Mucci La

Importance: There is insufficient evidence to determine whether physical activity lengthens survival among people with a history of cancers less commonly studied for such benefit. Objective: To examine the associations between physical activity assessed after a cancer diagnosis with cancer mortality and, secondarily, changes in physical activity before vs after diagnosis with cancer mortality among people previously diagnosed with 1 of 7 cancers. Design, Setting, and Participants: This study used a pooled dataset of 6 cohorts (Cancer Prevention Study-II Nutrition Cohort, Health Professionals Follow-Up Study, National Institutes of Health-AARP Diet and Health Study, Nurses' Health Study, Nurses' Health Study II, and Women's Health Study). Participants were survivors of bladder, endometrial, kidney, lung, oral cavity, ovarian, or rectal cancer who had completed surveys and had repeated measures of leisure-time physical activity. Baseline data were collected from 1976 through 1997. The mean (SD) follow-up was 10.9 (7.0) years. Data were analyzed from June 2023 to March 2024. Exposures: Leisure-time moderate to vigorous physical activity (MVPA) before and after cancer diagnosis. Main Outcomes and Measures: Association of MVPA in categories of metabolic equivalents of task hours per week (MET-h/wk) measured before and a mean (SD) of 2.8 (1.5) years after cancer diagnosis with cancer mortality. Results: This pooled analysis included 17 141 cancer survivors (mean [SD] age, 67 [8] years; 60% female). Engagement in low amounts of MVPA (>0 to <7.5 vs 0 MET-h/wk) was associated with lower risk of cancer mortality among survivors who had been diagnosed with bladder (hazard ratio [HR], 0.67 [95% CI, 0.50-0.91]), endometrial (HR, 0.62 [95% CI, 0.45-0.87]), and lung cancer (HR, 0.56 [95% CI, 0.43-0.75]). Doubling the recommended MVPA guideline or more (eg, >15 vs 0 MET-h/wk) was associated with lower risk of cancer mortality among oral (HR, 0.39 [95% CI, 0.15-0.99] for >22.5 to 30.0 MET-h/wk) and rectal (HR, 0.57 [95% CI, 0.33-0.97] for >15.0 to 22.5 MET-h/wk) cancer survivors. Point estimates were less than 1 for cancer mortality among kidney cancer survivors (HR, 0.51 [95% CI, 0.22-1.18] for >15.0 to 22.5 MET-h/wk), although the confidence interval included the null. Compared with survivors who did not meet the MVPA guidelines before or after diagnosis, lung (HR, 0.58 [95% CI, 0.47-0.71]) and rectal (HR, 0.51 [95% CI, 0.32-0.83]) cancer survivors who met guidelines after diagnosis had a lower risk of cancer mortality, even if they were inactive before their diagnosis. Conclusions and Relevance: In this analysis of 6 pooled cohorts, higher levels of MVPA after a cancer diagnosis were associated with lower risk of cancer mortality among people previously diagnosed with 1 of 7 cancers not commonly studied for their association with MVPA. Findings suggest that it is important for health care professionals to promote physical activity for longevity and overall health among people living with and beyond cancer.

Abstract Introduction: Though most deaths from prostate cancer occur in older men, screening guidelines recommend against screening prostate-specific antigen (PSA) for this group. We aimed to determine if total or free PSA level in men age 65-80 years predicts long-term risk of fatal prostate cancer over 39 years of follow-up Methods: We leveraged a nested case-control study within the Physicians’ Health Study, a randomized primary prevention trial among US male physicians initiated in 1982. Among men with a blood sample at enrollment, there were 37 fatal prostate cancer cases that occurred during follow-up, age-matched to 148 controls (within 2 years). Total and free PSA levels were measured in pre-diagnostic blood samples. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals (CI) for the association between baseline total PSA and fatal prostate cancer. We estimated Area Under the Curve (AUC) to evaluate predictive ability of total and free PSA. We also estimated the cumulative incidence of fatal prostate cancer by baseline PSA category. Results: Median (interquartile range) PSA at blood draw was 1.7 ng/mL (0.9-3.2) among controls, and median follow-up from blood draw to end of study was 19 years. The cumulative risk of fatal prostate cancer at 30 years was 0.9% for PSA &amp;lt;1.5 ng/mL, 7.9% for PSA ≥1.5 ng/mL, 8.9% for PSA ≥3 ng/mL, and 14.8% for PSA ≥5 ng/mL. Relative to those with total PSA &amp;lt;1.5 ng/mL, the odds ratios for fatal prostate cancer were 9.7 (95% CI 2.8, 33.0) for those with total PSA ≥1.5 ng/mL, 12.1 (95% CI 3.3, 44.2) for PSA ≥3 ng/mL, and 26.0 (95% CI 6.4, 105.1) for PSA ≥5 ng/mL. Adding the free/total PSA ratio to total PSA in men with total PSA ≥2 ng/mL improved prediction for fatal prostate cancer, with the AUC rising from 0.71 (95% CI 0.59, 0.83) to 0.82 (95% CI 0.73, 0.91). Restricting to those who survived at least 10 years after blood draw, the cumulative risk of fatal prostate cancer at 30 years remained higher for those with elevated baseline PSA: 1.1% for PSA &amp;lt;1.5 ng/mL, 7.1% for PSA ≥1.5 ng/mL, 7.0% for PSA ≥3 ng/mL, and 12.0% for PSA ≥5 ng/mL. Conclusions: A baseline PSA in older men age 65 to 80 predicts long-term risk of fatal prostate cancer across decades-long follow-up. The ratio of free to total PSA improved prediction in men with PSA ≥2 ng/mL and should be considered for reflex testing. These findings suggest healthy older men with PSA ≥3 ng/mL and an estimated life expectancy of at least 10 more years remain at increased risk for fatal prostate cancer and should consider shared decision-making about ongoing PSA monitoring. Citation Format: Hannah E. Guard, Kendrik Yim, Kathryn M. Wilson, Sigrid V. Carlsson, Lorelei A. Mucci, Travis Gerke, Mark A. Preston. Baseline prostate-specific antigen levels in men aged 65 to 80 and fatal prostate cancer: Implications for risk-stratified screening among older men [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr PR031.

96 Background: Preventing metastatic disease is the key goal of prostate cancer screening and local treatment. However, most evaluations of metastasis burden focus only on de novo metastatic disease at diagnosis and do not capture metastatic recurrences after local therapy, such as those based on cancer registries in the United States (U.S.). Methods: We inferred the full burden of metastatic prostate cancer in the Health Professionals Follow-up Study, a prospective cohort of U.S. male health professionals aged 40–75 years at enrollment in 1986 with follow-up in this analysis through January 2018. We captured three ways how metastatic prostate cancer manifested: (1) de novo metastases at initial diagnosis, (2) metastatic recurrences reported by participants during active follow-up, and (3) metastases were inferred from deaths attributed to prostate cancer, under the assumption that such deaths are almost invariably preceded by distant metastases. Cause-of-death adjudication assumed 90% specificity of coding, with a conservative 70% applied in sensitivity analyses. Absolute risk (cumulative incidence) of metastatic prostate cancer was estimated using the Aalen–Johansen method, accounting for death from other causes as a competing risk. Results: Our study population of 50,420 men had a median age of 54 years at enrollment (interquartile range, 46 to 63 years) when they were free from prostate cancer. The study population was predominantly of European descent (95%), with 2% Asian and 1% African American participants. Over up to 30 years of follow-up, we documented 8,305 prostate cancer diagnoses. Of these, 1,504 cases were adjudicated to be metastatic at diagnosis or to have metastasized after initial diagnosis. De novo metastatic disease accounted for only 249 (17%) of all metastatic cases. Conservative causes-of-death adjudication estimated 1,314 metastatic cases, with 19% being de novo metastases. The risk of metastatic prostate cancer among men was 0.8% (95% confidence interval [CI] 0.8, 0.9) by age 70, 2.4% by age 80 (95% CI 2.3, 2.6), and 4.0% (95% CI 3.8, 4.2) by age 90 years. Four in ten metastatic prostate cancers occurred after age 80 years. De novo metastatic disease risk represented about one-quarter of metastases by age 70, with lower relative contributions with advancing age. The risk of metastatic disease was particularly high in African-American men (3.6% by age 80, 95% CI 2.2, 5.8), while the risk among Asian men (2.3% by age 80, 95% CI 1.4, 3.7) was comparable to that among European men (2.5% by age 80, 95% CI 2.3, 2.6). Conclusions: One in 25 men in a widely PSA-screened population developed metastatic prostate cancer over the lifetime. Much of this substantial disease burden would remain hidden if using de novo disease as the only measure. Clinical and registry-based evaluations of early detection and local treatment need to capture the full burden of metastatic disease, which disproportionally impacts the oldest age groups.