Research Summary:
Sentinel lymph node biopsy (SLNB) is recommended for patients with melanoma and a likelihood of SLN positivity above 10 percent, and it should be considered in patients with a 5 to 10 percent likelihood of SLN positivity. Currently, up to 88 percent of SLNBs return negative results, so an improved method for stratifying patients is needed. The 31-gene expression profile (31-GEP) test for cutaneous melanoma has been shown to stratify patients at low- (Class 1A), intermediate- (Class 1B/2A), and high-risk (Class 2B) for disease recurrence, metastasis, mortality, and SLN positivity. The integrated 31-GEP (i31-GEP) combines the 31-GEP risk score and clinicopathological features to further improve risk stratification for SLN positivity. In this retrospective study, Kriza et al1 analyzed the utility of the i31-GEP in the prediction of SLN positivity among patients with cutaneous melanoma. Their findings are summarized below.
Data were gathered from patients treated at a single academic community hospital from 2015 to 2020. SLNB was offered to patients with melanoma lesions 0.8mm or greater and those with lesions 0.6mm or greater and shave biopsy with positive margin. All patients who received SLNB also underwent i31-GEP testing.
A total of 156 patients were included for analysis. Fifty-eight percent of patients were male, and the median age was 64 years. Most patients presented with T2 (T2a: 21.8%, T2b: 7.7%; total: 29.5%) or T1 (T1a: 10.9%, T1b: 18.0%; total: 28.9%) tumors. A total of 25.6 percent of patients had T3 tumors (T3a: 12.8%, T3b: 12.8%), and 16.1 percent had T4 tumors (T4a: 5.8%, T4b: 10.3%). The median Breslow thickness was 1.8mm. Fifty-four patients (34.6%) had ulceration, and the median mitotic rate was 2/mm2. Most tumors were located on the trunk (44.9%) or an extremity (43%), with only 12.2 percent of tumors located on the head and neck.
Overall, 32 patients (20.5%) had a positive SLN. Of the 17 T1a tumors included, 15 had at least one high-risk factor (e.g., mitotic rate ≥2/mm2, age <40 years, lymphovascular invasion, microsatellites, etc.), and thus were considered as having a 5-to-10-percent risk of SLN positivity.
According to i31-GEP test results, 30 patients were identified as having a less than five percent risk of SLN positivity. Thirty-two patients were identified as having a 5 to 10 percent risk of SLN positivity, and 94 were identified as having a risk above 10 percent. The classification of 30 patients with T1 to T2 tumors as having less than five percent risk of SLN positivity indicated a significant potential decrease in SLNB with the use of the i31-GEP test. Among 43 patients with T1a or T1b tumors, who were considered as having a 5-to-10-percent risk of SLN positivity as per current guidelines, 22 (51.2%) were reclassified as having less than five percent risk, and five (11.6%) were reclassified as having a greater-than-10-percent risk. Six of 111 patients with a greater-than-10-percent risk of SLN positivity per current guidelines (T2–T4 tumors) were determined to have less than five percent risk of SLN positivity with i31-GEP testing, and sixteen patients were reclassified as having 5 to 10 percent risk.
The SLN positivity rate was zero percent for all patients with less than five percent risk of SLN positivity as determined by the i31-GEP test. Two patients (6.3%) with 5-to-10-percent risk were positive for SLN. Thirty patients (31.9%) with a greater-than-10-percent risk as per the i31-GEP test had a positive SLN; among these patients, 10 had T1 to T2 tumors, and 20 had T3 to T4 tumors. The rate of SLN positivity was similar in patients with T1 to T2 tumors (33.3%) and those with T3 to T4 tumors (31.3%). Considering specific disease stages in the greater-than-10-percent risk group, the rate of SLN positivity was highest in highest in T2a (37.5%), T2b (33.3%), T3a (47.4%), and T3b (35.0%) tumors. The SLN positivity rate was zero percent for T1a tumors and 25.0 percent for T1b tumors. T4a and T4b tumors had SLN positivity rates of 22.2 and 12.5 percent, respectively.
The sensitivity and specificity of the i31-GEP test were 100 and 24.2 percent, respectively. Negative predictive value was 100 percent, and positive predictive value was 25.4 percent. Subgroup analysis of T1 to T2 tumors showed that the i31-GEP had 100-percent sensitivity and 37.5-percent specificity, as well as a negative predictive value of 100 percent and positive predictive value of 18 percent.
Limitations include the small sample size, the retrospective nature of the study, and the absence of follow-up data. Furthermore, this was a single-center study, so the broader patient population might not have been represented in this sample.
Based on these findings, Kriza et al concluded that utilization of the i31-GEP test can help improve the prediction of SLN positivity in patients with T1 to T4 cutaneous melanoma, which may reduce the number of unnecessary SLNB procedures. Furthermore, implementation of the i31-GEP test can help improve personalized patient care.
Reference
- Kriza C, Martin B, Bailey CN, Bennett J. Integrating the melanoma 31-gene expression profile test with clinical and pathologic features can provide personalized precision estimates for sentinel lymph node positivity: an independent performance cohort. World J Surg Oncol. 2024;22(1):228.