Sentinel Node Biopsy in Melanoma

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.


In this Article on Sentinel Node Biopsy


5 Key Points

What is the definition of a sentinel node biopsy? 

1st node to receive drainage from an area & represent a nodal basin

What is the role of a sentinel node biopsy?

Prognosis, staging, and adjuvant treatments. 

What are the indications of a sentinel node biopsy?

primary melanoma pT2a, pT1b with high-risk features.

What is the management of a positive sentinel node biopsy?

Observation, adjuvants, completion of lymph node dissection.

What guidelines are used in sentinel node biopsy?

Guidelines are AJCC Cancer Stage 8th Edition. There are also oncological adjuvant therapy studies and node dissection trials.


Definition of Sentinel Node Biopsy

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

The definition of "sentinel lymph node" has evolved since Morton et al’s initial publication on the role of lymphoscintigraphy for melanoma in 1992​​1​​.

Blue Node in Sentinel Lymph Node Biopsy in Melanoma


Role of Sentinel Node Biopsy in Melanoma

The recent adjustments to the 8th Edition of AJCC Melanoma Guidelines have shifted the landscape concerning 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 (SLNBx) provides prognostic data on all depths of melanoma​2. For example, a patient with pT1b melanoma has 2 options:

  • No SLNBx: melanoma is now classified as a clinical Stage 1B with 5-year and 10-year survival of 97% and 93%, respectively​3.
  • SLNBx: melanoma is now classified as a pathological Stage 1A with a 5-year and 10-year survival of 99% and 96%, respectively​3.

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

The role of sentinel node biopsy in melanoma is to upgrade or downgrade the staging of the disease from a pT1A or pT1b.
The Role of Sentinel Node Biopsy in Melanoma

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 therapy​6​.

For those with 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​.

💡
Clinical Tip: SLNBx in thick (>4 mm) melanomas (T4) has been questioned because of high rates of distant metastasis and poor prognosis. 


Performing Sentinel Node Biopsy in Melanoma

A sentinel node biopsy is indicated in melanoma ≥ pT2a or ≥ pT1b with high-risk features. Techniques include radioactive isotope, blue dye and indocyanine green

Indications

There are two main indications for sentinel node biopsy in melanoma.

  • Primary Cutaneous Melanoma ≥ pT2a
  • Primary Cutaneous Melanoma ≥ pT1b should be considered, especially if Lymphovascular Invasion or Mitotic rate ≥ 2/mm

The mitotic rate has been removed in version 8 of the AJCC guidelines. An increase in mitotic rate decreases melanoma-specific survival​3.

It is not currently indicated for T1a melanomas. The rationale for this cutoff is based on findings demonstrating that the frequency of sentinel lymph node metastasis is <5% (Swetter, 2019)

Risk of Positive Sentinel Node

The risk of finding a positive sentinel node is correlated to the stage of the depth of the disease, as described below:

  • pT1a: <10% 8,9
  • pT1b: 5-12% 6
  • BT > 4mm: 30% 8,10

💡
Clinical Tip: A false-negative case is a recurrence following a negative sentinel lymph node biopsy in a given nodal basin. This requires at least 2 years of follow up. 

Techniques

The 3 commonly used techniques for sentinel node biopsies are radioactive isotope, blue dye or indocyanine green. Here is an overview of their key points:

Radioactive Isotope

  • The current standard method of lymphatic mapping
  • Intradermal injection of a radiotracer at the tumour site & lymphoscintigraphy
  • Handheld gamma probe or a camera is used intraoperatively to guide dissection and detect the appropriate sentinel node(s).
  • Technetium-99m–labelled radiocolloids are the most commonly used radiotracers for lymphatic mapping

Blue Dyes

  • Blue dyes were initially used by Morton et al.
  • Blue dye alone has shown to have a sensitivity of 81% (Silvestri, 2019).
  • Patent Blue V, isosulfan blue and methylene blue are commonly used.
  • Rare risks include anaphylactic reactions, obscured intraoperative dissection, tattooing, and interference with pulse oximetry

Indocyanine Green

  • Indocyanine green is a fluorescent tricarbocyanine dye
  • The sensitivity of sentinel lymph node biopsy is reported as 91- 98%, a specificity of 100% (Clloyd, 2014).
  • It cannot be used in patients with iodine or shellfish allergies.

Timing of Sentinel Node Biopsy

The standard of care is to provide a sentinel lymph node biopsy at the time of wide local excision. Studies have found that sentinel lymph node biopsy after wide local excision is feasible with no difference in recurrence or survival with a delayed sentinel lymph node biopsy16-21.

💡
Tip: there is a risk of a "non-sentinel node". This is the presence of an involved non-sentinel node (false negative SNB or an involved node on CLND). It's a significantly poor prognostic factor for melanoma-specific survival​3​


Positive Sentinel Node Biopsy in Melanoma

Following a positive sentinel node, patients and doctors have three options: complete lymph node dissection, observation, and adjuvant therapies. These patients are now Stage III disease.

Completion Lymph Node Dissection in Melanoma

Complete lymph node dissection should not be routinely recommended for patients who have a positive sentinel node biopsy​6​. 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 Criteria​12​ (multifocal and extensive).
  • Node-only recurrence having failed first-line systemic treatment.

The MSLT-2​13​ and DeCOG​14​ 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 control​13​
  • Prognostic information​13​
  • No increase in melanoma-specific survival​13​
  • An increased risk of morbidity in nodal dissection patients​15​

With head and neck melanomas, adjuvant therapy is preferred to neck dissection​3​.

💡
Tip: Nodal Tumour Burden is an important factor in determining prognosis. Microscopic deposits >2–4 mm, >4–15 mm, and 15 mm have a respective 5-year survival of 86%, 72% and 66%​3​

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 consensus for ideal imaging in melanoma​7​

Current options include:

  • Ultrasound: MLST and DeCOG Trials but does have operator dependability​5​
  • CT/PET: more sensitive to picking up recurrences​5​
  • MRI is used in some UK centres​6​

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 updates​3​

  • 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

  1. Morton DL. Technical Details of Intraoperative Lymphatic Mapping for Early Stage Melanoma. Arch Surg. Published online April 1, 1992:392. doi:10.1001/archsurg.1992.01420040034005
  2. Dhakal S, Biswas T, Liesveld J, Friedberg J, Phillips G, Constine L. Patterns and timing of initial relapse in patients subsequently undergoing transplantation for Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys. 2009;75(1):188-192. doi:10.1016/j.ijrobp.2008.10.048
  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
  4. Lee JH, Park HS, Wei Q, Kim MN, Cho J-H. Difference of auditory brainstem responses by stimulating to round and oval window in animal experiments. Bioengineered. Published online September 30, 2016:8-13. doi:10.1080/21655979.2016.1226662
  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
  16. Leong SP, Thelmo MC, Kim RP, et al. Delayed harvesting of sentinel lymph nodes after previous wide local excision of extremity melanoma. Ann Surg Oncol. 2003;10:196–200.
  17. Leong WL, Ghazarian DM, McCready DR. Previous wide local excision of primary melanoma is not a contraindication for sentinel lymph node biopsy of the trunk and extremity. J Surg Oncol. 2003;82:143–146.
  18. Kelemen PR, Essner R, Foshag LJ, Morton DL. Lymphatic mapping and sentinel lymphadenectomy after wide local exci- sion of primary melanoma. J Am Coll Surg. 1999;189:247–252.
  19. Karakousis CP, Grigoropoulos P. Sentinel node biopsy before and after wide excision of the primary melanoma. Ann Surg Oncol. 1999;6:785–789.
  20. McCready DR, Ghazarian DM, Hershkop MS, Walker JA, Ambus U, Quirt IC. Sentinel lymph-node biopsy after previous wide local excision for melanoma. Can J Surg. 2001;44:432–434.
  21. May MM, Lohse CM, Moore EJ, et al. Wide local excision prior to sentinel lymph node biopsy for primary melanoma of the head and neck. Int J Dermatol. 2019;58:1184–1190.
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