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• W3047770462 abstract "To the Editor: Merkel cell carcinoma (MCC) is highly aggressive, with a propensity for recurrence and distant metastasis. Sentinel lymph node biopsy is critical for workup; however, optimal use of imaging is unclear.1Schmults C.D. Blitzblau R. Aasi S.Z. et al.Merkel Cell Carcinoma, Version 1.2020, NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network.J Natl Compr Canc Netw. 2018; 16: 742-774PubMed Google Scholar A large institutional registry recently identified that liver metastases were more common with a head/neck primary compared with other sites, which could guide workup and surveillance strategies.2Lewis C.W. Qazi J. Hippe D.S. et al.Patterns of distant metastases in 215 Merkel cell carcinoma patients: implications for prognosis and surveillance.Cancer Med. 2020; 9: 1374-1382Crossref PubMed Scopus (22) Google Scholar Thus, we sought to investigate the effect of the primary tumor site on metastasis patterns in a national cohort, hypothesizing that a relationship would exist. We identified patients with MCC (code 8247/3) in the Surveillance, Epidemiology, and End Results (SEER)-18 registries. Our inclusion criteria consisted of patients with metastatic disease upon initial presentation based on American Joint Committee on Cancer 8th Edition staging, diagnosed between 2010 and 2016. Our cohort was stratified by primary lesion site, which consisted of the trunk, head/neck, upper/lower extremities, and other disease sites encompassing visceral or primary nodal disease. We used χ2 tests and Student t tests (2-tailed P values) to assess for differences in clinical and pathologic characteristics and metastatic disease distributions based on primary site and performed Kaplan-Meier analysis to analyze overall survival and disease-specific survival (DSS). We performed multivariate Cox proportional hazards analysis to assess for independent prognosticators of DSS. Our cohort of 331 patients with M1 disease was predominantly male and White (Table I). Patients with a head/neck primary site had a higher proportion of liver metastasis (42.3%, P = .0003) relative to other primary sites, and patients with a trunk primary site had a higher proportion of bone metastasis (36.9%, P = .0049). Overall 5-year overall survival was 11.2%, and DSS was 16.2%. Increasing age and liver and brain metastases were independent prognosticators of poorer DSS by Cox proportional hazards analysis (Table II).Table ICohort characteristics stratified by Merkel cell carcinoma primary siteVariable∗Data are presented as number (%) unless indicated otherwise.Head/neckTrunkUpper/lower extremitiesOther†Owing to the nature of coding in the Surveillance, Epidemiology, and End Results database, the “other” category contains patients with overlapping primary skin sites and those with an unknown primary where Merkel cell carcinoma was first discovered in a lymph node or visceral location.P valueNumber (% of cohort)97 (29.3)38 (11.5)91 (27.5)105 (31.7).0039Age at diagnosis, mean (SD), y78.5 (9.7)71.7 (11.2)77.3 (11.6)70.8 (13.5)Sex.003 Male82 (84.5)26 (68.4)56 (61.5)77 (73.3) Female15 (15.5)12 (31.6)35 (38.5)28 (26.7)Race.107 White95 (98.0)33 (86.8)85 (93.4)98 (93.3) African American1 (1.0)2 (5.3)5 (5.5)1 (1.0) Other/unknown1 (1.0)3 (7.9)1 (1.1)6 (4.7)Tumor size<.0001 0-10 mm9 (9.3)1 (2.6)4 (4.4)35 (33.3) 11-20 mm14 (14.4)011 (12.1)1 (1.0) 21-30 mm16 (16.5)7 (18.4)8 (8.8)2 (1.9) 31-40 mm6 (6.2)5 (13.2)9 (9.9)0 41-50 mm3 (3.1)2 (5.3)8 (8.8)2 (1.9) >50 mm3 (3.1)10 (26.3)17 (18.7)1 (1.0) Unknown46 (47.4)13 (34.2)34 (37.3)64 (60.9)Bone metastasis.0049 Yes24 (24.7)14 (36.9)15 (16.5)15 (14.3) No70 (72.2)23 (60.5)73 (80.2)77 (73.3) Unknown3 (3.1)1 (2.6)3 (3.3)13 (12.4)Brain metastasis.0315 Yes3 (3.1)1 (2.6)02 (1.9) No89 (91.7)36 (94.8)88 (96.7)89 (84.8) Unknown5 (5.2)1 (2.6)3 (3.3)14 (13.3)Liver metastasis.0003 Yes41 (42.3)5 (13.2)21 (23.1)22 (20.9) No52 (53.6)32 (84.2)67 (73.6)70 (66.7) Unknown4 (4.1)1 (2.6)3 (3.3)13 (12.4)Lung metastasis.272 Yes13 (13.4)7 (18.4)18 (19.8)13 (12.4) No79 (81.4)30 (79.0)70 (76.9)81 (77.1) Unknown5 (5.2)1 (2.6)3 (3.3)11 (10.5)∗ Data are presented as number (%) unless indicated otherwise.† Owing to the nature of coding in the Surveillance, Epidemiology, and End Results database, the “other” category contains patients with overlapping primary skin sites and those with an unknown primary where Merkel cell carcinoma was first discovered in a lymph node or visceral location. Open table in a new tab Table IICox proportional hazards analysis for disease-specific survival (DSS) in patients with metastatic Merkel cell carcinomaVariableDSS hazard ratio (95% CI)P valueAge at diagnosis1.03 (1.02-1.05)<.0001Sex Female (Ref)1.0 Male1.14 (0.83-1.56).417Race White (Ref)1.0 African American1.82 (0.78-3.73).155Primary site Head and neck (Ref)1.0 Trunk1.39 (0.86-2.27).181 Upper and lower extremities Other1.05 (0.72-1.53).805 Other∗Owing to the nature of coding in the Surveillance, Epidemiology, and End Results database, the “other” category contains patients with overlapping primary skin sites and those with an unknown primary where Merkel cell carcinoma was first discovered in a lymph node or visceral location.1.53 (1.01-2.32).044Tumor size 0-10 mm (Ref)1.0 11-20 mm1.48 (0.79-2.78).222 21-30 mm1.07 (0.60-1.92).818 31-40 mm0.84 (0.42-1.68).627 41-50 mm1.63 (0.82-3.25).166 >50 mm1.61 (0.86-3.02).136Bone metastasis No (Ref)1.0 Yes1.18 (0.84-1.67).083Brain metastasis No (Ref)1.0 Yes3.85 (1.58-9.38).0030Liver metastasis No (Ref)1.0 Yes1.86 (1.37-2.52)<.0001Lung metastasis No (Ref)1.0 Yes1.12 (0.77-1.64).555CI, Confidence interval; Ref, reference.∗ Owing to the nature of coding in the Surveillance, Epidemiology, and End Results database, the “other” category contains patients with overlapping primary skin sites and those with an unknown primary where Merkel cell carcinoma was first discovered in a lymph node or visceral location. Open table in a new tab CI, Confidence interval; Ref, reference. Our analysis corroborates findings by Lewis et al,2Lewis C.W. Qazi J. Hippe D.S. et al.Patterns of distant metastases in 215 Merkel cell carcinoma patients: implications for prognosis and surveillance.Cancer Med. 2020; 9: 1374-1382Crossref PubMed Scopus (22) Google Scholar also suggesting that in metastatic MCC, a head/neck primary is associated with increased propensity for liver metastasis, generalizing this finding in a national cohort. Additionally, we demonstrate that a trunk primary is associated with bone metastasis compared with other primary sites and in our multivariate analysis that liver and brain metastases (although rare), but not lung or bone, are associated with poorer DSS. These findings may guide further research regarding imaging in MCC. Current guidelines suggest whole-body positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI), or CT imaging of the chest, abdomen, and pelvis with contrast, with or without neck CT or brain MRI, for evaluation of regional or distant disease, when clinically indicated.1Schmults C.D. Blitzblau R. Aasi S.Z. et al.Merkel Cell Carcinoma, Version 1.2020, NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network.J Natl Compr Canc Netw. 2018; 16: 742-774PubMed Google Scholar Guidelines however do not suggest that all clinically node-negative patients should be screened with PET/CT at the initial diagnosis, because PET/CT is more likely to change staging or management in those with features suggesting potential for advanced disease (large tumor size, lymphovascular invasion, immunosuppression). Considering our findings, unexplained liver function abnormalities in head/neck primary MCC may particularly raise clinical suspicion for distant disease and guide imaging decisions. Furthermore, imaging methods differ in sensitivity and specificity for metastasis detection, and limited data suggest greater utility of PET/CT for detection of bone metastases in MCC and for liver metastases (although studied on other malignancies) compared with CT.3Hawryluk E.B. O'Regan K.N. Sheehy N. et al.Positron emission tomography/computed tomography imaging in Merkel cell carcinoma: a study of 270 scans in 97 patients at the Dana-Farber/Brigham and Women's Cancer Center.J Am Acad Dermatol. 2013; 68: 592-599Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar In addition, an area of potential interest is whole-body PET/MRI, which has shown better detection of liver metastases compared with PET/CT, although these data are not in MCC.4Hong S.B. Choi S.H. Kim K.W. et al.Diagnostic performance of [(18)F]FDG-PET/MRI for liver metastasis in patients with primary malignancy: a systematic review and meta-analysis.Eur Radiol. 2019; 29: 3553-3563Crossref PubMed Scopus (13) Google Scholar This may be particularly relevant for patients with a head/neck primary, but cost-effectiveness would be important to consider. In addition, given the rarity of brain metastasis, further studies could focus on optimal selection of patients for brain MRI. Ultimately, future prospective studies will be needed to clarify imaging strategies in MCC with the consideration that patterns of metastasis can guide future research. Limitations include the retrospective nature and lack of details on immune status or metastatic location beyond bone, liver, lung, and brain. In addition, data from this study largely predate immune checkpoint inhibitors for advanced MCC, but optimizing surveillance and early detection of metastases may be increasingly relevant because metastatic tumor burden in melanoma has been shown to influence treatment response and progression-free survival with checkpoint blockade, which could also be the case for MCC.5Davis E.J. Perez M.C. Ayoubi N. et al.Clinical correlates of response to anti-PD-1–based therapy in patients with metastatic melanoma.J Immunother. 2019; 42: 221-227Crossref PubMed Scopus (16) Google Scholar Ultimately, our findings provide further insight into patterns of metastasis of MCC and may help guide future studies." @default.
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• W3047770462 title "Sites of distant metastasis in Merkel cell carcinoma differ by primary tumor site and are of prognostic significance: A population-based study in the Surveillance, Epidemiology, and End Results database from 2010 to 2016" @default.
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