Title

Prostate-specific antigen levels of ≤4 and >4 ng/mL and risk of prostate cancer-specific mortality in men with biopsy Gleason score 9 to 10 prostate cancer

Document Type

Article

Date of Original Version

7-1-2021

Abstract

Background: Defining workup beyond usual clinical practice that may improve treatment outcomes in men with a prostate-specific antigen (PSA) level of ≤4 ng/mL (vs >4 ng/mL) and Gleason score (GS) 9 to 10 prostate cancer (PC) remains to be determined. Methods: Between February 25, 1992, and February 25, 2016, 17,632 men with clinical T1-4 PC with a biopsy GS of 6 to 10 underwent radical prostatectomy at a single academic center. Multivariable Fine and Gray regressions were used to evaluate the risk of prostate cancer–specific mortality (PCSM) with an interaction model evaluating the prognostic significance of PSA ≤ 4 ng/mL versus PSA > 4 ng/mL among men with PC with a biopsy GS of 9 to 10 versus ≤8, with adjustments made for the time-dependent use of adjuvant and/or salvage radiation therapy and androgen deprivation therapy (ADT) in addition to known PC prognostic factors. Results: There was a significant interaction in men with a biopsy GS of 9 to 10 versus ≤8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (adjusted hazard ratio [AHR], 2.87; 95% confidence interval [CI], 1.02-8.08; P =.046). Specifically, among men with a biopsy GS of 9 to 10 and a PSA level of ≤4 ng/mL versus >4 ng/mL, there was a significantly higher rate of PCSM (AHR, 2.59; 95% CI, 1.19-5.67; P =.017); however, there was no significant difference in the risk of PCSM in men with a biopsy GS ≤ 8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (AHR, 0.90; 95% CI, 0.46-1.78; P =.771). Moreover, the time-dependent use of postoperative ADT was also associated with an increased risk of PCSM (AHR, 10.76; 95% CI, 6.88-16.81; P <.0001). Conclusions: Some men with PSA ≤ 4 ng/mL and a biopsy GS of 9 to 10 may have pathologic or genetic variants that make them less amenable to a cure with current standards of care. Additional workup assessing for small cell, neuroendocrine, and genetic variants should be considered.

Publication Title

Cancer

Volume

127

Issue

13

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