Investigations and follow-up for melanoma patients

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Clinical practice guidelines for the diagnosis and management of melanoma > Investigations and follow-up for melanoma patients


Background

Investigations for patients with any stage of melanoma are undertaken to determine the exact stage of the disease (whether melanoma has recurred locally or distant metastases have developed), to allow planning of the most appropriate treatments, and to permit patients to be given the best estimate of their prognosis. Investigations such as imaging and blood tests may be required for initial staging and may also be repeated as a part of a follow-up program after definitive surgical treatment.

The assessment of whether investigations should be performed can be measured in various ways; diagnostic accuracy, cost, morbidity and ease of performing the investigation. Diagnostic accuracy can be measured as being lesion based or patient based. Lesion based diagnostic accuracy assesses the number of metastatic lesions identified by an investigation and determines the specificity and sensitivity of the test. Patient based diagnostic accuracy assesses whether the investigation resulted in a treatment change for the patient.

The literature available to assess the various investigations has been poor and heterogeneous with small numbers, methodological deficiencies, inadequate descriptions of the patient group studied, whether they were of a retrospective or prospective design, the inconsistent availability of a diagnostic gold standard (biopsy or surgical pathology) and in particular for tests assessing diagnostic accuracy, not assessing both lesion based and patient based measures. This has resulted in wide ranges in sensitivity and specificity, and an inability to compare between studies. The recommendations in these sections should be considered in the light of these deficiencies.

Staging and follow up investigations, especially imaging, have previously been assessed in an era when treatment options for distant metastases were very limited. In recent years, substantial advances in systemic treatment with small molecule and immune checkpoint inhibitors have revolutionised treatment of advanced melanoma and resulted in high response rates and potential long term remissions see Systemic drug therapy. Currently available data indicate that both these types of systemic therapy are more likely to result in long term remissions when used when the amount of metastatic disease is low (measured by number of metastatic disease sites, level of LDH, presence of brain metastases, patient performance status etc). Therefore, follow up of patients at risk of developing recurrent or metastatic melanoma needs to considered in this context.

Follow-up

Ideally, routine follow-up in melanoma patients should be conducted in a cost-effective manner that has been scientifically proven to be beneficial. Unfortunately, however, guidelines for follow-up are typically based only on opinions of experts around the world as there have been no valid randomised trials comparing different follow-up schedules and patient survival. Previous guidelines on diagnosis, therapy and follow-up of melanoma[1] and systematic reviews of follow-up schedules were reviewed for these guidelines.[2][3] This section will focus on the follow up of asymptomatic patients with stages I-III melanoma after definitive treatment and not patients with stage IV disease. The reason for this is that patients with stage IV melanoma can be considered in one of two groups for the purposes of follow up: under active treatment where follow up with the treating doctor, including investigations, is aimed at determining treatment efficacy; or patients who are not undergoing active therapy either due to disease volume too limited to be considered for active therapy or those undergoing supportive care. The latter group may have follow up or investigations on an individual basis at the discretion of the patient and the treating doctor. Follow up of stage IV melanoma patients is considered in Systemic drug therapy.

The main purpose of follow-up is to detect recurrences quickly so that early treatment can be undertaken. This assumes that earlier treatment is likely to result in improvements in regional disease control, quality of life and survival. Therefore, follow-up should be mainly prognosis-oriented but should also include the detection of new invasive primary melanomas. The reported incidence of new primaries ranges from 2–8%.[2][3][4] The rate of second primary invasive melanomas is relatively constant over twenty years of follow-up at 6.01 per 1,000 person-years indicating a high, constant lifetime risk of second primary invasive melanoma.[5] This risk does not diminish over time and does not differ significantly between patients first diagnosed with lentigo maligna, in situ melanoma or invasive melanoma. The risk is even higher for patients with a parental history of melanoma.[6] A second invasive melanoma is most commonly thinner than the initial primary melanoma and has a more favourable prognosis.[7] However, a Queensland population-based study of 32,238 patients found that the hazard ratio of death within 10 years from melanoma was two times higher for those with two melanomas and nearly three times higher when three melanomas were diagnosed compared with people with a single melanoma.[8] In general, subsequent primary invasive melanomas are more likely to occur at the same body site as the initial invasive or in situ melanoma.[9] The rate of occurrence of a subsequent in-situ melanoma is about four times higher than the risk of a subsequent invasive melanoma,[10] but most series do not recommend follow-up for in-situ melanomas.[11]



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References

  1. Pflugfelder A, Kochs C, Blum A, Capellaro M, Czeschik C, Dettenborn T, et al. Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma". J Dtsch Dermatol Ges 2013 Aug;11 Suppl 6:1-116, 1-126 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24028775.
  2. 2.0 2.1 Francken AB, Bastiaannet E, Hoekstra HJ. Follow-up in patients with localised primary cutaneous melanoma. Lancet Oncol 2005 Aug;6(8):608-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16054572.
  3. 3.0 3.1 Nieweg OE, Kroon BB. The conundrum of follow-up: should it be abandoned? Surg Oncol Clin N Am 2006 Apr;15(2):319-30 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16632217.
  4. Ferrone CR, Ben Porat L, Panageas KS, Berwick M, Halpern AC, Patel A, et al. Clinicopathological features of and risk factors for multiple primary melanomas. JAMA 2005 Oct 5;294(13):1647-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16204664.
  5. McCaul KA, Fritschi L, Baade P, Coory M. The incidence of second primary invasive melanoma in Queensland, 1982-2003. Cancer Causes Control 2008 Jun;19(5):451-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18167620.
  6. Zhang H, Bermejo JL, Sundquist J, Hemminki K. Modification of second cancer risk after malignant melanoma by parental history of cancer. Br J Cancer 2008 Aug 5;99(3):536-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18628759.
  7. Jones MS, Torisu-Itakura H, Flaherty DC, Schoellhammer HF, Lee J, Sim MS, et al. Second Primary Melanoma: Risk Factors, Histopathologic Features, Survival, and Implications for Follow-Up. Am Surg 2016 Oct;82(10):1009-1013 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27779995.
  8. Youlden DR, Baade PD, Soyer HP, Youl PH, Kimlin MG, Aitken JF, et al. Ten-Year Survival after Multiple Invasive Melanomas Is Worse than after a Single Melanoma: a Population-Based Study. J Invest Dermatol 2016 Nov;136(11):2270-2276 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27019458.
  9. Youlden DR, Youl PH, Soyer HP, Aitken JF, Baade PD. Distribution of subsequent primary invasive melanomas following a first primary invasive or in situ melanoma Queensland, Australia, 1982-2010. JAMA Dermatol 2014 May;150(5):526-34 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25093216.
  10. Dicker TJ, Kavanagh GM, Herd RM, Ahmad T, McLaren KM, Chetty U, et al. A rational approach to melanoma follow-up in patients with primary cutaneous melanoma. Scottish Melanoma Group. Br J Dermatol 1999 Feb;140(2):249-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10233217.
  11. Roberts DL, Anstey AV, Barlow RJ, Cox NH, et al. U.K. guidelines for the management of cutaneous melanoma. Br J Dermatol 2002 Jan 1;146(1):7-17 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11841361.