Patterns of distant metastases in 215 Merkel cell carcinoma patients: Implications for prognosis and surveillance

Abstract

Approximately one‐third of Merkel cell carcinoma (MCC) patients eventually develop distant metastatic disease. Little is known about whether the location of the primary lesion is predictive of initial distant metastatic site, or if survival likelihood differs depending on the metastatic site. Such data could inform imaging/surveillance practices and improve prognostic accuracy. Multivariate and competing‐risk analyses were performed on a cohort of 215 MCC patients with distant metastases, 31% of whom had two or more initial sites of distant metastasis. At time of initial distant metastasis in the 215 patients, metastatic sites (n = 305) included non‐regional lymph nodes (present in 41% of patients), skin/body wall (25%), liver (23%), bone (21%), pancreas (8%), lung (7%), and brain (5%). Among the 194 patients who presented with MCC limited to local or regional sites (stage I‐III) but who ultimately developed distant metastases, distant progression occurred in 49% by 1 year and in 80% by 2 years following initial diagnosis. Primary MCC locations differed in how likely they were to metastasize to specific organs/sites (P < .001). For example, liver metastases were far more likely from a head/neck primary (43% of 58 patients) versus a lower limb primary (5% of 39 patients; P < .0001). Skin‐only distant metastasis was associated with lower MCC‐specific mortality as compared to metastases in multiple organs/sites (HR 2.7; P = .003), in the liver (HR 2.1; P = .05), or in distant lymph nodes (HR 2.0; P = .045). These data reflect outcomes before PD1‐pathway inhibitor availability, which may positively impact survival. In conclusion, primary MCC location is associated with a pattern of distant spread, which may assist in optimizing surveillance. Because it is linked to survival, the site of initial distant metastasis should be considered when assessing prognosis.

Patterns of Metastasis in Merkel Cell Carcinoma

“…33 Distant LNs and intra-abdominal organs were most often the first sites of distant metastases in the present study, consistent with previous findings that these sites are frequently involved in metastatic MCC. 12,13,34 While we found that the lung (0%) and brain (3%) were rarely the first sites of distant spread, they may be subsequently involved in 30% and 13% of patients, respectively. 34 Understanding these patterns of metastasis may help to guide follow-up imaging strategies.…”

“…[7][8][9][10][11] Distant metastasis also occurs frequently; institutional series demonstrate that approximately one-third of patients with MCC will eventually develop distant disease. 12,13 However, because of the relative infrequency of this disease, the timing and frequencies of regional and distant disease spread have not been well characterized, resulting in relatively vague baseline and surveillance imaging recommendations. The National Comprehensive Cancer Network guidelines propose that baseline imaging with computed tomography Meeting presentation: Accepted for poster presentation at the 2020 Society of Surgical Oncology International Conference on Surgical Cancer Care (not presented because of COVID-19 pandemic).…”

Merkel Cell Carcinoma of the Hand in a Young Patient

“…11,12 Primary sites of metastasis were distant lymph nodes (41%), liver (23%), bone (21%), pancreas (8%), and lung (7%). 11,12 Distant skin or body wall metastases were more common in patients with an upper-extremity primary site than any other primary site. 11,13 Clinically, MCC presents as a rapidly growing, firm, painless, pink or flesh-colored nodule.…”

Metastatic Merkel Cell Carcinoma Masquerading as Multiple Immune-Related Adverse Events

“…Though nonspecific on exam and histology, the patient's rash to the trunk and extremities was compatible with a pembrolizumab-mediated hypersensitivity irAE. 30–40% of patients treated with anti-PD-1 immunotherapy experience all-grade dermatologic irAEs, while the incidence of all-grade rash is 14–17% [ 7 , 8 ]. The usual onset of rash is after the second cycle of therapy [ 7 ].…”