Clinical validation of a prognostic 11-gene expression profiling score in prospectively collected FFPE tissue of patients with AJCC v8 stage II cutaneous melanoma

Abstract

Background: Adjuvant therapies have been approved for patients with AJCC (American Joint Committee on Cancer) stage III and stage IV cutaneous melanoma (CM) after complete resection. These therapies might also be indicated for patients with high-risk stage II CM. Material and methods: We included patients diagnosed with stage II melanoma between 2000 and 2016 and for which primary tumour tissue was available. The prognostic value of the 11gene expression profiling score (GEPS) was evaluated as a dichotomized parameter (GEPS 0 vs. >0). Endpoints of the analysis were melanoma specific survival (MSS), distant metastasis-free survival (DMFS) and relapse-free survival (RFS). Results: GEPS was determined in 245 patients ranging between À0.7 and 3.53. A total of 111 females and 134 males were included; the median follow-up was 41 months. Kaplan Meier analyses showed statistically significant survival differences between patients with high GEPS (n Z 154) and low GEPS (n Z 91) for MSS (p Z 0.018), DMFS (p Z 0.005) and RFS (p Z 0.009). The 5-year and 10-year MSS was 92% in the low-GEPS and 82% and 67% in

Molecular Biomarkers for Melanoma Screening, Diagnosis and Prognosis: Current State and Future Prospects

“…There is significant interest in using adjuvant therapy in Stage II high-risk melanomas, as evidenced by a large, double-blind, prospective, randomized clinical trial currently evaluating the safety and efficacy of immune checkpoint blockade in resected Stage II melanoma (KEYNOTE-716: https:// clinicaltrials.gov/ct2/show/NCT03553836). Recently an 11-gene GEP was published that demonstrated the ability to stratify patients with stage II melanoma into high GEP score groups and low GEP score groups, with the latter having significantly higher melanoma specific survival and relapse free survival rates (109). The authors of this study speculate that patients with higher GEP scores may be better candidates for adjuvant therapy due to the increased risk for relapse and death, potentially reflecting ambitions to test this hypothesis in a future study (109).…”

“…Recently an 11-gene GEP was published that demonstrated the ability to stratify patients with stage II melanoma into high GEP score groups and low GEP score groups, with the latter having significantly higher melanoma specific survival and relapse free survival rates (109). The authors of this study speculate that patients with higher GEP scores may be better candidates for adjuvant therapy due to the increased risk for relapse and death, potentially reflecting ambitions to test this hypothesis in a future study (109).…”

Identification of stage I/IIA melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model

“…Over the last decade, efforts have been made to define the molecular landscape of high-risk cutaneous melanoma and to develop assays for melanoma risk stratification. Several prognostic tests are commercially available that are based on gene expression profiling; however, these are still not used routinely clinically [24,25]. Moreover, according to the current treatment guidelines, although available GEP tests may provide additional information on individual risk of recurrence they should not replace pathologic staging procedures because these tests require further prospective investigation [10].…”

Adjuvant Therapy for Melanoma: Past, Current, and Future Developments

“…At the same time, most will recognize the fact that classic staging with histopathological and clinical factors will become obsolete once high-level molecular biomarkers are able to reliably predict prognosis. For instance, there are already a few panels of gene expression profiles (GEP) being tested for this purpose [29][30][31].…”