Research Summary:
Cutaneous melanoma is a significant public health concern, as it is the fifth most common cancer in the United States. Traditional prognostic assessment relies on clinicopathologic features such as Breslow thickness, ulceration status, and mitotic rate, but these factors do not always accurately identify patients at highest risk for recurrence or metastasis. Gene expression profiling assays have emerged as complementary tools that capture tumor biology beyond histopathologic parameters. The 31-gene expression profile (31-GEP) test categorizes primary melanomas into risk groups for recurrence, distant metastasis, and melanoma-specific mortality. To clarify the overall prognostic performance of the 31-GEP assay, Durgham et al1 conducted a systematic review and meta-analysis synthesizing all available evidence on its association with recurrence-free survival (RFS), distant metastasis-free survival (DMFS), melanoma-specific survival (MSS), and overall survival (OS) in patients with cutaneous melanoma.
This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed across PubMed, Scopus, PsycINFO, and Cochrane to identify studies published through July 2024 that evaluated the 31-GEP test in cutaneous melanoma. Eligible studies included patients with histologically confirmed cutaneous melanoma who underwent 31-GEP testing and reported survival outcomes with follow-up data obtained over at least three years. Notable endpoints included disease-free survival, RFS, DMFS, and OS. Two reviewers independently screened titles and abstracts for relevance and then reviewed the full texts of articles that were found to be eligible.
Thirteen studies including a total of 14,760 patients met inclusion criteria. Among the studies, six used prospective institutional data, five used retrospective data, and two used Surveillance, Epidemiology, and End Results (SEER) data from 2009 to 2018. In the overall population of 14,760 patients, 47.6 percent (95% confidence interval [CI]: 37.2–58.1%) of tumors were ulcerated, mean Breslow thickness was 3.94mm (95% CI: 2.6–5.2mm), and regarding tumor location, 77.1 percent (95% CI: 72.2–82.0%) were found on the extremities, 63.8 percent (95% CI: 16.5–100%) on the head and neck, and 60.2 percent (95% CI: 52.5–68%) on the trunk. In Class 1 tumors, 41.5 percent (95% CI: 20–63.1%) were ulcerated, while a higher proportion of Class 2 tumors (67.6%, 95% CI: 45.6–89.6%) showed ulceration; Class 1A tumors had the lowest ulceration rate at 14.1 percent (95% CI: 4.5–23.6%), with a mean Breslow thickness of 1.56mm (95% CI: 0.84–2.3 mm), while Class 2B tumors had the highest mean Breslow thickness at 3.74mm (95% CI: 1.64–5.84).
Survival outcomes varied significantly between 31-GEP classes across different metrics, with the five-year melanoma-specific survival (MSS) rate for the overall population being 97.5 percent (95% CI: 86.5–99.6%). When stratified by 31-GEP class, Class 1A showed the highest five-year MSS at 99.8 percent (95% CI: 98–100%), followed by Class 1B/2A at 97.6 percent (95% CI: 92.4–99.3%), and Class 2B at 83.4 percent (95% CI: 66.5–92.7%). Three-year OS rates demonstrated clear differences between classes, at 96.1 percent (95% CI: 95.5–96.6%) for Class 1 patients compared to 82.2 percent (95% CI: 81.1–83.2%) for Class 2 patients. Similar patterns were observed for RFS and DMFS rates; the five-year RFS rate for Class 1A was 95.0 percent (95% CI: 91.8–97.0%), which was significantly higher than the 50.5-percent (95% CI: 42.4–58.7%) RFS rate observed for Class 2B. DMFS rates showed a similar trend, with Class 1A having a five-year DMFS rate of 98.0 percent (95% CI: 96.1–98.9%) and Class 2B having a five-year DMFS rate of 62.4 percent (95% CI: 52.5–71.4%)
The findings demonstrated significant differences in survival outcomes between 31-GEP classes, with Class 1A consistently showing better outcomes compared to Class 2B across various survival metrics. The strong prognostic value of the 31-GEP assay suggests its potential role in personalized management strategies for patients with cutaneous melanoma, as a Class 1A result for a patient with early-stage melanoma might support less intensive follow-up, while a Class 2B result might prompt more frequent follow-up or consideration of adjuvant therapy. The authors suggest that the 31-GEP test complements existing prognostic frameworks by refining risk estimates, particularly for patients with Stage I to II disease, rather than replacing existing guidelines.
Limitations included the small number of studies available for each 31-GEP class, as well as a lack of information regarding treatment modalities beyond primary surgical treatment. Additionally, five-year follow-up might be too short to adequately capture recurrence risk, especially in T1 tumors. Further research is needed to fully define the clinical utility of the 31-GEP test in terms of clarifying which patients might benefit most from the prognostic insight provided by the assay, as well as how best to integrate these findings into the treatment and management of cutaneous melanoma. The 31-GEP assay represents a useful tool for improving risk stratification and potentially improving patient outcomes in the treatment of melanoma.
References
- Durgham RA, Nassar SI, Gun R, et al. The prognostic value of the 31-gene expression profile test in cutaneous melanoma: a systematic review and meta-analysis. Cancers (Basel). 2024;16(21):3714.