Surgical Treatment:
Reason for Sentinel
Node Biopsy
Dale Han, MD
Yale University
School of Medicine
Assistant Professor
Department of Surgery
Section of Surgical Oncology
Yale University School of Medicine
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)
Yale University
School of Medicine
Balch CM, et al. Final version of 2009 AJCC melanoma staging
and classification. J Clin Oncol 2009; 27(36):6199-206.
Disease Status at Presentation, 2013
Melanoma of the Skin
Yale University
School of Medicine
Siegel R, et al. Cancer Statistics, 2013. CA Cancer J Clin 2013;63:11-30.
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
Yale University
School of Medicine
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
Yale University
School of Medicine
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).
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
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).
• Radiotracer
– Lymphoscintigraphy
• Vital blue dye
Yale University
School of Medicine
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).
Efficacy and Value of SLNB:
Multi-center Selective Lymphadenectomy Trial - I
Breslow thickness:
- 1.2 – 3.5 mm
- >3.5 mm
Randomization:
- WLE and observe
- WLE and SLNB
1661 randomized
- 1347 intermediate
- 314 thick
Positive SLN:
- 16% intermediate
- 32.9% 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):599-609. doi:
10.1056/NEJMoa1310460.
• Within SLNB group, MSS differed significantly
between positive and negative SLN patients in both
intermediate and thick groups
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):599-609. doi:
10.1056/NEJMoa1310460.
SLN status 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):599-609. doi:
10.1056/NEJMoa1310460.
Efficacy and Value of SLNB:
Sunbelt Melanoma Trial
Over 3600
patients enrolled
Breslow
thickness: ≥1 mm
All patients had
SLNB
Positive SLNB:
19.8%
Yale University
School of Medicine
McMasters KM, et al. Lessons learned from the Sunbelt Melanoma
Trial. J Surg Oncol. 2004;86:212-223.
False-Negative Rate of SLNB
• Meta-analysis shows range of 0 to 34%
• Overall FNR of 12.5% (95% CI 11-14.2%)
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;29:1479-1487.
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
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
SLNB for Thick Melanoma
Morton et al. 2014
Yale University
School of Medicine
MSLT-I
Significant difference in MSS by SLN status
Gajdos C, et al. Is there a benefit to sentinel lymph node biopsy in
patients with T4 melanoma? Cancer. 2009;115:5752-5760.
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
5-10% 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
Yale University
School of Medicine
Studies Evaluating SLN
Metastasis in Thin Melanoma
N
+SLN
Han et al.
1250
Yonnick et al.
Thick
Clark
Ulc
5.2%
Yes
Yes
Yes
147
11%
Yes
Han et al.
271
8.1%
Kesmodel et al.
181
5%
Venna et al.
484
7%
Ranieri et al.
184
6.5%
Yes
Yes
Koskivuo et al.
56
5.4%
Yes
Yes
Murali et al.
432
6.7%
Yes
Oliveiri et al.
77
7.8%
Wright et al.
631
4.9%
Yes
Sondak et al.
42
9.5%
Yes
Olah et al.
89
13.5%
Bedrosian et al.
71
5.6%
Taylor et al.
135
5.2%
Yale University
School of Medicine
Age
MR
Gender
Regress
TIL
VGP
LVI
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
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;30:2912-2918.
Coit DG, et al. Melanoma clinical practice guidelines in oncology. J Natl
Compre Cancer Netw. 2012;10:366-400.
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
Yale University
School of Medicine
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;17:3324-3329
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 311-3.
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
Thank You