The incidence of melanoma is increasing worldwide. In the United States, it is estimated that there will be 76,380 new cases of invasive melanoma and 68,480 cases of melanoma in situ diagnosed in the year 2016.¹ Despite an overall decline in cancer rates, melanoma is one of the few cancers with an increasing incidence.² As summarized in other chapters, many elements of contemporary diagnosis and management of melanoma are guided by decades of clinical data and experience, but there is evidence of significant variation in practice patterns.

In the setting of sufficient uncertainty (or controversy) about treatment recommendations, clinicians often refer to clinical practice guidelines when establishing treatment plans for their patients. Because of the sheer volume of medical literature clinicians are faced with, practice guidelines offer an ideal means of synthesizing data to inform evidence-based care for patients. Numerous guidelines for the treatment of melanoma exist and are readily available to clinicians (Table 19-1). Ideally, guideline development is based on a systematic review of the literature by content and methodologic experts, with thoughtful evaluation of data leading to practical recommendations for multidisciplinary patient care.

However, recent evidence suggests that guidelines (inclusive of clinical practice guidelines and consensus recommendations) formulated by various organizations vary in their quality and content.³ Suboptimal guidelines may contribute to lower quality care and this issue will merit ongoing attention as clinical outcomes are increasingly measured and followed. The clinician is advised to consider key elements of trustworthy guidelines when referencing these practice tools. The Institute of Medicine’s recent report “Clinical Practice Guidelines We Can Trust” established standards for guideline development and includes tenets such as use of systematic literature reviews, rating of strength of evidence, transparent processes, and multidisciplinary panel membership that is held to conflict of interest policies.⁴

With appropriate treatment, most melanoma patients have a favorable prognosis. Based on data from 2007, it was estimated that there were 800,000 people with a past diagnosis of melanoma in the United States alone. Follow-up care has been estimated to cost up to $500 million per year.⁵ As the number of melanoma survivors increases, surveillance considerations and follow-up care are increasingly important topics, particularly as more effective treatment options for advanced disease are developed.^6–9

Early detection of recurrent nodal or distant disease in melanoma patients is important if detection offers a survival advantage, less morbidity with treatment, or a difference in treatment approach. Historically, treatment options for patients with either stage III or stage IV disease have been minimally effective in only a small percentage of patients. Generally speaking, a lack of treatment options for those patients with recurrent disease plays a role in determination of an adequate follow-up schedule. If no survival advantage is gained by discovery of asymptomatic metastases, then time and procedure intensive follow-up schedules are not cost-effective.

During the follow-up period, patients who develop isolated regional nodal disease are treated with completion nodal dissection, with the goal to reduce tumor burden, reduce the risk of uncontrollable regional disease, and ideally provide surgical cure. Following resection, patients with stage III disease are also candidates for systemic therapy with interferon alpha-2b therapy, ipilimumab, or entrance into a clinical trial.

Traditionally, for patients with stage IV disease the role of metastasectomy has been limited, although it has been utilized in select patients with one or a small number of metastatic lesions that are relatively stable and amenable to surgical resection.

Systemic options for stage IV disease have increased dramatically over the past several years. High-dose IL-2 was previously the only systemic immunotherapy option with potential durable response for patients with metastatic melanoma. However, since 2011, several new therapies including ipilimumab, vemurafenib, dabrafenib, trametinib, pembrolizumab, and nivolumab were approved by the FDA for use in stage IV melanoma.^6–11

Ultimately, if the new systemic therapies that are currently being developed, either in isolation or in conjunction with surgical resection, are found to improve survival rates in patients with recurrent regional or distant disease, significant revisions on follow-up care and tests for melanoma patients with an increased emphasis on early detection of recurrence may be necessary.

The current goals of melanoma follow-up care include identification of additional primary lesions, monitoring for local or regional recurrence, and monitoring for the development of distant disease.

Risk of Developing a Second Primary Melanoma

The reported rate of development of multiple primary melanomas ranges within the literature from 1.2% to 8.2%.¹² There are subpopulations of melanoma patients with an increased risk for development of a second primary melanoma (SPM), particularly those with an underlying genetic mutation (such as a mutation in the tumor suppressor gene CDKN2A), patients with a family history of melanoma, or those with dysplastic nevi.^12–14 Several reports within the literature show that a SPM typically has a thinner Breslow depth than the first primary melanoma, presumably due to increased self-skin examination and increased frequency of physician skin examinations.^12,13,15,16

A review of data from over 9000 patients from the John Wayne Cancer Institute demonstrated a 3.5% rate of development of a SPM within 10 years of the first.¹⁵ A separate study of 1240 patients in Italy reported an average of 53.6 months between treatment of the first and second melanomas for patients with multiple primary lesions. A study of 4484 patients reported an 8.6% rate of multiple primary melanomas, with 59% of patients having the SPM diagnosed within 1 year of the first.¹⁴ A study of 1482 patients from the University of Michigan from 1990 to 1995 reported that 60 (4%) patients developed a SPM. Of these patients, 42% developed the SPM within 3 years, 17% developed the SPM between 3 to 7 years, and 42% developed the SPM more than 7 years after the first.¹⁷ A study of 5963 patients with stage III and stage IV melanoma from the Melanoma Institute Australia Melanoma Research Database showed that 5% of patients with stage III disease and 1% of patients with stage IV disease developed a SPM. The 6-month, 1-year, and 10-year cumulative incidence rates of SPM for patients with stage III disease were 1.2%, 1.8%, and 5.9%.¹⁸

While the majority of patients with melanoma will not go on to develop additional primary lesions, for those that do, the highest risk is likely during the first year after initial diagnosis but remains elevated for more than 20 years.¹⁸ Studies have shown that patient self-examination and physician examination are associated with identification of the SPM at an earlier Breslow depth than the first. As the prognosis of melanoma improves dramatically with early identification, patients with a history of melanoma should be educated regarding their risk and their physicians should continue to look for additional lesions, even many years after the first primary lesion has been treated.

Risk of Recurrence

In 2009, the American Joint Committee on Cancer released updated staging guidelines for melanoma.¹⁹ Prognosis for patients with melanoma depends on the stage and follow-up strategies for melanoma patients must take into consideration these differences. Higher risk patients may be considered for more intensive follow-up screening protocols.

Localized Melanoma

For localized melanoma (stages I and II), Breslow depth, ulceration status, and mitotic rate of the primary tumor are important prognostic factors. Even though the general prognosis for patients with stage I and II melanoma is excellent, reported 10-year survival rates vary considerably—93% for patients with T1aN0M0 melanoma (stage IA) and 39% for patients with T4bN0M0 melanoma (stage IIC).¹⁹