Richard J Straker1, Michael J Carr2, Andrew J Sinnamon2, Adrienne B Shannon1, James Sun2, Karenia Landa3, Kirsten M Baecher4, Christian Wood1, Kevin Lynch5, Harrison G Bartels6, Robyn Panchaud2, Michael C Lowe4, Craig L Slingluff5, Mark J Jameson6, Kenneth Tsai2, Mark B Faries7, Georgia M Beasley3, Vernon Sondak2, Giorgos C Karakousis8, Jonathan S Zager2,9, John T Miura10. 1. Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. 2. Department of Cutaneous Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 3. Department of Surgery, Duke University, Durham, NC, USA. 4. Department of Surgery, Emory University, Atlanta, GA, USA. 5. Division of Surgical Oncology, Department of Surgery, University of Virginia, Charlottesville, VA, USA. 6. Division of Head and Neck Surgical Oncology, Department of Otolaryngology - Head and Neck Surgery, University of Virginia, Charlottesville, VA, USA. 7. Cedars-Sinai Medical Center, The Angeles Clinic and Research Institute, Los Angeles, CA, USA. 8. Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. 9. Department of Oncological Sciences at the University of South Florida, Morsani College of Medicine, Tampa, FL, USA. 10. Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. John.Miura@pennmedicine.upenn.edu.
Abstract
BACKGROUND: Sentinel lymph node biopsy (SLNB) is routinely recommended for clinically localized Merkel cell carcinoma (MCC); however, predictors of false negative (FN) SLNB are undefined. METHODS: Patients from six centers undergoing wide excision and SLNB for stage I/II MCC (2005-2020) were identified and were classified as having either a true positive (TP), true negative (TN) or FN SLNB. Predictors of FN SLNB were identified and survival outcomes were estimated. RESULTS: Of 525 patients, 28 (5.4%), 329 (62.7%), and 168 (32%) were classified as FN, TN, and TP, respectively, giving an FN rate of 14.3% and negative predictive value of 92.2% for SLNB. Median follow-up for SLNB-negative patients was 27 months, and median time to nodal recurrence for FN patients was 7 months. Male sex (hazard ratio [HR] 3.15, p = 0.034) and lymphovascular invasion (LVI) (HR 2.22, p = 0.048) significantly correlated with FN, and increasing age trended toward significance (HR 1.04, p = 0.067). The 3-year regional nodal recurrence-free survival for males >75 years with LVI was 78.5% versus 97.4% for females ≤75 years without LVI (p = 0.009). Five-year disease-specific survival (90.9% TN vs. 51.3% FN, p < 0.001) and overall survival (69.9% TN vs. 48.1% FN, p = 0.035) were significantly worse for FN patients. CONCLUSION: Failure to detect regional nodal microscopic disease by SLNB is associated with worse survival in clinically localized MCC. Males, patients >75 years, and those with LVI may be at increased risk for FN SLNB. Consideration of increased nodal surveillance following negative SLNB in these high-risk patients may aid in early identification of regional nodal recurrences.
BACKGROUND: Sentinel lymph node biopsy (SLNB) is routinely recommended for clinically localized Merkel cell carcinoma (MCC); however, predictors of false negative (FN) SLNB are undefined. METHODS:Patients from six centers undergoing wide excision and SLNB for stage I/II MCC (2005-2020) were identified and were classified as having either a true positive (TP), true negative (TN) or FN SLNB. Predictors of FN SLNB were identified and survival outcomes were estimated. RESULTS: Of 525 patients, 28 (5.4%), 329 (62.7%), and 168 (32%) were classified as FN, TN, and TP, respectively, giving an FN rate of 14.3% and negative predictive value of 92.2% for SLNB. Median follow-up for SLNB-negative patients was 27 months, and median time to nodal recurrence for FN patients was 7 months. Male sex (hazard ratio [HR] 3.15, p = 0.034) and lymphovascular invasion (LVI) (HR 2.22, p = 0.048) significantly correlated with FN, and increasing age trended toward significance (HR 1.04, p = 0.067). The 3-year regional nodal recurrence-free survival for males >75 years with LVI was 78.5% versus 97.4% for females ≤75 years without LVI (p = 0.009). Five-year disease-specific survival (90.9% TN vs. 51.3% FN, p < 0.001) and overall survival (69.9% TN vs. 48.1% FN, p = 0.035) were significantly worse for FN patients. CONCLUSION: Failure to detect regional nodal microscopic disease by SLNB is associated with worse survival in clinically localized MCC. Males, patients >75 years, and those with LVI may be at increased risk for FN SLNB. Consideration of increased nodal surveillance following negative SLNB in these high-risk patients may aid in early identification of regional nodal recurrences.
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