Castle Biosciences, a developer of tests that guide patient care, announced a study that demonstrated its gene expression profile test for melanoma prognosis outperformed a nomogram in predicting the risk of sentinel lymph node (SLN) positivity in patients with cutaneous melanoma (CM).
Castle Biosciences’ DecisionDx-Melanoma test outperformed a nomogram developed at the Memorial Sloan Kettering Cancer Center (MSKCC) in predicting the risk of sentinel lymph node. The study is available online in Anticancer Research.
“Nearly 90% of patients receive a negative result after undergoing the sentinel lymph node biopsy (SLNB) procedure,1-2 indicating there is a significant need for more precise methods to identify which patients can safely forego the surgery and still experience good outcomes,” says Michael Tassavor, MD, study author, board-certified dermatologist and fellowship-trained Mohs surgeon currently practicing in New Jersey. “By providing an accurate prediction of a patient’s likelihood of having a positive SLN, DecisionDx-Melanoma test results can inform important conversations between clinicians and patients and provide added confidence in decisions to proceed without the surgery if a patient’s risk is low.”
Further reading: Can Gene Expression Profiling Guide Melanoma Management?
The study evaluated the performance of two tools used to identify patients at low and high risk of SLN positivity:
- Castle’s DecisionDx-Melanoma test, which uses advanced algorithms to integrate a patient’s clinical and pathologic factors with his/her tumor biology to provide a personalized prediction of the risk of SLN positivity, and melanoma recurrence and metastasis.
- The MSKCC nomogram, which uses logistic regression and only clinical and pathologic factors to predict a patient’s SLN positivity risk.
Patients from previously published multicenter cohorts with T1-T2 tumors who had undergone the SLNB procedure (n=465) were analyzed using both DecisionDx-Melanoma and the MSKCC nomogram. Following current National Comprehensive Cancer Network (NCCN) guidelines, a risk prediction of less than 5% in the study was considered low risk for SLN positivity, where patients could safely forego the SLNB procedure. A true-to-false-negative ratio was evaluated using this 5% risk threshold. A 5% threshold represents 19 truly negative nodes for one positive SLN missed (19:1 ratio; 1/20 [5%]), meaning that for every 100 patients who avoided SLNB based on NCCN criteria, 5 would have had a missed positive SLN.
The DecisionDx-Melanoma test resulted in a 36:1 true-to-false-negative ratio (108/3), meaning that for every 100 patients who avoided SLNB based on the test’s results, only 2.7 would have had a positive SLN. This is well below the 5% low-risk threshold established by NCCN. DecisionDx-Melanoma’s performance was better than that of the MSKCC nomogram, which resulted in a 9:1 true-to-false-negative ratio, suggesting that for every 100 patients avoiding SLNB using the MSKCC nomogram, 10 would have had a positive SLN. DecisionDx-Melanoma also demonstrated better accuracy in predicting SLN positivity, including higher sensitivity (95% vs. 81%) and negative predictive value (97% vs. 90%) than the MSKCC nomogram, according to the company.
Importantly, in patients with T1 tumors, for whom the decision to perform SLNB is least clear, using the DecisionDx-Melanoma test to help guide decision-making could have reduced the number of SLNBs by 43.7%, compared with standard NCCN SLNB guidance using American Joint Committee on Cancer staging, while maintaining a low false-negative rate.
DecisionDx-Melanoma has been validated to identify patients who have less than a 5% risk of a positive SLN, indicating that these patients may consider avoiding the SLNB surgical procedure.3-4 The results of this study support these findings and demonstrate that DecisionDx-Melanoma outperforms the MSKCC nomogram in identifying patients at low risk of SLN positivity. The study provides further evidence that using DecisionDx-Melanoma to help guide decisions regarding the SLNB procedure could improve patient selection, reduce unnecessary surgical procedures and ultimately improve the care of patients with melanoma.
References:Â
- Joyce KM, McInerney NM, Piggott RP, et al. Analysis of sentinel node positivity in primary cutaneous melanoma: an 8-year single institution experience. Ir J Med Sci. 2017;186(4):847-853. doi:10.1007/s11845-017-1559-2
- Chen J, Xu Y, Wang Y, et al. Prognostic role of sentinel lymph node biopsy for patients with cutaneous melanoma: A retrospective study of surveillance, epidemiology, and end-result population-based data. Oncotarget. 2016;7(29):45671-45677. doi:10.18632/oncotarget.10140
- Vetto JT, Hsueh EC, Gastman BR, et al. Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling. Future Oncol. 2019;15(11):1207-1217. doi:10.2217/fon-2018-0912
- Whitman ED, Koshenkov VP, Gastman BR, et al. Integrating 31-gene expression profiling with clinicopathologic features to optimize cutaneous melanoma sentinel lymph node metastasis prediction. JCO Precis Oncol. 2021;5:1466-79. doi:10.1200/PO.21.00162