Abstract
Background
Locoregional treatment is often insufficient to guarantee long-term disease-free survival (DFS) in American Joint Committee on Cancer stage IIIB melanoma, and, in order to improve survival, effective neoadjuvant and adjuvant strategies are needed . Selecting patients for these strategies requires risk stratification, for which clinical and molecular biomarkers can be used. We aimed to detect clinical biomarkers to identify high-risk stage IIIB melanoma patients.
Patients and Methods
We performed retrospective analysis of stage IIIB melanoma patients who underwent lymph node dissection (LND) in our institution between 2000 and 2015. Sentinel node-positive patients with ulcerated primary tumors, as well as patients with clinically detectable nodal metastasis with non-ulcerated tumors, were included. Baseline characteristics, melanoma-specific survival (MSS), and DFS were assessed, and prognostic factors for recurrence and survival were analyzed, using univariate and multivariate analysis.
Results
Overall, 250 patients were included. Median follow-up was 52 months (interquartile range 29–108 months), median MSS was 141 months, and median DFS was 36 months. Five- and 10-year MSS was 59 and 52 %, respectively, and 5- and 10-year DFS was 47 and 41 %, respectively. Age >50 years, Breslow thickness >2 versus ≤2 mm, and N2 versus N1 disease all carried an increased risk of death by melanoma. Age >50 years and extracapsular extension carried an increased risk of disease recurrence after LND.
Conclusions
Age >50 years, Breslow thickness >2 mm and N2 versus N1 disease are prognostic factors for poor survival in stage IIIB melanoma. These characteristics can be used to further stratify risk of death by melanoma in this already high-risk patient population and to help select the appropriate population for adjuvant therapy (trials).
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References
Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin. 2012;62(2):118–28.
Hollestein LM, van den Akker SA, Nijsten T, Karim-Kos HE, Coebergh JW, de Vries E. Trends of cutaneous melanoma in The Netherlands: increasing incidence rates among all Breslow thickness categories and rising mortality rates since 1989. Ann Oncol. 2012;23(2):524–30.
IKNL. Cijfers over kanker 2016. http://www.cijfersoverkanker.nl/selecties/Dataset_1/img56cefeaa63b56.
Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206.
Henderson MA, Burmeister BH, Ainslie J, Fisher R, Di Iulio J, Smithers BM, et al. Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled trial. Lancet Oncol. 2015;16(9):1049–60.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.
Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.
Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107–14.
Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127(4):392–9.
Uren RF, Thompson JF, Howman-Giles R. Sentinel lymph node biopsy in patients with melanoma and breast cancer. Intern Med J. 2001;31(9):547–53.
Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Ding S, Byrd DR, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010;28(14):2452–9.
Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19(16):3622–34.
Spillane AJ, Cheung BL, Winstanley J, Thompson JF. Lymph node ratio provides prognostic information in addition to American Joint Committee on Cancer N stage in patients with melanoma, even if quality of surgery is standardized. Ann Surg. 2011;253(1):109–15.
Badgwell B, Xing Y, Gershenwald JE, Lee JE, Mansfield PF, Ross MI, et al. Pelvic lymph node dissection is beneficial in subsets of patients with node-positive melanoma. Ann Surg Oncol. 2007;14(10):2867–75.
Karakousis CP, Driscoll DL. Positive deep nodes in the groin and survival in malignant melanoma. Am J Surg. 1996;171(4):421–2.
Karakousis CP, Driscoll DL, Rose B, Walsh DL. Groin dissection in malignant melanoma. Ann Surg Oncol. 1994;1(4):271–7.
Spillane AJ, Pasquali S, Haydu LE, Thompson JF. Patterns of recurrence and survival after lymphadenectomy in melanoma patients: clarifying the effects of timing of surgery and lymph node tumor burden. Ann Surg Oncol. 2014;21(1):292–9.
Sandro P, Andrea M, Nicola M, Simone M, Giuseppe M, Lorenzo B, et al. Lymph-node ratio in patients with cutaneous melanoma: a multi-institution prognostic study. Ann Surg Oncol. 2015;22(7):2127–34.
Xing Y, Badgwell BD, Ross MI, Gershenwald JE, Lee JE, Mansfield PF, et al. Lymph node ratio predicts disease-specific survival in melanoma patients. Cancer. 2009;115(11):2505–13.
Eggermont AM, Suciu S, Rutkowski P, Kruit WH, Punt CJ, Dummer R, et al. Long term follow up of the EORTC 18952 trial of adjuvant therapy in resected stage IIB-III cutaneous melanoma patients comparing intermediate doses of interferon-alpha-2b (IFN) with observation: ulceration of primary is key determinant for IFN-sensitivity. Eur J Cancer. 2016;55:111–21.
Eggermont AM, Suciu S, Testori A, Santinami M, Kruit WH, Marsden J, et al. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. J Clin Oncol. 2012;30(31):3810–8.
Suciu S, Ives, N, Eggermont AM. Predictive importance of ulceration on the efficacy of adjuvant interferon-a (IFN): an individual patient data (IPD) meta-analysis of 15 randomized trials in more than 7,500 melanoma patients (pts). J Clin Oncol. 2014;32(5S):9067. [abstract no. 9067]
Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16(5):522–30.
Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694–703.
Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–65.
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Madu, M.F., Wouters, M.W., Klop, W.M.C. et al. Clinical Prognostic Markers in Stage IIIB Melanoma. Ann Surg Oncol 23, 4195–4202 (2016). https://doi.org/10.1245/s10434-016-5396-8
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DOI: https://doi.org/10.1245/s10434-016-5396-8