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Melanoma clinical practice guidelines — synthesis

TL;DR — The major melanoma guidelines converge on excision margins (1–2 cm), on offering sentinel node biopsy at ≥1.0 mm or ≥0.8 mm with additional risk factors, on adjuvant therapy for completely resected stage IIB–IV, and on stage-based imaging and follow-up (Garbe 2025, PMID 39709737; PMID 39700658). They diverge on screening — the USPSTF finds evidence insufficient for population visual skin examination (I statement, three times: 2009, 2016, 2023) (Bibbins-Domingo 2016, PMID 27458948; Mangione 2023, PMID 37071089) while Germany runs a national program (Hübner 2018, PMID 30411137) and Australia recommends risk-targeted surveillance (Adler 2019, PMID 30636296); on stage IIIA adjuvant therapy, which one validation cohort explicitly questions (Kanaki 2019, PMID 31401470); and on how quickly to adopt neoadjuvant sequencing, which the 2024 European update already recommends (PMID 39709737). The most striking honest admission in the current European guideline is that sentinel node biopsy "shall be offered" despite "no clear survival benefit for this approach" (PMID 39709737). The document-level registry, with supersession chains and access dates, is ../literature/guidelines/REGISTRY.md.

What the guidelines say

European (EADO / EDF / EORTC), update 2024

Part 1 — diagnostics (Garbe 2025, PMID 39700658), valid until end of 2026:

Domain Recommendation
Clinical diagnosis Melanoma may be diagnosed clinically but must always be confirmed by dermoscopy; histopathological examination is always required if melanoma is suspected
High-risk patients Sequential digital dermoscopy and whole-body photography to improve early-stage detection; confocal reflectance microscopy in special cases if available
Staging system AJCC 8th edition
Imaging None beyond examination for melanoma ≤0.8 mm; lymph-node sonography from stage IB with no further imaging; whole-body CT or PET-CT plus brain MRI from stage IIB/C
Molecular testing Mutation testing from stage IIB/C, especially BRAF V600
Follow-up Structured, stage-based, to detect relapse and second primaries early; the group notes further studies may be warranted

Part 2 — treatment (Garbe 2025, PMID 39709737):

Domain Recommendation
Margins 1–2 cm safety margins
Sentinel node biopsy Offered at tumour thickness ≥1.0 mm, or ≥0.8 mm with additional histological risk factors — "although there is as yet no clear survival benefit for this approach"
Decision-making Primarily by an interdisciplinary tumour board
Adjuvant therapy Proposed in completely resected stage IIB–IV. Stage II: only PD-1 inhibitors approved. Stage III: anti-PD-1, or dabrafenib plus trametinib for BRAF V600-mutant disease. Resected stage IV: nivolumab, or ipilimumab plus nivolumab in selected high-risk patients
Neoadjuvant therapy For clinically detected macroscopic resectable disease: ipilimumab plus nivolumab followed by complete resection and adjuvant therapy according to pathological response and BRAF status; neoadjuvant pembrolizumab followed by resection and adjuvant pembrolizumab is also recommended
Recurrence after (neo)adjuvant therapy Further treatment should consider the type of prior therapy and whether recurrence occurred on or off therapy
Unresectable stage III/IV Systemic treatment always indicated; first line PD-1 antibody alone or combined with CTLA-4 or LAG-3 antibody. In BRAF V600-mutant stage IV, BRAF/MEK inhibitors are an alternative first line in selected cases

Other current documents

Body Document Note
ESMO Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, 2025 (Amaral 2025, PMID 39550033) Supersedes the 2019 edition (Michielin 2019, PMID 31566661)
ESMO-EURACAN Uveal melanoma Clinical Practice Guideline, 2026 (Piperno-Neumann 2026, PMID 42020098) First dedicated ESMO uveal document; explicitly scoped to exclude other melanoma types, with ESMO-MCBS scores attached to treatment choices
ASCO Systemic Therapy for Melanoma: ASCO Guideline Update, 2023 (Seth 2023, PMID 37579248) Updated systematic review identified 21 additional randomised trials
ASCO Management of Immune-Related Adverse Events, 2021 update (Schneider 2021, PMID 34724392) 175 studies met eligibility; recommendations are expert consensus because of the paucity of high-quality evidence
European Society of Endocrinology Endocrine-related adverse conditions with checkpoint inhibition, 2022 (Husebye 2022, PMID 36149449) GRADE-based; baseline endocrine testing before each cycle; no clear benefit from high-dose glucocorticoids except severe thyroid eye disease and hypophysitis affecting vision
American Academy of Dermatology Guidelines of care for the management of primary cutaneous melanoma, 2019 (Swetter 2019, PMID 30392755) Sets margins by thickness category
USPSTF Screening for Skin Cancer, 2023 (Mangione 2023, PMID 37071089); 2016 (Bibbins-Domingo 2016, PMID 27458948) I statement in both
USPSTF Behavioral Counseling to Prevent Skin Cancer, 2018 (Grossman 2018, PMID 29558558) B for ages 6 months–24 years with fair skin; C for selective counselling above 24; I for counselling adults about skin self-examination
Japanese Dermatological Association / Japanese Skin Cancer Society Guidelines for Melanoma 2025 (Fukushima 2025, PMID 40511899) Explicitly incorporates East Asian data because melanoma subtypes and drug efficacy differ between Western and East Asian populations; supersedes the 2019 outline (PMID 31782186)
Australian Methods of melanoma detection and skin monitoring for individuals at high risk, 2019 (Adler 2019, PMID 30636296) Risk-targeted rather than population monitoring; sentinel-node indications updated separately (PMID 28718222)
Ontario Health (Cancer Care Ontario) Locoregional management of in-transit metastasis, 2020 (Wright 2020, PMID 32669939) Stratifies by minimal / moderate / maximal in-transit burden
UK Revised UK guidelines for the management of cutaneous melanoma, 2010 (Marsden 2010, PMID 20608932; PMID 20728418) Superseded in practice by NICE and by the BAD/RCPath TNM-8 review (PMID 29923189); the 2002 UK guidelines (PMID 11841361) preceded them
Chinese Society of Clinical Oncology Chinese Guidelines on the Diagnosis and Treatment of Melanoma, 2015 edition (Guo 2015, PMID 26734632; PMID 27164849) Surgical treatment consensus for cutaneous/acral melanoma issued separately (PMID 32135640)
NCCN NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous Web-published and versioned continuously rather than as a journal article (NCCN — "Melanoma: Cutaneous", https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1492, accessed 2026-09-01)

Where they agree

Domain Convergent position Anchor
Excision margins 1–2 cm depending on thickness; no wider PMID 39709737; PMID 30392755; and the trial evidence in surgical management and margins
Sentinel node biopsy Offered for staging at ≥0.8–1.0 mm with risk factors; not as a therapeutic procedure PMID 39709737
Completion lymph-node dissection Not routine after a positive sentinel node PMID 28591523; PMID 31557067
Staging AJCC 8th edition for cutaneous disease PMID 39700658; PMID 29028110
Imaging Stage-graduated; none for thin melanoma, cross-sectional plus brain MRI from stage IIB/C PMID 39700658
BRAF testing From stage IIB/C PMID 39700658
First-line advanced disease PD-1 antibody alone or with CTLA-4 or LAG-3 blockade PMID 39709737
Multidisciplinary decision-making Tumour board PMID 39709737

Where they disagree, and why

  1. Population screening. The USPSTF has reached an I statement three times, resting on a single fair-quality ecological study with important methodological limitations (PMID 27458948; PMID 37071089). Germany implemented a national program in 2008 whose mortality benefit has not appeared (PMID 30411137; Hübner 2026, PMID 42268621). Australia recommends risk-stratified surveillance rather than population screening (PMID 30636296). The disagreement is not about the data but about what to do in their absence — see screening and overdiagnosis.
  2. Adjuvant therapy in stage IIIA. The European guideline includes stage III generally (PMID 39709737), while validation data show stage IIIA 5-year melanoma-specific survival of 89%, higher than stage IIB (80%) and IIC (67%), leading those authors to call the stage IIIA indication questionable (PMID 31401470). Retrospective multicentre data in 628 stage IIIA patients are confounded by indication (Grover 2025, PMID 40204154).
  3. How fast to adopt neoadjuvant sequencing. The 2024 European update already recommends both neoadjuvant ipilimumab–nivolumab and neoadjuvant pembrolizumab regimens (PMID 39709737); the underlying evidence is one phase 3 trial with 9.9 months' median follow-up and one phase 2 trial whose analysis has been challenged for time-related bias (Blank 2024, PMID 38828984; Patel 2023, PMID 36856617; Olivier 2024, PMID 38621314).
  4. Regional adaptation. The Japanese 2025 guideline states explicitly that previous Japanese versions mirrored global standards because of scarce East Asian evidence, and that recent findings of subtype and drug-efficacy differences motivated incorporating regional data (PMID 40511899). This is the clearest guideline-level acknowledgement that the evidence base is not transportable — the same point the ethnicity and subtype data make in acral and mucosal melanoma.
  5. Mucosal staging. No consensus on which system to use; mmTNM, Ballantyne/Prasad and squamous-cell TNM all have advocates and conflicting validation data (Moya-Plana 2019, PMID 31421470; Michel 2014, PMID 23729399).
  6. Toxicity management is consensus, not evidence. ASCO's own guideline says so (PMID 34724392), and the ESE guideline reaches a partly contrary conclusion about corticosteroids for endocrine events (PMID 36149449).

Where guidelines outrun their evidence

  • Sentinel node biopsy is recommended while its survival benefit is explicitly disclaimed in the same sentence (PMID 39709737).
  • Margins for T1 melanoma and melanoma in situ have never been randomised; recommendations there are extrapolation (PMID 30392755).
  • Stage IIB/IIC adjuvant therapy rests on recurrence-free and distant-metastasis-free survival, with trial-level surrogacy for overall survival only moderate (R² = 0.59, 95% CI 0.08–1.00) (Coart 2020, PMID 32777716).
  • Follow-up schedules are proposed on expert experience; the European guideline says so directly, and the one randomised trial found reduced-intensity follow-up equally safe (PMID 39700658; Moncrieff 2022, PMID 35866644).

Interpretation rules for this page

  • Cite the version and its validity window. The European guideline states validity to end-2026 (PMID 39700658); NCCN versions continuously.
  • A guideline recommendation is not an effect size. Where a document recommends a practice while disclaiming its survival benefit, quote both halves (PMID 39709737).
  • Regional guidelines encode regional epidemiology, not only local preference (PMID 40511899).
  • Screening disagreement is a decision-under-uncertainty disagreement, not an evidence disagreement (PMID 37071089; PMID 42268621).
  • Toxicity guidance is consensus-based and should be labelled as such (PMID 34724392).
  • Document-level details, supersession chains and access dates belong in ../literature/guidelines/REGISTRY.md, not here.

Open questions

  • Should stage IIIA remain an adjuvant-therapy indication (PMID 31401470; PMID 40204154)?
  • Should any guideline recommend population skin-cancer screening, given a national program with no detectable mortality effect (PMID 42268621; PMID 37071089)?
  • Is a guideline justified in recommending neoadjuvant sequencing on 9.9 months of phase 3 follow-up (PMID 38828984; PMID 39709737)?
  • What should replace sentinel node status as the adjuvant-eligibility criterion if the procedure is prognostic rather than therapeutic (PMID 39709737; PMID 28591523)?
  • Which mucosal melanoma staging system should be standard (PMID 31421470; PMID 23729399)?
  • How should guidelines encode the non-transportability of Western trial evidence to East Asian and skin-of-colour populations (PMID 40511899; PMID 35293617)?

References

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  4. Mangione CM, et al. Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2023;329:1290-1295. PMID 37071089
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