Highlights
- •Regional node recurrence risk ~40% without sentinel node biopsy or immunotherapy.
- •Risk lowered to ~27% with adjuvant immunotherapy alone.
- •Risk lowered to ~14% with sentinel node biopsy alone.
- •Risk lowered to ~9% with both adjuvant immunotherapy and sentinel node biopsy.
Abstract
The prognostic value of sentinel node biopsy (SNB) is well established and SNB was
therefore adopted as a requirement for pathological staging of melanomas >1 mm thick
in the AJCC-8th edition. Consequently, a negative SNB status became an eligibility
criterion for clinical trials of adjuvant systemic therapy in resected stage IIB/C
melanoma. However, since the Keynote 716 trial demonstrated an improvement in relapse-free
survival (RFS) in patients with Stage IIB/C melanoma, all of whom had SNB staging,
some have argued that SNB is no longer required for patients with T3 and T4 primary
melanomas. The rationale for omitting SNB is that these patients will be able to access
adjuvant immunotherapy regardless of SNB status, avoiding the costs and potential
complications of SNB. However, this argument overlooks the prognostic value of knowing
a patient’s nodal status and the therapeutic benefit of SNB in regional disease control.
Based on extrapolation of data from multiple sources, we demonstrate that the risk
of regional node-field relapse with SNB and immunotherapy for T3b and T4 melanomas
is around 7–9% but is 20–27% without SNB. Similarly, the node-field recurrence rate
with SNB alone is around 14% compared to around 40% with no SNB or immunotherapy.
Consequently, in the absence of prospective data, we propose that the optimal management
of the regional node-field for high-risk T3b and T4 primary melanomas is likely to
be achieved by combining SNB and adjuvant immunotherapy for those patients who are
suitable, rather than either treatment alone.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Sentinel node biopsy in patients with melanoma improves the accuracy of staging when added to clinicopathological features of the primary tumor.Ann Oncol. 2021; 32: 375-383
- Therapeutic value of sentinel lymph node biopsy in patients with melanoma: a randomized clinical trial.JAMA Surg. 2022; 157: 835-842
- Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual.CA: Cancer J Clin. 2017; 67: 472-492
(NCCN) NCCN. Melanoma: Cutaneous NCCN Clinical Practice Guidelines in Oncology. 2.2021 ed. 2021.
- Updated evidence-based clinical practice guidelines for the diagnosis and management of melanoma: definitive excision margins for primary cutaneous melanoma.Med J Aust. 2018; 208: 137-142
- Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-updagger.Ann Oncol. 2019; 30: 1884-1901
- Guidelines of care for the management of primary cutaneous melanoma.J Am Acad Dermatol. 2019; 80: 208-250
- Sentinel node biopsy for melanoma: unnecessary treatment?.BMJ. 2013; 346e8645
- Adjuvant interferon-alpha for the treatment of high-risk melanoma: an individual patient data meta-analysis.Eur J Cancer. 2017; 82: 171-183
- Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial.Lancet Oncol. 2021; 22: 643-654
- Five-year analysis of adjuvant dabrafenib plus trametinib in stage III melanoma.N Engl J Med. 2020; 383: 1139-1148
- Adjuvant nivolumab versus ipilimumab in resected stage IIIB–C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial.Lancet Oncol. 2020; 21: 1465-1477
- Distant metastasis-free survival with pembrolizumab versus placebo as adjuvant therapyin stage IIB or IIC melanoma: the phase 3 KEYNOTE-716 study.J Clin Oncol. 2022; 40 (Chicago, IL, USA: ASCO; 2022): LBA9500
Bristol-Myers Squibb, Bristol Myers Squibb Presents Data from CheckMate -76K Showing Opdivo (nivolumab) Reduced the Risk of Recurrence or Death by 58% Versus Placebo in Patients with Completely Resected Stage IIB or IIC Melanoma. 2022.
- Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial.Ann Surg. 2005; 242 (discussion 11-3): 302-311
- Sentinel lymph node biopsy in melanoma: The Oxford ten year clinical experience.J Plast Reconstr Aesthet Surg. 2011; 64: 1284-1290
- Negative sentinel lymph node biopsy in patients with melanoma: the patient's perspective.Ann Surg Oncol. 2019; 26: 2263-2267
- Sentinel lymph node biopsy for T1b melanoma: balancing prognostic value and cost.Ann Surg Oncol. 2020; 27: 5248-5256
- Therapeutic value of sentinel lymph node biopsy in patients with melanoma: a randomized clinical trial.JAMA Surg. 2022; 157: 835-842
- Long-term safety of pembrolizumab monotherapyand relationship with clinical outcome: a landmarkanalysis in patients with advanced melanoma.Eur J Cancer. 2021; 144 (Oxford, England: 1990): 182-191
- Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis.JAMA Oncol. 2018; 4: 1721-1728
- Cost-effectiveness of adjuvant systemic therapies for patients with high-risk melanoma in Europe: a model-based economic evaluation.ESMO Open. 2021; 6100303
- Final trial report of sentinel-node biopsy versus nodal observation in melanoma.N Engl J Med. 2014; 370: 599-609
- 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
- Completion dissection or observation for sentinel-node metastasis in melanoma.N Engl J Med. 2017; 376: 2211-2222
- Non-Sentinel Node Risk Score (N-SNORE): a scoring system for accurately stratifying risk of non-sentinel node positivity in patients with cutaneous melanoma with positive sentinel lymph nodes.J Clin Oncol. 2010; 28: 4441-4449
- Impact of completion lymph node dissection on patients with positive sentinel lymph node biopsy in melanoma.J Am Coll Surg. 2016; 223: 9-18
- Nodal recurrence is a primary driver of early relapse for patients with sentinel lymph node-positive melanoma in the modern therapeutic era.Ann Surg Oncol. 2021; 28: 3480-3489
- Nodal and systemic recurrence following observation of a positive sentinel lymph node in melanoma.Br J Surg. 2020;
- Prognosis of patients with primary melanoma stage I and II according to American Joint Committee on Cancer Version 8 validated in two independent cohorts: implications for adjuvant treatment.J Clin Oncol. 2022; (JCO2200202)
- Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial.The Lancet. 2022;
Article info
Publication history
Published online: March 17, 2023
Accepted:
March 12,
2023
Received in revised form:
February 15,
2023
Received:
December 14,
2022
Publication stage
In Press Uncorrected ProofIdentification
Copyright
© 2023 Elsevier Ltd. All rights reserved.
