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Clinical Trial
. 2012 Nov 1;30(31):3819-26.
doi: 10.1200/JCO.2011.40.0887. Epub 2012 Sep 24.

Association between circulating tumor cells and prognosis in patients with stage III melanoma with sentinel lymph node metastasis in a phase III international multicenter trial

Sojun Hoshimoto  1 , Tatsushi Shingai, Donald L Morton, Christine Kuo, Mark B Faries, Kelly Chong, David Elashoff, He-Jing Wang, Robert M Elashoff, Dave S B Hoon
Affiliations
Clinical Trial

Association between circulating tumor cells and prognosis in patients with stage III melanoma with sentinel lymph node metastasis in a phase III international multicenter trial

Sojun Hoshimoto et al. J Clin Oncol. .

Abstract

Purpose: The outcomes of patients with melanoma who have sentinel lymph node (SLN) metastases can be highly variable, which has precluded establishment of consensus regarding treatment of the group. The detection of high-risk patients from this clinical setting may be helpful for determination of both prognosis and management. We report the utility of multimarker reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) detection of circulating tumor cells (CTCs) in patients with melanoma diagnosed with SLN metastases in a phase III, international, multicenter clinical trial.

Patients and methods: Blood specimens were collected from patients with melanoma (n = 331) who were clinically disease-free after complete lymphadenectomy (CLND) before entering onto a randomized adjuvant melanoma vaccine plus bacillus Calmette-Guérin (BCG) versus BCG placebo trial from 30 melanoma centers (United States and international). Blood was assessed using a verified multimarker RT-qPCR assay (MART-1, MAGE-A3, and GalNAc-T) of melanoma-associated proteins. Cox regression analyses were used to evaluate the prognostic significance of CTC status for disease recurrence and melanoma-specific survival (MSS).

Results: Individual CTC biomarker detection ranged from 13.4% to 17.5%. There was no association of CTC status (zero to one positive biomarkers v two or more positive biomarkers) with known clinical or pathologic prognostic variables. However, two or more positive biomarkers was significantly associated with worse distant metastasis disease-free survival (hazard ratio [HR] = 2.13, P = .009) and reduced recurrence-free survival (HR = 1.70, P = .046) and MSS (HR = 1.88, P = .043) in a multivariable analysis.

Conclusion: CTC biomarker status is a prognostic factor for recurrence-free survival, distant metastasis disease-free survival, and MSS after CLND in patients with SLN metastasis. This multimarker RT-qPCR analysis may therefore be useful in discriminating patients who may benefit from aggressive adjuvant therapy or stratifying patients for adjuvant clinical trials.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram. (*) Coadministered on days 0 and 14. BCG, bacillus Calmette-Guérin; CTC, circulating tumor cells; ECOG, Eastern Cooperative Oncology Group; PS, performance score; RT-qPCR, reverse-transcriptase quantitative polymerase chain reaction; SLN, sentinel lymph node.
Fig 2.
Fig 2.
Distant metastasis–free and disease-free survival curves for patients with circulating tumor cell (CTC) biomarker detection. P = .025 (log-rank test).
Fig 3.
Fig 3.
Melanoma-specific survival curves for patients with circulating tumor cell (CTC) biomarker detection. P = .031(log-rank test).
See this image and copyright information in PMC

References

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