Abstract 2347: Lethal progression risks of low risk and favorable-intermediate risk prostate cancer in a prospective cohort of US health professionals.

Abstract Background Low-risk (grade group 1, stage≤cT2a, PSA10) or favorable-intermediate risk (grade group 1, stage cT2b-cT2c or PSA 10-20, or grade group 2, stage≤cT2a and PSA10) prostate cancer patients are at risk of progressing to lethal disease (prostate cancer death or metastasis, or receipt of hormones). We estimated 35-year lethal progression risks in a prospective cohort of health professionals with low/favorable-risk prostate cancer. Methods We followed 2872 men from diagnosis (1986-2019) to lethal progression, censoring at other-cause death or December 2022. We estimated 35-year cumulative incidences using Kaplan-Meier techniques and assessed lethal progression risk by treatment, sociodemographics, PSA, stage, grade group, and lifestyle with Cox models. Results We saw 260 lethal progressions over a median follow-up of 15.7 years (IQR: 8.6 years). The 35-year cumulative lethal progression incidence was 16.7% (95% confidence interval (CI): 13.3 - 20.4%). Lethal progression risks were higher in patients older at diagnosis (Hazard Ratio (HR): 1.08, 95% CI: 1.06 - 1.10) and with higher PSA at diagnosis (HR: 1.08, 95% CI: 1.05 - 1.12), and were lower in patients that received curative-intent treatment (radical prostatectomy, radiotherapy, brachytherapy, or cryosurgery) (HR: 0.34, 95% CI: 0.24 - 0.48) or or had healthier post-diagnostic lifestyles (increase of 1 in joint measure of physical activity, BMI, and smoking, scored 0-3 - HR: 0.74, 95% CI: 0.60 - 0.91). Conclusion Over 35 years of follow-up, we saw higher lethal progression risks in patients older at diagnosis or with higher PSA at diagnosis, and lower risks in patients that had curative-intent treatment or with healthier post-diagnosis lifestyles. These results may inform clinical management of low/favorable-intermediate risk prostate cancer. Citation Format: Isaac Allen, Jane Bailey Vaselkiv, Hannah E. Guard, Sinead Flanagan, Hari Iyer, Kevin Kensler, Jaime E. Hart, Mark A. Preston, Andreas Pettersson, Keyan Salari, Edward L. Giovannucci, Meir Stampfer, Adam S. Kibel, Lorelei A. Mucci, Timothy Rebbeck. Lethal progression risks of low risk and favorable-intermediate risk prostate cancer in a prospective cohort of US health professionals abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2347.