Objectives: To describe the scientific evidence regarding adjuvant treatment for stage III and IV cutaneous melanoma and the unresolved issues in this setting. Methods: This review examines the main studies on adjuvant medical therapies approved over the years by the Food and Drug Administration and European Medicines Agency together with the main evidence related to the treatments referred to in the National Comprehensive Cancer Network and European Society of Clinical Oncology guidelines at the time of submission (May 2026) for stage III and IV cutaneous melanoma. A particular focus on immunotherapy (interferon, ipilimumab, and anti-PD-1 antibodies, both as monotherapy and in combination) and targeted therapy with anti-BRAF agents, either as monotherapy or in combination with MEK inhibitors, is given. Besides that, this work also evaluates the role of radiation therapy and addresses some unresolved issues, such as adjuvant therapy in stage IIIA and treatment selection in BRAF-mutated melanoma. Results: Adjuvant therapy for stage III and IV cutaneous melanoma has evolved over the years, starting with interferon and progressing to the use of immunocheckpoint inhibitors and targeted therapy. However, not all treatments that have proven effective in metastatic disease have subsequently played a role in the adjuvant setting. Conclusions: Currently, adjuvant treatment for stage III and IV cutaneous melanoma involves the use of anti-PD-1 antibodies (nivolumab and pembrolizumab) and dabrafenib plus trametinib if the patient has a BRAF V600 mutation. It was not possible to identify the adjuvant therapy of choice for BRAF-mutated melanoma, and several factors must be considered when deciding between immunotherapy and targeted therapy. The role of radiation therapy remains controversial and could be discussed by the multidisciplinary team as part of the adjuvant strategy in selected patients. Likewise, adjuvant therapy for stage IIIA melanoma should be carefully evaluated in light of the risk–benefit ratio.

Background : Sensitive detection of EGFR mutations in liquid biopsies of advanced non-small-cell lung cancer (aNSCLC) is vital for guiding targeted treatments. Real-time PCR offers a quick turnaround time but relatively low sensitivity while Next-Generation Sequencing (NGS) offers broader EGFR coverage, co-mutation evaluation and high sensitivity. Methods: This study evaluated the amplicon-based NGS Plasma-SeqSensei™ Solid Cancer In Vitro Diagnostics (IVD) Kit (Sysmex) against the real-time PCR-based cobas^® EGFR Mutation Test v2 (Roche), the current routine standard at the Veneto Institute of Oncology IOV-IRCCS. We enrolled 130 patients with aNSCLC in the RARE Study between April 2022 and August 2025 who were referred to our institute. Liquid biopsies were taken at diagnosis or at progression and analyzed using two methods with the primary objective of assessing diagnostic concordance for EGFR profiling. Sysmex NGS libraries were sequenced on a NextSeq 550 sequencer (Illumina), with the NextSeq 500/550 Mid Output Kit v2.5 (150 Cycles) in single-end mode. Results: Among 129 evaluable samples, the NGS assay demonstrated a marginally higher EGFR mutation detection rate, identifying mutations in 31/129 cases (24.0%, 95% CI: 17–33), versus 28/129 (21.7%, 95% CI: 15–30) by cobas, specifically for variants covered by both assays. Overall concordance was almost perfect (Cohen’s Kappa = 0.89, 95% CI: 0.80–0.98), confirming the high reliability of both methods. Furthermore, we identified a cfDNA input threshold of at least 20 ng as critical for ensuring optimal assay sensitivity and reliable mutation detection (Odds Ratio = 4.41 for inputs ≥ 20 ng, p = 0.006). Conclusions: Ultimately, the Sysmex NGS proved to be a robust and highly sensitive assay. It delivers performance comparable to that of standard RT-PCR while providing the clinical advantage of concurrently detecting a broader spectrum of EGFR variants and actionable mutations in other genes.