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

Background Low-risk (grade group 1, stage≤cT2a, PSA<10) or favorable-intermediate risk (grade group 1, stage cT2b-cT2c or PSA 10-20, or grade group 2, stage≤cT2a and PSA<10) 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.