The response rate with the combination of nivolumab and ipilimumab could be higher than reported, as a result of unconventional responses, notes Mario Sznol, MD. In clinical trials, treatment with the combination caused tumor regression in all except one discordant lesion, raising the question of whether surgery could be utilized.

Metastasectomies have demonstrated a five-year survival rate of approximately 40% with in patients with resectable stage IV melanoma in randomized studies, notes Robert H. I. Andtbacka, MD, CM. This approach could be considered, in patients with oligometastatic disease. Utilizing surgery following systemic therapy has some advantages, since it provides a look into the tumors biology and whether it responds to systemic therapy, Andtbacka suggests.

For patients who have been on treatment with a mixed response, a resection can be completed with minimal morbidity, Andtbacka suggests. In some situations, it could be possible to utilize targeted or immuno-therapies as neoadjuvant treatments prior to surgery for patients with advanced melanoma. These therapies could effectively minimize disease burden, making surgery possible, Andtbacka notes.

Patients treated with targeted therapies who experience isolated progression are candidates for resection, believes Jeffrey A. Sosman, MD. This treatment strategy can produce durable responses and keeps patients on an effective therapy for longer. Additionally, specifically in patients treated with a single-agent BRAF inhibitor, it is important to ascertain whether a new lesion is melanoma, since other secondary malignancies can occur, Sosman notes.

Identifying the right therapies for these patients still requires further research. Removing the entire tumor and lymph nodes could potentially have the opposite effect with immunotherapies, since regional nodes could be involved in immune activity, suggests Sznol. Results from the phase III MSLT-II study will provide more data on whether completion lymphadenectomy produces superior results.