INTRODUCTION
The use and implementation of PD-1 inhibitors are revolutionizing cancer treatment. This is evident in the treatment of metastatic Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC). Metastatic MCC has been amenable to chemotherapy, however, the duration of response is short, 4 to 15 months.1 Advanced SCC that is not amenable to surgery or radiation has typically been treated with platinum-based regimens or epidermal growth factor receptor antibodies. Unfortunately, the treatment responses to these regimens are often brisk and plagued by recurrences.2 With response rates upwards of 50% and durability of responses lasting 6 to 24 months, it is easy to see how PD-1 inhibitors have become the leading treatment for advanced SCC and MCC.3,4
For patients with high risk resectable MCC and SCC, there are currently no approved, effective adjuvant treatment options to reduce the risk of recurrence. Therefore, neoadjuvant treatment is the only current opportunity to alter recurrence risk. The early clinical trials are yielding impressive results which may alter our future treatment of these difficult malignancies.5,6 Here we present a case series of neoadjuvant PD-1 inhibitors.
For patients with high risk resectable MCC and SCC, there are currently no approved, effective adjuvant treatment options to reduce the risk of recurrence. Therefore, neoadjuvant treatment is the only current opportunity to alter recurrence risk. The early clinical trials are yielding impressive results which may alter our future treatment of these difficult malignancies.5,6 Here we present a case series of neoadjuvant PD-1 inhibitors.
CASE 1
In March 2021, an 85-year-old male noticed an enlarging lesion on his right inferior lip. Subsequently, he noticed enlarging lymph nodes on the right side of his neck which prompted him to seek advice from his primary care physician. The lip lesion was biopsied and pathology was compatible with MCC. In May 2021, the patient was referred to medical oncology, where the palpable lymph node underwent fine need aspiration (FNA), and a positron emission topography/computed tomography (PET/CT) scan was performed. The FNA confirmed metastatic MCC and the PET/CT scan demonstrated uptake in the lip, right-sided cervical lymph nodes, and unknown left-sided cervical nodes. No distant foci were demonstrated. The patient was diagnosed with stage IIIB disease (Figure 1). 
The patient received one cycle (480 mg) of nivolumab one week after his initial visit and was scheduled for MMS 3 weeks later. A Repeat PET scan prior to surgery demonstrated a marked reduction in size and metabolic activity at all sites of disease. Clinically, the lip area appeared considerably smaller (Figure 2). Histopathologic examination of the first MMS layer showed inflammation with no residual tumor. Lymph node dissection
Treatment options were discussed and the patient was agreeable to off label neoadjuvant therapy with one cycle of nivolumab followed by Mohs micrographic surgery (MMS), lymph node dissection, and adjuvant radiation therapy.
The patient received one cycle (480 mg) of nivolumab one week after his initial visit and was scheduled for MMS 3 weeks later. A Repeat PET scan prior to surgery demonstrated a marked reduction in size and metabolic activity at all sites of disease. Clinically, the lip area appeared considerably smaller (Figure 2). Histopathologic examination of the first MMS layer showed inflammation with no residual tumor. Lymph node dissection
