1. Surgical Treatment: Reason for Sentinel Node Biopsy
Dale Han, MD
Assistant Professor Department of Surgery Section of Surgical Oncology Yale University School of Medicine
Yale University
School of Medicine

2. Prognostic Features Correlated with Melanoma-Specific Survival
Breslow thickness (T1-4)
Thin ≤1 mm (T1)
Intermediate >1 - ≤4 mm (T2, T3)
Thick >4 mm (T4)
Ulceration (Ta/b)
Mitotic rate in thin lesions (Ta/b)*
Nodal status (N0-3)
Distant metastasis (M0-1)
Clark level for the first time not included in AJCC staging
MR included and correlated with survival in thin lesions
Yale University
School of Medicine
Balch CM, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27(36):

3. Disease Status at Presentation, 2013
Melanoma of the Skin
Yale University
School of Medicine
Siegel R, et al. Cancer Statistics, CA Cancer J Clin 2013;63:11-30.

4. Nodal Status for Melanoma
Primary treated with wide local excision
Predilection for nodal spread
Nodal status prognostic for survival
Majority with no clinical evidence of nodal metastasis
Possibility for microscopic nodal spread?
Elective lymph node dissection once routinely performed to evaluate nodal status
Only 20% harbor nodal metastasis
Many unnecessarily exposed to risks and morbidity of lymphadenectomy without proven survival benefit
Now melanoma has a predilection for nodal spread
And nodal status has been shown to be prognostic for survival
For patients who present with nodal disease and no evidence of distant disease, lymph node dissection is recommended
However, the majority of patients are clinically node negative
So what is the possibility for microscopic nodal spread?
Elective lymph node dissection was once routinely performed to evaluate nodal status due to this possibility
But only 20% of patients were found to harbor nodal disease and many patients were unnecessarily exposed to the risks of lymphadenectomy without proven survival benefit
Yale University
School of Medicine

5. Sentinel Lymph Node Biopsy
Morton et al. reported on sentinel lymph node biopsy (SLNB) for melanoma as a less invasive technique to evaluate nodal status
Hypotheses:
Each area of skin drains to specific lymph nodes
1st draining nodes of a primary first to harbor nodal metastases and could be used to determine nodal status
In 1992, Morton et al. reported on SLNB for melanoma as a less invasive technique to evaluate nodal status
The hypotheses behind this technique was that each are of skin drained to specific lymph nodes and the first draining nodes of a primary would be the first to harbor nodal metastasis and could be used to determine nodal status
Morton DL, et al.: The sentinel lymph node and regional melanoma micrometastases. In: Cutaneous melanoma, 5th ed. Eds: Balch CM, Houghton AN, Sober AJ, Soong S, Atkins MB, Thompson, JF. Quality Medical Publishing, Inc., St. Louis, MO (2009).
Yale University
School of Medicine

6. Sentinel Lymph Node Biopsy
Peri-tumoral and intradermal injection of localizing agents
Accumulates in interstitial fluid and drains via lymphatics into regional nodes
Accumulates in 1st order nodes which are traced intra-operatively
Radiotracer
Lymphoscintigraphy
Vital blue dye
Uren RF, et al.: Lymphoscintigraphy in patients with melanoma. In: Cutaneous melanoma, 5th ed. Eds: Balch CM, Houghton AN, Sober AJ, Soong S, Atkins MB, Thompson, JF. Quality Medical Publishing, Inc., St. Louis, MO (2009).
Tufaro AP, et al.: Neck dissection and parotidectomy for melanoma. In: Cutaneous melanoma, 5th ed. Eds: Balch CM, Houghton AN, Sober AJ, Soong S, Atkins MB, Thompson, JF. Quality Medical Publishing, Inc., St. Louis, MO (2009).
Yale University
School of Medicine

7. Efficacy and Value of SLNB: Multi-center Selective Lymphadenectomy Trial - I
Breslow thickness: – 3.5 mm >3.5 mm
Randomization: WLE and observe WLE and SLNB
1661 randomized intermediate thick
Several studies have demonstrated the efficacy of SLNB.
The first was the MSLT-I which enrolled over 1300 patients and included melanomas mm thickness.
Patients were randomized to either WLE with nodal observation and lymph node dissection for nodal recurrences or WLE with SLNB and CLND for a positive SLN.
A positive SLN was seen in 16% of cases.
Positive SLN: % intermediate % thick
Yale University
School of Medicine
Morton DL, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7): doi: /NEJMoa

8. Within SLNB group, MSS differed significantly between positive and negative SLN patients in both intermediate and thick groups
However, when the SLNB group was evaluated, there was a significant difference in DFS and MSS between + and – SLN patients
In addition, in looking at all patient with nodal disease, there was a significant difference in 5 year survival between patients who had a SLNB and immediate CLND vs patients who were observed and had a delayed CLND for macroscopic nodal recurrence.
Yale University
School of Medicine
Morton DL, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7): doi: /NEJMoa

9. SLN status most powerful predictor of survival
In addition, in the multivariable analysis looking at prognostic factors for survival in the SLNB group, SLN status was the most powerful predictor of survival
Significant prognostic value for evaluating SLN status for intermediate group
Yale University
School of Medicine
Morton DL, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7): doi: /NEJMoa

10. Efficacy and Value of SLNB: Sunbelt Melanoma Trial
Over 3600 patients enrolled
Breslow thickness: ≥1 mm
All patients had SLNB
Positive SLNB: 19.8%
The second large study that evaluated SLNB was the sunbelt melanoma trial which enrolled over 3600 patients
Of note, Yale through Dr. Ariyan was a major contributor of patients to this study.
Patients with melanomas >=1 mm were included and all patients had a SLNB.
A positive SLN was seen in 19.8% of cases.
Yale University
School of Medicine
McMasters KM, et al. Lessons learned from the Sunbelt Melanoma Trial. J Surg Oncol. 2004;86:

11. False-Negative Rate of SLNB
Meta-analysis shows range of 0 to 34%
Overall FNR of 12.5% (95% CI %)
Yale University
School of Medicine
Valsecchi ME, et al. Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma: a meta-analysis. J Clin Oncol.2011;29:

12. SLNB for Intermediate Thickness Melanoma
Primary group evaluated for SLNB are patients with intermediate thickness melanoma
SLN status powerful prognostic value in this population
Positive SLNB rate ~15-20%
Identifies who will need node dissection and spares node-negative patients morbidity of lymphadenectomy
False-negative rate ~10-15%
Complication rate ~5-10%
Lower number of harvested nodes allows for more rigorous evaluation of each node
Yale University
School of Medicine

13. SLNB for Thick Melanoma
Controversy exists over use of SLNB for thick melanoma (≥4 mm)
30-40% of patients with thick melanoma ultimately develop systemic metastases
Regional staging may have limited utility in patients who ultimately develop distant disease
For patients who do not develop systemic disease, staging of regional nodes may provide benefit since 25-40% of these patients will harbor SLN metastases
Yale University
School of Medicine

14. SLNB for Thick Melanoma
Morton et al MSLT-I Significant difference in MSS by SLN status
Yale University
School of Medicine
Gajdos C, et al. Is there a benefit to sentinel lymph node biopsy in patients with T4 melanoma? Cancer. 2009;115:

15. SLNB for Thin Melanoma
70% of newly diagnosed melanomas are thin melanomas (≤1 mm)
Most patients with thin melanoma have a good prognosis with 10-year survival rates of ~90%
Controversy exists
Subset of thin melanoma patients do poorly with % developing regional recurrences and these patients may benefit from nodal staging
Low incidence of nodal metastasis
Uncertain prognostic value
Several high-risk factors for nodal disease in thin melanomas reported with no consensus
Most patients with thin melanoma <=1 mm, as defined by AJCC criteria, have a good prognosis w/ 10 yr survival rates of ~90%
However, a subset of thin melanoma patients do poorly with 5-10% developing regional recurrences
SLNB is widely recommended for melanomas >1 mm as recently reported in the SSO/ASCO and NCCN guidelines
However, SLNB for melanomas <=1 m is debated
Several high risk factors for nodal disease in thin melanomas are reported with no consensus that has been established
Yale University
School of Medicine

16. Studies Evaluating SLN Metastasis in Thin Melanoma
Age
Thick
Clark
Ulc MR
Gender
Regress
TIL
VGP
LVI
Han et al.
1250
5.2%
Yes
Yonnick et al.
147
11%
271
8.1%
Kesmodel et al.
181 5%
Venna et al.
484 7%
Ranieri et al.
184
6.5%
Koskivuo et al. 56
5.4%
Murali et al.
432
6.7%
Oliveiri et al. 77
7.8%
Wright et al.
631
4.9%
Sondak et al. 42
9.5%
Olah et al. 89
13.5%
Bedrosian et al. 71
5.6%
Taylor et al.
135
This slide shows the various predictors for SLN metastasis in thin melanoma that have been report
A boldfaced yellow “yes” indicates predictive on a multivariable analysis performed specifically in thin melanoma patients while a white yes refers to predictive on univariable analysis or based on extrapolations from a predictive model
As you can see, various predictors have been reported with no consistent markers shown
Yale University
School of Medicine

17. Guidelines for SLNB for Melanoma
SSO/ASCO and NCCN published guidelines
Intermediate thickness melanoma: SLNB is recommended for patients with intermediate thickness cutaneous melanoma (Breslow thickness 1-4 mm) of any anatomic site.
Thick melanomas: SLNB may be recommended for staging purposes and to facilitate regional disease control for patients with cutaneous melanomas that are T4 or >4 mm in Breslow thickness.
Thin melanomas: There is insufficient evidence to support routine SLNB for patients with melanomas that are T1 or <1 mm in Breslow thickness, although it may be considered in high-risk patients.
Yale University
School of Medicine
Wong SL, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. J Clin Oncol. 2012;30:
Coit DG, et al. Melanoma clinical practice guidelines in oncology. J Natl Compre Cancer Netw. 2012;10:

18. Why is CLND Recommended?
Gold standard is completion lymph node dissection (CLND) for positive SLNB and no evidence of distant disease
Rate of additional nodes with metastasis in CLND after positive SLNB:
Range: 15-32%
MSLT-I: 16%, Sunbelt: 16%
Meta-analysis: 20.1%
SSO/ASCO and NCCN guidelines recommend CLND for all patients with a positive SLNB
Once a positive SLN is found, the gold standard is for a completion lymph node dissection
The reason is that there is a significant chance for finding additional nodes with metastatic melanoma in the CLND specimen.
In both MSLT-I and the Sunbelt trials, the rate was 16% and a meta-analysis demonstrated a rate of 20.1%.
However, 80% of patients with a positive SLN only have 1 node with metastasis and this begs the question…
Yale University
School of Medicine

19. Why is CLND Recommended? MSLT-I
Yale University
School of Medicine
Faires MB, et al. The impact on morbidity and length of stay of early versus delayed complete lymphadenectomy in melanoma: results of the Multicenter Selective Lymphadenectomy Trial (I). Ann Surg Oncol. 2010;17:

20. Does Every Positive SLN Case Require CLND: MSLT-II
80-85% of positive SLN cases with no additional nodal metastasis outside of SLN disease
70-80% of positive SLN patients only have 1 node with metastasis
Yale University
School of Medicine
Morton DL, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005;242:302-11; discussion

21. Summary Sentinel lymph node biopsy
Recommended for intermediate and may be recommended for thick melanomas
May be considered for thin melanomas with high-risk features
Sentinel node status is prognostic for survival
Until results of MSLT-II are available, CLND is recommended for a positive SLNB
Yale University
School of Medicine

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