The Utility of Positron Emission Tomography (PET) Surveillance Following Definitive Therapy For Merkel Cell Carcinoma – An Australian Case Series

Abbreviations: CT: Computed Tomography; F: Female; FDG: Fluorodeoxyglucose; Gy: Gray; Immuno: Immunotherapy; M: Male; MCpyV: Merkel Cell Polyomavirus; MCC: Merkel Cell Carcinoma; PET: Positron emission tomography; Pt: Patient; +ve: Positive; RT: Radiotherapy; SBRT: Stereotactic Body Radiotherapy; Sx: Surgery; Rx: Treatment; Unk: Unknown; UV: Ultraviolet; WLE: Wide Local Excision ARTICLE INFO abstract


Introduction
Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine tumour of the skin [1,2]. Australia has the highest incidence in the world [3]. Risk factors for poor outcomes include advanced age [4] immunosuppression [5] and Merkel cell polyomavirus (MCPyV) infection [6][7][8]. MCC is prone to recurrence with a high proportion of patients succumbing to metastatic disease [4,9]. Close follow-up following initial treatment is important, including imaging. Poulsen et al showed 18-Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) to be a useful functional imaging modality for MCC staging [10]. This paper describes five cases where surveillance PET scanning on asymptomatic patients after initial treatment was performed as part of one clinician's follow-up protocol. These scans changed the management of these patients with MCC. This case series adds to the argument of the importance of funding surveillance PET scans in MCC.

Methods
Medical records of a radiation oncologist, with an interest in MCC, were searched over the years 2014-2018. This clinician sees on average five new MCC cases per year, with 80% being treated with radical intent. The follow-up protocol in this practice is a surveillance PET scan every 6 months following completion of definitive initial treatment, irrespective of whether symptoms or signs are present. Patients with MCC who had a PET scan when asymptomatic, that discovered new disease and changed management, were specifically sought.

Results
Five cases were found of patients who had a surveillance PET scan when asymptomatic that discovered more disease and, as a result, changed management. They represent 25% of radical cases and 20% of all cases seen during that time. These cases are detailed below:

Case One
A 64-year-old Vietnamese woman had multiple surgeries on her right eyelid for what was thought to be recurrent poorly differentiated cutaneous squamous cell carcinoma. Histopathology review revealed margin-positive MCC. PET scan prior to radiotherapy (RT) found no distant disease, making initial staging T1N0 (AJCC 8th edition) [11]. Superficial RT to the right eyelid to a total dose of 50Gy in 25 fractions was given. She had already palpable recurrence at the beginning of the RT, which resolved completely during RT. Six months later, she had a routine PET as part of follow-up. This found regional recurrence in the posterior orbit, and she was treated with curative intent with surgical resection and post-operative RT, followed by immunotherapy. She eventually succumbed to brain metastases a year after completion of her salvage local therapy, 30 months after her first initial surgery.

Case Two
An 81-year-old Caucasian male had a 10 mm MCC staged as T1N0 removed from his right middle finger with a wide local excision (WLE) and flap repair. He was treated with adjuvant RT to the ipsilateral epitrochlear node and axilla, all in continuity, to a total dose of 50Gy in 25 fractions. He was then followed with routine PETs every six months. At 24 months, he was noted on PET to have an asymptomatic, solitary distant recurrence in the right adrenal gland, biopsy-proven as MCC. This lesion had grown in six months after a negative PET. He then had stereotactic body radiotherapy (SBRT) to that lesion followed by immunotherapy with complete metabolic response on PET four months after SBRT. He continues with stable disease in the right adrenal mass on computed tomography (CT) scan, cold on PET, five years after original diagnosis.

Case Four
An 85-year-old woman with palpable lymph nodes of biopsyproven MCC in the left groin from an unknown primary that was staged as TxN1. Baseline PET showed no other disease. She was treated with definitive RT, to a total dose of 50Gy in 25 fractions with complete resolution of the nodal disease. Routine follow-up with PET scan at 12 months showed multiple distant recurrences, higher up the para-aortic chain, and she was treated with radical intent immunotherapy and RT, and continues with stable disease, 33 months post original diagnosis. Routine surveillance PET done six months following RT showed multiple distant recurrences with liver metastases, and he was treated with immunotherapy. An MRI brain scan performed a year later due to symptoms showed multiple brain metastases and he was treated with palliative intent with further RT, now years out from primary diagnosis with progressive disease. The relevant details for these patients are shown in Table 1. The female to male ratio was 3:2; average age was 73 years with a range 64 to 84 years; three had a head and neck primary, two had a limb primary; three were initially staged T1N0; four were initially treated with both surgery and RT. Average time to recurrence was with a range of 6 to 24 months. Majority failed with distant recurrence, and four had further radical intent treatment including immunotherapy. None of these patients were immunosuppressed.

Discussion
In this series, five radically-treated cases of MCC had a surveillance PET scan when asymptomatic. This scan discovered more disease and as a result, changed management as described.