Cancer history and second cancer risk in polycythemia vera and essential thrombocythemia.
Key claim: In PV and ET, prior cancer, older age, male sex, and hyperlipidemia independently predict second-cancer risk (with prior NMSC strongly predicting subsequent NMSC), supporting risk-adapted surveillance and regular dermatologic monitoring.
Abstract
Patients with myeloproliferative neoplasms (MPN), including polycythemia vera (PV) and essential thrombocythemia (ET), have an increased risk of second cancers (SC), although determinants of risk remain incompletely defined. We retrospectively analyzed 1968 consecutive patients with PV or ET (median follow-up 11.2 years) to identify predictors of SC. Cumulative incidence functions were estimated using competing-risk methodology, and predictors were assessed using Fine-Gray regression. During follow-up, SC occurred in 404 patients (20%), with non-melanoma skin cancer (NMSC) representing the most frequent subtype. In multivariable models including all cancer types, prior cancer (sHR 2.02, p < 0.001), older age (per 10 years: sHR 1.20, p < 0.001), male sex (sHR 1.39, p = 0.002), and hyperlipidemia (sHR 1.41, p = 0.003) independently predicted SC. After excluding NMSC, prior cancer remained associated with SC risk (sHR 1.48, p = 0.048). Notably, prior NMSC strongly predicted subsequent NMSC (sHR 6.48, p < 0.001), followed by prior non-NMSC cancer (sHR 2.11, p < 0.001), age (sHR 1.29, p < 0.001), and male sex (sHR 1.43, p = 0.018). TET2 mutations showed a borderline association with NMSC risk (sHR 1.73, p = 0.055), while hydroxyurea was not associated with SC, with a non-significant trend toward increased NMSC risk (sHR 1.82, p = 0.110). These findings support risk-adapted cancer surveillance in PV and ET, with particular emphasis on regular dermatologic monitoring.
Why this matters
Second cancers are an underappreciated component of PV and ET natural history, and the hydroxyurea-carcinogenicity question has long complicated cytoreductive choice in these subtypes. By quantifying host/comorbidity predictors (prior cancer, age, sex, hyperlipidemia) and finding no significant HU association with overall second-cancer risk, this analysis reframes second-cancer risk as largely patient-intrinsic and operationalizes risk-adapted surveillance — especially dermatologic follow-up for prior-NMSC patients — across both PV and ET.