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Stage IV Skin Cancer

MedGen UID:
233536
Concept ID:
C1336439
Neoplastic Process
Synonyms: Carcinoma of Skin Stage IV; Carcinoma of the Skin Stage IV; Skin Cancer Stage IV; Skin Carcinoma Stage IV; Stage IV Skin Cancer AJCC v7; Stage IV Skin Carcinoma

Definition

Stage IV includes: (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T Any, N3, M0); (T4, N Any, M0); (T Any, N Any, M1). T1: Tumor 2 cm or less in greatest dimension with less than two high-risk features. T2: Tumor size greater than 2 cm in greatest dimension or tumor of any size with two or more high-risk features. T3: Tumor with invasion of maxilla, mandible, orbit, or temporal bone. T4: Tumor with invasion of skeleton or perineural invasion of skull base. N0: No regional lymph node metastasis. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M1: Distant metastases. (AJCC 7th Ed.) [from NCI]

Professional guidelines

PubMed

Seth R, Agarwala SS, Messersmith H, Alluri KC, Ascierto PA, Atkins MB, Bollin K, Chacon M, Davis N, Faries MB, Funchain P, Gold JS, Guild S, Gyorki DE, Kaur V, Khushalani NI, Kirkwood JM, McQuade JL, Meyers MO, Provenzano A, Robert C, Santinami M, Sehdev A, Sondak VK, Spurrier G, Swami U, Truong TG, Tsai KK, van Akkooi A, Weber J
J Clin Oncol 2023 Oct 20;41(30):4794-4820. Epub 2023 Aug 14 doi: 10.1200/JCO.23.01136. PMID: 37579248
Huuhtanen J, Kasanen H, Peltola K, Lönnberg T, Glumoff V, Brück O, Dufva O, Peltonen K, Vikkula J, Jokinen E, Ilander M, Lee MH, Mäkelä S, Nyakas M, Li B, Hernberg M, Bono P, Lähdesmäki H, Kreutzman A, Mustjoki S
J Clin Invest 2023 Mar 15;133(6) doi: 10.1172/JCI164809. PMID: 36719749Free PMC Article
Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Basset-Seguin N, Bastholt L, Bataille V, Del Marmol V, Dréno B, Fargnoli MC, Forsea AM, Grob JJ, Hoeller C, Kaufmann R, Kelleners-Smeets N, Lallas A, Lebbé C, Lytvynenko B, Malvehy J, Moreno-Ramirez D, Nathan P, Pellacani G, Saiag P, Stratigos AJ, Van Akkooi ACJ, Vieira R, Zalaudek I, Lorigan P; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC)
Eur J Cancer 2022 Jul;170:256-284. Epub 2022 May 24 doi: 10.1016/j.ejca.2022.04.018. PMID: 35623961

Recent clinical studies

Etiology

Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I
Cochrane Database Syst Rev 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2. PMID: 36648215Free PMC Article
Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A
Med Sci (Basel) 2021 Oct 20;9(4) doi: 10.3390/medsci9040063. PMID: 34698235Free PMC Article
Pérez LL, Bashline B
FP Essent 2019 Jun;481:11-16. PMID: 31188547
Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Chiarion-Sileni V, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Moutouh-de Parseval LA, Pickard MD, Sandor V, Robert C, Flaherty KT
Lancet Oncol 2018 May;19(5):603-615. Epub 2018 Mar 21 doi: 10.1016/S1470-2045(18)30142-6. PMID: 29573941
Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbé C, Linette GP, Milella M, Brownell I, Lewis KD, Lorch JH, Chin K, Mahnke L, von Heydebreck A, Cuillerot JM, Nghiem P
Lancet Oncol 2016 Oct;17(10):1374-1385. Epub 2016 Sep 1 doi: 10.1016/S1470-2045(16)30364-3. PMID: 27592805Free PMC Article

Diagnosis

Wollina U
Dermatol Ther 2022 Dec;35(12):e15966. Epub 2022 Nov 16 doi: 10.1111/dth.15966. PMID: 36336954
Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Basset-Seguin N, Bastholt L, Bataille V, Del Marmol V, Dréno B, Fargnoli MC, Forsea AM, Grob JJ, Hoeller C, Kaufmann R, Kelleners-Smeets N, Lallas A, Lebbé C, Lytvynenko B, Malvehy J, Moreno-Ramirez D, Nathan P, Pellacani G, Saiag P, Stratigos AJ, Van Akkooi ACJ, Vieira R, Zalaudek I, Lorigan P; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC)
Eur J Cancer 2022 Jul;170:256-284. Epub 2022 May 24 doi: 10.1016/j.ejca.2022.04.018. PMID: 35623961
Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A
Med Sci (Basel) 2021 Oct 20;9(4) doi: 10.3390/medsci9040063. PMID: 34698235Free PMC Article
Pérez LL, Bashline B
FP Essent 2019 Jun;481:11-16. PMID: 31188547
Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, Lazar AJ, Faries MB, Kirkwood JM, McArthur GA, Haydu LE, Eggermont AMM, Flaherty KT, Balch CM, Thompson JF; for members of the American Joint Committee on Cancer Melanoma Expert Panel and the International Melanoma Database and Discovery Platform
CA Cancer J Clin 2017 Nov;67(6):472-492. Epub 2017 Oct 13 doi: 10.3322/caac.21409. PMID: 29028110Free PMC Article

Therapy

Patel SP, Othus M, Chen Y, Wright GP Jr, Yost KJ, Hyngstrom JR, Hu-Lieskovan S, Lao CD, Fecher LA, Truong TG, Eisenstein JL, Chandra S, Sosman JA, Kendra KL, Wu RC, Devoe CE, Deutsch GB, Hegde A, Khalil M, Mangla A, Reese AM, Ross MI, Poklepovic AS, Phan GQ, Onitilo AA, Yasar DG, Powers BC, Doolittle GC, In GK, Kokot N, Gibney GT, Atkins MB, Shaheen M, Warneke JA, Ikeguchi A, Najera JE, Chmielowski B, Crompton JG, Floyd JD, Hsueh E, Margolin KA, Chow WA, Grossmann KF, Dietrich E, Prieto VG, Lowe MC, Buchbinder EI, Kirkwood JM, Korde L, Moon J, Sharon E, Sondak VK, Ribas A
N Engl J Med 2023 Mar 2;388(9):813-823. doi: 10.1056/NEJMoa2211437. PMID: 36856617Free PMC Article
Gross ND, Miller DM, Khushalani NI, Divi V, Ruiz ES, Lipson EJ, Meier F, Su YB, Swiecicki PL, Atlas J, Geiger JL, Hauschild A, Choe JH, Hughes BGM, Schadendorf D, Patel VA, Homsi J, Taube JM, Lim AM, Ferrarotto R, Kaufman HL, Seebach F, Lowy I, Yoo SY, Mathias M, Fenech K, Han H, Fury MG, Rischin D
N Engl J Med 2022 Oct 27;387(17):1557-1568. Epub 2022 Sep 12 doi: 10.1056/NEJMoa2209813. PMID: 36094839Free PMC Article
Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Butler MO, Hill A, Márquez-Rodas I, Haanen JBAG, Guidoboni M, Maio M, Schöffski P, Carlino MS, Lebbé C, McArthur G, Ascierto PA, Daniels GA, Long GV, Bas T, Ritchings C, Larkin J, Hodi FS
J Clin Oncol 2022 Jan 10;40(2):127-137. Epub 2021 Nov 24 doi: 10.1200/JCO.21.02229. PMID: 34818112Free PMC Article
Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A
Med Sci (Basel) 2021 Oct 20;9(4) doi: 10.3390/medsci9040063. PMID: 34698235Free PMC Article
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD
N Engl J Med 2015 Jul 2;373(1):23-34. Epub 2015 May 31 doi: 10.1056/NEJMoa1504030. PMID: 26027431Free PMC Article

Prognosis

Qian DC, Kleber T, Brammer B, Xu KM, Switchenko JM, Janopaul-Naylor JR, Zhong J, Yushak ML, Harvey RD, Paulos CM, Lawson DH, Khan MK, Kudchadkar RR, Buchwald ZS
Lancet Oncol 2021 Dec;22(12):1777-1786. Epub 2021 Nov 12 doi: 10.1016/S1470-2045(21)00546-5. PMID: 34780711
Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A
Med Sci (Basel) 2021 Oct 20;9(4) doi: 10.3390/medsci9040063. PMID: 34698235Free PMC Article
Topalian SL, Bhatia S, Amin A, Kudchadkar RR, Sharfman WH, Lebbé C, Delord JP, Dunn LA, Shinohara MM, Kulikauskas R, Chung CH, Martens UM, Ferris RL, Stein JE, Engle EL, Devriese LA, Lao CD, Gu J, Li B, Chen T, Barrows A, Horvath A, Taube JM, Nghiem P
J Clin Oncol 2020 Aug 1;38(22):2476-2487. Epub 2020 Apr 23 doi: 10.1200/JCO.20.00201. PMID: 32324435Free PMC Article
Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, Lazar AJ, Faries MB, Kirkwood JM, McArthur GA, Haydu LE, Eggermont AMM, Flaherty KT, Balch CM, Thompson JF; for members of the American Joint Committee on Cancer Melanoma Expert Panel and the International Melanoma Database and Discovery Platform
CA Cancer J Clin 2017 Nov;67(6):472-492. Epub 2017 Oct 13 doi: 10.3322/caac.21409. PMID: 29028110Free PMC Article
Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK
J Clin Oncol 2009 Dec 20;27(36):6199-206. Epub 2009 Nov 16 doi: 10.1200/JCO.2009.23.4799. PMID: 19917835Free PMC Article

Clinical prediction guides

Gross ND, Miller DM, Khushalani NI, Divi V, Ruiz ES, Lipson EJ, Meier F, Su YB, Swiecicki PL, Atlas J, Geiger JL, Hauschild A, Choe JH, Hughes BGM, Schadendorf D, Patel VA, Homsi J, Taube JM, Lim AM, Ferrarotto R, Kaufman HL, Seebach F, Lowy I, Yoo SY, Mathias M, Fenech K, Han H, Fury MG, Rischin D
N Engl J Med 2022 Oct 27;387(17):1557-1568. Epub 2022 Sep 12 doi: 10.1056/NEJMoa2209813. PMID: 36094839Free PMC Article
Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Butler MO, Hill A, Márquez-Rodas I, Haanen JBAG, Guidoboni M, Maio M, Schöffski P, Carlino MS, Lebbé C, McArthur G, Ascierto PA, Daniels GA, Long GV, Bas T, Ritchings C, Larkin J, Hodi FS
J Clin Oncol 2022 Jan 10;40(2):127-137. Epub 2021 Nov 24 doi: 10.1200/JCO.21.02229. PMID: 34818112Free PMC Article
Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A
Med Sci (Basel) 2021 Oct 20;9(4) doi: 10.3390/medsci9040063. PMID: 34698235Free PMC Article
Topalian SL, Bhatia S, Amin A, Kudchadkar RR, Sharfman WH, Lebbé C, Delord JP, Dunn LA, Shinohara MM, Kulikauskas R, Chung CH, Martens UM, Ferris RL, Stein JE, Engle EL, Devriese LA, Lao CD, Gu J, Li B, Chen T, Barrows A, Horvath A, Taube JM, Nghiem P
J Clin Oncol 2020 Aug 1;38(22):2476-2487. Epub 2020 Apr 23 doi: 10.1200/JCO.20.00201. PMID: 32324435Free PMC Article
Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, Manne S, Kraya AA, Wubbenhorst B, Dorfman L, D'Andrea K, Wenz BM, Liu S, Chilukuri L, Kozlov A, Carberry M, Giles L, Kier MW, Quagliarello F, McGettigan S, Kreider K, Annamalai L, Zhao Q, Mogg R, Xu W, Blumenschein WM, Yearley JH, Linette GP, Amaravadi RK, Schuchter LM, Herati RS, Bengsch B, Nathanson KL, Farwell MD, Karakousis GC, Wherry EJ, Mitchell TC
Nat Med 2019 Mar;25(3):454-461. Epub 2019 Feb 25 doi: 10.1038/s41591-019-0357-y. PMID: 30804515Free PMC Article

Recent systematic reviews

Seth R, Agarwala SS, Messersmith H, Alluri KC, Ascierto PA, Atkins MB, Bollin K, Chacon M, Davis N, Faries MB, Funchain P, Gold JS, Guild S, Gyorki DE, Kaur V, Khushalani NI, Kirkwood JM, McQuade JL, Meyers MO, Provenzano A, Robert C, Santinami M, Sehdev A, Sondak VK, Spurrier G, Swami U, Truong TG, Tsai KK, van Akkooi A, Weber J
J Clin Oncol 2023 Oct 20;41(30):4794-4820. Epub 2023 Aug 14 doi: 10.1200/JCO.23.01136. PMID: 37579248
Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I
Cochrane Database Syst Rev 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2. PMID: 36648215Free PMC Article
Stahlie EHA, Mulder EEAP, Reijers S, Balduzzi S, Zuur CL, Klop WMC, van der Hiel B, Van de Wiel BA, Wouters MWJM, Schrage YM, van Houdt WJ, Grunhagen DJ, van Akkooi ACJ
Crit Rev Oncol Hematol 2022 Jul;175:103705. Epub 2022 May 13 doi: 10.1016/j.critrevonc.2022.103705. PMID: 35569723
Zikry J, Chapman LW, Korta DZ, Smith J
Dermatol Surg 2017 Jun;43(6):765-770. doi: 10.1097/DSS.0000000000001072. PMID: 28291064
Dunn J, Watson M, Aitken JF, Hyde MK
Psychooncology 2017 Nov;26(11):1722-1731. Epub 2016 Nov 7 doi: 10.1002/pon.4290. PMID: 27696578

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