Familial Risks in 317 000 Patients With Prostate Cancer in Relation to Metastases and Survival-Guiding Diagnostics

Abstract

BackgroundSwedish nationwide family and cancer data offer the largest global resource for study of familial cancer. We focus here on familial risks in prostate cancer (PC) with questions on risk in individuals from families of multiple affected members and association of familial risk with metastatic disease and survival.MethodsFamilial relative risk of PC was estimated using standardized incidence ratios (SIRs) for second-generation men with a father or brother affected with PC, considering distinct groups by number and type of affected relatives.ResultsFamilial SIRs ranged from 2.22 (2 brothers with PC) to 11.5 (≥5 brothers with PC). The proportions of affected men increased from about 15% (2-case families) to 50% (≥5-case families). Age-incidence curves showed successively higher rates for men from multi-case families. Older patients with PC had the highest proportion of metastases at diagnosis, but in each age group, familial patients presented with a lower proportion of metastases compared with nonfamilial cases. Among brothers, the proportion of metastasis was higher in brothers first diagnosed compared with brothers with subsequent diagnosis. Survival in familial cases was better compared with nonfamilial cases among patients without metastases. Among such patients, brothers diagnosed first survived worse than subsequent brothers.Conclusions and clinical implicationsThe largest family study yet conducted on PC was based on 34 468 familial cases. Risk varied greatly by family constellations, emphasizing the need for a detailed family history at diagnosis as basis for clinical decision-making and genetic counseling. The reported high risks should encourage implementation of familial risk into schemes for PC screening.Patient summaryPatients with prostate cancer often have a relative who has prostate cancer. When PC is diagnosed, it is important that the patient reports a reliable history of relatives earlier diagnosed with PC. It may influence his treatment.