- The prognostic significance of the pathologic status of the sentinel lymph node (SLN):
- Has been convincingly demonstrated
- Data from MD Anderson demonstrated that SLN status was:
- The most significant clinicopathologic prognostic factor with respect to survival in patients with melanoma
- In an analysis of 1,487 patients who underwent SLNB (median tumor thickness, 1.5 mm):
- The 5-year survival rate for patients with:
- Positive SLNs was 73.3%:
- Compared to 96.8% for patients with negative SLNs
- Positive SLNs was 73.3%:
- The 5-year survival rate for patients with:
- Several other multivariate regression analyses:
- Have shown that regional lymph node status is the most powerful predictor of recurrence (both regional and distant) and survival:
- Even among patients with thick melanomas
- Have shown that regional lymph node status is the most powerful predictor of recurrence (both regional and distant) and survival:
- Taken together with patients who have clinical regional disease, according to analysis done by the International Melanoma Database and Discovery Platform (IMDDP) that provided revisions to the 8th edition AJCC melanoma staging system:
- 5-year melanoma-specific survival rates for patients with:
- Stage III disease range from 93% for patients with IIIA disease to 32% for patients with IIID disease
- 5-year melanoma-specific survival rates for patients with:
- The prognostic importance of distinguishing between:
- Clinically occult and clinically detected lymph nodes:
- Has been emphasized by incorporation of this criterion into the 8th edition AJCC melanoma staging system
- Clinically occult and clinically detected lymph nodes:
- The concept of tumor burden has become important in the era of SLNB:
- As accurate microscopic staging of SLNs allows patients to be better stratified into similar risk subgroups
- Several studies have shown that the diameter of the largest SLN tumor nodule and the total SLN tumor volume:
- Are significant predictors of recurrence and survival
- The prognostic significance of sentinel node tumor burden continues to be an active area of investigation worldwide
- The landmark prospective Multicenter Selective Lymphadenectomy Trial-I (MSLT-I):
- Was designed in 1994 to assess whether a selective approach to regional lymphadenectomy limiting completion lymph node dissection:
- To patients with microscopic disease in SLNs:
- Confers a survival benefit compared to wide excision of the primary melanoma and observation of the regional nodal basin
- To patients with microscopic disease in SLNs:
- Patients with primary cutaneous melanomas at least 1 mm thick or with Clark level IV or V tumors with any Breslow thickness were eligible for the trial
- Two thousand and one patients were randomly assigned to:
- Wide excision alone and observation of the regional nodal basin(s) (40%) or wide excision and lymphatic mapping and SLNB (60%), with subsequent CLND if any SLNs were positive
- In 2014, the final trial report was published with 10 years of follow-up data:
- Ten-year disease-free survival rates were significantly higher in the SLNB group than in the observation group among patients with intermediate-thickness melanomas:
- 71.3 ± 1.8% in the SLNB group compared to 64.7 ± 2.3% in the observation group (hazard ratio for recurrence or metastasis, 0.76; 95% CI 0.62 to 0.94; P =.01)
- When the SLNB group was further explored:
- It was noted that patients who had evidence of microscopic SLN involvement did worse than patients with a negative SLNB
- For patients with intermediate-thickness primary melanoma (defined in MSLT-I as 1.2 to 3.5 mm):
- The melanoma-specific survival at 10 years was significantly worse in patients with a positive SLNB compared to those who had a negative SLNB:
- 62% vs. 85%, HR 3.09, 95% CI 2.12 to 4.49
- For patients with thick melanoma (defined in MSLT-I as > 3.50 mm):
- The melanoma-specific survival rate at 10 years was again significantly worse in patients with lymph node involvement compared to those who had a negative lymph node biopsy (48.0% vs. 64.6%, HR 1.75, 95% CI 1.07 to 2.87)
- Interestingly, when applied to the study cohort, a statistical approach called latent-subgroup analysis (a technique that accounts for the observation that nodal status was initially only known in the SLNB group):
- Showed a clear benefit of SLNB
- Among patients who had SLNB and a positive SLN compared to those who developed clinical regional melanoma metastasis after wide excision alone:
- There was doubling of melanoma-specific and distant disease–free survival and a tripling of disease-free survival
- The melanoma-specific survival at 10 years was significantly worse in patients with a positive SLNB compared to those who had a negative SLNB:
- Ten-year disease-free survival rates were significantly higher in the SLNB group than in the observation group among patients with intermediate-thickness melanomas:
- Was designed in 1994 to assess whether a selective approach to regional lymphadenectomy limiting completion lymph node dissection:
- Sentinel Lymph Node Biopsy (SLNB):
- Purpose:
- Identifies microscopic nodal metastases in patients with clinically node-negative melanoma
- Provides accurate staging (AJCC 8th edition) and guides adjuvant therapy decisions
- Prognostic Significance:
- SLN-positive status is the strongest independent prognostic factor for recurrence and survival:
- In intermediate-thickness melanomas
- 5-year melanoma-specific survival (MSS):
- SLN-negative: ~ 90% to 95%
- SLN-positive: ~ 60% to 70%
- SLN-negative: ~ 90% to 95%
- References:
- Morton DL, Thompson JF, Cochran AJ, et al. N Engl J Med. 2006;355(13):1307–1317. doi:10.1056/NEJMoa060903
Balch CM, Gershenwald JE, Soong SJ, et al. J Clin Oncol. 2009;27(36):6199–6206.
- Morton DL, Thompson JF, Cochran AJ, et al. N Engl J Med. 2006;355(13):1307–1317. doi:10.1056/NEJMoa060903
- SLN-positive status is the strongest independent prognostic factor for recurrence and survival:
- Tumor Burden in SLN Matters:
- Greater nodal tumor burden equals worse prognosis:
- < 0.1 mm deposits:
- Very low risk
- > 1 mm or multiple SLNs involved
- Significantly reduced survival
- < 0.1 mm deposits:
- Reference:
- van der Ploeg AP, van Akkooi AC, Rutkowski P, et al. Ann Surg Oncol. 2011;18(2):519–528.
- Greater nodal tumor burden equals worse prognosis:
- Impact on Treatment Decisions:
- SLN status determines eligibility for:
- Adjuvant immunotherapy:
- Nivolumab, pembrolizumab
- Targeted therapy in BRAF-mutant patients:
- Dabrafenib + trametinib
- Surveillance protocols
- Adjuvant immunotherapy:
- Reference:
- Weber J, Mandala M, Del Vecchio M, et al. N Engl J Med. 2017;377(19):1824–1835.
- Eggermont AMM, Blank CU, Mandala M, et al. N Engl J Med. 2018;378(19):1789–1801.
- SLN status determines eligibility for:
- Supporting Trials:
- MSLT-I:
- SLN status is prognostic for recurrence-free and melanoma-specific survival
- MSLT-II and DeCOG-SLT:
- No survival benefit with completion lymph node dissection (CLND)
- References:
- Morton DL, Thompson JF, Cochran AJ, et al. N Engl J Med. 2006;355(13):1307–1317.
- Faries MB, Thompson JF, Cochran AJ, et al. N Engl J Med. 2017;376(23):2211–2222.
- Leiter U, Stadler R, Mauch C, et al. Lancet Oncol. 2016;17(6):757–767.
- MSLT-I:
- AJCC Staging Integration:
- SLN status incorporated in Stage III classification:
- Stage IIIA:
- Micrometastases + no ulceration = best prognosis
- Higher sub-stages = greater tumor burden or ulceration
- Stage IIIA:
- Reference:
- Gershenwald JE, Scolyer RA, Hess KR, et al. CA Cancer J Clin. 2017;67(6):472–492.
- SLN status incorporated in Stage III classification:
- Guidelines:
- SLNB recommended for:
- Breslow depth ≥ 1 mm
- 0.8mm to 1.0 mm with high-risk features:
- Ulceration, high mitotic index
- Reference:
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma, Version 2.2024.
- SLNB recommended for:
- Purpose:
- Conclusion:
- Sentinel lymph node status is a powerful prognostic marker in cutaneous melanoma and has direct implications for staging, risk stratification, treatment planning, and surveillance
Rodrigo Arrangoiz MS, MD, FACS, FSSO 