxin, plus Bacille Calmette-Guerin (BCG) versus placebo plus BCG. Blood specimens obtained pretreatment (n = 244) and during treatment (n = 214) were evaluated by quantitative real-time reverse-transcriptase polymerase chain reaction (qPCR) for expression of MART-1, MAGE-A3, and PAX3 mRNA biomarkers. Univariate and multivariate Cox analyses examined CTC biomarker expression with respect to clinicopathological variables.


RESULTS
CTC biomarker(s) (≥ 1) was detected in 54% of patients pretreatment and in 86% of patients over the first 3 months. With a median follow-up of 21.9 months, 71% of patients recurred and 48% expired. CTC levels were not associated with known prognostic factors or treatment arm. In multivariate analysis, pretreatment CTC (> 0 vs. 0 biomarker) status was significantly associated with disease-free survival (DFS; HR 1.64, P = 0.002) and overall survival (OS; HR 1.53, P = 0.028). Serial CTC (>0 vs. 0 biomarker) status was also significantly associated with DFS (HR 1.91, P = 0.02) and OS (HR 2.57, P = 0.012).


CONCLUSIONS
CTC assessment can provide prognostic discrimination before and during adjuvant treatment for resected stage IV melanoma patients.
Department of Molecular Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.
Sojun
S
Hoshimoto
Mark B
MB
Faries
Donald L
DL
Morton
Tatsushi
T
Shingai
Christine
C
Kuo
He-Jing
HJ
Wang
Robert
R
Elashoff
Nicola
N
Mozzillo
Mark C
MC
Kelley
John F
JF
Thompson
Jeffrey E
JE
Lee
Dave S B
DS
Hoon
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D019496:Cancer Vaccines / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D058965:MART-1 Antigen / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000097:blood; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000097:blood; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; C464842:Canvaxin; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; D009363:Neoplasm Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors