Evidence for Radiation Therapy in Stage III Locoregionally Advanced Cutaneous Melanoma in the Post-Immunotherapy Era: A Literature Review

Abstract

In the landscape of Stage III locoregionally advanced cutaneous melanoma treatment, the post-immunotherapy era has sparked a number of questions on the management of the nodal basin. However, much of the available literature is not focused on radiation therapy as an adjuvant therapy. This literature review aims to illuminate the evidence surrounding radiation therapy's potential to mitigate regional recurrences in the adjuvant setting for melanoma. Additionally, it seeks to identify adjunct systemic therapy options and explore the synergy between systemic therapy and radiation. Despite strides in surgical techniques and systemic therapies, controlling regional Stage III melanoma remains a formidable clinical hurdle. While historical data strongly suggest the efficacy of adjuvant radiation therapy in reducing regional recurrence risk, its evaluation predates the advent of MAPK pathway inhibitors and robust immunotherapy options. Notably, clinical trials have yet to definitively demonstrate a survival advantage with adjuvant radiation therapy. Additional research should focus on refining the definition of high risk for regional recurrence through gene expression profiling or tumor immune profiling scores and elucidate the optimal role of adjuvant radiation therapy in patients treated with neoadjuvant systemic therapy.

Keywords: immune checkpoint inhibitors; melanoma; radiation therapy; stage III melanoma.

Figure 1

Nomogram calculating risk of recurrence, distant metastasis, and death.

Figure 2

Proportion free of lymph-node field relapse from TROG 02.01 study. (A) Time to lymph-node field relapse in eligible population (B) Time to lymph-node field relapse in intention-to-treat population.

Figure 3

Survival rates from original TROG 02.01 study. (A) Relapse free survival (B) Overall survival rates.