Relationship of tumor DNA-ploidy to serum prostate-specific antigen doubling time after radiotherapy for prostate cancer.

OBJECTIVES

DNA-ploidy is a strong prognostic factor for prostate cancer patients treated 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 non-diploidy (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 PSA-DT 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 PSA-DTs, 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.