Second Primary Cancers in a Population-Based Mesothelioma Registry

SIMPLE SUMMARY: The occurrence of second primary cancers (SPCs) in patients with pleural mesothelioma (PM) included in the Lombardy Mesothelioma Registry (Italy) was investigated, with the aim of assessing its prognostic implications. The results of our study showed that the presence of an SPC in a patient’s history did not significantly impact survival in the overall PM population; however, patients with non-epithelioid PM had a worse prognosis when an SPC was diagnosed. Further studies, including next-generation sequencing of cancer susceptibility genes on germline DNA, are needed to clarify the role of SPCs as markers of genetic susceptibility in mesothelioma. ABSTRACT: Background: The presence of a second primary cancer (SPC) in patients with pleural mesothelioma (PM) may impact overall survival and suggest a common mechanism of carcinogenesis or an underlying germline genetic alteration. Methods: We evaluated the occurrence of SPCs within PM cases collected from 2000 to 2018 by the Lombardy Mesothelioma Registry and their prognostic implications. Kaplan–Meier analysis was performed to estimate median survival times, together with univariate and multivariate Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of death. Results: The median overall survival (OS) of the entire study population (N = 6646) was 10.9 months (95% CI: 10.4–11.2); patient age and histotype were the strongest prognostic factors. No substantial survival difference was observed by the presence of an SPC (10.5 months in 1000 patients with an SPC vs. 10.9 months in 5646 patients in the non-SPC group, HR 1.03, p = 0.40). Shorter OS in the SPC group was only observed in 150 patients with the non-epithelioid subtype (median OS of 5.4 vs. 7.1 months, HR 1.21, p = 0.03). Conclusions: The diagnosis of an SPC did not influence the outcome of PM patients in the overall study population but was associated with shorter OS in non-epithelioid cases. Further studies are needed to clarify the role of SPCs as markers of genetic susceptibility in mesothelioma.