Weight trajectories throughout adulthood and prostate cancer incidence, aggressiveness, and death in 258 494 men

BACKGROUND: Obesity assessed at a single time point in adulthood has shown no consistent association with prostate cancer (PCa) incidence but has been positively associated with PCa death. We investigated the association of total and age-specific adult weight trajectories with PCa aggressiveness and death. METHODS: We analyzed data from 258,494 men in Sweden with at least 3 weight observations between ages 17 and 60. Individual weight trajectories were estimated using linear mixed-effects models with natural cubic and linear splines for age, incorporating random intercepts and slopes. These estimates were included in multivariable-adjusted Cox proportional hazards models. RESULTS: Over a median follow-up of 25 years, 22 055 men were diagnosed with PCa and 4547 died from the disease. Steep weight gain was inversely associated with PCa diagnosed during the PSA testing era (1997 onwards) and via asymptomatic PSA testing, but not with aggressive PCa. Among men with PCa, steep weight gain was associated with increased risk of PCa death (HR quintile 5 vs. 1 = 1.23, 95% CI = 1.08 to 1.40), primarily driven by weight gain between ages 45 and 60 (HR per 1 kg/year = 1.31, 95% CI = 1.10 to 1.57). CONCLUSIONS: The associations observed for incident PCa appear to be influenced by PSA testing uptake; however, the extent to which detection bias contributes remains uncertain. Conversely, late midlife weight gain was associated with an elevated risk of PCa death, underscoring the importance of weight management during this period as a potentially modifiable factor for reducing PCa death.