In-transit melanoma metastases
ITM; satellite metastasis; cutaneous in-transit metastasis
In-transit metastases are intralymphatic melanoma cells in the skin or subcutaneous tissue between the primary tumour site and the regional lymph-node basin (defined as > 2 cm from the primary). Together with satellite metastases (≤ 2 cm) and microsatellites (histological), they convert the nodal stage to the "c" sub-variant (N1c, N2c, N3c) in AJCC 8. Management is multidisciplinary and individualised — depending on the number, size, distribution, BRAF status and the patient's prior therapy. Options range from surgical excision of solitary in-transits, regional therapies (talimogene laherparepvec, isolated limb perfusion / infusion), systemic immunotherapy, BRAF-targeted therapy and radiotherapy. Outcomes vary widely; modern ICI-based therapy has substantially improved survival.
Definition and staging
- Satellite metastasis — < 2 cm from the primary or excision scar.
- In-transit metastasis — > 2 cm from the primary, between primary and regional nodal basin.
- Microsatellite — histologically detected microscopic tumour foci adjacent to the primary, separated from the main tumour.
- AJCC 8 — any of these convert N to the "c" sub-variant (N1c, N2c, N3c) depending on coexistent nodal disease.
- Stage III at least; restaging investigations should exclude distant disease before any locoregional intervention.
Workup
- Full skin and nodal examination — count and map lesions, document with photography.
- Imaging — CT NCAP, MRI brain, FDG-PET-CT for staging.
- Biopsy of at least one in-transit lesion if diagnosis uncertain or for molecular characterisation (BRAF V600E/K, NRAS Q61, c-KIT).
- MDT discussion before any intervention — surgical, regional therapy, systemic therapy options weighed.
Surgical management
- Solitary or few in-transit metastases with no other disease — wide local excision with histological clearance, often with primary closure or local flap.
- Multiple lesions in a confined limb area — staged excision can be considered but does not address subclinical disease.
- SLNB is not repeated for in-transit metastases — the basin is treated as known stage III.
- Reconstruction principles — see reconstruction atlas.
Regional therapy
- Talimogene laherparepvec (T-VEC, Imlygic) — oncolytic HSV-1; intralesional injection. NICE TA410 for unresectable stage IIIB / IIIC / IVM1a melanoma not previously treated with systemic immunotherapy and where systemic immunotherapy is unsuitable. Repeat injections every 2 weeks.
- Isolated limb perfusion (ILP) — high-dose melphalan ± TNF via isolated limb circulation under hyperthermia. UK supraregional service; complete response 50–70%, durable benefit in selected.
- Isolated limb infusion (ILI) — less complex than ILP, lower complication rate, slightly lower complete response.
- Intralesional therapies — IL-2, rose bengal (PV-10 in trials), electrochemotherapy. See electrochemotherapy for the established UK pathway.
- Radiotherapy — palliative for symptomatic in-transit disease unfit for systemic or regional therapy; emerging evidence for hypofractionated RT combined with ICI (abscopal effect).
Systemic therapy
- Anti-PD-1 monotherapy (pembrolizumab, nivolumab) or combination ipilimumab + nivolumab — particularly for multifocal in-transit disease that is not amenable to surgery / regional therapy.
- BRAF-mutant disease — dabrafenib + trametinib or encorafenib + binimetinib (see D+T).
- NHS England URN 2426 commissions neoadjuvant followed by adjuvant pembrolizumab for macroscopic resectable stage III melanoma, including appropriate in-transit / satellite disease, age ≥ 12.
- Adjuvant systemic therapy after complete locoregional control of stage III disease — pembrolizumab (TA766), nivolumab (TA684), or dabrafenib + trametinib (TA544) for BRAF V600-mutant disease.
Prognosis
- 5-year survival historically 20–50% depending on burden and treatment response.
- Modern ICI-based therapy has substantially improved outcomes — complete-response durability now drives long-term survival.
- Recurrence after locoregional control should prompt repeat staging and MDT discussion.
References
- Andtbacka RH et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol; 2015.
- Kroon HM et al. Isolated limb infusion vs perfusion for in-transit melanoma metastases. Ann Surg Oncol; 2016.
- NICE NG14. Melanoma: assessment and management. London: NICE; 2015 (last updated 27 July 2022). NICE TA410. Talimogene laherparepvec for treating unresectable metastatic melanoma. London: NICE; 2016.
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