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

## TL;DR

This paper reviews the role of radiation therapy in treating advanced melanoma after immunotherapy, focusing on its potential to reduce regional recurrence.

## Contribution

The paper provides a literature review on the use of radiation therapy in the post-immunotherapy era for locoregionally advanced melanoma.

## Key findings

- Radiation therapy may help reduce regional recurrence in melanoma but lacks definitive survival evidence.
- Current research should explore gene or immune profiling to identify high-risk patients for radiation therapy.
- Combining radiation with systemic therapies remains an area of interest for improved treatment outcomes.

## Abstract

Melanoma is the deadliest of all skin cancers. Therapy paradigms in cutaneous melanoma have changed significantly over the past 20 years, following both changes in the initial staging work-up of melanoma as well as in the available therapies. Regional recurrences after initial surgery are normally treated with nodal basin resection. However, some regional recurrences may present as bulky masses that can pose significant challenges in the treatment and control of the disease. It is well established that radiation therapy (RT) plays a role in locoregional control of malignancies in general. This review will attempt to discuss evidence for radiation therapy’s role in reducing regional recurrence in the adjuvant setting in melanoma, identify adjuvant systemic therapy options, discuss systemic therapy–radiation therapy combinations, and identify paradigms and emerging evidence for the use of radiation therapy after neoadjuvant systemic therapy strategies are employed.

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.