DecisionDx®-Melanoma is designed to identify cutaneous melanoma patients who can safely forgo sentinel lymph node biopsy without experiencing early recurrence

J. Michael Guenther, M.D

More than 100,000 people are diagnosed with cutaneous melanoma every year in the United States, but studies suggest melanoma diagnoses are underreported and the actual number diagnosed is higher.1 Most patients will be diagnosed with early-stage, localized cancer, and these patients generally have a good prognosis. Of concern, it is estimated that 30–60% of patients who develop metastatic cutaneous melanoma were originally diagnosed with early-stage disease.2 As a result, it is critical for clinicians to be able to identify which patients have low risks and which patients have high risks of metastasis and mortality.

Sentinel lymph node biopsy (SLNB) is a procedure used as a part of cutaneous melanoma staging to provide information about a patient's prognosis; however, the surgical procedure carries additional costs and almost 15% of patients have complications from the procedure, albeit mostly minor, that may require additional postoperative care.3 Current SLNB management recommendations from the National Comprehensive Cancer Network (NCCN) Guidelines for Cutaneous Melanoma advise patients with <5% risk of sentinel lymph node (SLN) positivity (T1a tumors without high-risk factors) to forgo SLNB and those with >10% risk of SLN positivity (T2 and higher tumors) to undergo the procedure.4 However, management guidelines only advise that clinicians and patients discuss and consider SLNB for those lesions with a 5–10% risk of SLN positivity (T1a tumors with high-risk features and T1b tumors). To further complicate clinical management decisions, some patients with a negative SLN (e.g., those with stage IIB and IIC cutaneous melanoma) have higher risk of recurrence and mortality than some patients with a positive SLN (e.g., those with stage IIIA).5 Additionally, adjuvant immunotherapy treatments are now FDA-approved for certain patients with SLN negative disease, so the role of SLNB is becoming even more ill-defined.

The 31-GEP test (DecisionDx-Melanoma, Castle Biosciences) is designed to identify patients as having the lowest risk (Class 1A), an increased risk (Class 1B/2A), or the highest risk (Class 2B) of SLN positivity, recurrence, metastasis, and mortality. Previous studies have shown that incorporating 31-GEP testing into clinical decision-making may reduce the number of unnecessary SLNBs in low-risk patients and improve outcomes in high-risk patients by identifying patients who may benefit from increased surveillance and clinical management.6,7 A study using the 31-GEP test result to identify patients with cutaneous melanoma who may benefit from surveillance imaging found recurrences were detected ten months earlier and were substantially smaller than in patients whose management was not guided by the 31-GEP test.7 In a large cohort of almost 5,000 real-world patients in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program covering patients across the United States, 31-GEP testing was associated with a reduced melanoma specific and overall mortality compared with patients with similar characteristics who had not received the 31-GEP test results.8

Recent prospective study data published in the journal Cancer Medicine looked at health outcomes of 130 patients with T1–T2 cutaneous melanoma considered low risk by the 31-GEP test (Class 1A) and followed patients for a median 2 years after diagnosis.9 However, relying upon traditional clinicopathologic features to guide SLNB resulted in up to 88% of SLNB returning a negative node biopsy. In this prospective study, after receiving 31-GEP test results and shared decision-making with their clinician, over half of the patients with a predicted low-risk (Class 1A) 31-GEP test result elected to not undergo the SLNB procedure. Of those who did undergo SLNB, the positivity rate was only 3.2%, less than the 5% NCCN threshold used to guide the procedure. Most importantly, none of the 130 patients who had a Class 1A (lowest risk) 31-GEP test result experienced recurrence of melanoma at a median 2-year follow up. The current study demonstrates that patients with cutaneous melanoma with a Class 1A result may safely forgo the SLNB.

Figure 1: Flow chart incorporating 31-GEP testing into SLNB and clinical management decisions for patients with T1-T2 cutaneous melanoma tumors

These study data shows clinicians are using the 31-GEP test to appropriately select patients with a low-risk (Class 1A) 31-GEP test result who may safely avoid the SLNB procedure, with no recurrences detected in follow up. These results suggest that using the 31-GEP test to guide SLNB decisions benefits patients who may choose to forgo SLNB without adversity. Using the 31-GEP test to help guide personalized, risk-aligned clinical management in cutaneous melanoma can potentially reduce healthcare-related financial toxicity, which is of critical importance for patients and the healthcare systems to optimize patient outcomes.

References

1. Melanoma of the Skin - Cancer Stat Facts. SEER. 2025. Accessed March 31, 2025. https://seer.cancer.gov/statfacts/html/melan.html
2. Gallicchio L, Devasia TP, Tonorezos E, Mollica MA, Mariotto A. Estimation of the Number of Individuals Living With Metastatic Cancer in the United States. J Natl Cancer Inst. 2022;114(11):1476-1483. doi:10.1093/jnci/djac158
3. Gonzales M, Grosh K, Coster S, et al. Better-Defined Morbidity of Sentinel Lymph Node Biopsy in Patients with Melanoma. Ann Surg Oncol. Published online February 13, 2025. doi:10.1245/s10434-025-16987-6
4. Swetter S. NCCN Clinical Practice Guidelines in Oncology. Cutaneous Melanoma. Version 2.2025. Ann Surg Oncol. Published online 2025. doi:10.1245/s10434-024-16379-2
5. Helvind NM, Weitemeyer MB, Chakera AH, et al. Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021: A National Observational Cohort Study of 25 720 Patients With Stage IA to IV Melanoma. JAMA Dermatology. Published online 2023.
6. Yamamoto M, Sickle-Santanello B, Beard T, et al. The 31-gene expression profile test informs sentinel lymph node biopsy decisions in patients with cutaneous melanoma: results of a prospective, multicenter study. Curr Med Res Opin. 2023;39(3):417-423. doi:10.1080/03007995.2023.2165813
7. Dhillon S, Duarte-Bateman D, Fowler G, et al. Routine imaging guided by a 31-gene expression profile assay results in earlier detection of melanoma with decreased metastatic tumor burden compared to patients without surveillance imaging studies. Arch Dermatol Res. 2023;315(8):2295-2302. doi:10.1007/s00403-023-02613-6
8. Bailey CN, Martin BJ, Petkov VI, et al. 31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration. JCO Precis Oncol. 2023;7:e2300044. doi:10.1200/PO.23.00044
9. Guenther JM, Ward A, Martin BJ, et al. A Prospective, Multicenter Analysis of Recurrence-Free Survival After Sentinel Lymph Node Biopsy Decisions Influenced by the 31-GEP. Cancer Med. 2025;14(7):e70839. doi:10.1002/cam4.70839