The impact of pretreatment PSA on risk stratification in men with Gleason 6 prostate cancer: Implications for active surveillance

Abstract

Background: There are limited data to support the safety of active surveillance in men with favorable-intermediate risk prostate cancer due only to a prostate specific antigen (PSA) above 10 ng/ml. We therefore evaluated the impact of pretreatment PSA on risk-stratification in men with Gleason 6 prostate cancer.

Methods: We identified men aged 18 to 75 with cT1-2cN0cM0, pre-treatment PSA < 20 ng/ml, Gleason 6 prostate cancer diagnosed from 2010 to 2016 in the National Cancer Database who underwent radical prostatectomy. The associations of patient and disease features with Gleason score upgrading or adverse pathologic features at prostatectomy were evaluated using logistic regression. To evaluate for non linear relationships between PSA and each outcome, we examined predicted marginal event rates standardized for baseline characteristics with PSA modeled using restricted cubic splines RESULTS: A total of 75,566 patients were included in the cohort. In unadjusted analyses, patients with pretreatment PSA ≥ 10 ng/ml had higher rates of Gleason core upgrading (58.8% vs. 47.9%; P< 0.001) and adverse pathologic features (19.7% vs. 10.0%; P< 0.001) compared to patients with PSA < 10 ng/ml. In multivariable analyses, PSA ≥ 10 ng/ml was associated with statistically significantly increased risks of Gleason score upgrading (OR 1.47;95%CI 1.39 - 1.55) and adverse pathologic features (OR 2.15;95%CI 2.01 - 2.30). When modeled as a non linear continuous covariate, PSA was associated with increased adjusted rates of Gleason score upgrading and adverse pathologic features without a clear dichotomization at a threshold of 10 ng/ml.

Conclusion: Higher pretreatment PSA was independently associated with increased risks of Gleason score upgrading and adverse pathologic features at prostatectomy. Flexible modeling of the relationship between PSA and each outcome did not support dichotomization at a threshold of 10 ng/ml. These results can be used to improve patient risk-stratification for active surveillance.

Keywords: Active surveillance; Adverse pathologic features; Gleason score upgrading; Prostate cancer; Prostate specific antigen.