The incidence of early‐onset prostate cancer (EOPC) is rising, and by 2045 a 24.5% increase in cases and a 50% rise in mortality are projected. Accumulating evidence indicates that EOPC represents a distinct disease entity, characterized by unique molecular features, risk factor profiles, and clinical behavior that differ from standard‐onset prostate cancer (SOPC). Nevertheless, research in this field remains nascent, and no consensus exists regarding the optimal management of EOPC. We synthesize current evidence on the epidemiology, molecular pathology, clinicopathological characteristics, survival, management, and early detection of EOPC. EOPC exhibits a distinctive molecular landscape, with TMPRSS2–ERG fusions occurring in 63–90% of cases as a hallmark alteration, whereas mutations in PTEN, SPOP, and CHD1 are significantly less frequent. Notably, the prevailing focus on hereditary EOPC has inadvertently led to the neglect of sporadic cases, which dominate clinical practice. Although localized EOPC confers no significant prognostic advantage over SOPC, high‐risk or metastatic early‐onset disease substantially elevates prostate‐cancer‐specific mortality. By critically appraising the existing evidence, we identify key knowledge gaps, such as the understudied sporadic EOPC subgroup and the lack of dedicated clinical trials, and propose future research directions to inform early detection and optimize therapeutic strategies for this unique patient population.
Abstract Objectives To investigate the association between exposure to specific endocrine-disrupting chemicals (EDCs), air pollutants and the risk of localised prostate cancer (PCa) and to evaluate the combined effect of mixed EDC exposures. Design A case–control study. Setting Secondary care; a single tertiary hospital in Western China. Participants A total of 580 patients with histologically confirmed localised PCa who underwent radical prostatectomy between May 2021 and June 2023 were included as cases. They were matched 1:2 with 1160 cancer-free controls from the same cohort on age (±5 years) and date of biological sample collection. Key exclusion criteria were a history of other malignancies, androgen deprivation therapy prior to surgery or acute urinary infection. Primary and secondary outcome measures The primary outcome was the odds of PCa associated with individual and mixed exposures. Primary exposures were urinary concentrations of nine bisphenols (BPs) and nine phthalate metabolites (quantified via high-performance liquid chromatography–tandem mass spectrometry) and estimated ambient air pollution exposure (sulphur dioxide (SO2) and PM₂.₅) based on geocoded residential addresses. Results A total of 580 cases and 1160 controls were included in the final analysis. Exposure to the highest quartile of sulphur dioxide (SO2) over 5 years (9.37–28.79 µg/m3) was significantly associated with PCa, yielding an OR of 1.65 (95% CI 1.08 to 2.72; p<0.001) compared with the lowest quartile (3.61–6.89 µg/m3). Urinary concentrations of multiple phthalate metabolites (MECPP, MEHHP and MEHP) and BPs (bisphenol A (BPA) and BPZ) were significantly higher in cases (all p<0.05). Weighted quantile sum (WQS) regression analysis demonstrated a significant positive association between the mixture of EDCs and PCa risk (WQS OR=1.26, 95% CI 1.20 to 1.33; p<0.001). Conclusions Exposure to SO2 and specific EDCs (both individually and as a mixture) is significantly associated with localised PCa. Trial registration number ChiCTR1900024623.
Xianghong Zhou, Yuchong He, Yumin Jin et al.· BMJ Open· 0 citations