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Sentinel node biopsy and nodal management in melanoma

TL;DR — Two randomised trials converged on the same answer: completion lymph-node dissection after a positive sentinel node does not improve survival. MSLT-II found no increase in melanoma-specific survival across 1,934 evaluable patients (3-year MSS 86 ± 1.3% with dissection versus 86 ± 1.2% with observation, P = .42), with a small disease-free-survival difference driven entirely by regional nodal control (92 ± 1.0% versus 77 ± 1.5%, P < .001) and lymphoedema in 24.1% of dissected patients (Faries 2017, PMID 28591523). DeCOG-SLT reached the same conclusion in 483 randomised patients at 72 months' median follow-up, with 5-year distant-metastasis-free survival 67.6% versus 64.9% (Leiter 2019, PMID 31557067). Sentinel node biopsy itself, in MSLT-I's final report of 2,001 patients, showed no melanoma-specific survival difference in the overall population but improved 10-year disease-free survival in intermediate-thickness (71.3 ± 1.8% versus 64.7 ± 2.3%; HR 0.76, P = .01) and thick melanoma (Morton 2014, PMID 24521106) — a result whose design and analysis have been formally challenged (Thomas 2009, PMID 19246272). What remains uncontested is that sentinel-node status is the strongest single prognostic input into the AJCC N category and the gate for adjuvant-therapy eligibility, so a procedure whose therapeutic action has been withdrawn still directs systemic treatment.

The three randomised trials

Trial Question n Result
MSLT-I (Morton 2014, PMID 24521106) Sentinel-node biopsy + immediate lymphadenectomy vs wide excision + nodal observation with delayed lymphadenectomy 2,001 No significant difference in 10-year melanoma-specific survival overall. 10-year DFS improved with biopsy for intermediate-thickness (1.20–3.50 mm) melanoma: 71.3 ± 1.8% vs 64.7 ± 2.3%, HR 0.76, P = .01; also improved for thick (>3.50 mm) melanoma
MSLT-II (Faries 2017, PMID 28591523) Completion dissection vs nodal observation with ultrasonography after a positive sentinel node 1,934 evaluable (1,755 per protocol) 3-year MSS 86 ± 1.3% vs 86 ± 1.2%, P = .42. 3-year DFS 68 ± 1.7% vs 63 ± 1.7%, P = .05, attributed to regional nodal control 92 ± 1.0% vs 77 ± 1.5%, P < .001. Non-sentinel-node metastases in 11.5% of dissected patients and independently prognostic for recurrence (HR 1.78, P = .005). Lymphoedema in 24.1% of dissected patients
DeCOG-SLT (Leiter 2019, PMID 31557067) Completion dissection vs observation, trunk and extremity melanoma 483 randomised of 1,256 sentinel-positive identified from 5,547 screened Median follow-up 72 months (IQR 67–77). 5-year distant-metastasis-free survival 67.6% (observation) vs 64.9% (dissection), no significant treatment difference

The critique of MSLT-I is substantive and should be presented, not smoothed over. Almost half the patients in the observation arm were investigated with lymphoscintigraphy and regular targeted high-resolution ultrasound contrary to the protocol, detecting nodal metastasis in some before it became palpable and thereby affecting the primary endpoint; the method of calculating disease-free survival has also been successfully challenged (Thomas 2009, PMID 19246272).

If dissection is not therapeutic, is the biopsy?

MSLT-II's own long-term analysis of the observation arm reframes the question. Among 823 observed patients and 855 observed basins, 80.2% (actuarial, 95% CI 77–83) of basins were free of nodal recurrence at 10 years — that is, removal of the positive sentinel node alone cleared the basin in most patients (Crystal 2022, PMID 35921122). Freedom from in-basin recurrence was associated with:

Factor (multivariable) HR (95% CI) P
Age <50 years 0.57 (0.39–0.84) .004
Thinner primary melanoma 0.40 (0.22–0.70) .002
Axillary basin 0.55 (0.31–0.96) .03
SLN metastasis diameter <1 mm 0.52 (0.33–0.81) .007
SLN metastasis area <5% 0.58 (0.38–0.88) .01

Five-year basin disease-free rates by number of risk factors (age ≥50, ulceration, Breslow >3.5 mm, non-axillary basin, deposit ≥1 mm and/or ≥5% area): 96% (0 factors), 89% (1), 86% (2), 80% (3), 61% (4), 54% (5–6) (PMID 35921122). The authors conclude sentinel node biopsy "may also be regarded as therapeutic in some patients" — a claim derived from a single-arm analysis of a randomised trial's observation arm, which is hypothesis-generating rather than confirmatory.

Who should have a sentinel node biopsy?

Thin (T1) melanoma

Evidence Positivity rate Predictors
Meta-analysis of 34 studies, 3,651 patients (2009) 5.6% pooled Significant heterogeneity (P = .005), no publication bias (Warycha 2009, PMID 19117354)
Meta-analysis of 66 studies, 38,844 patients (2022) 5.1% (95% CI 4.9–5.3) Thickness ≥0.8 mm (adjusted OR 1.94, 1.28–2.95; positivity 7.0%), ulceration (AOR 3.09, 1.75–5.44; positivity 4.2%), mitotic rate >0 (Huang 2022, PMID 35155254)
International multi-institution, 676 T1 patients, 5 centres, 2005–2018 7.8% Breslow thickness and mitotic rate independently predictive; odds rose 50% per 0.1 mm above 0.7 mm (95% CI 1.05–2.13) and 22% per mitosis (Walker 2022, PMID 35676603)
Danish national, 7,148 T1 patients, AJCC7 (2016–17) vs AJCC8 (2018–19) 6.7% → 4.7% (P = .118) SLNB rate rose 16.2% → 22.2% (P < .001) with no increase in positivity; younger age and mitotic rate ≥1 predicted positivity (Weitemeyer 2022, PMID 34672372)

The Danish population data are the cleanest natural experiment available on the 8th-edition T1 redefinition: 37% more biopsies, no more positive nodes. A validated nomogram for T1 sentinel-node metastasis exists (Maurichi 2020, PMID 32167862).

Desmoplastic melanoma

Pooled sentinel-node positivity across 18 studies and 1,671 patients was 9% (95% CI 7–12), but 6% (4–8) for pure and 15% (10–20) for mixed desmoplastic melanoma, with no association between positivity and Breslow depth (β = 0.058, P = .749) or ulceration (β = 0.763, P = .677) (Yee 2026, PMID 41870859). The standard thickness/ulceration selection criteria do not work here — see histopathology and prognostic factors.

Head and neck

Complex lymphatic drainage in head-and-neck cutaneous melanoma is associated with different sentinel-node outcomes (Pasha 2023, PMID 36892824), and long-term outcomes, prognostic value, accuracy and safety of the procedure in this region have been separately reported (Hanks 2020, PMID 32041486). Scalp and neck primaries carry independently worse melanoma-specific survival (adjusted HR 1.28, 1.16–1.41) than other head-and-neck sites (Rashid 2026, PMID 41803580).

Nodal tumour burden as the missing variable

Sentinel-node status is binary in the AJCC N category, but the deposit's size is continuous and prognostic.

  • In 736 sentinel-positive patients with mean follow-up 64.4 months, maximum deposit diameter was an independent predictor of melanoma-specific survival within stage IIIA/B/C, at cut-offs ≤0.5 mm (AUC 0.617) and ≤1 mm (0.599); the authors argue a cut-off below 1 mm is preferable and that burden should enter future classifications (Satzger 2019, PMID 31677550).
  • Central review of 146 node-positive MSLT-I patients found median 1 involved node, median maximum metastasis dimension 1.11 mm and median nodal area involvement 1.5%; tumour thickness, ulceration, non-sentinel-node metastasis and multiple burden measures related to melanoma-specific survival, and primary ulceration plus extent of metastasis predicted non-sentinel-node involvement (Cochran 2022, PMID 35246348).
  • The EORTC-DeCOG nomogram predicts recurrence, distant metastasis and overall mortality in sentinel-positive patients from ulceration, age, sentinel-node tumour burden and Breslow thickness, derived in 1,080 patients across nine EORTC centres and externally validated in 705 German patients including 473 DeCOG-SLT participants — explicitly "without the need for completion lymph node dissection" (Verver 2020, PMID 32454396).
  • Lymph node ratio adds prognostic information beyond AJCC N stage even with standardised surgery (Spillane 2011, PMID 21119509).

Morbidity, which is the reason the trials mattered

Lymphoedema occurred in 24.1% of patients randomised to completion dissection in MSLT-II (PMID 28591523). Morbidity after inguinal sentinel-node biopsy versus completion dissection has been quantified separately (de Vries 2006, PMID 16806794), as has morbidity after axillary sentinel-node biopsy (de Vries 2005, PMID 15993029). Risk factors for complications and long-term outcomes after completion dissection have been characterised in a retrospective cohort (Sars 2020, PMID 32467082), and national analysis has examined recurrence rates and lymphoedema risk after lymphadenectomy (Shen 2024, PMID 38556691). Factors associated with melanoma-related limb lymphoedema have been reported from registry data (Gjorup 2021, PMID 33793386).

Technique

Sentinel node identification rests on lymphoscintigraphy with a radiocolloid, historically supplemented by blue dye. Fluorescence tracers are the main technical change.

Approach Evidence
Radioisotope + blue dye vs radioisotope + indocyanine green Retrospective cohort of 311 melanoma patients at one centre: detection rates 100% (RI+BD, n = 227) vs 98.8% (RI+ICG, n = 84), P = .1; fewer nodes resected with ICG (P = .047); positive-node rates 9.5% vs 6.2%, P = .3. ICG alone could not identify all positive nodes (Lavy 2024, PMID 39581000)
Hybrid tracer (ICG-⁹⁹ᵐTc-nanocolloid) Prospective study of 104 patients with head-and-neck, trunk or extremity melanoma 2010–2013, combining gamma tracing with fluorescence imaging after intradermal hybrid-tracer administration, with lymphoscintigraphy and SPECT/CT (van den Berg 2015, PMID 25521776)
Fluorescence generally Indocyanine green fluorescence lymphangiography has been evaluated as a mapping adjunct (Namikawa 2011, PMID 21498148; Cloyd 2014, PMID 25124992), including in head-and-neck melanoma alongside lymphoscintigraphy (PMID 29907233), with a 2026 comparison against conventional mapping (PMID 42108206)
Tilmanocept ⁹⁹ᵐTc-tilmanocept sentinel node biopsy with long-term outcomes has been reported in a cohort study and literature review (PMID 42617582)

Technique changes detection, not indication. None of these comparisons alters who should have the procedure or what the result means — the questions this page's randomised evidence leaves open.

The inheritance problem

Sentinel-node status entered practice as a staging variable justified partly by an assumed therapeutic action of early lymphadenectomy. MSLT-II and DeCOG-SLT removed the therapeutic action (PMID 28591523; PMID 31557067). Sentinel-node status nonetheless remains:

  1. a defining input to AJCC 8th-edition stage III subgrouping (Gershenwald 2017, PMID 29028110);
  2. the eligibility criterion on which the adjuvant trials — KEYNOTE-054, COMBI-AD, CheckMate 238 — were built, and therefore the gate for adjuvant therapy (see adjuvant therapy);
  3. the entry criterion for the neoadjuvant trials that are now reshaping stage III care (see neoadjuvant therapy).

Nobody has re-derived the eligibility rules from the post-MSLT-II evidence base. If the biopsy is a prognostic instrument rather than a therapeutic one, the question of whether adjuvant eligibility should be defined by a nodal procedure or by a multivariable risk model (as the EORTC-DeCOG nomogram or the 31-gene profile would allow) is open (PMID 32454396; Zager 2018, PMID 29402264).

Interpretation rules for this page

  • Distinguish the biopsy from the dissection. MSLT-I tested the biopsy, MSLT-II and DeCOG-SLT tested the dissection; conclusions do not transfer between them.
  • Distinguish regional control from survival. Completion dissection improves nodal control substantially and survival not at all (PMID 28591523).
  • Positivity rate is not benefit. More biopsies in T1 melanoma after AJCC 8 produced no more positive nodes (PMID 34672372).
  • Report deposit size, not just status — it is independently prognostic within AJCC stage III (PMID 31677550; PMID 35246348).
  • Desmoplastic and head-and-neck melanoma break the standard selection rules (PMID 41870859; PMID 36892824).
  • MSLT-II's therapeutic-value analysis is single-arm. It describes what happened to the observation arm; it does not randomise biopsy against no biopsy (PMID 35921122).

Open questions

  • If completion dissection has no survival benefit, what exactly is sentinel-node status for — prognosis, trial eligibility, or therapy (PMID 28591523; PMID 35921122)?
  • Should adjuvant-therapy eligibility be re-derived from multivariable risk rather than nodal status (PMID 32454396; PMID 29402264)?
  • Should sentinel-node tumour burden enter the AJCC N category, and at what threshold (PMID 31677550)?
  • Does sentinel-node biopsy have a therapeutic effect in the low-risk-factor subgroup where 96% of basins stayed clear at 5 years, and how would that be tested (PMID 35921122)?
  • Is any sentinel-node biopsy justified in T1 melanoma at a 5.1% pooled positivity rate, and does the answer change with modern adjuvant options (PMID 35155254; PMID 34672372)?
  • Should desmoplastic melanoma have its own selection criteria given the pure/mixed positivity gap (PMID 41870859)?

References

  1. Faries MB, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. The New England journal of medicine. 2017;376:2211-2222. PMID 28591523
  2. Leiter U, et al. Final Analysis of DeCOG-SLT Trial: No Survival Benefit for Complete Lymph Node Dissection in Patients With Melanoma With Positive Sentinel Node. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019;37:3000-3008. PMID 31557067
  3. Morton DL, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. The New England journal of medicine. 2014;370:599-609. PMID 24521106
  4. Thomas JM. Concerns relating to the conduct and statistical analysis of the Multicenter Selective Lymphadenectomy Trial (MSLT-1) in patients with melanoma. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2009;62:442-6. PMID 19246272
  5. Crystal JS, et al. Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial. JAMA surgery. 2022;157:835-842. PMID 35921122
  6. Warycha MA, et al. Meta-analysis of sentinel lymph node positivity in thin melanoma (<or=1 mm). Cancer. 2009;115:869-79. PMID 19117354
  7. Huang H, et al. Predictive Values of Pathological and Clinical Risk Factors for Positivity of Sentinel Lymph Node Biopsy in Thin Melanoma: A Systematic Review and Meta-Analysis. Frontiers in oncology. 2022;12:817510. PMID 35155254
  8. Walker RJB, et al. Predictors of Sentinel Lymph Node Metastasis in Patients with Thin Melanoma: An International Multi-institutional Collaboration. Annals of surgical oncology. 2022;29:7010-7017. PMID 35676603
  9. Weitemeyer MB, et al. More sentinel lymph node biopsies for thin melanomas after transition to AJCC 8th edition do not increase positivity rate: A Danish population-based study of 7148 patients. Journal of surgical oncology. 2022;125:498-508. PMID 34672372
  10. Maurichi A, et al. Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;38:1591-1601. PMID 32167862
  11. Yee P, et al. Sentinel Lymph Node Biopsy for Desmoplastic Melanoma: A Systematic Review and Meta-analysis. Annals of surgical oncology. 2026;33:6719-6727. PMID 41870859
  12. Pasha T, et al. Association of Complex Lymphatic Drainage in Head and Neck Cutaneous Melanoma With Sentinel Lymph Node Biopsy Outcomes: A Cohort Study and Literature Review. JAMA otolaryngology-- head & neck surgery. 2023;149:416-423. PMID 36892824
  13. Hanks JE, et al. Sentinel Lymph Node Biopsy in Head and Neck Melanoma: Long-term Outcomes, Prognostic Value, Accuracy, and Safety. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2020;162:520-529. PMID 32041486
  14. Rashid S, et al. Prognostic Implications of Primary Site in Cutaneous Head and Neck Melanoma After the Implementation of Sentinel Node Biopsy: A SEER-Based Analysis (2011-2020). Annals of surgical oncology. 2026;33:5002-5008. PMID 41803580
  15. Satzger I, et al. Melanoma-specific survival in patients with positive sentinel lymph nodes: Relevance of sentinel tumor burden. European journal of cancer (Oxford, England : 1990). 2019;123:83-91. PMID 31677550
  16. Cochran AJ, et al. Sentinel lymph node melanoma metastases: Assessment of tumor burden for clinical prediction of outcome in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I). European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2022;48:1280-1287. PMID 35246348
  17. Verver D, et al. The EORTC-DeCOG nomogram adequately predicts outcomes of patients with sentinel node-positive melanoma without the need for completion lymph node dissection. European journal of cancer (Oxford, England : 1990). 2020;134:9-18. PMID 32454396
  18. Spillane AJ, et al. Lymph node ratio provides prognostic information in addition to american joint committee on cancer N stage in patients with melanoma, even if quality of surgery is standardized. Annals of surgery. 2011;253:109-15. PMID 21119509
  19. de Vries M, et al. Morbidity after inguinal sentinel lymph node biopsy and completion lymph node dissection in patients with cutaneous melanoma. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2006;32:785-9. PMID 16806794
  20. de Vries M, et al. Morbidity after axillary sentinel lymph node biopsy in patients with cutaneous melanoma. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2005;31:778-83. PMID 15993029
  21. Sars C, et al. Risk Factors for Complications and Long-Term Outcomes Following Completion Lymph Node Dissection for Cutaneous Melanoma: A Retrospective Cohort Study. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2020;73:1540-1546. PMID 32467082
  22. Shen C, et al. Lymphadenectomy After Melanoma-A National Analysis of Recurrence Rates and Risk of Lymphedema. Annals of plastic surgery. 2024;92:S284-S292. PMID 38556691
  23. Gjorup CA, et al. Factors associated with melanoma-related limb lymphoedema. Acta oncologica (Stockholm, Sweden). 2021;60:779-784. PMID 33793386
  24. Lavy D, et al. ICG-guided sentinel lymph node biopsy in melanoma is as effective as blue dye: A retrospective analysis. Surgical oncology. 2024;57:102167. PMID 39581000
  25. van den Berg NS, et al. Multimodal Surgical Guidance during Sentinel Node Biopsy for Melanoma: Combined Gamma Tracing and Fluorescence Imaging of the Sentinel Node through Use of the Hybrid Tracer Indocyanine Green-(99m)Tc-Nanocolloid. Radiology. 2015;275:521-9. PMID 25521776
  26. Namikawa K, et al. Sentinel lymph node biopsy guided by indocyanine green fluorescence for cutaneous melanoma. European journal of dermatology : EJD. 2011;21:184-90. PMID 21498148
  27. Cloyd JM, et al. Indocyanine green and fluorescence lymphangiography for sentinel lymph node identification in cutaneous melanoma. Journal of surgical oncology. 2014;110:888-92. PMID 25124992
  28. Knackstedt RW, et al. Indocyanine green fluorescence imaging with lymphoscintigraphy for sentinel node biopsy in head and neck melanoma. The Journal of surgical research. 2018;228:77-83. PMID 29907233
  29. Zhang Y, et al. Sentinel lymph node detection in melanoma: indocyanine green fluorescence compared with conventional mapping techniques. Melanoma research. 2026;36:339-343. PMID 42108206
  30. Roshan A, et al. [(99m)Tc]Tc-Tilmanocept sentinel node biopsy and long-term outcomes in melanoma: A cohort study and literature review. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2026;52:112065. PMID 42617582
  31. Gershenwald JE, 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. 2017;67:472-492. PMID 29028110
  32. Zager JS, et al. Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC cancer. 2018;18:130. PMID 29402264