Relationship of tumor DNA-ploidy toserum prostate-specific antigen doubling time after radiotherapy for prostate cancer

Objectives.: DNA-ploidy is a strong prognostic factor for prostate cancer patientstreated with definitive external beam radiotherapy. Using DNA/nuclear protein flow cytometry, three prognostic groups based on DNA-ploidy were identified: from good to poor, these are diploid, near-diploid, and nondiploid tumors. Since recent evidence indicates that the rate at which prostate-specific antigen (PSA) increases in the presence of biochemical failure is predictive of the time to clinical relapse, we examined the relationship between DNA-ploidy and PSA doubling time (PSA-DT). Methods.: Formalin-fixed paraffin-embedded tissues from 76 patients treated at M.D. Anderson Cancer Center with definitive radiotherapy alone were analyzed for ploidy using DNA/nuclear protein flow cytometry. Of these, 24 of the 27 patients with a rising PSA profile had three or more post-treatment PSA values from which the PSA-DTs were calculated. PSA-DTs were estimated using nonlinear regression techniques. Results.: The average PSA-DT for the 24 patients in this cohort was 11.3 ± 10.5 months(±SD) with a median of 8.4 months. Diploidy (n = 3) was associated with a PSA-DT of 27.0 ± 22.8 months, near-diploidy (n = 7) with a PSA-DT of 12.2 ± 5.7 months, and nondiploidy (n = 14) with a PSA-DT of 7.5 ± 5.7 months (p = 0.004, Spearman rank test). Stage, grade, and pretreatment PSA, as well as the endpoints of local control, freedom from metastases, and freedom from any relapse, did not correlate significantly with PSADT values. However, when patients were subdivided by PSA-DT into those with values 10 months or less (n = 14) and those more than 10 months (n = 10), there was a correlation with 3-year actuarial freedom from relapse: 28% and 74%, respectively (p < 0.01, log-rank). This subdivision of PSA DT also correlated with DNA ploidy (p = 0.03, chi-square) and stage (p = 0.04). Conclusions.: The results show that there is a significant correlation of DNA-ploidy with PSA-DT Diploidy was associated with the longest PSADTs, near-diploidy with intermediate PSA-DTs, and nondiploidy with short PSA-DTs. Patients with short PSA-DTs also had significantly higher actuarial rates of disease relapse at 3 years. These data confirm that PSA-DT is a strong predictor of tumor behavior and that patients who have nondiploid tumors probably require more aggressive, combined modality, treatment.