Reevaluating tumor regression in T1 melanoma: Implications for sentinel lymph node biopsy and nodal positivity

Summary: The prognostic significance of tumor regression in melanoma remains controversial. While regression may indicate a favorable immune-mediated response, it can also obscure tumor depth, potentially concealing micro-metastases and influencing sentinel lymph node biopsy(SLNB) decisions. Current SLNB guidelines do not consider regression, despite its potential clinical relevance. This study examined the relationship between tumor regression, SLNB utilization, and regional lymph node positivity(RNP) in T1 melanoma. We analyzed 27,855 patients with T1 superficial spreading and nodular melanomas(Breslow depth <1.0mm) from the National Cancer Database (NCDB, 2004–2022). Regression was present in 5,924 (21.3%) patients and SLNB was performed in 11,033 (14.4%) cases. Multivariable logistic regression, adjusting for Breslow depth, ulceration, mitotic rate, age, insurance status, and T1 subcategory, assessed the association between regression and SLNB. A separate analysis evaluated regression as an independent predictor of RNP among SLNB patients. Regression was associated with an 11% increased likelihood of SLNB (OR 1.11, 95% CI 1.03–1.20, p=0.008), suggesting it does not deter SLNB utilization. However, regression was not significantly associated with RNP (OR 0.99, 95% CI 0.68–1.45, p=0.976). Ulceration (OR 1.44, p=0.157), higher mitotic rate (OR 2.05 for ≥11 mitoses, p=0.015), and younger age (OR 0.60 for 40–59 years, OR 0.55 for ≥60 years, both p<0.02) were independently associated with RNP. Results were consistent across T1a and T1b subgroups, with no significant interaction between regression and ulceration(p=0.329). These large-scale findings suggest that tumor regression does not deter SLNB but is not independently linked to nodal metastasis. Given its potential influence on biopsy decisions and lack of consideration in current guidelines, further research integrating molecular and immunologic markers is needed to better define its role, particularly in T1a melanomas. Bryan Nolasco¹, Gabrielle Benesh³, Rafi Kabarriti² 1. Montefiore Health System, New York, NY, United States. 2. Radiation Oncology, Montefiore Health System, New York, NY, United States. 3. Dermatology, Montefiore Health System, New York, NY, United States. Clinical Research: Epidemiology and Observational Research