Gender Influences Epidemiologic Characteristics of Secondary Malignant Neoplasms in Classical Ph Negative Myeloproliferative Neoplasms

Objectives: To explore the influence of gender on the incidence of secondary malignant neoplasms (SMNs) among patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), based on The Surveillance, Epidemiology and End Results (SEER). Methods: We used the ICD (International Classification of Diseases) for Oncology, third edition (codes 9950, 9961, and 9962) to assemble a retrospective cohort of patients with PV, ET and PMF diagnosed between 2000 and 2018 in SEER 18. SMNs were defined as new cancer diagnoses occurring in patients with diagnosis of PV, ET and PMF at least 6 months prior to the diagnosis of a new malignancy. Other exclusion criteria included unknown age and diagnosis by autopsy or death certificate only. Results: The cohorts enrolled 35645 patients with myeloproliferative neoplasms (MPNs), including 17416 male patients (48.9%) and 18229 female patients (51.1%). The incidence of SMNs in male patients was higher than female patients (11.7% versus 9.1%，P＜0.001). This trend was also observed across PV,ET and PMF patients (11.4% versus 9.8%, 12.6% versus 8.7%, 10.9% versus 8.3% respectively，all P value＜0.05). The median time from diagnosis of MPNs to SMNs in male and female patients were similar [48 (6-217) versus 49.5 (6-207) months, P=0.884]. In subgroup analysis, the median time from diagnosis of PV and ET to SMNs in male patients were 54 (6-200) and 50.5 (6-207) months respectively, similar to those in female patients [54 (6-227) and 49 (6-201) months with P=0.994 and 0.645, respectively]. However, the median time from diagnosis of PMF to SMNs in male patients was shortened when compared with female patients [30(6-159) versus 38 (7-186) months, P=0.046]. In terms of the spectrum of SMNs, the most common site of non-hematological solid SMNs in male patients were prostate (2.5%), lung (1.5%), skin (0.7%), bladder (0.5%), gastrointestinal (0.4%) and kidney (0.4%), while breast (1.5%), lung (1.2%), reproductive system (0.5%), skin (0.3%), gastrointestinal (0.3%), kidney (0.3%) and thyroid (0.2%) cancers dominated the top of non-hematological solid SMNs in female patients. Survival analysis showed that the cumulative incidence of SMNs, leukemia, non-leukemic hematological cancers (including myelodysplastic syndromes and lymphoma) and solid SMNs were similar between male and female patients with PV and ET (all P value＞0.05). However, male patients with PMF suffered higher incidence of SMNs and leukemia than female patients with PMF (P=0.002 and 0.005, respectively), but the cumulative incidence of non-leukemic hematological cancers and solid SMNs in male PMF patients did not differ with female PMF patients (P=0.52 and 0.081, respectively). Conclusion: Gender influences incidence and spectrum of SMNs in MPNs. Male patients with PMF developed SMNs earlier and suffered higher incidence of SMNs, especially leukemia, over time.