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Staging work-up and surveillance of cutaneous melanoma

Staging work-up and surveillance of cutaneous melanoma
Literature review current through: Jan 2024.
This topic last updated: Jan 03, 2023.

INTRODUCTION — Cutaneous melanoma has the potential to metastasize to any organ, including the skin, lymph nodes, subcutaneous tissues, lungs, liver, bone, brain, and visceral organs. Various laboratory tests, histologic evaluations, and imaging studies are necessary to accurately stage patients with cutaneous melanoma prior to definitive treatment and for surveillance (during therapy and after treatment completion).

Because there have been important advances in the treatment of patients with melanoma and many can be cured of their disease, it is important to accurately identify even low-volume systemic disease at initial evaluation and during surveillance. However, there are limited high-quality data that define the appropriate tests for initial evaluation and subsequent follow-up in such patients [1]. Additionally, the options for and availability of these imaging studies may also vary by institutional practice and geographic location. As such, we acknowledge that there may be variations in clinical practice and guidelines.

For patients with a confirmed pathological diagnosis of primary cutaneous melanoma, our approach to initial staging work-up and surveillance is presented here. The clinical features and diagnosis of melanoma; the tumor, node, metastasis (TNM) melanoma staging system; imaging studies used in melanoma; and clinical features, diagnosis, and management of noncutaneous (ie, mucosal, uveal, conjunctival) melanoma are discussed separately.

(See "Melanoma: Clinical features and diagnosis".)

(See "Tumor, node, metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma".)

(See "Imaging studies in melanoma".)

(See "Locoregional mucosal melanoma: Epidemiology, clinical diagnosis, and treatment".)

(See "Initial management of uveal and conjunctival melanomas".)

IMAGING MODALITIES — Available imaging modalities for patients with melanoma who are undergoing staging work-up or surveillance include (see "Imaging studies in melanoma"):

Computed tomography (CT) of the chest, abdomen, pelvis

CT of the neck is indicated for patients with primary tumors or lymph node involvement in the head and neck region

Whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT (ie, scalp to toes and all extremities)

Magnetic resonance imaging (MRI) of the brain

Nodal basin ultrasound (US) for assessment of regional lymph nodes (see 'Indications for nodal ultrasound during surveillance' below and "Evaluation and management of regional nodes in primary cutaneous melanoma")

Chest radiographs are less commonly and nonuniformly used across institutions [2]

Bone scans are not routinely used due to limited specificity and relatively low incidence of isolated melanoma bone metastases. (See "Imaging studies in melanoma", section on 'Bone metastases'.)

CT and MRI should be performed with appropriate intravenous contrast (and oral contrast for CT imaging) unless the patient has a clinical contraindication to such contrast. (See "Patient evaluation prior to oral or iodinated intravenous contrast for computed tomography" and "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging".)

STAGING WORK-UP — For patients with a new diagnosis of primary cutaneous melanoma, the purpose of initial staging work-up is to assess for disease involvement of the locoregional lymph node and distant metastases. Such information will contribute to the final disease staging (based on the American Joint Committee on Cancer [AJCC] eighth edition staging system for melanoma (table 1A-B)) and guide treatment options.

Prior to initial staging work-up, patients should have a confirmed pathological diagnosis of the primary melanoma (via biopsy or surgical excision). Depending upon Breslow depth and ulceration, some patients may undergo wide local excision and sentinel lymph node biopsy (SLNB) prior to staging work-up. These interventions are discussed in detail separately. (See "Melanoma: Clinical features and diagnosis" and "Surgical management of primary cutaneous melanoma or melanoma at other unusual sites" and "Evaluation and management of regional nodes in primary cutaneous melanoma".)

Clinically negative nodes at presentation

Melanoma in situ and clinical or pathological stage IA — Patients with melanoma in situ and clinical or pathological stage I melanoma present with no clinical evidence of lymph node involvement on physical exam (table 1A and table 1B). For those who are asymptomatic, there is no established role for routine laboratory or imaging studies. Imaging studies have limited ability to identify metastatic disease in these patients with excellent ten-year melanoma-specific survival (MSS) rates of 98 percent or greater (figure 1) [3,4]. Chest radiographs [5-10]; CT of the brain, neck, chest, abdomen, and pelvis [6,7,9-11]; and positron emission tomography (PET)-CT [12-17] have low detection rates for occult regional lymph node involvement and distant metastases and can result in false-positive imaging findings.

For patients with invasive melanoma who are symptomatic, systemic imaging may be obtained to evaluate specific signs and symptoms, as indicated. (See 'Symptomatic disease or suspected metastases' below.)

Clinical stage IIC (pT4b cN0) — Patients with a pT4b primary tumor (ie, primary tumor thickness >4 mm with ulceration) and clinically negative nodes have clinical stage IIC disease (table 1A-B). If possible, we typically obtain systemic imaging with a CT of the chest, abdomen, and pelvis to assess for metastatic disease prior to wide excision and SLNB, since these patients are at higher risk for metastatic disease than other patients who present with primary cutaneous melanoma. We also obtain a CT of the neck for those with a primary melanoma in the head and neck region. Patients with imaging studies that demonstrate no evidence of metastatic disease may proceed with planned initial definitive surgical treatment, which usually includes wide excision of the primary tumor and regional nodal evaluation with lymphatic mapping and sentinel node biopsy. (See 'Pathological stage IIC and IIIB' below.)

It is important to consider systemic imaging in patients with clinical stage IIC disease because the presence of ulceration and tumor thickness >4 mm of the primary tumor are high-risk prognostic features [1,18]. Patients with pathological stage IIC disease also have lower five- and ten-year MSS rates (82 and 75 percent, respectively (figure 1)) than those with stage IIIA disease (93 and 88 percent, respectively (figure 2)) [3] who are typically imaged for metastatic disease at diagnosis. (See "Tumor, node, metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma".)

Clinically suspicious or equivocal clinical nodes — Patients with a primary melanoma of any tumor thickness and clinically suspicious or equivocal lymph nodes on physical exam are candidates for nodal basin ultrasound (US) prior to lymph node biopsy [19]. Lymph nodes suspicious for disease on nodal basin US are typically sampled using image-guided (eg, US or CT) fine needle aspiration or core biopsy; excisional lymph node biopsy is generally not recommended. Patients with a normal nodal basin US should undergo SLNB, if clinically indicated at the time of primary tumor wide excision, based on clinical factors and pathological features of the primary tumor. (See "Evaluation and management of regional nodes in primary cutaneous melanoma".)

Any confirmed disease involvement in the lymph nodes would subsequently modify tumor stage to stage III disease and influence further imaging work-up. (See 'Following pathological lymph node assessment' below.)

Further details on the initial evaluation and treatment of regional lymph nodes in melanoma are discussed separately. (See "Evaluation and management of regional nodes in primary cutaneous melanoma".)

Clinically evident lymph nodes or in-transit/satellite metastases — For patients who present with clinically detected locoregional melanoma, such as clinically evident nodal disease or in-transit/satellite metastases (table 1A-B), we obtain systemic imaging with whole-body PET-CT prior to further regional nodal evaluation, if possible. In particular, those with an extremity primary may present with soft tissue metastases on the extremities that may be missed on CT imaging alone or physical exam. CT of the neck, chest, abdomen, and pelvis is also an option for those with primary tumors of the head, neck, and trunk who are less likely to present with metastatic disease in the extremities. We also obtain central nervous system (CNS) imaging with magnetic resonance imaging (MRI) of the brain to assess for intracranial metastases as part of staging work-up. Other indications for CNS imaging include the presence of neurologic symptoms, documented extracranial metastatic disease on initial CT imaging, or evaluation for clinical trials.

Data from observational studies [1,20-22] and several meta-analyses [23,24] support the accuracy of PET-CT in detecting metastases during the staging of patients with more extensive nodal disease. As an example, one systematic review and meta-analysis of nine studies investigating the value of PET-CT in 623 patients with stage III melanoma included a subset of 418 patients (67 percent) with clinically palpable nodes and/or in-transit disease. In this study, for all patients, the sensitivity and specificity of a staging PET-CT for detecting distant metastases were 89 percent each, respectively [24]. Additionally, a change in management based on PET-CT results was noted in 22 percent of all patients and 26 percent of those with clinically palpable nodes and/or in-transit disease. However, the interpretation of PET-CT can still be complicated by false negatives, false positives, and the identification of second primaries [1]. (See "Imaging studies in melanoma", section on 'FDG PET and PET/CT'.)

Following pathological lymph node assessment — Patients with a completed SLNB or other pathological lymph node evaluation that is either positive or negative for disease will have a confirmed pathological nodal (N) category (table 1A-B). SLNB identifies patients with clinically occult, pathologically positive sentinel lymph nodes who are at increased risk for developing metastatic disease [25]. Therefore, we assess for distant metastases (M category) using a common approach for specific groups that have similar prognoses and true-positive detection rates for metastatic disease (figure 3). In general, as prognostic stage group increases, the chances of detecting a true positive increases and false positive decreases. However, we recognize that there is significant variability in clinical practice and alternatives exist to the staging work-up suggested below.

Pathological stage IB and IIA — For patients with pathological stage IB and stage IIA melanoma who are asymptomatic, most UpToDate contributors do not obtain routine imaging studies, as the chances of detecting true metastatic disease is extremely low. Alternatively, one UpToDate contributor offers a chest radiograph and abdominal US for baseline imaging.

For symptomatic patients, systemic imaging may be obtained to evaluate specific signs and symptoms, as indicated. (See 'Symptomatic disease or suspected metastases' below.)

Pathological stage IIB and IIIA — For patients with pathological stage IIB or IIIA melanoma (table 1A-B), we obtain a CT of the chest, abdomen, and pelvis. We also obtain a CT of the neck for those with primary tumors or lymph node involvement in the head and neck region. These CT scans may also serve as baseline imaging for patients with indications for adjuvant therapy. (See "Adjuvant and neoadjuvant therapy for cutaneous melanoma", section on 'Factors that influence therapy'.)

We offer the same initial staging work-up for stage IIB and IIIA disease, which have similar prognoses and risk for metastatic disease [3]. While CT imaging is frequently obtained to stage patients with stage III disease, data are limited in those with stage IIB disease [26]. CT imaging has a low yield for detecting distant metastases, but it can often identify false-positive abnormalities at staging and thereby function as a baseline for future surveillance imaging.

We do not generally obtain a whole-body PET-CT or CNS imaging with MRI of the brain [27-29]. However, some patients may still receive such imaging in select situations, such as potential disease-related symptoms, further evaluation of equivocal findings for metastatic disease on initial CT imaging, or enrollment in clinical trials. For these imaging studies, observational data suggest low detection rates (less than 5 percent true-positive rate) [27-31] and high false-positive rates (approximately 10 percent or more) for metastatic disease in both stage IIB [32-34] and IIIA disease [35]. (See 'Symptomatic disease or suspected metastases' below and "Adjuvant and neoadjuvant therapy for cutaneous melanoma".)

Pathological stage IIC and IIIB — For patients with pathological stage IIC and IIIB melanoma, we obtain a CT of the chest, abdomen, and pelvis. We also obtain a CT of the neck for those with primary tumor or lymph nodes involving the head and neck region. Some UpToDate contributors offer the option of a whole-body PET-CT at diagnosis as a baseline imaging study to compare with future imaging studies. We do not generally obtain CNS imaging unless patients have suspected neurologic symptoms related to disease, documented extracranial metastatic disease on initial imaging, or are being evaluated for clinical trials [29].

Pathological stage IIIC and IIID — For patients with pathological stage IIIC and IIID melanoma, options for initial staging include CT of the chest, abdomen, and pelvis (and neck for those with primary tumor or lymph nodes involving the head and neck region) or whole-body PET-CT. The choice between these imaging studies is based on clinician preference and the chosen adjuvant therapy.

Some UpToDate contributors obtain whole-body PET-CT imaging in these high-risk patients to enhance the detection of distant metastatic disease.

Other contributors prefer CT imaging over PET-CT because it images lesions more accurately at baseline and can also be used as comparison for future surveillance imaging studies obtained during adjuvant therapy. Additionally, for patients actively receiving adjuvant therapy with checkpoint inhibitor immunotherapy, an active immune response could falsely increase the standardized uptake value on PET-CT in tumor tissue and create a false impression of disease progression [36]. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation", section on 'Imaging studies'.)

We obtain CNS imaging with MRI of the brain in all patients with pathological stage IIIC or IIID melanoma. (See "Imaging studies in melanoma" and 'Symptomatic disease or suspected metastases' below.)

Symptomatic disease or suspected metastases — Patients with symptomatic disease or clinically suspected systemic metastases (eg, based on physical exam, laboratory evaluation, or imaging studies obtained for other indications) should receive the following staging work-up prior to regional nodal evaluation, if possible. (See 'Symptoms of recurrence or metastatic disease' below.)

Options for cross-sectional imaging include CT of the chest, abdomen, and pelvis (and neck for those with primary tumors or lymph nodes involving the head and neck region) or whole-body PET-CT.

A serum lactate dehydrogenase (LDH) can be obtained. LDH is incorporated into the TNM staging system (for stage IV, distant metastasis [M-category], only) and is a marker of more aggressive disease in patients with distant metastasis. (See "Tumor, node, metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma".)

MRI of the brain should also be obtained in all patients with neurologic symptoms and/or suspected metastatic disease.

CT is an adequate and reliable baseline for measuring future response to therapy, in particular immunotherapy. This is discussed in detail separately. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation", section on 'Imaging studies'.)

PET-CT can be used to rule out systemic metastases in patients eligible for potentially curable resection or to evaluate an area suspicious for metastatic disease that is being targeted for biopsy [22,37-39]. In one retrospective study with 250 patients with cutaneous melanoma, PET-CT detected significantly more visceral and nonvisceral metastases (98.7 percent) versus CT (69.7 percent) [40]. Similarly, in a systematic review, PET-CT had higher sensitivity for detecting metastases in stage IIIC or IV disease versus less-advanced disease (100 versus 84 percent, respectively) [1].

Other imaging studies may also be ordered on the basis of symptoms and disease site. (See "Imaging studies in melanoma", section on 'Approach to patient imaging based on disease site'.)

SURVEILLANCE — In patients with cutaneous melanoma, the primary objective of surveillance during and after treatment is to identify locoregional recurrences that are potentially curable, second primary melanomas, and low-volume distant metastatic disease that can be effectively treated with systemic therapy. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation" and "Systemic treatment of metastatic melanoma with BRAF and other molecular alterations".)

Prior to the era of contemporary therapies for melanoma, the major value of surveillance visits was to detect locoregional recurrences that could potentially be cured with resection. With the advent of effective systemic therapies, such as immunotherapy and targeted therapy, the paradigm for surveillance continues to evolve [1]. Since there is no consensus as to the optimal strategy for surveillance, we acknowledge that there are significant variations in clinical practice [19,41,42] based on institutional practices, geographic location, available imaging resources [43,44], goals of care, and patient preferences.

Important clinical factors that influence our approach to the surveillance of treated melanoma include stage of disease, risk of recurrence, choice of therapy (eg, locoregional versus systemic treatment), and treatment response. For older adults or those with extensive comorbidities, clinicians may also take into account a patient's preferences on extent and duration of surveillance. We do not routinely use gene expression profiling to determine surveillance of cutaneous melanoma, which is discussed separately. (See "Tumor, node, metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma", section on 'Gene expression profiling and proteomics'.)

These surveillance guidelines are intended for patients without signs or symptoms of recurrence, progression, or new primary melanoma; such patients should undergo appropriate restaging work-up as clinically indicated. (See 'Staging work-up' above.)

Symptoms of recurrence or metastatic disease — All patients who are undergoing surveillance for melanoma should be educated on symptoms that could potentially indicate recurrence of melanoma or metastatic disease and warrant further work-up [45], such as:

Fatigue

Weight loss

Cutaneous, intradermal, or subcutaneous nodules

Swollen or painful lymph nodes

Shortness of breath or cough

Abdominal swelling or pain

Bone pain or fractures

Central nervous system (CNS) symptoms (eg, headaches, seizures, weakness, or numbness)

Pathological stage IA — For most patients with pathological stage I disease (table 1A and table 1B) who are asymptomatic, we offer routine physical exam, including total-body skin examination (see "Screening for melanoma in adults and adolescents", section on 'Performing skin examination') and clinical evaluation of regional lymph nodes, every six months for the first two years, then annually [19,46]; however, patients with Familial Atypical Mole and Melanoma (FAMM) syndrome or a family history suggestive of hereditary melanoma should continue to be clinically evaluated every six months. No other routine laboratory tests or imaging tests are indicated [11]. Patients may be referred to the primary care physician, dermatologist, and/or a survivorship clinic after two years and should be educated on the potential symptoms of recurrence or metastases. (See 'Symptoms of recurrence or metastatic disease' above and "Inherited susceptibility to melanoma".)

Patients should undergo continued dermatologic surveillance including total-body skin examination (see "Screening for melanoma in adults and adolescents", section on 'Performing skin examination') because of the risk of a second primary, particularly if atypical nevi are present. The incidence of a second melanoma is increased in melanoma survivors, with the cumulative risk ranging from 2 to 5 percent at periods 5 to 20 years after initial diagnosis [41,47,48]. (See "Melanoma: Epidemiology and risk factors", section on 'Personal history of melanoma' and "Screening for melanoma in adults and adolescents".)

Pathological stage IB and IIA — For patients with pathological stage IB and IIA disease who are asymptomatic (table 1A-B), we offer a physical exam, including a total-body skin examination (see "Screening for melanoma in adults and adolescents", section on 'Performing skin examination') and clinical evaluation of regional lymph nodes, every four to six months for the first two years, then annually. Follow-up can be managed by the patient's dermatologist and primary care physician; survivorship clinics are also an option. Patients should also be educated on the potential symptoms of disease recurrence. (See 'Symptoms of recurrence or metastatic disease' above.)

UpToDate contributors diverge on the use of routine laboratory and imaging tests. Some contributors do not offer routine laboratory testing or imaging studies as part of surveillance because recurrences are less common in this population [49]. Most retrospective series also demonstrate that the majority of recurrences (80 to 90 percent) are discovered by history and physical examination and not by imaging or laboratory studies [45,50-53].

However, other contributors obtain a complete blood count (CBC), serum lactate dehydrogenase (LDH) [44], chest radiograph, and/or abdominal ultrasound (US) at each visit. While such studies may detect metastatic disease early, the overall yield is low. Routine blood tests (such as CBC, liver function tests, serum LDH), chest radiographs, and other imaging studies detect distant metastases in less than 10 percent of patients with early-stage disease [51,54].

Pathological stage IIB and IIIA — Patients with stage IIB or IIIA disease (table 1A-B) who are receiving adjuvant therapy should initiate surveillance at the time they start treatment. Otherwise, we use a similar surveillance strategy for patients receiving adjuvant therapy and those on surveillance alone. (See "Adjuvant and neoadjuvant therapy for cutaneous melanoma".)

A physical exam, including a total-body skin examination (see "Screening for melanoma in adults and adolescents", section on 'Performing skin examination') and clinical evaluation of regional lymph nodes, every three to four months for the first two to three years, then every six months for up to five years. After five years, patients can continue with a physical exam annually with their dermatologist and primary care physician (with or without an oncologist) for surveillance of second or subsequent primary melanoma. (See "Screening for melanoma in adults and adolescents", section on 'Performing skin examination'.)

CT of the chest, abdomen, and pelvis (and neck for those with primary tumors or lymph nodes involvement of the head and neck region) every six months for up to three years, then annually for up to five years. After five years, asymptomatic patients may be offered the option to discontinue imaging surveillance, after an informed discussion about the potential risks of recurrence.

Regional nodal US for those with a positive sentinel lymph node biopsy (SLNB) who did not undergo completion lymph node dissection (CLND). (See 'Indications for nodal ultrasound during surveillance' below.)

We do not obtain CNS imaging unless neurologic symptoms are present or extracranial metastatic disease is identified on other imaging studies.

Pathological stage IIC, IIIB, IIIC, IIID

General approach — Patients with stage IIC, IIIB, IIIC, and IIID disease are at higher risk for developing locoregional or metastatic disease [52,55-57]. Therefore, surveillance of these patients typically involves more frequent follow-up and imaging studies than those with less-advanced disease. Patients who are receiving adjuvant therapy should initiate surveillance at the start of treatment. Our approach is as follows:

A physical exam, including a total-body skin examination (see "Screening for melanoma in adults and adolescents", section on 'Performing skin examination') and clinical evaluation of regional lymph nodes, and CT of the chest, abdomen, and pelvis (and neck for those with primary tumors or lymph node involvement of the head and neck region) every three months for up the first three years, then every six months for up to five years.

After five years, patients can continue with a physical exam annually with their dermatologist and primary care physician (with or without an oncologist) for surveillance of second or subsequent primary melanoma. Additionally, asymptomatic patients may be offered the option to discontinue imaging surveillance, after an informed discussion about the potential risk of recurrence, which is estimated to be 5 percent or less [58].

CNS imaging is typically not indicated except for patients with neurologic symptoms or extracranial systemic disease recurrence. As an example, one observational study demonstrated limited utility for surveillance using MRI of the brain among patients with asymptomatic and continuously disease-free stage IIB-IIIC melanoma [59].

Regional nodal US for those with a positive SLNB who did not undergo CLND. (See 'Indications for nodal ultrasound during surveillance' below.)

Regular surveillance with CT has consistent sensitivity and specificity over five years of follow-up in the contemporary era of systemic therapy for melanoma. As an example, in one retrospective study, 332 patients with stage IIIA to IIID melanoma received imaging surveillance with either CT or positron emission tomography (PET)-CT on a structured 6- and 12-month follow-up schedule [60]. Using this schedule, CT imaging had a consistent sensitivity and specificity of 79 and 88 percent, respectively.

Patients with in-transit/satellite metastases — For patients with in-transit/satellite metastases, surveillance is similar to those with pathological stage IIC, IIIB, IIIC, and IIID disease. (See 'Pathological stage IIC, IIIB, IIIC, IIID' above.)

One alternative approach is to obtain a whole-body fluorodeoxyglucose (FDG) PET-CT twice a year, in lieu of the surveillance CT scan planned for that time, to assess more broadly for soft tissue metastases in the trunk and extremities [60]. (See 'Indications for PET-CT during surveillance' below.)

Distant metastatic disease — Surveillance and early disease detection may be of consequence in the contemporary era of therapy for distant metastatic melanoma (algorithm 1), where some patients can achieve complete responses and durable treatment-free survival. Our approach to surveillance in patients with metastatic disease is mainly based upon their treatment response. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation", section on 'Assessing treatment response'.)

In an observational study (PHAMOUS) of 1013 patients with distant metastasis diagnosed and treated in either Australia or the United States, median overall survival (OS) was higher for patients in the United States than Australia (16 versus 10 months) [44]. This OS benefit was related to a six-month lead time in the detection of such metastases and was largely attributable to more aggressive surveillance in the United States, including more frequent visits and imaging surveillance.

Patients with stable disease or partial responses to therapy — Surveillance is individualized for patients with metastatic disease with stable or partial responses to initial systemic therapy (algorithm 1). Our general approach is to obtain a physical exam and cross-sectional imaging every three months. Options for imaging include CT of the chest, abdomen, and pelvis (and neck for those with primary tumors or lymph node involvement of the head and neck region) or whole-body PET-CT. The choice between these options is based upon the location of the tumors, timing of therapy, scan availability, and clinician preference.

For patients on immunotherapy, some UpToDate contributors prefer CT scans to precisely measure tumor lesions and their response to therapy, especially during the first 12 weeks of therapy. PET-CT can be misleading during this early treatment period due to possible therapy-related immune responses. A whole-body PET-CT can be obtained at least once, ideally twelve months after initiating therapy, to identify a complete metabolic response to therapy (eg, residual tumor lesions on CT scans that are no longer FDG-avid) [61] and to more broadly assess the trunk and extremities for evidence of disease. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation", section on 'Imaging studies'.)

Patients with extracranial distant metastatic disease only should be monitored for the development of CNS metastases. In these patients, we obtain magnetic resonance imaging (MRI) of the brain every six months for up to three years from the start of systemic therapy, then annually up to five years. After five years, patients may opt to discontinue CNS imaging after informed discussion of the risk of recurrence. MRI should also be obtained for restaging in patients who develop extracranial metastatic disease progression. Surveillance for those receiving therapy directed at CNS metastases is discussed separately. (See "Management of brain metastases in melanoma", section on 'Surveillance and recurrent disease'.)

Patients with complete response to therapy — Patients treated with checkpoint inhibitor immunotherapy have the opportunity for treatment-free survival. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation", section on 'Treatment-free survival'.)

For patients with metastatic disease who achieve a complete response to therapy and have discontinued treatment, our general surveillance approach is to repeat CT of the chest, abdomen, and pelvis (and neck as indicated) every three months and MRI of the brain every six months for the first two years, then every six months for the third year, and then annually for years four and five. After year five, patients may discontinue imaging surveillance after an informed discussion on recurrence risk.

Special considerations

Indications for PET-CT during surveillance — Indications for obtaining a PET-CT during surveillance include the following:

In-transit/satellite disease, particularly when the primary melanoma is located on an extremity. (See 'Patients with in-transit/satellite metastases' above.)

To assess for a complete metabolic response to therapy. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation", section on 'Imaging studies'.)

To evaluate lesions that are equivocal on CT for evidence of FDG-uptake more consistent with disease recurrence and require further imaging follow-up.

To rule out additional systemic metastases in patients who are contemplating surgery for isolated or oligometastatic disease.

When used as part of surveillance, we prefer a full diagnostic CT scan as part of the PET-CT study, including contrast administration. Further technical details on this approach are discussed separately. (See "Imaging studies in melanoma", section on 'FDG PET and PET/CT'.)

PET-CT or PET-MRI may be used outside the United States as part of surveillance [62], but there are limited data supporting its routine use. Further data on the use of PET-MRI for imaging melanoma are discussed separately. (See "Imaging studies in melanoma", section on 'MRI and PET/MRI' and "Imaging studies in melanoma", section on 'Brain'.)

Several systematic reviews suggest that surveillance PET-CT has reasonable accuracy to detect metastatic disease, with sensitivity ranging from 85 to 96 percent and specificity ranging from 79 to 95 percent [1,63]. However, patients should be informed that an OS advantage with surveillance PET-CT imaging has not been established, and that the false-positive rate related to the stage of the disease can be relatively high (ranging from 10 to 15 percent) [17,32,64].

Indications for nodal ultrasound during surveillance — For any patients with a positive SLNB who do not undergo a CLND, we obtain regional lymph node US every four months during the first two years, and every six months for up to five years. Alternatively, patients on surveillance who are being evaluated every three months may be offered nodal US at every other visit. Nodal US surveillance may be discontinued after five years after an informed discussion with the patient about the potential risks of recurrence.

This approach is preferred over CLND and is based on the active surveillance protocol used for patients in the observation arm of the Multicenter Selective Lymphadenectomy (MSLT) and DeCOG-SLT trials, which are discussed separately. (See "Evaluation and management of regional nodes in primary cutaneous melanoma".)

GENETIC TESTING — During staging work-up and surveillance, patients may be identified who are at risk for hereditary melanoma syndromes. The indications to refer such patients for genetic testing are discussed separately. (See "Inherited susceptibility to melanoma", section on 'Genetic testing'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Melanoma screening, prevention, diagnosis, and management".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Melanoma treatment; localized melanoma (Beyond the Basics)" and "Patient education: Melanoma treatment; advanced or metastatic melanoma (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Staging work-up – Variability exists for the staging work-up of patients with cutaneous melanoma. (See 'Introduction' above.)

For those with a confirmed pathological diagnosis of primary melanoma (table 1A-B), our approach is as follows (see 'Staging work-up' above):

Clinically negative lymph nodes at presentation

-Melanoma in situ and clinical/pathological stage IA – For asymptomatic patients, there is no established role for routine laboratory or imaging studies. (See 'Melanoma in situ and clinical or pathological stage IA' above.)

-Clinical stage IIC (pT4 cN0) – CT of the chest, abdomen, and pelvis (CAP) and neck (the latter for primary tumors or regional nodes involving the head and neck region) prior to wide excision and sentinel lymph node biopsy (SLNB), if possible. (See 'Clinical stage IIC (pT4b cN0)' above.)

Clinically evident nodal disease or in-transit/satellite metastases – For patients with an extremity primary, whole-body positron emission tomography (PET)-CT and magnetic resonance imaging (MRI) of the brain prior to further regional nodal evaluation, if possible. CT of the neck, chest, abdomen, and pelvis is an option for those with primary tumors of the head, neck, and trunk. (See 'Clinically evident lymph nodes or in-transit/satellite metastases' above.)

Following pathological lymph node assessment

-Pathological stage IB and IIA – For asymptomatic patients, most UpToDate contributors do not obtain routine imaging studies. (See 'Pathological stage IB and IIA' above.)

-Pathological stage IIB and IIIA; IIC and IIIB – CT of the CAP (and neck, if indicated). For stage IIC and IIIB, whole-body PET-CT is an option for baseline imaging. (See 'Pathological stage IIB and IIIA' above and 'Pathological stage IIC and IIIB' above.)

We do not generally obtain central nervous system (CNS) imaging unless patients have neurologic symptoms, extracranial metastatic disease, or are on clinical trials.

-Pathological stage IIIC and IIID – Options include CT of the CAP (and neck, if indicated) or whole-body PET-CT, based on clinician preference and choice of adjuvant therapy. We obtain MRI of the brain in all patients. (See 'Pathological stage IIIC and IIID' above.)

Symptomatic disease or suspected metastases – Patients should be assessed prior to regional nodal evaluation, if possible, with CT of the CAP (and neck, as indicated) or whole-body PET-CT, serum lactate dehydrogenase (LDH), and MRI of the brain. (See 'Symptomatic disease or suspected metastases' above.)

Surveillance – Variability also exists for the surveillance of patients who are treated (or actively receiving systemic therapy), and our approach is as follows (see 'Surveillance' above):

Total-body skin examination for all patients – For all patients, physical exam includes a total-body skin examination and clinical evaluation of regional lymph nodes. (See "Screening for melanoma in adults and adolescents", section on 'Performing skin examination'.)

Pathological stage IA – For most asymptomatic patients, physical exam every six months for the first two years, then annually. No routine laboratory or imaging tests are indicated. (See 'Pathological stage IA' above.)

Pathological stage IB and IIA – For asymptomatic patients, physical exam every four to six months for the first two years, then annually. UpToDate contributors diverge on the use of routine laboratory or imaging tests. (See 'Pathological stage IB and IIA' above.)

Pathological stage IIB and IIIA – For those on adjuvant therapy, surveillance should be initiated at the start of treatment. Otherwise, we use a similar strategy for those on adjuvant therapy and those on surveillance alone (see 'Pathological stage IIB and IIIA' above):

-Physical exam every three to four months for the first two to three years, then every six months for up to five years, then annually.

-CT of the CAP (and neck, if indicated) every six months for up to three years, then annually for up to five years. After five years, asymptomatic patients may be offered the option to discontinue imaging surveillance after risk-benefit discussion.

-Regional nodal ultrasound (US) as indicated. (See 'Indications for nodal ultrasound during surveillance' above.)

-We do not obtain CNS imaging unless neurologic symptoms or extracranial metastatic disease is present.

Pathological stage IIC, IIIB, IIIC, IIID – For those on adjuvant therapy, surveillance should be initiated at the start of treatment, which includes (see 'Pathological stage IIC, IIIB, IIIC, IIID' above):

-Physical exam and CT of the CAP (and neck, if indicated) every three months for up to the first three years, then every six months for up to five years. After five years, physical exam can be continued annually, and asymptomatic patients may be offered the option to discontinue imaging surveillance after risk-benefit discussion.

-For those with in-transit/satellite metastases, PET-CT may be offered twice a year, in lieu of the surveillance CT scan planned for that time. (See 'Patients with in-transit/satellite metastases' above.)

-CNS imaging is typically not indicated except for neurologic symptoms or extracranial systemic disease recurrence.

-Regional nodal US as indicated. (See 'Indications for nodal ultrasound during surveillance' above.)

Distant metastatic disease – Surveillance is individualized and based upon response to therapy. (See 'Distant metastatic disease' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Merrick Ross, MD, who contributed to an earlier version of this topic review.

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