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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

Small Cell Lung Cancer: A Review

Author/s: 
So Yeon Kim, Henry S Park, Anne C Chiang

Importance: Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma with an incidence of 4.7 cases per 100 000 individuals in 2021 in the US and a 5-year overall survival of 12% to 30%.

Observations: Cigarette smoking is the primary risk factor for development of SCLC, as 95% of patients diagnosed with SCLC have a history of tobacco use. Patients with SCLC may present with respiratory symptoms such as cough (40%), shortness of breath (34%), hemoptysis (10%), or metastases with corresponding local symptoms (30%) such as pleuritis or bone pain; approximately 60% of patients with SCLC may be asymptomatic at diagnosis. Chest imaging may demonstrate central hilar (85%) or mediastinal lymphadenopathy (75%). At diagnosis, approximately 15% of patients have brain metastases, which may present as headache or focal weakness. Diagnosis is confirmed by biopsy of a primary lung mass, thoracic lymph node, or metastatic lesion. Small cell lung cancer is classified into limited stage (LS-SCLC; 30%) vs extensive stage (ES-SCLC; 70%) based on whether the disease can be treated within a radiation field that is typically confined to 1 hemithorax but may include contralateral mediastinal and supraclavicular nodes. For patients with LS-SCLC, surgery or concurrent chemotherapy with platinum-etoposide and radiotherapy is potentially curative in 30% of patients. More recently, median survival for LS-SCLC has reached up to 55.9 months with the addition of durvalumab, an immunotherapy. First-line treatment for ES-SCLC is combined treatment with platinum-etoposide chemotherapy and immunotherapy with the programmed cell death 1 ligand 1 (PD-L1) inhibitors durvalumab or atezolizumab followed by maintenance immunotherapy until disease progression or toxicity. Although initial rates of tumor shrinkage are 60% to 70% with platinum-etoposide and immunotherapy treatment, the median overall survival of patients treated for ES-SCLC is approximately 12 to 13 months, with 60% of patients relapsing within 3 months. Second-line therapy for patients with ES-SCLC includes the DNA-alkylating agent lurbinectedin (35% overall response rate; median progression-free survival, 3.7 months) and a bispecific T-cell engager against delta-like ligand 3, tarlatamab (40% overall response rate; median progression-free survival, 4.9 months).

Conclusions and relevance: Small cell lung cancer is a smoking-related malignancy that presents at an advanced stage in 70% of patients. Three-year overall survival is approximately 56.5% for LS-SCLC and 17.6% for ES-SCLC. First-line treatment for LS-SCLC is radiation targeting the tumor given concurrently with chemotherapy and followed by consolidation immunotherapy. For ES-SCLC, first-line treatment is chemotherapy and immunotherapy followed by maintenance immunotherapy.

Keywords 
small cell lung cancer small cell lung cancer Lung
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