Development and validation of a nomogram to predict recurrence and melanoma-specific mortality in patients with negative sentinel lymph nodes

Abstract

Background: Patients with melanoma and negative sentinel nodes (SNs) have varying outcomes, dependent on several prognostic factors. Considering all these factors in a prediction model might aid in identifying patients who could benefit from a personalized treatment strategy. The objective was to construct and validate a nomogram for recurrence and melanoma-specific mortality (MSM) in patients with melanoma and negative SNs.

Methods: A total of 3220 patients with negative SNs were identified from a cohort of 4124 patients from four EORTC Melanoma Group centres who underwent sentinel lymph node biopsy. Prognostic factors for recurrence and MSM were studied with Cox regression analysis. Significant factors were incorporated in the models. Performance was assessed by discrimination (c-index) and calibration in cross-validation across the four centres. A nomogram was developed for graphical presentation.

Results: There were 3180 eligible patients. The final prediction model for recurrence and the calibrated model for MSM included three independent prognostic factors: ulceration, anatomical location and Breslow thickness. The c-index was 0·74 for recurrence and 0·76 for the calibrated MSM model. Cross-validation across the four centres showed reasonable model performance. A nomogram was developed based on these models. One-third of the patients had a 5-year recurrence probability of 8·2 per cent or less, and one-third had a recurrence probability of 23·0 per cent or more.

Conclusion: A nomogram for predicting recurrence and MSM in patients with melanoma and negative SNs was constructed and validated. It could provide personalized estimates useful for tailoring surveillance strategies (reduce or increase intensity), and selection of patients for adjuvant therapy or clinical trials.

Figure 1

The curves refer to predicted recurrence or melanoma‐specific mortality (MSM) at 5 years. The histogram refers to the risk score distribution in the cohort; each bar represents the proportion of patients in the cohort that was assigned that specific score. The histogram was divided in tertiles: light pink bars, first tertile (low risk); medium pink bars, second tertile (intermediate risk); dark pink bars, third tertile (high risk). The nomogram incorporates three factors: ulceration, anatomical location and Breslow thickness. To calculate an individual's probability of 5‐year recurrence and MSM, values for the prognostic factors must be determined first (for example: ulceration; leg; Breslow thickness 2·5 mm). Second, for each value the corresponding points can be obtained by drawing a line from each value towards the points axis (in example: 2, 1 and 7 points respectively). Third, the points must be added up to obtain the total risk score (in example: risk score of 10). Finally, the 5‐year recurrence and MSM probability can be read by moving vertically from the x‐axis (total risk score) to the predicted risk curves and corresponding probabilities on the left y‐axis (for example: 23·0 per cent for recurrence and 11·0 per cent for MSM). The percentage of patients in the entire population (3180) that also had a total risk score of 10 can be determined from the histogram, as well as the corresponding percentage of patients on the right y‐axis (for example: 17·5 per cent)