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Cutaneous Melanoma: A Review

Author/s: 
Urvashi Mitbander Joshi, Mohammed Kashani-Sabet, John M. Kirkwood

Importance: Melanoma, the fifth most common cancer in the US, has increased from 8.8 per 100 000 in 1975 to 28.42 per 100 000 in 2022. Cutaneous melanoma comprises 94% of cases, with 104 960 US cases projected for 2025.

Observations: Cutaneous melanoma presents as a new, changing, or irregularly pigmented skin lesion. Cutaneous melanoma subtypes include superficial spreading (≈70%), lentigo maligna (≈15%), nodular (≈5%), desmoplastic (≈4%), amelanotic (2%-8%), spitzoid (<2%), and acral (≈1%). Risk factors for cutaneous melanoma include UV radiation exposure, skin type (eg, skin that always burns, never tans), presence of benign and atypical nevi, and personal or family history of melanoma. Primary prevention consists of avoiding direct sunlight and indoor tanning, and photoprotection (sunscreen and sun-protective clothing). Based on United States Cancer Statistics data from 1999 to 2021, 77% of patients with cutaneous melanoma had localized disease (involving only the primary site), 9.5% had regional (nodal) disease, 4.7% had distant metastasis, and 8.8% were unstaged. Melanoma staging, which includes tumor thickness and ulceration and presence of lymph node or distant metastasis, ranges from stage 0 (melanoma in situ) to stage IV (distant metastasis). Localized melanoma (stage IA-IIA) is surgically excised, with margins of 0.5 cm to 2 cm based on depth of invasion. Sentinel lymph node biopsy is recommended for cutaneous melanoma that is ulcerated or 0.8 mm or more thick. Following surgery, patients with stage IIB-C melanoma have improved recurrence-free survival with adjuvant anti-PD-1 immunotherapy compared with placebo (hazard ratio [HR] for recurrence or death, 0.62 [95% CI, 0.49-0.79] for pembrolizumab and 0.42 [95% CI, 0.30-0.59] for nivolumab). For stage III disease, recurrence risk is decreased with nivolumab (HR, 0.72 [95% CI, 0.60-0.86]), pembrolizumab (HR, 0.61 [95% CI, 0.51-0.72]), or BRAF + MEK inhibitor therapy (dabrafenib + trametinib) (HR, 0.52 [95% CI, 0.43-0.63]). First-line treatment for distant metastatic or unresectable melanoma is dual checkpoint blockade with ipilimumab (anti-CTLA-4) and nivolumab. In 2017, 10-year melanoma-specific survival rates were 98% to 94% for stage IA-B, 88% to 75% for stage IIA-C, 88% for stage IIIA, 77% to 60% for stage IIIB-C, and 24% for stage IIID. In 2024, patients with distant metastatic or unresectable melanoma treated with ipilimumab and nivolumab had a 10-year overall survival rate of 43%.

Conclusions and relevance: Melanoma is a common cancer in the US. Treatment for stage IA-IIA melanoma is surgical resection. Anti-PD-1 immunotherapy after surgical excision improves recurrence-free survival in stages IIB-C melanoma. For stage III melanoma, anti-PD-1 immunotherapy or BRAF + MEK inhibitor therapy decreases risk of melanoma recurrence. First-line therapy for metastatic melanoma is dual checkpoint blockade with ipilimumab and nivolumab.

Keywords 
dermatology oncology skin cancer melanoma Targeted and Immune Therapy

Melanoma crash course

Author/s: 
Ashton, R., Wilkinson, A.N.

Cutaneous melanoma represents about 4% of skin cancers but is responsible for more than 75% of deaths from skin cancer. The incidence of cutaneous melanoma is reported as 25 per 100,000 people in North America and 60 per 100,000 people in Australia and New Zealand. Melanoma diagnoses are increasing worldwide, possibly owing to improved detection; in Canada the largest increase in age-standardized incidence of melanoma has occurred in males, with an increase of 2.2% per year between 1984 and 2019. Mortality rates for melanoma have declined since 2013 due to the use of immunotherapy; however, there has been no noted reduction in mortality among non-White patients or among populations with lower socioeconomic status, with a study demonstrating that these populations have higher incidences of thick melanoma with poorer prognoses.

There is insufficient evidence to support the effectiveness of skin cancer screening in reducing melanoma mortality, with an Australian study published in 2022 finding that skin screening increases the risks of biopsy and melanoma in situ without increasing the detection rate of invasive melanoma, compared with unscreened individuals. The United States Preventive Services Task Force also does not recommend regular skin checks in the average individual as part of age-appropriate screening guidelines. A guideline published by the Canadian Task Force on Preventive Health Care, based on reports from Australia and New Zealand, recommends regular skin examinations for those at high risk of melanoma (Table 1).

Keywords 
melanoma

Impact of Biopsy Technique on Clinically Important Outcomes for Cutaneous Melanoma: A Systematic Review and Meta-analysis

Author/s: 
Shellenberger, R.A., Fayyaz, F., Sako, Z., Tawagi, K., Scheidel, C., Nabhan, M.

We performed a systematic review and meta-analysis to examine the relationship between the type of biopsy technique employed in the diagnosis of cutaneous melanoma and 4 clinically important outcomes: melanoma-specific mortality, all-cause mortality, Breslow tumor depth, or melanoma recurrence. Our database was obtained by searching PubMed, Ovid MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Library from inception until December 6, 2019. Studies were identified that compared biopsy techniques used to diagnose cutaneous melanoma with any of our study outcomes. We included 7 observational studies for our meta-analysis after screening 3231 titles and abstracts. Pooled data identified a significantly higher all-cause mortality in the punch biopsy group (risk ratio [RR], 1.520; P=.02). A higher, but nonsignificant, rate of melanoma-specific mortality (RR, 1.96; P=.22) and melanoma recurrence (RR, 1.20; P=.186) was also found for the punch biopsy group. Breslow tumor thickness was not significantly lower for punch incision (standardized mean difference, −0.42; P=.27). We found limited evidence for differences in clinically important outcomes across the spectrum of the most common methods employed in clinical practice for the initial diagnosis of cutaneous melanoma. A small, but significant, increase (P=.02) in all-cause mortality with punch biopsies was not seen for the other outcomes and was most likely due to small sample sizes and demographic differences in the included studies and unlikely represents a clinically important outcome. Our findings support the use of existing clinical practice guidelines for evaluating pigmented lesions suspicious for cutaneous melanoma.

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