How do you treat an isolated in-transit recurrence of melanoma without evidence of clinical nodal involvement in a patient with a history of previously resected primary melanoma?

TVEC is an option.

I could also agree on NADINA or pembrolizumab, depending on the patient's other comorbidities.

Resection is also a possibility, but then would need a discussion of adjuvant therapy.

Indeed, there are many options, and none has been studied in detail.

I like neoadjuvant, as it gives an indication of the sensitivity of the melanoma to immunotherapy.

Yes, I would be in favor of neoadjuvant IO based on their trials, as they have shown better outcomes vs adjuvant IO. Patients with in-transit mets are at least stage IIIB (based on the AJCC 8th edition melanoma staging), so that fits the type of patients studied in SWOG 1801 and NADINA.

If the patient does not have a clinical lymph node, then neither of those two trials is applicable. We treat "isolated" in-transit metastasis with T-VEC first. Surgical resection can be done later if there is less than a complete pathologic response.