Risk of prostate cancer in relatives of prostate cancer patients in Sweden: A nationwide cohort study

Author summary Why was this study done? Family history is the strongest known risk factor for prostate cancer (PCa), and current guidelines concur that an earlier screening for men with a family history of PCa is necessary. However, limited evidence-based guidance is available on at what age actually this early screening should start. This study was conducted to provide precise recommendations about at what age should relatives of PCa patients start screening based on the number of affected relatives and the age at onset of PCa in the family. What did the researchers do and find? In this nationwide study on 6,343,727 men, the risk of stage III/IV or fatal PCa in close family members of patients with PCa was estimated. It was observed that men with family history of PCa reach the screening risk threshold up to 12 years earlier than the general population. This study found that age, age at diagnosis of PCa in relative/s, and number of affected first-degree relatives (FDRs) are important elements in increased risk of stage III/IV or fatal PCa, and these factors accordingly resulted in different risk-adapted starting ages of PCa screening. Comparison between our evidence-based risk-adapted starting age of screening and recommended age of PCa screening by different guidelines showed a difference ranging from -2 to 11 years. What do these findings mean? This study made use of the largest dataset available, to our knowledge, to identify the optimal age for starting PCa screening in relatives of patients with PCa. This study took into account not only the number of relatives but also age at onset of PCa in the family members, which is an additional important piece of information for the guidelines. The results may contribute to a more evidence-based personalized PCa screening guidance in real-world settings, and clinicians could inform patients with PCa about this possibility and encourage individualized counseling for their relatives. Background Evidence-based guidance for starting ages of screening for first-degree relatives (FDRs) of patients with prostate cancer (PCa) to prevent stage III/IV or fatal PCa is lacking in current PCa screening guidelines. We aimed to provide evidence for risk-adapted starting age of screening for relatives of patients with PCa. Methods and findings In this register-based nationwide cohort study, all men (aged 0 to 96 years at baseline) residing in Sweden who were born after 1931 along with their fathers were included. During the follow-up (1958 to 2015) of 6,343,727 men, 88,999 were diagnosed with stage III/IV PCa or died of PCa. The outcomes were defined as the diagnosis of stage III/IV PCa or death due to PCa, stratified by age at diagnosis. Using 10-year cumulative risk curves, we calculated risk-adapted starting ages of screening for men with different constellations of family history of PCa. The 10-year cumulative risk of stage III/IV or fatal PCa in men at age 50 in the general population (a common recommended starting age of screening) was 0.2%. Men with >= 2 FDRs diagnosed with PCa reached this screening level at age 41 (95% confidence interval (CI): 39 to 44), i.e., 9 years earlier, when the youngest one was diagnosed before age 60; at age 43 (41 to 47), i.e., 7 years earlier, when >= 2 FDRs were diagnosed after age 59, which was similar to that of men with 1 FDR diagnosed before age 60 (41 to 45); and at age 45 (44 to 46), when 1 FDR was diagnosed at age 60 to 69 and 47 (46 to 47), when 1 FDR was diagnosed after age 69. We also calculated risk-adapted starting ages for other benchmark screening ages, such as 45, 55, and 60 years, and compared our findings with those in the guidelines. Study limitations include the lack of genetic data, information on lifestyle, and external validation. Conclusions Our study provides practical information for risk-tailored starting ages of PCa screening based on nationwide cancer data with valid genealogical information. Our clinically relevant findings could be used for evidence-based personalized PCa screening guidance and supplement current PCa screening guidelines for relatives of patients with PCa.

Automated summary

This study aimed to provide evidence-based recommendations for the optimal age to start prostate cancer (PCa) screening for relatives of patients with PCa based on family history. The research found that men with a family history of PCa should start screening earlier than the general population, and the age at onset of PCa in relatives and the number of affected first-degree relatives are important factors in determining the risk of advanced PCa. The study provides valuable information for personalized PCa screening guidance and suggests potential benefits for informing patients with PCa and offering individualized counseling for their relatives.