Skip to main content
Top
Published in: Journal of Translational Medicine 1/2019

Open Access 01-12-2019 | Melanoma | Review

New paradigm for stage III melanoma: from surgery to adjuvant treatment

Authors: Paolo Antonio Ascierto, Lorenzo Borgognoni, Gerardo Botti, Michele Guida, Paolo Marchetti, Simone Mocellin, Paolo Muto, Giuseppe Palmieri, Roberto Patuzzo, Pietro Quaglino, Ignazio Stanganelli, Corrado Caracò

Published in: Journal of Translational Medicine | Issue 1/2019

Login to get access

Abstract

Background

Recently the 8th version of the American Joint Committee on Cancer (AJCC) classification has been introduced, and has attempted to define a more accurate and precise definition of prognosis in line with the major progresses in understanding the biology and pathogenesis of melanoma. This new staging system introduces major changes in the stage III staging system. Indeed, surgical practice is changing in stage III patients, since, according to recent evidence, there is no survival benefit in radical lymph node dissection following a positive sentinel lymph node dissection. Therefore, some patients currently staged IIIB-C after dissection could be downgraded to IIIA (as in the case of patients with metastatic non-sentinel lymph nodes) since many completion lymph node dissections will no longer be performed. Moreover, new and effective targeted and immune strategies are being introduced in the pharmacological armamentarium in the adjuvant setting, showing major efficacy.

Conclusions

This article provides the authors’ personal view on the above-mentioned topics.
Literature
1.
go back to reference Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, For members of the American Joint Committee on Cancer Melanoma Expert Panel and the International Melanoma Database and Discovery Platform, et al. Melanoma staging: Evidencebased changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472e92.CrossRef Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, For members of the American Joint Committee on Cancer Melanoma Expert Panel and the International Melanoma Database and Discovery Platform, et al. Melanoma staging: Evidencebased changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472e92.CrossRef
2.
go back to reference Grob JJ, Schadendorf D, Lorigan P, Ascierto P, Larkin J, Nathan P, et al. Eighth American Joint Committee on Cancer (AJCC) melanoma classification: Let us reconsider stage III. Eur J Cancer. 2018;91:168–70.CrossRef Grob JJ, Schadendorf D, Lorigan P, Ascierto P, Larkin J, Nathan P, et al. Eighth American Joint Committee on Cancer (AJCC) melanoma classification: Let us reconsider stage III. Eur J Cancer. 2018;91:168–70.CrossRef
3.
go back to reference Leiter U, Stadler R, Mauch C, Hohenberger W, Brockmeyer N, Berking C, German Dermatologic Cooperative Oncology Group (DeCOG), et al. Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2016;17(6):757e67.CrossRef Leiter U, Stadler R, Mauch C, Hohenberger W, Brockmeyer N, Berking C, German Dermatologic Cooperative Oncology Group (DeCOG), et al. Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2016;17(6):757e67.CrossRef
4.
go back to reference Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376(23):2211–22.CrossRef Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376(23):2211–22.CrossRef
5.
go back to reference Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, et al. Adjuvant Nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–35.CrossRef Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, et al. Adjuvant Nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–35.CrossRef
6.
go back to reference Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1813–23.CrossRef Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1813–23.CrossRef
7.
go back to reference Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. 2018;378(19):1789–801.CrossRef Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. 2018;378(19):1789–801.CrossRef
8.
go back to reference Verver D, van Klaveren D, van Akkooi ACJ, Rutkowski P, Powell BWEM, Robert C, et al. Risk stratification of sentinel node-positive melanoma patients defines surgical management and adjuvant therapy treatment considerations. Eur J Cancer. 2018;96:25–33.CrossRef Verver D, van Klaveren D, van Akkooi ACJ, Rutkowski P, Powell BWEM, Robert C, et al. Risk stratification of sentinel node-positive melanoma patients defines surgical management and adjuvant therapy treatment considerations. Eur J Cancer. 2018;96:25–33.CrossRef
10.
go back to reference Rossi CR, Mocellin S, Campana LG, Borgognoni L, Sestini S, Giudice G, Italian Melanoma Intergroup (IMI), et al. Prediction of non-sentinel node status in patients with melanoma and positive sentinel node biopsy: an italian melanoma intergroup (IMI) study. Ann Surg Oncol. 2018;25(1):271–9.CrossRef Rossi CR, Mocellin S, Campana LG, Borgognoni L, Sestini S, Giudice G, Italian Melanoma Intergroup (IMI), et al. Prediction of non-sentinel node status in patients with melanoma and positive sentinel node biopsy: an italian melanoma intergroup (IMI) study. Ann Surg Oncol. 2018;25(1):271–9.CrossRef
11.
go back to reference Mocellin S, Lens MB, Pasquali S, Pilati P, Chiarion Sileni V. Interferon alpha for the adjuvant treatment of cutaneous melanoma. Cochrane Database Syst Rev. 2013;6:CD008955. Mocellin S, Lens MB, Pasquali S, Pilati P, Chiarion Sileni V. Interferon alpha for the adjuvant treatment of cutaneous melanoma. Cochrane Database Syst Rev. 2013;6:CD008955.
12.
go back to reference Ives NJ, Suciu S, Eggermont AMM, Kirkwood J, Lorigan P, Markovic SN, International Melanoma Meta-Analysis Collaborative Group (IMMCG), et al. Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis. Eur J Cancer. 2017;82:171–83.CrossRef Ives NJ, Suciu S, Eggermont AMM, Kirkwood J, Lorigan P, Markovic SN, International Melanoma Meta-Analysis Collaborative Group (IMMCG), et al. Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis. Eur J Cancer. 2017;82:171–83.CrossRef
13.
go back to reference Ugurel S, Röhmel J, Ascierto PA, Flaherty KT, Grob JJ, Hauschild A, et al. Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017. Eur J Cancer. 2017;83:247–57.CrossRef Ugurel S, Röhmel J, Ascierto PA, Flaherty KT, Grob JJ, Hauschild A, et al. Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017. Eur J Cancer. 2017;83:247–57.CrossRef
14.
go back to reference Maio M, Lewis K, Demidov L, Mandalà M, Bondarenko I, Ascierto PA, BRIM8 Investigators., et al. Adjuvant vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2018;19(4):510–20.CrossRef Maio M, Lewis K, Demidov L, Mandalà M, Bondarenko I, Ascierto PA, BRIM8 Investigators., et al. Adjuvant vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2018;19(4):510–20.CrossRef
15.
go back to reference Hauschild A, Dummer R, Schadendorf D, Santinami M, Atkinson V, Mandalà M, et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-mutant stage III melanoma. J Clin Oncol. 2018;36:3441–9.CrossRef Hauschild A, Dummer R, Schadendorf D, Santinami M, Atkinson V, Mandalà M, et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-mutant stage III melanoma. J Clin Oncol. 2018;36:3441–9.CrossRef
16.
go back to reference Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375(19):1845–55.CrossRef Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375(19):1845–55.CrossRef
18.
go back to reference Ascierto PA, Dummer R. Immunological effects of BRAF + MEK inhibition. Oncoimmunology. 2018;7(9):e1468955.CrossRef Ascierto PA, Dummer R. Immunological effects of BRAF + MEK inhibition. Oncoimmunology. 2018;7(9):e1468955.CrossRef
19.
go back to reference van Akkooi AC, Nowecki ZI, Voit C, Schäfer-Hesterberg G, Michej W, de Wilt JH, et al. Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes. Ann Surg. 2008;248(6):949–55.CrossRef van Akkooi AC, Nowecki ZI, Voit C, Schäfer-Hesterberg G, Michej W, de Wilt JH, et al. Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes. Ann Surg. 2008;248(6):949–55.CrossRef
22.
go back to reference Blank CU, Rozeman EA, Fanchi LF, Sikorska K, van de Wiel B, Kvistborg P, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018;24(11):1655–61.CrossRef Blank CU, Rozeman EA, Fanchi LF, Sikorska K, van de Wiel B, Kvistborg P, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018;24(11):1655–61.CrossRef
23.
go back to reference Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, et al. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med. 2019;25(3):454–61.CrossRef Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, et al. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med. 2019;25(3):454–61.CrossRef
25.
Metadata
Title
New paradigm for stage III melanoma: from surgery to adjuvant treatment
Authors
Paolo Antonio Ascierto
Lorenzo Borgognoni
Gerardo Botti
Michele Guida
Paolo Marchetti
Simone Mocellin
Paolo Muto
Giuseppe Palmieri
Roberto Patuzzo
Pietro Quaglino
Ignazio Stanganelli
Corrado Caracò
Publication date
01-12-2019
Publisher
BioMed Central
Keywords
Melanoma
Melanoma
Published in
Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-019-2012-2

Other articles of this Issue 1/2019

Journal of Translational Medicine 1/2019 Go to the issue