Predictors of False Negative Sentinel Lymph Node Biopsy in Clinically Localized Merkel Cell Carcinoma

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, = 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 (= 0.009). Five-year disease-specific survival (90.9% TN vs. 51.3% FN, < 0.001) and overall survival (69.9% TN vs. 48.1% FN, = 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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Authors

Contributions

Conception and design of the study: RJS, GCK, JSZ, JTM. Acquisition of data: RJS, MJC, AJS, ABS, JS, KL, KMB, CW, KL, HGB, RP. Analysis and interpretation of data: RJS, MJC, AJS, ABS, MCL, CLS, MJJ, KT, MBF, GMB, VS, GCK, JSZ, JTM. Drafting and critically revising the manuscript: RJS, MJC, AJS, ABS, JS, KL, KMB, CW, KL, HGB, RP, MCL, CLS, MJJ, KT, MBF, GMB, VS, GCK, JSZ, JTM. All authors have reviewed and approved the submitted manuscript.

Corresponding author

Correspondence to John T. Miura MD.

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Disclosures

Vernon Sondak reports relevant financial activities outside the submitted work from Merck, BMS, Novartis, Regeneron, Array, Pylonoma, Pfizer, Genentech/Roche, Eisai, Aduro, Amgen, TRM Oncology. Richard J. Straker III, Michael J. Carr, Andrew J. Sinnamon, Adrienne B. Shannon, James Sun, Karenia Landa, Kirsten M. Baecher, Christian Wood, Kevin Lynch, Harrison G. Bartels, Robyn Panchaud, Michael C. Lowe, Craig L. Slingluff, Mark J. Jameson, Kenneth Tsai, Mark B. Faries, Georgia M. Beasley, Giorgos C. Karakousis, Jonathan S. Zager, and John T. Miura have no conflicts of interest to declare.

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Straker, R.J., Carr, M.J., Sinnamon, A.J. et al. Predictors of False Negative Sentinel Lymph Node Biopsy in Clinically Localized Merkel Cell Carcinoma. Ann Surg Oncol (2021). https://doi.org/10.1245/s10434-021-10031-z

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