Sentinel Node Biopsy in Melanoma

The role of sentinel node biopsy in melanoma is an ongoing discussion. Recent revisions to the AJCC Criteria have shifted the landscape. This article explores melanoma guidelines and recent revisions.

5 Key Points

1. What is a sentinel node?

The sentinel node is defined as the first node receiving lymphatic drainage from an area and is representative of that nodal basin.

2. What is the role of a sentinel node biopsy?

The role of sentinel node biopsies is centered on prognosis, staging, and individualising management plans

3. What are the indications of sentinel node biopsy?

Current indications for sentinel node biopsy include primary cutaneous melanoma pT2a or more and those pT1b with high risk features (lymphovascular invasion, mitosis), after discussion at a multi-disciplinary meeting.

4. What are management options for a positive sentinel node?

Current management options for positive sentinel node include observation, adjuvant therapy, and completion lymph node dissection. This article discusses current evidence for each of those options.

5. What are the major melanoma guidelines?

Current evidence is centered on the AJCC Cancer Stage 8th Edition, oncological adjuvant therapy studies, and node dissection trials. Other guidelines, such as NICE guidelines, do exist.

Blue Node in Sentinel Lymph Node Biopsy in Melanoma

Definition of Sentinel Node Biopsy

A sentinel node is the first lymph node receiving lymphatic drainage from a specific area (i.e site of lesion) and and is representative of that nodal basin.

This definition has evolved since Morton et al’s initial publication on the role of lymphoscintigraphy for melanoma in 1992¹.

Role of Sentinel Node Biopsy in Melanoma

The recent adjustments to the 8th Edition of AJCC Melanoma Guidelines have shifted the landscape in relation to the role of sentinel node biopsy in melanoma. There is clear evidence for its role in prognosis, treatment pathways and staging. This impacts both patient and doctor.

Prognosis

Sentinel Node Biopsy provides prognostic data on all depths of melanoma².

For example, a patient with pT1b melanoma has 2 options:

Option 1 – No SLNBx: This patient’s melanoma is now classified as clinical Stage 1B. This patient has a 5-year and 10-year survival of 97% and 93% respectively³.
Option 2 – SLNBx: This patient’s melanoma is now classified as a pathological Stage 1A. This patient has a 5-year and 10-year survival of 99% and 96% respectively³.

These prognostic implications are also relevant to thin melanomas (BT<1mm)^4,5

Treatment Pathways

The primary role of sentinel node biopsy is changing from that of a prognostic indicator to one that now influences access to adjuvant therapy⁶.

For those that have a positive sentinel node, upstaging the disease allows earlier identification for adjuvant therapies. It also allows them to be categorized in a “high-risk follow-up group”⁷.

Performing Sentinel Node Biopsy in Melanoma

Indications

Primary Cutaneous Melanoma pT2a and above
Primary Cutaneous Melanoma pT1b should be considered, especially if:
Lymphovascular Invasion
Mitotic rate ≥ 2/mm

The mitotic rate has been removed in version 8 of the AJCC guidelines. Nonetheless, an increase in mitotic rate decreases melanoma-specific survival³.

Risk of Positive Sentinel Node

Melanoma Stage	Positive Sentinel Node
pT1a	≤ 10%^8,9
pT1b	5%−12%⁶
BT > 4mm	30%^8,10

Risk of Positive Sentinel Nodes

In addition to a node being positive, other factors to consider are:

Nodal Tumour Burden: microscopic deposits >2–4 mm, >4–15 mm, 15 mm have a respective 5-year survival of 86%, 72% and 66%³
Non-sentinel node: the presence of an involved non-sentinel node (false negative SNB or an involved node on CLND) is a significantly poor prognostic factor for melanoma-specific survival³. It is also linked to tumour nodal burn¹¹and anatomical site of the melanoma deposit within the SLN¹²

Positive Sentinel Node Biopsy in Melanoma

Following a positive sentinel node, patients and doctors have three options: complete lymph node dissection, observation, adjuvant therapies.

Completion Lymph Node Dissection in Melanoma

Complete lymph node dissection should not be routinely recommended for patients who have a positive sentinel node biopsy⁶. Consider this treatment option in patients who are high risk of regional relapse based on their sentinel node results:

Extra-capsular spread
3 or more sentinel nodes
Dewar Criteria¹² (multifocal and extensive).
Node-only recurrence having failed first-line systemic treatment.

The MSLT-2¹³ and DeCOG¹⁴ Trials reported on the outcome of patients with a positive sentinel node randomised into observation and surgery. Key results include:

No survival advantage of completion lymph node dissection over radiological observation
Increase risk of nodal recurrence in those patients with observation

Patients undergoing immediate lymph node dissection have

Increased rate of regional disease control¹³
Prognostic information¹³
No increase in melanoma-specific survival¹³
An increased risk of morbidity in nodal dissection patients¹⁵

In relation to head and neck melanomas, adjuvant therapy is preferred to neck dissection³.

Adjuvant Therapy in Melanoma

Discussed in more detail: Oncological Adjuvant Therapies in Melanoma

Current guidelines state adjuvant therapy should be available to Stage 3 patients.

Generally speaking, patients deemed at high risk with a positive sentinel node should be considered for melanoma adjuvant therapy. A lymph node dissection could be considered if they have a node-only recurrence post-adjuvant treatment.

Radiological Observation in Melanoma

There is currently no general consensus with for ideal imaging in melanoma⁷

Current options include:

Ultrasound: Used in MLST and DeCOG Trials but does have operator dependability⁵
CT/PET: more sensitive to picking up recurrences⁵
MRI is used in some UK centres⁶

Imaging surveillance will differ for those on adjuvant systemic therapy.

Ultrasound Evaluation of the Lymphatic Spread in Melanoma

AJCC Version 8 Updates

This article is written with the most recent version of AJCC and other publications, as referenced below. The following is a list of V8 updates³

Tumor thickness: record to the nearest 0.1 mm, not 0.01 mm
New pT1a <0.8 mm without ulceration
New pT1b 0.8‐1.0 mm with or without ulceration or <0.8 mm with ulceration
Mitotic rate no longer a T category criterion
Pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB);
The N category descriptors “microscopic” and “macroscopic” for regional node metastasis are redefined as “clinically occult” and “clinically apparent and subcategories are revised, with the presence of microsatellites, satellites, or in‐transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor‐involved regional lymph node
Descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c)
A new M1d designation is added for central nervous system metastases.

References

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3. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA: A Cancer Journal for Clinicians. Published online October 13, 2017:472-492. doi:10.3322/caac.21409
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5. Lee A, Droppelmann N, Panageas K, et al. Patterns and Timing of Initial Relapse in Pathologic Stage II Melanoma Patients. Ann Surg Oncol. 2017;24(4):939-946. doi:10.1245/s10434-016-5642-0
6. Peach H, Board R, Cook M, et al. Current role of sentinel lymph node biopsy in the management of cutaneous melanoma: A UK consensus statement. J Plast Reconstr Aesthet Surg. 2020;73(1):36-42. doi:10.1016/j.bjps.2019.06.020
7. National Collaborating Centre for Cancer (UK). Melanoma: Assessment and Management. Published online July 1, 2015. https://www.ncbi.nlm.nih.gov/pubmed/26334080
8. Kachare SD, Singla P, Vohra NA, Zervos EE, Wong JH, Fitzgerald TL. Sentinel lymph node biopsy is prognostic but not therapeutic for thick melanoma. Surgery. Published online September 2015:662-668. doi:10.1016/j.surg.2015.05.012
9. Wat H, Senthilselvan A, Salopek TG. A retrospective, multicenter analysis of the predictive value of mitotic rate for sentinel lymph node (SLN) positivity in thin melanomas. Journal of the American Academy of Dermatology. Published online January 2016:94-101. doi:10.1016/j.jaad.2015.09.014
10. Ribero S, Osella-Abate S, Sanlorenzo M, et al. Sentinel Lymph Node Biopsy in Thick-Melanoma Patients (N=350): What is Its Prognostic Role? Ann Surg Oncol. Published online November 12, 2014:1967-1973. doi:10.1245/s10434-014-4211-7
11. Madu MF, Wouters MWJM, van Akkooi ACJ. Sentinel node biopsy in melanoma: Current controversies addressed. European Journal of Surgical Oncology (EJSO). Published online March 2017:517-533. doi:10.1016/j.ejso.2016.08.007
12. Dewar D, Newell B, Green M, Topping A, Powell B, Cook M. The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. J Clin Oncol. 2004;22(16):3345-3349. doi:10.1200/JCO.2004.12.177
13. Faries MB, Thompson JF, Cochran AJ, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. Published online June 8, 2017:2211-2222. doi:10.1056/nejmoa1613210
14. Leiter UM, Stadler R, Mauch C, et al. Final analysis of DECOG-SLT trial: Survival outcomes of complete lymph node dissection in melanoma patients with positive sentinel node. JCO. Published online May 20, 2018:9501-9501. doi:10.1200/jco.2018.36.15_suppl.9501
15. Faries MB, Thompson JF, 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. Published online July 8, 2010:3324-3329. doi:10.1245/s10434-010-1203-0