Predictors of Metastasis and Outcome Following True Negative Sentinel Node Biopsy

Author(s): Johanna S Palve, Tiina H Luukkaala, Minna T Kääriäinen

Up to 30% of sentinel node-negative patients develop metastases during follow-up. Negative sentinel node biopsies (SNB) can be classified to false (FN) and true negative (TN) categories. Little attention has been paid to the characteristics and outcomes of patients who experience direct distant metastasis following TN-SNB. In this retrospective study of a melanoma database at Tampere university hospital we analyzed characteristics and outcome following metastases after TN-SNB. A total of 506 patients underwent SNB between 2006 and 2016. After review, SNBs were classified FN, TN and true positive (TP). Follow-up was performed until 30.4.2019.

Of SN-negative patients, 74 of 396 (19%) developed recurrence, including 17 (4%) local, 22 (6%) regional lymph node (FN) and 35 (9%) direct distant metastases (TN-D). False negative rate was 16% and negative predictive value 93.8%. Locoregional recurrences occurred earlier compared to distal metastases (median of 2.14 /2.93 years). Compared to patients without recurrence, thickness ≥ 2 mm (univariable p<0.001), male gender (p=0.021), nodular melanoma (p=0.001), ulceration (p<0.001) and location in upper limb region (p=0.062) were predictors of TN-D. The 5-year melanoma specific survival in TN-D patients did not differ significantly from TP patients (2.36 /2.26 years).

TN-D is associated with nodular melanomas in upper limb region, male gender, cervical SNBs and ulcerated tumors with Breslow thickness ≥ 2 mm. These patients should be considered at high-risk relapse and mortality. Surveillance imaging to detect distant metastases is mandatory regardless of SNB status. In future, inclusion criteria for therapy trials for high-risk SNB-negative patients might also be worth considering.

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