Risk Stratification of Sentinel Node Metastasis Disease Burden and Phenotype in Stage III Melanoma Patients.

BACKGROUND: Currently, all patients with American Joint Committee on Cancer (AJCC) pT2b-pT4b melanomas and a positive sentinel node biopsy are now considered for adjuvant systemic therapy without consideration of the burden of disease in the metastatic nodes. METHODS: This was a retrospective cohort analysis of 1377 pT1-pT4b melanoma patients treated at an academic cancer center. Standard variables regarding patient, primary tumor, and sentinel node characteristics, in addition to sentinel node metastasis maximum tumor deposit size (MTDS) in millimeters and extracapsular spread (ECS) status, were analyzed for predicting disease-specific survival (DSS). RESULTS: The incidence of SN+ was 17.3% (238/1377) and ECS was 10.5% (25/238). Increasing AJCC N stage was associated with worse DSS. There was no difference in DSS between the IIIB and IIIC groups. Subgroup analyses showed that the optimal MTDS cut-point was 0.7 mm for the pT1b-pT4a SN+ subgroups, but there was no cut-point for the pT4b SN+ subgroup. Patients with MTDS <0.7 mm and no ECS had similar survival outcomes as the N0 patients with the same T stage. Nodal risk categories were developed using the 0.7 mm MTDS cut-point and ECS status. The incidence of low-risk disease, according to the new nodal risk model, was 22.3% (53/238) in the stage III cohort, with 49% (26/53) in the pT2b-pT3a and pT3b-pT4a subgroups and none in the pT4b subgroup. Similar outcomes were observed for overall and distant metastasis-free survival. CONCLUSION: We propose a more granular classification system, based on tumor burden and ECS status in the sentinel node, that identifies low-risk patients in the AJCC IIIB and IIIC subgroups who may otherwise be observed.

Evaluation of the Indications for Sentinel Node Biopsy in Early-Stage Melanoma with the Advent of Adjuvant Systemic Therapy: An International, Multicenter Study.

BACKGROUND: Patients presenting with early-stage melanoma (AJCC pT1b-pT2a) reportedly have a relatively low risk of a positive SNB (~5-10%). Those patients are usually found to have low-volume metastatic disease after SNB, typically reclassified to AJCC stage IIIA, with an excellent prognosis of ~90% 5-year survival. Currently, adjuvant systemic therapy is not routinely recommended for most patients with AJCC stage IIIA melanoma. The purpose was to assess the SN-positivity rate in early-stage melanoma and to identify primary tumor characteristics associated with high-risk nodal disease eligible for adjuvant systemic therapy METHODS: An international, multicenter retrospective cohort study from 7 large-volume cancer centers identified 3,610 patients with early primary cutaneous melanomas 0.8-2.0 mm in Breslow thickness (pT1b-pT2a; AJCC 8th edition). Patient demographics, primary tumor characteristics, and SNB status/details were analyzed. RESULTS: The overall SNB-positivity rate was 11.4% (412/3610). Virtually all SNB-positive patients (409/412; 99.3%) were reclassified to AJCC stage IIIA. Multivariate analysis identified age, T-stage, mitotic rate, primary site and subtype, and lymphovascular invasion as independent predictors of sentinel node status. A mitotic rate of >1/mm2 was associated with a significantly increased SN-positivity rate and was the only significant independent predictor of high-risk SNB metastases (>1 mm maximum diameter). CONCLUSIONS: The new treatment paradigm brings into question the role of SNB for patients with early-stage melanoma. The results of this large international cohort study suggest that a reevaluation of the indications for SNB for some patients with early-stage melanoma is required.

Clinical Outcomes and Risk Stratification of Early-Stage Melanoma Micrometastases From an International Multicenter Study: Implications for the Management of American Joint Committee on Cancer IIIA Disease.

PURPOSE: Indications for offering adjuvant systemic therapy for patients with early-stage melanomas with low disease burden sentinel node (SN) micrometastases, namely, American Joint Committee on Cancer (AJCC; eighth edition) stage IIIA disease, are presently controversial. The current study sought to identify high-risk SN-positive AJCC stage IIIA patients who are more likely to derive benefit from adjuvant systemic therapy. METHODS: Patients were recruited from an intercontinental (Australia/Europe/North America) consortium of nine high-volume cancer centers. All were adult patients with pathologic stage pT1b/pT2a primary cutaneous melanomas who underwent SN biopsy between 2005 and 2020. Patient data, primary tumor and SN characteristics, and survival outcomes were analyzed. RESULTS: Three thousand six hundred seven patients were included. The median follow-up was 34 months. Pairwise disease comparison demonstrated no significant survival difference between N1a and N2a subgroups. Survival analysis identified a SN tumor deposit maximum dimension of 0.3 mm as the optimal cut point for stratifying survival. Five-year disease-specific survival rates were 80.3% and 94.1% for patients with SN metastatic tumor deposits ≥ 0.3 mm and < 0.3 mm, respectively (hazard ratio, 1.26 [1.11 to 1.44]; P < .0001). Similar findings were seen for overall disease-free and distant metastasis-free survival. There were no survival differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients. The newly identified high-risk (≥ 0.3 mm) subgroup comprised 271 (66.4%) of the AJCC IIIA cohort, whereas only 142 (34.8%) patients had SN tumor deposits > 1 mm in maximum dimension. CONCLUSION: Patients with AJCC IIIA melanoma with SN tumor deposits ≥ 0.3 mm in maximum dimension are at higher risk of disease progression and may benefit from adjuvant systemic therapy or enrollment into a clinical trial. Patients with SN deposits < 0.3 mm in maximum dimension can be managed similar to their SN-negative, AJCC IB counterparts, thereby avoiding regular radiological surveillance and more intensive follow-up.