Advanced basal cell carcinoma: What dermatologists need to know about diagnosis.

Basal cell carcinoma (BCC) is the most common human cancer, with approximately 3.6 million cases diagnosed each year. About 2000 deaths annually in the United States are attributed to basal and squamous cell skin cancers. There is a direct link between ultraviolet exposure and the development of BCC, as UV exposure damages DNA and induces mutations in tumor suppressor genes. Aberrations in the hedgehog pathway can also result in BCC, highlighted by the fact that most cases of sporadic BCCs have been found to have mutations in different genes involved in the hedgehog pathway. There are several genetic syndromes that are associated with BCCs, including basal cell nevus syndrome, xeroderma pigmentosum, Bazex-Dupré-Christol syndrome, Rombo syndrome, and Oley syndrome. Other risk factors include age, male gender, occupational hazards, radiation, and immunosuppression. BCCs are not typically staged but are instead stratified by their risk of recurring or metastasizing. Locally advanced BCCs are those tumors that are not amenable to surgery or radiation therapy.

Advanced basal cell carcinoma: What dermatologists need to know about treatment.

The treatment of advanced basal cell carcinoma (BCC) often requires therapies beyond local surgical excision or radiation due to the invasiveness of the tumor. Historically, cytotoxic chemotherapy was used to treat advanced BCC, but with limited data, no standard regimens were established. The discovery of cyclopamine, a natural inhibitor in the Hedgehog pathway, led to the development of the 2 currently approved Hedgehog inhibitors, vismodegib and sonidegib. Both agents are indicated for locally advanced BCC, while vismodegib is also indicated for metastatic BCC. In patients who progress on hedgehog inhibitors or cannot tolerate hedgehog inhibitors, the programmed cell death protein 1 inhibitor cemiplimab can be used to treat locally advanced or metastatic disease. Complex cases of locally advanced or metastatic BCC may be best discussed through a multidisciplinary approach in order to determine the optimal treatment approach for the individual patient.

The impact of corticosteroid use during anti-PD1 treatment.

BACKGROUND: The advent of anti-PD1 therapy for cancer treatment has led to improvements in response rates and overall survival. However, anti-PD1 therapy has the potential to cause immune-related adverse events (irAEs), which can be treated with corticosteroids if severe. The clinical implications of concomitant immunotherapy and systemic steroids remain unclear, as short courses of steroids do not significantly suppress T-cell function. The primary objective of this study is to determine if the use of concomitant steroids impacts the efficacy of anti-PD1 therapy. METHODS: This retrospective, single-center study reviewed adult patients who received at least four cycles of nivolumab or pembrolizumab for the treatment of melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma from November 2014 to February 2016. Patients who received steroids (prednisone equivalent >10 mg) during anti-PD1 therapy were divided into two main cohorts based on the duration of steroid administration of ≤2 weeks or >2 weeks. Time to disease progression, overall response, and overall survival were assessed. RESULTS: Twenty-seven of 55 patients (13 melanoma, 11 NSCLC, 3 renal cell carcinoma) required steroids during anti-PD1 therapy. In patients who received steroids, median time to disease progression was 5.6 months for melanoma, 5.8 for NSCLC, and 2.0 for renal cell carcinoma. The overall response rate (ORR) was 3/13 (23%) for melanoma, 6/11 (54%) for NSCLC, and 1/3 (33%) for renal cell carcinoma. Median overall survival was 11.9 months for melanoma, 9.9 for NSCLC, and not reached for renal cell carcinoma. Thirteen patients who had received steroids expired; 11 of these patients had received prednisone >10 mg/day for >2 weeks. CONCLUSION: High-dose steroids for long durations during anti-PD1 therapy may be associated with poorer survival outcomes.