Clinical original contribution

The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma

Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients’ age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy of the skin. Its incidence is increasing with half of cases involving the head and neck. To the best of our knowledge, few large studies have been published in the UK, and to date this is the largest reported series of head and neck MCC. We retrospectively reviewed the outcomes of patients with MCC in three hospitals in the south-east of England over a 12-year period (2008–2019). Diagnosis was based on histological data following biopsy. Overall survival and disease-specific survival were calculated using Kaplan–Meier and log-rank tests. Fifty-eight patients met the inclusion criteria (24 stage I, 22 stage II, 9 stage III, and 3 unclassified). Median disease-free survival was 36 months (95% CI 0 to 77.2) and median overall survival 50 months (95% CI 29.9 to 70). Overall five-year survival was 34.4% (95% CI 17% to 52%) with two-year survival at 62% (95% CI 48% to 76%). Five-year disease-free survival was 26.7% (95% CI 17 to 52%) with two-year disease-free survival at 54% (95% CI 40% to 68%). To date, this is the largest UK based study reporting overall and disease-free survival associated with MCC of the head and neck. Half the patients presented late, and surgery was the mainstay of treatment, augmented by adjuvant radiotherapy. There is a need to better stratify patients at risk of developing metastatic disease, with the use of sentinel lymph node biopsy and positron-emission tomography-computed tomography (PET-CT), as immunotherapy and targeted agents are now available to treat advanced disease.

This is the third of three articles that give an overview of the current evidence for management of the neck and parotid in patients with cutaneous cancers of the head and neck. In this paper we discuss Merkel cell carcinoma (MCC) and review the latest evidence for management of the regional nodes.

The surgical management of non-melanoma skin cancers has seen some significant changes over the past 20 years, as a result of developments in three equally important and overlapping specialties that deal with this specific pathology: plastic and reconstructive surgery, surgical oncology and dermatological surgery. Better understanding of vascular and particularly microvascular anatomy, coupled with technological advances in operating microscopes, microsurgical instrumentation and preoperative planning via advanced imaging, allows functional and aesthetic restoration of any radical oncological skin and soft-tissue surgery defect from head to toe. As reconstruction has practically lost its technical boundaries, resectional surgery can be executed without compromising on surgical margins, thus reducing rates of local recurrences and metastatic spread. The increasing use of Mohs surgery and its several advantages for difficult high-risk non-melanoma skin cancer in facial sites especially, offers optimal cure rates while reducing functional impairment and optimising cosmetic outcomes. Advances in preoperative planning utilising computed tomography and magnetic resonance imaging scans can help to predict the degree of resectability and tailor further treatments, including radiotherapy, accordingly. From the reconstructive point of view, these techniques provide a roadmap to select the best blood supply for the transplanted flap, thereby reducing complications and increasing success rates. The focus of skin cancer surgery has therefore shifted from pure cancer clearance and flap survival, to a high degree of functional and aesthetic reconstruction.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy with a high propensity for local recurrence and regional and distant metastases. The main treatment is surgery with narrow excision margins and draining nodes, plus or minus adjuvant radiotherapy (RT) on the surgical bed and/or lymph nodes. We performed a systematic review and meta-analysis of the benefits of adjuvant RT in MCC treatment. PubMed, EMBASE, and the Cochrane Library were systematically searched to identify relevant studies published before September 2018. Prospective trials and retrospective series comparing adjuvant RT vs. no RT in resected primary MCCs were included. Primary endpoint was to evaluate the outcomes of MCC patients who received adjuvant RT in term of overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) for OS and DFS were aggregated according to a fixed or random effect model. Secondary endpoints were local, locoregional, and distant DFS.

A total of 17,179 MCCs across 29 studies were analysed. There was a significant difference in OS between the RT and no RT arms (HR = 0.81, 95%CI 0.75–0.86, P < 0.001). There was also a significant difference in DFS in favour of adjuvant RT (HR = 0.45, 95%CI 0.32–0.62, P < 0.001). Adjuvant RT improved locoregional DFS and local DFS but not distant DFS (HR = 0.3, 95%CI 0.22–0.42; HR = 0.21, 95%CI 0.14–0.33, and HR = 0.79, 95%CI 0.49–1.14, respectively). Meta-regression analysis showed that high Newcastle–Ottawa scale scores, stage I–II MCCs, shorter follow-up durations, size >2 cm, and being of a younger age were associated with increased OS. This systematic review and meta-analysis suggests a survival and DFS benefit for postoperative radiation of MCCs. Intermediate stage MCCs derive the maximum benefit with local and regional relapses reduced by 80% and 70%, respectively. Conversely, distant metastases were not significantly prevented.

Merkel cell carcinoma (MCC) is an uncommon radiosensitive, neuroendocrine malignancy. Treatment often involves surgery; however, older, sicker patients may not be candidates for an operation. Institutions have published data favoring the role of definitive radiotherapy for macroscopic locoregional disease.

Our objective was to report the outcome of patients treated with definitive radiotherapy.

We performed a systematic review of Medline, PubMed, and Embase databases for reported cases or series of definitive radiotherapy for macroscopic locoregional MCC.

The mean radiation dose did not significantly differ between primary and regional sites (48.7 ± 13.2 vs 49.4 ± 10.1 Gy, P = .74). The rate of recurrence was calculated on the basis of the site of disease (11.7%) and per patient (14.3%). Recurrence was significantly more likely to occur at regional than at primary irradiated sites (16.3% vs 7.6%, P = .02). There was no association between radiotherapy dose and incidence of recurrence or nonrecurrence; primary (42.7 ± 23 vs 49.3 ± 11.8 Gy, P = .197) and regional (48.6 ± 10 vs 49.5 ± 10.3 Gy, P = .77).

A limitation of this report is that most publications were retrospective; heterogeneity was present in the size of MCC and in radiotherapy details.

Definitive radiotherapy for locoregional macroscopic MCC was found to confer clinically meaningful local and regional in-field control.