The relative contribution of the decreasing trend in tumour thickness to the 2010s increase in net survival from cutaneous malignant melanoma in Italy: a population-based investigation

Abstract

Background: The long-term increase in survival from cutaneous malignant melanoma (CMM) is generally attributed to the decreasing trend in tumour thickness, the single most important prognostic factor.

Objectives: To determine the relative contribution of decreased tumour thickness to the favourable trend in survival from CMM in Italy.

Methods: Eleven local cancer registries covering a population of 8 056 608 (13.4% of the Italian population in 2010) provided records for people with primary CMM registered between 2003 and 2017. Age-standardized 5-year net survival was calculated. Multivariate analysis of 5-year net survival was undertaken by calculating the relative excess risk (RER) of death. The relative contribution of the decrease in tumour thickness to the RER of death was evaluated using a forward stepwise flexible parametric survival model including the available prognostic factors.

Results: Over the study period, tumour thickness was inversely associated with 5-year net survival and multivariate RER in both sexes. The median thickness was 0.90 mm in 2003-2007, 0.85 mm in 2008-2012 and 0.75 mm in 2013-2017 among male patients, and 0.78 mm, 0.77 mm and 0.68 mm among female patients, respectively. The 5-year net survival was 86.8%, 89.2% and 93.2% in male patients, and 91.4%, 92.0% and 93.4% in female patients, respectively. In 2013-2017, male patients exhibited the same survival as female patients despite having thicker lesions. For them, the increasing survival trend was more pronounced with increasing thickness, and the inclusion of thickness in the forward stepwise model made the RER in 2013-2017 vs. 2003-2007 increase from 0.64 [95% confidence interval (CI) 0.51-0.80] to 0.70 (95% CI 0.57-0.86). This indicates that the thickness trend accounted for less than 20% of the survival increase. For female patients, the results were not significant but, with multiple imputation of missing thickness values, the RER rose from 0.74 (95% CI 0.58-0.93) to 0.82 (95% CI 0.66-1.02) in 2013-2017.

Conclusions: For male patients in particular, decrease in tumour thickness accounted for a small part of the improvement in survival observed in 2013-2017. The introduction of targeted therapies and immune checkpoint inhibitors in 2013 is most likely to account for the remaining improvement.

Figure 1

Time trend in median Breslow tumour thickness of cutaneous malignant melanoma and in 5‐year per cent net survival from the disease, by sex, Italy, 2003–2017. Median tumour thickness was computed for those cases from patients for whom the numerical value of tumour thickness was found (n = 14 247). Five‐year net survival was computed for the ‘core subset’ of eligible patients (n = 16 130), that is, those whose case could be categorized according to the American Joint Committee on Cancer staging criteria. Five‐year net survival was age‐standardized using the International Cancer Survival Standard‐2 weights. P‐values for trend are from a Poisson regression model for net survival including the time period of diagnosis as a numeric variable. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 2

Time trend in tumour thickness category‐specific 5‐year per cent net survival from cutaneous malignant melanoma, by sex, Italy, 2003–2017. Tumour thickness was categorized according to the American Joint Committee on Cancer staging criteria. Five‐year net survival was computed for the ‘core subset’ of eligible patients (n = 16 130), that is, those whose case could be categorized according to the above criteria. P‐values for trend are from a Poisson regression model for net survival including the time period of diagnosis as a numeric variable. M, men; W, women. [Colour figure can be viewed at wileyonlinelibrary.com]