Melanoma Overview

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Melanoma Overview

Contents 

Overview
 Prognosis
 Follow-up
 Recurrence
 Prevention
 Diagnosis
 Melanoma Cancer Staging
 Surgery
 Observation
 Pharmacological Therapy
 Radiation Therapy
 Patient Education
 Guideline References

OVERVIEW

  • Melanoma is a form of skin cancer that arises from melanocytic cells w/c make the pigment melanin that colors the skin
    • May also occur in mucosal surfaces or other sites where neural crest cells migrate eg oral, genital, & rectal mucosa, eyes & nail beds
  • Predominantly occurs in adults, commonly on extremities in women & on trunk or head & neck in men
  • Metastases are via lymphatic & hematogenous routes
    • Common sites of metastases are under the skin, liver, lungs, brain, & bone
    • In-transit metastases are skin or subcutaneous intralymphatic tumors that develop between the primary tumor & draining lymph nodes (LN)
  • Malignant melanoma may regress spontaneously but complete regression is <1%
  • Risk factors include:
    • Sun exposure
    • Fair skin & freckling: Less commonly, dark-skinned individuals may have melanoma & the nail beds, palms, & soles are frequently affected
    • Family & personal history of melanoma
    • Suppressed immune system
    • Environmental exposures [ultraviolet A (UVA) or psoralen plus UVA (PUVA) therapies]
    • Increased numbers of nevi & pigmentation, eg familial atypical mole-melanoma syndrome, giant congenital nevi, dysplastic nevus syndrome
  • Malignant transformation in a nevus includes changes in size & shape including border changes, discoloration, changes in consistency, presence of inflammation, & satellites
    • Deep invasion of the skin by the melanoma is shown by an increase in size, ulceration, darkening, or bleeding
Cellular Classification of Melanoma
  • Clinicopathologic cellular subtypes of malignant melanoma are descriptive terms & are w/o significance prognostically or therapeutically
  • Superficial spreading: Most common subtype, starts as an initially slow-growing, asymptomatic, brown macule or plaque w/ irregular borders & changes in size, shape, & color
  • Nodular: Second most common subtype, a rapidly enlarging, vertically growing, blue or gray to black nodule that may ulcerate
  • Lentigo maligna & lentigo maligna melanoma: Begin as irregular tan macules that grow slowly to become larger lesions
    • When normal & malignant melanocytes are limited to the epidermis, it is called lentigo maligna; when it extends into the dermis, it is then called lentigo maligna melanoma
    • Most often occur in older people w/ heavy sun exposure, in the head & neck area, & in non-melanoma skin cancer
  • Acral-lentiginous: Has a similar appearance as superficial spreading melanoma & histologic picture as lentigo maligna melanoma
    • Develops on the palms, soles, & subungual skin
    • Equally common in dark-skinned individuals & may not be related to UV exposure
  • Unusual variants of melanoma: Subungual, mucosal lentiginous, amelanotic, desmoplastic, verrucous
Molecular Classification of Melanoma
  • Molecular subtypes of melanoma resulted from identification of activating mutations in the mitogen-activated protein kinase pathway & are the targets of drug therapy
  • BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the most common mutation & occurs in superficial spreading & nodular melanoma
    • Majority have a substitution at position 600 BRAF (V600E)
  • NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog] also occurs in superficial spreading & nodular melanoma
  • C-KIT mutation or increased copy number & CDK4 (cyclin-dependent kinase 4) mutation are seen in mucosal & acral melanomas
    • C-KIT mutation occurs in lentigo maligna melanoma & is the most common subtype in Asians and African Americans

Below is the overview of disease management of MELANOMA:

Melanoma_1

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Management of stage I melanoma

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Management of stage II melanoma

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Management of stage III melanoma

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Management of stage IV melanoma

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PROGNOSIS

  • Important prognostic factors include the Breslow depth, ulceration, mitotic rate, SLN status, & systemic metastasis
    • Breslow depth & mitotic rate are strong survival predictors
    • SLN status is the most significant prognostic factor for disease-specific survival in tumors >1 mm thick, though its impact on overall survival (OS) is still unclear
  • Cure rates are high in early superficial lesions but are low w/ ulceration & deeper levels of tumor, vascular, or lymphatic invasion
  • Other significant factors include age & gender of patient
    • Younger female patients w/ extremity melanomas have better prognosis

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FOLLOW-UP

  • The purpose of follow-up is to detect recurrences & recognize new primary melanoma or additional skin tumors
  • There is no existing consensus on the optimal frequency of follow-up for patients w/ melanoma at any stage
    • However, it seems logical to tailor follow-up intervals based on individual risk
      • Patients w/ the highest risk of recurrence or of developing new primary melanomas will need to be seen more frequently than those w/ lower risk, particularly in the 1st 2 yr
  • History & physical examination are significant components of follow-ups
    • Recommended to be performed at least annually
    • Comprehensive assessment of skin & LNs is done; findings help direct further workup
    • For Stage IA-IIA NED, history & PE w/ emphasis on the regional nodes & skin should be performed every 6-12 mth for 5 yr, then annually
    • For Stage IIB-IV NED, history & PE should be performed every 3-6 mth for 2 yr, every 3-12 mth for 3 yr, then annually
      • Chest x-ray, CT scan, &/or PET/CT scans every 3-12 mth, & cranial MRI annually may be requested to screen for metastasis/recurrence
  • Routine surveillance lab tests & imaging studies in asymptomatic patients are generally not helpful & not recommended, though it may be used to check signs and symptoms
    • May consider imaging studies in high-risk patients but its impact on survival has not been shown
    • Consider ultrasound of regional LN when PE of LN is uncertain, in patients who were offered SLNB but did not undergo the procedure, in SLNB-positive patients who did not have CLND
    • Serum LDH is an important survival predictor in stage IV disease, but serum S-100 has a higher disease progression specificity & is the most accurate blood test for follow-up of patients
  • Follow-up & additional workup of patients on adjuvant or palliative therapy should depend on the particular therapy prescribed

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RECURRENCE

  • Type of recurrent disease is confirmed through biopsy or FNA; workup includes baseline imaging for staging
  • For persistent disease or true recurrence of local scar (indicated by positive in situ &/or radial phase of growth), may do re-excision of tumor & consider SLNB or lymphatic mapping
    • Treatment recommendations should depend on stage of recurrence
  • For local, satellite, &/or in-transit recurrence, kindly refer to the Management of Stage III Melanoma algorithm above for treatment recommendations
  • For nodal recurrence, treatment is as follows:
    • W/o prior dissection: May do CLND followed by adjuvant therapy w/ clinical trial, observation or interferon alfa; consider radiation to nodal basin in selected patients
    • W/ prior dissection:
      • If resectable, may do CLND then consider adjuvant therapy as above
      • If incompletely resected, unresectable, or w/ systemic disease, consider clinical trial, systemic therapy, radiation, or supportive care

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PREVENTION

  • Patients should be instructed on the following:
    • Sunburn avoidance
    • Prolonged, unprotected, sun or artificial UV exposure
    • Lifelong, regular, skin & LN self-examinations
      • Patients should be educated on monthly self-examinations for detection & recognition of LN enlargement

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Version: 24 Feb 2016

Guideline References:
  1. Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2011 Nov;65(5):1032-1047. http://pic2.cmt.com.cn/WebImages/Res/20130528/20130528_777961e9-aab4-432d-9349-860041357fe1.pdf. Accessed 19 Dec 2013. PMID: 21868127
  2. Coit DG, Andtbacka R, Anker CJ et al. Melanoma, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2013;11:395-407. http://www.jnccn.org/content/11/4/395.full.pdf. Accessed 08 Jan 2014. PMID: 23584343
  3. Dummer R, Guggenheim M, Arnold AW, et al. Updated Swiss guidelines for the treatment and follow-up of cutaneous melanoma. Swiss Med Wkly. 2011 Dec;141:w13320. doi: 10.4414/smw.2011.13320. Accessed 19 Dec 2013. PMID: 22180245
  4. Dummer R, Hauschild A, Guggenheim M, et al. Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii86-vii91. http://annonc.oxfordjournals.org/content/23/suppl_7/vii86.full.pdf+html. Accessed 19 Dec 2013. PMID: 22997461
  5. European Society for Medical Oncology. FDA approves pembrolizumab for advanced melanoma. ESMO. http://www.esmo.org/Oncology-News/FDA-Approves-Pembrolizumab-for-Advanced-Melanoma. 05 Sep 2014. Accessed 09 Sep 2014.
  6. Fuerst M. Metastatic melanoma: immunotherapy with pembrolizumab induces durable responses. Oncology Times. 2014 Jul;36(13):35-36. doi: 10.1097/01.COT.0000452086.09862.55. Accessed 09 Sep 2014.
  7. Melanoma. Medicines Complete. http://www.medicinescomplete.com/mc/martindale/current/1800-a4-737-j.htm#m1800-a4-814-h . 20 Aug 2010. Accessed 06 Jan 2014.
  8. National Cancer Institute: PDQ® Melanoma Treatment. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/melanoma/HealthProfessional/page9/AllPages/Print. 11 Jul 2014. Accessed 01 Sep 2014.
  9. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: melanoma. Version 4.2014. NCCN. http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Accessed 28 Aug 2014.
  10. Shenenberger DW. Cutaneous malignant melanoma: a primary care perspective. Am Fam Physician. 2012 Jan;85(2):161-168. http://www.aafp.org/afp/2012/0115/p161.html. Accessed 19 Dec 2013. PMID: 22335216
  11. Sosman JA. Melanoma treatment; advanced or metastatic melanoma (beyond the basics). UpToDate. http://www.uptodate.com/contents/melanoma-treatment-advanced-or-metastatic-melanoma-beyond-the-basics. 30 May 2013. Accessed 19 Dec 2013.
  12. Tan WW. Malignant melanoma treatment protocols. Medscape. http://emedicine.medscape.com/article/2006810-overview. 14 Jan 2014. Accessed 01 Sep 2014.
  13. Thompson JF, Scolyer RA, Kefford RF. Melanoma, a management guide for GPs. Australian Family Physician. 2012 Jul;41(7):470-473. http://www.racgp.org.au/download/documents/AFP/2012/July/201207thompson.pdf. Accessed 20 Dec 2013.
  14. Wells GL. Melanoma. The Merck Manual. http://www.merckmanuals.com/professional/dermatologic_disorders/cancers_of_the_skin/melanoma.html. May 2013. Accessed 20 Dec 2013.
  15. Wong SL, Balch CM, Hurley P, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. Journal of Clinical Oncology. 2012 Aug;30(23):2912-2917. http://jco.ascopubs.org/content/30/23/2912.full.pdf+html. Accessed 20 Dec 2013. PMID: 22778321