Prognostic value of lymphovascular invasion in early-stage Merkel cell carcinoma: a retrospective analysis in the National Cancer Database

Abstract Purpose Early stage Merkel cell carcinoma (MCC) is a rare and aggressive primary skin cancer. The standard of care for MCC is broad excision and adjuvant external beam radiation therapy (EBRT). However, for some patients, anesthesia is contraindicated, while others run the risk of serious aesthetic sequelae. In such cases, exclusive radiotherapy is an interesting alternative to surgery. Though limited data is available, this study evaluates exclusive radiotherapy for MCC, using data from the largest retrospective study to date. Methods All patients who were followed in our center between 1989 and 2019 for histologically proven early stage MCC were included in the study. They were treated either by surgery with a 2-cm clear margin followed by adjuvant radiotherapy (RT) or by exclusive RT. Survival rates with adjuvant and exclusive EBRT were analyzed using Cox model and Fine and Gray model depending on the type of survival. p value < 0.05 was considered significant. Results Eighty-four patients treated for MCC were included. Fifty-three of them (63.1%) were treated by exclusive RT, and 31 (36.9%) had surgical excision followed by adjuvant RT. Local relapse rate was 13.7% (95% CI 8.0–43.7) in the RT monotherapy group (group A) and 25.8% (95% CI 10.3–56.2) in the surgery + RT group (group B) (p = 0.42). No statistical difference was found for nodal relapse (p = 0.81), metastatic relapse (p = 0.10), disease free survival (p = 0.83) or overall survival (p = 0.98). Conclusion Our study suggests that exclusive radiotherapy for early Merkel cell carcinoma leads to a similar oncological outcome as combined treatment, with fewer aesthetic sequelae. The approach is interesting for elderly patients with comorbidities or patients for whom surgery would cause significant functional or aesthetic sequelae.

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Primary Merkel Cell Carcinoma: A Retrospective Analysis of 31 Cases in Poland

Dermatology and Therapy ◽

10.1007/s13555-020-00424-5 ◽

2020 ◽

Vol 10 (5) ◽

pp. 1003-1012

Author(s):

Magdalena Ciążyńska ◽

Katarzyna Szczepaniak ◽

Marta Pabianek ◽

Dariusz Nejc ◽

Adam Reich ◽

...

Keyword(s):

Cell Carcinoma ◽

Retrospective Analysis ◽

Merkel Cell Carcinoma ◽

Merkel Cell

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Tumor infiltrating lymphocyte grade in Merkel cell carcinoma: relationships with clinical factors and independent prognostic value

Acta Oncologica ◽

10.1080/0284186x.2020.1794033 ◽

2020 ◽

Vol 59 (12) ◽

pp. 1409-1415

Author(s):

Mehran Yusuf ◽

Jeremy Gaskins ◽

Steven Mandish ◽

Michael E. May ◽

Weston Wall ◽

...

Keyword(s):

Cell Carcinoma ◽

Merkel Cell Carcinoma ◽

Prognostic Value ◽

Merkel Cell ◽

Clinical Factors ◽

Tumor Infiltrating Lymphocyte

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Single-Institution Series of Early-Stage Merkel Cell Carcinoma: Long-Term Outcomes in 95 Patients Managed with Surgery Alone

Yearbook of Dermatology and Dermatologic Surgery ◽

10.1016/s0093-3619(10)79752-5 ◽

2011 ◽

Vol 2011 ◽

pp. 361-362

Author(s):

R.I. Ceilley ◽

J. Wilson

Keyword(s):

Cell Carcinoma ◽

Merkel Cell Carcinoma ◽

Early Stage ◽

Merkel Cell ◽

Long Term Outcomes ◽

Single Institution

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Demographics and outcomes of stage I and II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer Database

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2018.01.041 ◽

2018 ◽

Vol 79 (1) ◽

pp. 126-134.e3 ◽

Cited By ~ 14

Author(s):

Babu Singh ◽

Muhammad M. Qureshi ◽

Minh Tam Truong ◽

Debjani Sahni

Keyword(s):

Cell Carcinoma ◽

Merkel Cell Carcinoma ◽

Local Excision ◽

Wide Local Excision ◽

Stage I ◽

National Cancer Database ◽

Merkel Cell ◽

Mohs Micrographic Surgery ◽

Micrographic Surgery

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Optimal adjuvant radiotherapy dose for stage I, II or III Merkel cell carcinoma: an analysis of the National Cancer Database

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyz153 ◽

2019 ◽

Cited By ~ 1

Author(s):

Mehran Yusuf ◽

Jeremy Gaskins ◽

Weston Wall ◽

Paul Tennant ◽

Jeffrey Bumpous ◽

...

Keyword(s):

Overall Survival ◽

Cell Carcinoma ◽

Merkel Cell Carcinoma ◽

Adjuvant Radiotherapy ◽

Recursive Partitioning ◽

Stage I ◽

National Cancer Database ◽

Overall Survival Rate ◽

Merkel Cell ◽

Conventionally Fractionated

Abstract Background We performed an analysis of the National Cancer Database to determine optimal doses of conventionally-fractionated adjuvant radiotherapy for patients with stage I/II or III Merkel cell carcinoma. Methods The cohort included 2735 patients with resected Merkel cell carcinoma of the head and neck, trunk or extremities receiving radiotherapy. Exclusion criteria included doses of radiotherapy <30 or >80 Gy, or dose per fraction >200 or <180 cGy. Recursive partitioning analysis and spline models were used to select dose thresholds. Multivariable Cox regression was performed to validate thresholds with respect to overall survival. Results Recursive partitioning analysis models defined a threshold of 57 Gy for stage I/II Merkel cell carcinoma, above which 3-year overall survival rate was decreased (P < 0.0001). The 3-year overall survival rate for patients receiving 50.0–57.0 Gy (81.2%) was greater compared to doses of 30.0–49.9 Gy (75.3%) or >57.0 Gy (70%, P < 0.0001). Doses > 57.0 Gy were associated with an increased hazard of death (1.31, confidence interval 1.07–1.60) with respect to doses of 50.0–57.0 Gy. Doses < 50.0 Gy for stage III Merkel cell carcinoma were associated with worsened 3-year overall survival (P < 0.0001) and increased hazard of death (2.01, confidence interval 1.43–2.82) with respect to doses between 50.0 and 57.0 Gy. Conclusions Our results support doses of 50–57 Gy for most patients with stage I/II Merkel cell carcinoma receiving conventionally-fractionated adjuvant radiotherapy. In contrast to a prior National Cancer Database analysis, our results suggest doses ≥ 50 Gy should be strongly considered for patients with stage III Merkel cell carcinoma regardless of anatomic subsite.

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Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature

Endocrine Pathology ◽

10.1007/s12022-020-09640-3 ◽

2020 ◽

Vol 31 (4) ◽

pp. 392-400 ◽

Cited By ~ 1

Author(s):

Stefano La Rosa ◽

Matteo Bonzini ◽

Amedeo Sciarra ◽

Sofia Asioli ◽

Roberta Maragliano ◽

...

Keyword(s):

Multivariate Analysis ◽

Cell Carcinoma ◽

Merkel Cell Carcinoma ◽

Prognostic Value ◽

Univariate Analysis ◽

Youden Index ◽

Merkel Cell ◽

Prognostic Role ◽

Proliferative Index

AbstractThe exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only.

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