Environmental Exposure Context and Advanced Stage at Diagnosis in Thyroid Cancer: A Population-Based SEER Analysis

Factors affecting lung cancer stage at diagnosis and receipt of surgery in Ontario: A population-based analysis

Lung cancer is the leading cause of cancer mortality in Canada, with most cases diagnosed at advanced stage. Despite universal healthcare, social determinants of health may impact stage at diagnosis and access to treatment. We examined the association between these factors, stage at diagnosis, and receipt of surgery in Ontario. We conducted a population-based retrospective cohort study of adults diagnosed with lung cancer in Ontario from 2007–2023 using linked administrative health data. Stage was obtained from the Ontario Cancer Registry. Factors included income, primary care attachment, immigration status, geographic region, and distance to the nearest cancer centre. Logistic regression identified factors associated with stage IV diagnosis. Among 106,867 patients with available stage data, 52.6% were diagnosed with stage IV disease; 19.1% were stage I. Patients without a family physician were significantly more likely to present with stage IV cancer compared with those fully rostered (62.1% vs 51.5%; adjusted OR 1.55, p < 0.001). Females had lower likelihood of stage IV diagnosis than males (OR 0.85, p < 0.001). Increasing household income was associated with reduced likelihood of stage IV disease (OR 0.92 for highest vs lowest quintile, p < 0.001). Immigrants were less likely to be diagnosed with stage IV cancer than non-immigrants (OR 0.77, p = 0.001). Frailty was associated with higher odds of stage IV disease (OR 1.01, p = 0.009). Surgical resection was performed in 56.1% of patients with stage I disease and 1.4% with stage IV disease. Receipt of surgery decreased with advancing age (27.0% < 50 years vs 7.3% ≥ 80 years), higher comorbidity burden (25.4% with 0 vs 5.0% with ≥5 comorbidities), and lack of primary care attachment. Marked social inequities in lung cancer stage at diagnosis and surgical treatment persist in Ontario. Interventions addressing primary care attachment and upstream social determinants may improve early detection and access to curative therapy.

Traditional Risk Factors Are Not Associated with the Rise of Early-Onset Colorectal Cancer: An All of Us Study.

BACKGROUND Colorectal cancer incidence is increasing among adults under age 50, yet the etiologic drivers remain unclear. The All of Us Research Program provides a unique opportunity to examine age-specific genetic and environmental associations with colorectal cancer risk in a diverse national cohort. OBJECTIVE To determine whether a significant association exists between traditional environmental risk factors and established genetic variants and age-specific incidence patterns of early-onset colorectal cancer. DESIGN Retrospective stratified case-control study using whole genome sequencing and electronic health records. Conditional logistic regression adjusted for genetic ancestry. SETTINGS Diverse national cohort with integrated genomic data, electronic health records, and lifestyle surveys. PATIENTS A total of 2,455 colorectal cancer patients (485 early-onset diagnosed before age 50, 1,970 late-onset diagnosed at age ≥50) matched 4:1 to 9,820 controls on birth year, sex, and race. MAIN OUTCOME MEASURES Age-specific associations between environmental factors (family history, smoking timing, alcohol use disorders, body mass index) and 283 genetic variants with colorectal cancer risk. RESULTS Family history was associated with higher odds uniformly across ages (odds ratio 2.10, 95% confidence interval 1.69-2.61). Heavy smoking during ages 20-40 was associated with late-onset but not early-onset disease (interaction p = 0.006). Alcohol use disorders and body mass index showed no age-specific effects. In genetic analyses, no variants demonstrated age-specific effects after correction for multiple comparisons (283 variants tested). No genetic pathways differed between early-onset and late-onset disease. Two variants were associated with rectal-specific risk (VTI1A rs4554812, FMN2 rs2078095). LIMITATIONS Causal inference is limited by observational design. Self-reported exposures are subject to recall bias. Age-stratified analyses had limited power for rare genetic effects. CONCLUSIONS Traditional environmental risk factors and established common genetic variants are not associated with the rising incidence of early-onset colorectal cancer. Thus, drivers of early-onset disease might include novel environmental exposures or early-life factors beyond traditional risk assessment. See Video Abstract.

Real-World Evidence for Breast Cancer Risk Stratification: Insights from the P.I.N.K. Study

Simple Summary Early detection of breast cancer greatly improves outcomes, with the 5-year survival rate reaching 99% when the disease is found at an early stage. One promising approach to improve early detection is risk-based breast screening, which tailors screening recommendations according to a woman’s individual risk factors, including medical history, personal characteristics, and lifestyle habits. The Prevention, Imaging, Network, Knowledge (P.I.N.K.) study was created to collect real-world data from a large group of women across Italy and to support the development of more personalized breast cancer screening strategies. By combining information gathered during routine breast clinic visits with answers provided by women through a structured questionnaire, we examined factors associated with the development of breast cancer. Our findings identified several personal characteristics that were more strongly linked to breast cancer occurrence, highlighting the value of integrating clinical and self-reported information to better understand individual risk and support more targeted prevention and screening efforts. By providing additional evidence on the contribution of potentially modifiable risk factors, this study helps identify priorities for future research aimed at improving breast cancer risk stratification, informing the development of more targeted screening strategies, and facilitating discussions with women about the impact of lifestyle on breast cancer risk.

Reducing the burden of active surveillance monitoring examinations in prostate cancer: Insights from real-world data to inform clinical practice.

BACKGROUND Active surveillance (AS) is standard for early-stage prostate cancer, though intensive monitoring continues due to concerns about reclassification to Grade Group (GG) ⩾ 2. We hypothesized that simple and inexpensive clinical parameters could identify patients with indolent disease for whom less intensive monitoring is safe. METHODS We analyzed upgrading to ISUP Grade Group (GG) ⩾ 2 in a large cohort of low-risk prostate cancer (PCa) patients on AS. We used mixed-effects logistic regression to develop a model predicting non-upgrading at the next follow-up biopsy, based on routine time-updated clinical-pathological variables. RESULTS While annual reclassification persisted at a rate between 10.4% and 17.5% up to the 7th year, upgrades were predominantly GG2. Routine parameters powerfully stratified risk. Patients with a very unfavorable Prostate Specific Antigen (PSA) doubling time had a 40.5% upgrading rate versus 9.5% for those with a favorable value. The final model is based on baseline PSA density and number of positive cores, time-updated age and PSA doubling time category, detection of cancer in the last surveillance biopsy. The model showed moderate discrimination (0.73) in predicting non-upgrading. CONCLUSIONS Many patients on AS have indolent disease but steady upgrading justifies monitoring. A model using simple, routine parameters and PSA doubling time can identify those at minimal risk of reclassification, enabling a safe reduction in biopsy intensity. This advocates for a risk-adaptive AS protocol, reserving advanced tools like MRI or biomarkers for the few higher-risk cases.

The Predictive Accuracy of PREDICT:A Personalized Decision-Making Tool for Southeast Asian Women With Breast Cancer

Early-onset lung cancer: etiologic heterogeneity, genomic features, and age-informed clinical management.

Early-onset lung cancer, commonly defined as disease diagnosed at or before 50 years of age, represents a growing but insufficiently characterized subset of lung cancer in clinical practice. However, much of the evidence informing current diagnostic and therapeutic practice has been generated from age-unselected or older, smoking-dominant populations and may not fully capture the clinical characteristics of younger patients. Consequently, younger individuals with lung cancer may face delayed risk recognition, incomplete molecular evaluation, and treatment decisions not fully informed by age-associated clinicobiological features. Accumulating evidence indicates that early-onset non-small cell lung cancer (NSCLC) is enriched for actionable oncogenic alterations, particularly gene fusions and selected HER2/ERBB2 alterations, and is frequently associated with lower tumor mutational burden and a less inflamed tumor microenvironment. Although these features do not yet establish early-onset NSCLC as a separate treatment category, they support age-informed refinement of guideline-based management, particularly in initial molecular testing, interpretation of immunotherapy-relevant immune features, treatment transitions, and survivorship planning. In this review, we synthesize current evidence on disease burden, etiologic heterogeneity, age-related genomic features, and treatment-relevant tumor immune context in early-onset lung cancer, with a focus on issues relevant to clinical interpretation and management prioritization. We further outline age-informed clinical management for molecular evaluation, resistance reassessment, and survivorship care, aiming to complement rather than replace established NSCLC guidelines for patients aged ≤50 years.