Prognostic value of circulating tumor cells in stage III and IV melanoma: a systematic review and meta-analysis

Significant heterogeneity in circulating tumor cells (CTCs) assessments has limited their use in melanoma. We sought to evaluate the prognostic value of CTCs in advanced melanoma using a standardized CTC platform. A PubMed search was conducted up to March 2024. Studies enumerating CTCs using CellSearch with outcomes data were included. Of 196 studies identified, nine met inclusion criteria. In total, 678 patients were included – 337 (49.6%) were stage III and 342 (50.4%) were stage IV. Four studies defined CTC positivity using a cutoff greater than or equal to 1, while two studies used greater than or equal to 2 and two studies used both. Median follow-up was 13.4 (range: 5.9–48) months. CTC positivity rates were 55.8% ( N  = 330/591), 28.0% ( N  = 144/514), and 10.6% ( N  = 45/426) for CTC cutoffs greater than or equal to 1, greater than or equal to 2, and greater than or equal to 3, respectively. Pooled analysis demonstrated significantly worse overall survival with CTC greater than or equal to 1 (hazard ratio: 1.7, 95% confidence interval: 1.0–2.6, P  = 0.04) and with CTC greater than or equal to 2 (hazard ratio: 2.1, 95% confidence interval: 1.4–3.1, P  < 0.001). Moderate heterogeneity was observed, though not statistically significant ( I ²  = 43.4%, P  = 0.13). Sensitivity analyses confirmed the prognostic value of CTC greater than or equal to 2 (pooled hazard ratio: 1.9–2.4). Regardless of the CTC cutoff used, the presence of any CTCs was a significant prognostic marker in stages III–IV melanoma. Incorporation of CTC assessments in clinical practice may help risk stratify patients and guide treatment decision-making.