Management of local or regional non‐nodal disease

Abstract

Some melanomas develop a striking avidity for lymphatic spread. In spite of multiple recurrences, patients can remain years without visceral metastasis. There is clearly a biologic reason for this lymphotrophic pattern of growth and dissemination, which we have yet to uncover. In-transit metastases have widely diverse clinical presentations and can be a stubborn disease to cure. As a result, a host of treatments exist that should be tailored to the individual patient. K E Y W O R D S diphenylcyclopropenone, in transit, intralesional therapy, limb perfusion, melanoma, stage III, talimogene laherparepvec 1 | INTRODUCTION Non-nodal locoregional metastasis in the setting of melanoma includes microsatellites, satellites, and in-transit metastasis (ITM). This pattern of spread is primarily the result of dermal and subcutaneous intralymphatic contamination. The presence of melanoma cells within this rich lymphatic plexus can result in recurrent disease anywhere from the primary site to the regional nodal basin and rarely retrograde, distal to the primary lesion. Historically, microsatellites were defined as microscopic foci identified on pathologic analysis, adjacent or deep to the primary. Clinically detected cutaneous and/or subcutaneous locoregional metastases were arbitrarily categorized based on their proximity to the primary melanoma; satellite lesions occurring within 2 cm of the primary and ITM lesions >2 cm from the melanoma. All these disease patterns have similar prognoses and the 8th edition of The American Joint Committee on Cancer Staging System has added clarity to this issue. 1The updated edition categorizes all regional nodal and intralymphatic disease as N1-N3 disease. Additionally, number of lesions differentiates N1-N3 and the subcategories a-c are distinguished based on clinically occult, clinically detected, matted and/or intralymphatic disease. One should make a distinction, when possible, between a true local recurrence, which represents subclinical persistent primary tumor after initial management; often in the setting of inadequate management such as incomplete resection, as opposed to intralymphatic disease. A true local recurrence portends a better prognosis than cutaneous metastases. 2 The distinction between distant skin, subcutaneous or lymph node metastasis is even more important as these are categorized as M1a, stage IV disease.In-transit metastases occur in 5% to 10% of patients with intermediate thickness melanoma [3][4][5][6][7] and have a propensity for the lower extremities. 8,9 In-transit metastasis often appear indolent and easily treatable, particularly when few in number. However, due to the aforementioned concept of lymphatic contamination, recurrence remains the rule and not the exception especially when management consists of targeted treatment of individual lesions rather than a more holistic approach that addresses the involved lymphatic network and nodal basin. Before embarking on treatment of new ITM, we obtain systemic imaging, PET scan preferred, to rule out clinically ...

Sentinel Node Biopsy for Melanoma Patients with a Local Recurrence or In-Transit Metastasis

“…In our database, ITM is defined as a lesion occurring more than 5 cm from the primary lesion instead of the 2 cm used in the staging manual. 22 In conclusion, this study showed that SNB can be performed for patients experiencing LR or ITM with a high identification rate, although the false-negative rate was considerable (27%). A tumor-positive SN was found in 13% of the patients and was associated with more recurrences and a worse overall survival rate.…”

“…For unknown reasons, some melanomas predominantly metastasize through lymphatics. 22 Read et al 5 reported that disease was limited to ITMs without distant metastases in 36% of the 190 patients with ITM as the first site of recurrence.…”

Early Cost-effectiveness Analysis of Electrochemotherapy as a Prospect Treatment Modality for Skin Melanoma

“…However, research has shown that even then, only 19% of patients remain without evidence of recurrence, within a median follow-up of 40 months. 45 Other treatment options, including electrochemotherapy, are thus used in cases of a higher number of skin lesions. New systemic therapies are promising; nonetheless, due to the high cost, as well as to the treatment-related adverse events, it is still advised to treat skin lesions locally, for as long as possible.…”

Association of tumor molecular factors with in‐transit metastasis in primary cutaneous melanoma

“…4 Many locoregional treatment options exist with varying local control rates and few offering durable improvements in overall survival. 5 Evaluating the efficacy of contemporary systemic therapy compared with the efficacy of locoregional interventions has been a challenge secondary to systemic therapy trials excluding patients with ITM or not reporting them separately as well as the inherent limitations of cross-study comparisons.…”