Abstract
Although now commonplace in contemporary cancer care, the systematic approach to classification of disease-specific cancers into a formalized staging system is a relatively modern concept. Overall, the goals of cancer staging are to characterize the status of cancer at a specific moment in time, risk stratify, facilitate prognostication, and inform clinical decision making. The revisions to the American Joint Committee on Cancer (AJCC) melanoma staging system over time reflect changes in our understanding of the biology of the disease. Since the 1st edition, where tumor thickness was defined anatomically by its relationship to the reticular or papillary dermis (Clark level) as well as tumor thickness (Breslow thickness), there have been significant strides in our use of clinicopathological variables to stratify low- versus high-risk patients. Management of the regional nodal basin has also changed dramatically over time, impacted by techniques such as lymphatic mapping and sentinel lymph node biopsy (SLNB) and changes in pathological evaluation of the regional lymph nodes. Additionally, stratification of distant metastases has evolved as survival outcomes have been shown to vary based upon anatomic site of metastases and serum lactate dehydrogenase levels. The variables in use in the current (7th edition) AJCC staging system are surrogate markers of biology with validated impact of survival outcomes. Going forward, it is likely that these and additional clinicopathological factors will be integrated with molecular and other correlates of melanoma tumor biology to further refine and personalize melanoma staging.
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References
Commission TWotC (1927) The health organization of the league of nations: the work of the cancer commission, 1923–1927. Br Med J 1157
Weiss L (2000) The morphologic documentation of clinical progression, invasion metastasis—staging. Cancer Metastasis Rev 19(3–4):303–313. doi:10.1023/a:1010658607570
Weiss L (2000) Metastasis of cancer: a conceptual history from antiquity to the 1990s. Cancer Metastasis Rev 19(3–4):I–XI, 193–383
International Union against Cancer, TNM history, evolution and milestones. http://www.uicc.org/resources/tnm/resources
Ackerman L, DRJ (1947) Cancer diagnosis, treatment and prognosis. St Louis, CV Mosby, pp 169–181
Macneer G, Dasgupta T (1964) Prognosis in malignant melanoma. Surgery 56:512–518
Smith GJ (1975) Histopathology of melanoma. Yale J Biol Med 48(5):409–416
Breslow A (1970) Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172(5):902–908
Breslow A, Cascinelli N, van der Esch EP et al (1978) Stage I melanoma of the limbs: assessment of prognosis by levels of invasion and maximum thickness. Tumori 64(3):273–284
Balch CM, Murad TM, Soong SJ et al (1978) A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark’s and Breslow’s staging methods. Ann Surg 188(6):732–742
Breslow A (1975) Tumor thickness, level of invasion and node dissection in stage I cutaneous melanoma. Ann Surg 182(5):572–575
Leong SP, Kashani-Sabet M, Desmond RA et al (2005) Clinical significance of occult metastatic melanoma in sentinel lymph nodes and other high-risk factors based on long-term follow-up. World J Surg 29(6):683–691. doi:10.1007/s00268-005-7736-x
Cascinelli N, Bombardieri E, Bufalino R et al (2006) Sentinel and nonsentinel node status in stage IB and II melanoma patients: two-step prognostic indicators of survival. J Clin Oncol Official J Am Soc Clin Oncol 24(27):4464–4471. doi:10.1200/JCO.2006.06.3198 JCO.2009.27.1627 [pii]
Balch CM, Soong SJ, Gershenwald JE et al (2001) Prognostic factors analysis of 17,600 melanoma patients: validation of the American joint committee on cancer melanoma staging system. J Clin Oncol Official J Am Soc Clin Oncol 19(16):3622–3634
Balch CM, Buzaid AC, Soong SJ et al (2001) Final version of the American joint committee on cancer staging system for cutaneous melanoma. J Clin Oncol Official J Am Soc Clin Oncol 19(16):3635–3648
American Joint Committee for Cancer Staging and End Results Reporting (1978) Staging for malignant melanoma. Manual for staging of cancer, pp 131–140
Gershenwald JE, Buzaid AC, Ross MI (1998) Classification and staging of melanoma. Hematol Oncol Clin North Am 12(4):737–765
American Joint Committee for Cancer Staging and End Results Reporting (1977) Staging of malignant melanoma. American Joint Committee, Manual for Staging in Cancer
Balch CM, Gershenwald JE, Soong SJ et al (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol Official J Am Soc Clin Oncol 27(36):6199–6206. doi:10.1200/JCO.2009.23.4799 JCO.2009.23.4799 [pii]
Gershenwald JE, Thompson W, Mansfield PF et al (1999) Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol Official J Am Soc Clin Oncol 17(3):976–983
Morton DL, Wen DR, Wong JH et al (1992) Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127(4):392–399
Yee VS, Thompson JF, McKinnon JG et al (2005) Outcome in 846 cutaneous melanoma patients from a single center after a negative sentinel node biopsy. Ann Surg Oncol 12(6):429–439. doi:10.1245/ASO.2005.03.074
Francken AB, Shaw HM, Thompson JF et al (2004) The prognostic importance of tumor mitotic rate confirmed in 1317 patients with primary cutaneous melanoma and long follow-up. Ann Surg Oncol 11(4):426–433. doi:10.1245/ASO.2004.07.014 ASO.2004.07.014 [pii]
Eigentler TK, Buettner PG, Leiter U et al (2004) Impact of ulceration in stages I to III cutaneous melanoma as staged by the American joint committee on cancer staging system: an analysis of the German central malignant melanoma registry. J Clin Oncol Official J Am Soc Clin Oncol 22(21):4376–4383. doi:10.1200/JCO.2004.03.075 22/21/4376 [pii]
Balch CM, Wilkerson JA, Murad TM et al (1980) The prognostic significance of ulceration of cutaneous melanoma. Cancer 45(12):3012–3017
Averbook BJ, Fu P, Rao JS et al. (2002) A long-term analysis of 1018 patients with melanoma by classic cox regression and tree-structured survival analysis at a major referral center: Implications on the future of cancer staging. Surgery 132(4):589–602; discussion 602–584. S003960600200137X [pii]
Balch CM, Gershenwald JE, Soong S et al (2009) Melanoma of the skin. In: Edge SE, Byrd DR, Compton CA, Fritz AG, Greene FL, Trotti III A (eds) AJCC cancer staging manual, 7th edn. Springer, Berlin pp 325–346
Gimotty PA, Elder DE, Fraker DL et al (2007) Identification of high-risk patients among those diagnosed with thin cutaneous melanomas. J Clin Oncol Official J Am Soc Clin Oncol 25(9):1129–1134. doi:10.1200/JCO.2006.08.1463 25/9/1129 [pii]
Gimotty PA, Guerry D, Ming ME et al (2004) Thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than American joint committee on cancer staging. J Clin Oncol Official J Am Soc Clin Oncol 22(18):3668–3676. doi:10.1200/JCO.2004.12.015 JCO.2004.12.015 [pii]
Karakousis GC, Gimotty PA, Czerniecki BJ et al (2007) Regional nodal metastatic disease is the strongest predictor of survival in patients with thin vertical growth phase melanomas: a case for SLN staging biopsy in these patients. Ann Surg Oncol 14(5):1596–1603. doi:10.1245/s10434-006-9319-y
Kesmodel SB, Karakousis GC, Botbyl JD et al (2005) Mitotic rate as a predictor of sentinel lymph node positivity in patients with thin melanomas. Ann Surg Oncol 12(6):449–458. doi:10.1245/ASO.2005.04.027
Thompson JF, Soong SJ, Balch CM et al (2011) Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American joint committee on cancer melanoma staging database. J Clin Oncol 29(16):2199–2205. doi:10.1200/JCO.2010.31.5812
Scheri RP, Essner R, Turner RR et al (2007) Isolated tumor cells in the sentinel node affect long-term prognosis of patients with melanoma. Ann Surg Oncol 14(10):2861–2866. doi:10.1245/s10434-007-9472-y
van Akkooi AC, de Wilt JH, Verhoef C et al (2006) Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? Ann Oncol 17(10):1578–1585. doi:10.1093/annonc/mdl176 mdl176 [pii]
Cascinelli N, Belli F, Santinami M et al (2000) Sentinel lymph node biopsy in cutaneous melanoma: the WHO melanoma program experience. Ann Surg Oncol 7(6):469–474
Morton DL, Thompson JF, Cochran AJ et al (2006) Sentinel-node biopsy or nodal observation in melanoma. New Engl J Med 355(13):1307–1317. doi:10.1056/NEJMoa060992 355/13/1307 [pii]
Morton DL, Thompson JF, Cochran AJ et al (2014) Final trial report of sentinel-node biopsy versus nodal observation in melanoma. New Engl J Med 370(7):599–609. doi:10.1056/NEJMoa1310460
Yu LL, Flotte TJ, Tanabe KK et al (1999) Detection of microscopic melanoma metastases in sentinel lymph nodes. Cancer 86(4):617–627. doi:10.1002/(SICI)1097-0142(19990815)86:4<617:AID-CNCR10>3.0.CO;2-S [pii]
Spanknebel K, Coit DG, Bieligk SC et al (2005) Characterization of micrometastatic disease in melanoma sentinel lymph nodes by enhanced pathology: recommendations for standardizing pathologic analysis. Am J Surg Pathol 29(3):305–317. 00000478-200503000-00003 [pii]
Gibbs JF, Huang PP, Zhang PJ et al (1999) Accuracy of pathologic techniques for the diagnosis of metastatic melanoma in sentinel lymph nodes. Ann Surg Oncol 6(7):699–704
van Akkooi AC, Bouwhuis MG, van Geel AN et al (2007) Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma. Eur J Surg Oncol 33(1):102–108. doi:10.1016/j.ejso.2006.10.032 S0748-7983(06)00426-4 [pii]
Meyer T, Merkel S, Gohl J et al. (2002) Lymph node dissection for clinically evident lymph node metastases of malignant melanoma. Eur J Surg Oncol 28 (4):424–430. S0748798301912624 [pii]
Badgwell B, Xing Y, Gershenwald JE et al (2007) Pelvic lymph node dissection is beneficial in subsets of patients with node-positive melanoma. Ann Surg Oncol 14(10):2867–2875. doi:10.1245/s10434-007-9512-7
Balch CM, Thompson JF, Gershenwald JE et al (2014) Age as a predictor of sentinel node metastasis among patients with localized melanoma: an inverse correlation of melanoma mortality and incidence of sentinel node metastasis among young and old patients. Ann Surg Oncol 21(4):1075–1081. doi:10.1245/s10434-013-3464-x
Bartlett EK, Gupta M, Datta J et al (2014) Prognosis of patients with melanoma and microsatellitosis undergoing sentinel lymph node biopsy. Ann Surg Oncol 21(3):1016–1023. doi:10.1245/s10434-013-3388-5
Shaikh L, Sagebiel RW, Ferreira CM et al (2005) The role of microsatellites as a prognostic factor in primary malignant melanoma. Arch Dermatol 141(6):739–742. doi:10.1001/archderm.141.6.739 141/6/739 [pii]
Keilholz U, Martus P, Punt CJ et al (2002) Prognostic factors for survival and factors associated with long-term remission in patients with advanced melanoma receiving cytokine-based treatments: second analysis of a randomised EORTC melanoma group trial comparing interferon-alpha2a (IFNalpha) and interleukin 2 (IL-2) with or without cisplatin. Eur J Cancer 38(11):1501–1511. S0959804902001235 [pii]
Keilholz U, Conradt C, Legha SS et al (1998) Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients. J Clin Oncol Official J Am Soc Clin Oncol 16(9):2921–2929
Franzke A, Probst-Kepper M, Buer J et al (1998) Elevated pretreatment serum levels of soluble vascular cell adhesion molecule 1 and lactate dehydrogenase as predictors of survival in cutaneous metastatic malignant melanoma. Br J Cancer 78(1):40–45
Eton O, Legha SS, Moon TE et al (1998) Prognostic factors for survival of patients treated systemically for disseminated melanoma. J Clin Oncol Official J Am Soc Clin Oncol 16(3):1103–1111
Dickson PV, Gershenwald JE (2011) Staging and prognosis of cutaneous melanoma. Surg Oncol Clin N Am 20(1):1–17. doi:10.1016/j.soc.2010.09.007 S1055-3207(10)00095-5 [pii]
Barth A, Wanek LA, Morton DL (1995) Prognostic factors in 1521 melanoma patients with distant metastases. J Am Coll Surg 181(3):193–201
Manola J, Atkins M, Ibrahim J et al (2000) Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials. J Clin Oncol 18(22):3782–3793
Unger JM, Flaherty LE, Liu PY et al (2001) Gender and other survival predictors in patients with metastatic melanoma on Southwest oncology group trials. Cancer 91(6):1148–1155. doi:10.1002/1097-0142(20010315)91:6<1148:AID-CNCR1111>3.0.CO;2-# [pii]
Balch CM (1992) Cutaneous melanoma: prognosis and treatment results worldwide. Semin Surg Oncol 8(6):400–414
Staudt M, Lasithiotakis K, Leiter U et al (2010) Determinants of survival in patients with brain metastases from cutaneous melanoma. Br J Cancer 102(8):1213–1218. doi:10.1038/sj.bjc.6605622 6605622 [pii]
Ascierto PA, Grimaldi AM, Curti B et al (2012) Future perspectives in melanoma research. Meeting report from the “Melanoma research: a bridge from Naples to the World. Napoli, December 5th-6th 2011”. J Transl Med 10:83. doi:10.1186/1479-5876-10-83 1479-5876-10-83 [pii]
Soong SJ, Ding S, Coit D et al (2010) Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC melanoma database. Ann Surg Oncol 17(8):2006–2014. doi:10.1245/s10434-010-1050-z
Balch CM, Gershenwald JE, Soong SJ et al (2010) Multivariate analysis of prognostic factors among 2313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol Official J Am Soc Clin Oncol 28(14):2452–2459. doi:10.1200/JCO.2009.27.1627 JCO.2009.27.1627 [pii]
Bowles TL, Xing Y, Hu CY et al (2010) Conditional survival estimates improve over 5 years for melanoma survivors with node-positive disease. Ann Surg Oncol 17(8):2015–2023. doi:10.1245/s10434-010-1051-y
Gershenwald JE, Soong SJ, Balch CM (2010) 2010 TNM staging system for cutaneous melanoma and beyond. Ann Surg Oncol 17(6):1475–1477. doi:10.1245/s10434-010-0986-3
Jakob JA, Bassett RL Jr, Ng CS et al (2012) NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer 118(16):4014–4023. doi:10.1002/cncr.26724
Soong SJ, Ding S, Coit D et al (2010) Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC melanoma database. Ann Surg Oncol 17(8):2006–2014. doi:10.1245/s10434-010-1050-z
Boland GM, Meric-Bernstam F (2014) The role of surgeons in building a personalized medicine program. J Surg Oncol. doi:10.1002/jso.23684
Chapman PB, Hauschild A, Robert C et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New Engl J Med 364(26):2507–2516. doi:10.1056/NEJMoa1103782
Flaherty KT, Yasothan U, Kirkpatrick P (2011) Vemurafenib. Nat Rev Drug Discov 10(11):811–812. doi:10.1038/nrd3579 nrd3579 [pii]
Flaherty KT, Infante JR, Daud A et al (2012) Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. New Engl J Med 367(18):1694–1703. doi:10.1056/NEJMoa1210093
Flaherty KT, Robert C, Hersey P et al (2012) Improved survival with MEK inhibition in BRAF-mutated melanoma. New Engl J Med 367(2):107–114. doi:10.1056/NEJMoa1203421
Larkin J, Ascierto PA, Dreno B et al (2014) Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. New Engl J Med 371(20):1867–1876. doi:10.1056/NEJMoa1408868
Long GV, Stroyakovskiy D, Gogas H et al (2014) Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. New Engl J Med 371(20):1877–1888. doi:10.1056/NEJMoa1406037
Sosman JA, Kim KB, Schuchter L et al (2012) Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. New Engl J Med 366(8):707–714. doi:10.1056/NEJMoa1112302
Bucheit AD, Syklawer E, Jakob JA et al (2013) Clinical characteristics and outcomes with specific BRAF and NRAS mutations in patients with metastatic melanoma. Cancer 119(21):3821–3829. doi:10.1002/cncr.28306
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Boland, G.M., Gershenwald, J.E. (2016). Principles of Melanoma Staging. In: Kaufman, H., Mehnert, J. (eds) Melanoma. Cancer Treatment and Research, vol 167. Springer, Cham. https://doi.org/10.1007/978-3-319-22539-5_5
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