Effect of Sentinel Lymph Node Biopsy and LVI on Merkel Cell Carcinoma Prognosis and Treatment

Abstract

Objective Prognostic factors and optimal treatment approaches for Merkel cell carcinoma (MCC) remain uncertain. This study evaluated the influences of sentinel lymph node (SLN) biopsy and lymphovascular invasion (LVI) on treatment planning and prognosis. Study Design Retrospective cohort study. Methods Stage 1 to 3 MCC patients treated 2005 to 2018. Predictors of nodal radiation were tested using logistic regression. Predictors of recurrence‐free, disease‐specific, and overall survival were tested in Cox proportional hazard models. Results Of 122 patients, 99 were without clinically apparent nodal metastases. Of these, 76 (77%) underwent excision and SLN biopsy; 29% had metastasis in SLNs, including 20% of MCCs 1 cm or less. Primary tumor diameter, site, patient age, gender, and immunosuppressed status were not significantly associated with an involved SLN. Among patients who underwent SLN biopsy, 13 of 21 (62%) MCCs with LVI had cancer in SLNs compared with 14 of 44 (25.5%) without LVI (P = .003). Although local radiation was common, nodal radiation was infrequently employed in SLN negative (pathologic N0) patients (21.8% vs. 76.2% for patients with SLN metastases, P = .0001). Survival of patients with positive SLNs was unfavorable, regardless of completion lymphadenectomy and/or adjuvant radiation. After accounting for tumor (T) and node (N) classification, age, immunosuppression, and primary site, a positive SLN and LVI were independently associated with worse survival (LVI/recurrence‐free survival [RFS]: hazard ratio [HR] 2.3 (1.04–5, P = .04; LVI/disease‐specific survival [DSS]: HR 5.2 (1.8–15, P = .007); N1a vs. pN0/RFS HR 3.6 (1.42–9.3, P = .007); DSS HR5.0 (1.3–19, P = .17). Conclusion SLN biopsy assists in risk stratification and radiation treatment planning in MCC. LVI and disease in SLNs, independently associated with worse survival, constitute markers of high‐risk disease warranting consideration for investigational studies. Level of Evidence III Laryngoscope, 131:E828–E835, 2021

Predictors of time to definitive surgery and survival in Merkel cell carcinoma: analysis of the US National Cancer Database

“…The exact causes of delays in treatment post‐diagnosis are yet to be fully understood, but studies have suggested possible causes ranging from race to socioeconomic status of patients 3,4 . The current standard of care for patients with MCC includes surgical resection, possibly accompanied by sentinel lymph node biopsy and followed by adjuvant radiotherapy and/or systemic therapy, if indicated 5 . Larger studies investigating the elapsed time between patient presentation and receipt of care, and how these durations influence ultimate patient outcomes, are vital in understanding the management of MCC, but are yet to be performed.…”

Treatment of Locally Advanced Merkel Cell Carcinoma—A Multi-Center Study

“…Based on the literature, occult lymph node disease is present in up to 50% of patients [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]; thus, SLNB should be performed in all patients. We confirmed the value of SLNB by showing that patients with clinically less-suspicious lymph nodes who have not undergone the SLNB had over 5-times higher risk of disease recurrence and nearly 2.5 times higher risk of death.…”

“…Approximately 50–65% of MCC patients have localized disease at presentation, and 25–50% have regional metastases [ 3 , 4 ]. Subclinical nodal metastases are present in 30–50% of patients with primary MCC, with an increased presence in patients with a primary tumor greater than 1 cm in diameter [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The sentinel lymph node biopsy (SLNB) is recommended in cases without clinical nodal involvement.…”

Merkel cell carcinoma: An updated review of pathogenesis, diagnosis, and treatment options

“…69 A recent retrospective study of 122 patients found that a positive SLNB and lymphovascular invasion were independently associated with worse survival after considering tumor T and node N classification, immunosuppression, age, and the primary site of the tumor. 70 Tumor thickness and size, lymphovascular invasion, immunosuppression, presence of tumor-infiltrating lymphocytes, mitotic rate, and tumor growth pattern have been associated…”