The Association of p27 With Prostate Cancer Outcomes: A Secondary Analysis of NRG/RTOG 8610 and 9202.

PURPOSE: The cyclin-dependent kinase inhibitor p27 is a well-profiled modulator of cell cycle progression. Low nuclear p27 levels have been demonstrated to have a negative prognostic impact on outcomes in patients undergoing prostatectomy. The prognostic value of p27 after radiation therapy (RT) for prostate cancer is unknown.

METHODS AND MATERIALS: Levels of p27 were evaluated in pre-RT prostate biopsy samples from 2 randomized, phase 3 trials, NRG/RTOG 8610 and 9202, which treated patients with RT with or without androgen deprivation therapy (ADT). Nuclear p27 was analyzed using immunohistochemistry and quantified using automated imaging analysis. The association of p27 as both a continuous and categorical measure (≤ median vs > median) with clinical outcome was estimated using both univariable (UVA) and multivariable Cox proportional hazards models. The primary clinical outcome measure was overall survival, and secondary measures were disease-specific survival (DSS), disease-free survival, distant metastases, and biochemical failure.

RESULTS

In the analytical cohort (n = 361), no association of p27 with overall survival was observed on UVA. The only statistically significant association observed on UVA was between categorical p27 high levels and DSS (hazard ratio [HR] 1.57 [95% CI, 1.01-2.43], P = .044) in the combined cohort. However, a similar association was not observed with DSS when analyzing continuous p27 (P = .09). On multivariable analyses, no statistically significant association was observed between p27 and any evaluated clinical outcome measure (all P > .05).

CONCLUSIONS

This study produced insufficient evidence to conclude that nuclear p27 level is prognostic of outcome in patients undergoing RT ± ADT. The observed trend was opposite in direction to the prior observations in the postprostatectomy literature, which served as a basis for this study. Given this, these data generate the hypothesis that the negative prognostic value of low nuclear p27 level in patients undergoing prostatectomy may be obviated by the receipt of RT ± ADT. Although this does appear congruent with known mechanistic differences between the two treatments, further studies are required to confirm this finding.