Evaluating the combined effect of comorbidity and prostate-specific antigen kinetics on the risk of death in men after prostate-specific antigen recurrence

Abstract

Purpose: We examined whether time-dependent continuous prostate-specific antigen (PSA) velocity at recurrence was associated with all cause mortality (ACM) adjusting for comorbidity levels among men treated with definitive radiation therapy (RT) alone with or without androgen suppression therapy (AST) in the setting of a randomized controlled trial.

Patients and methods: From 1995 to 2001, 206 men with localized, unfavorable prostate cancer were randomly assigned to receive RT alone or RT and AST combined. Cox multivariate regression analysis was performed to evaluate the relationship between PSA velocity at recurrence and ACM, adjusting for known prostate cancer prognostic factors, including Adult Comorbidity Evaluation 27 comorbidity level.

Results: With a median follow-up of 8.4 years, 89 biochemical recurrences and 74 ACM deaths occurred. Among all patients, higher PSA velocity was associated with increased ACM (hazard ratio [HR], 1.47; 95% CI, 1.07 to 1.44; P < .001) after adjusting for age, treatment arm, comorbidity score, and salvage AST. For 89 patients with biochemical recurrence, increasing PSA velocity at recurrence (HR, 1.60; 95% CI, 1.23 to 2.09; P < or = .001) and moderate to severe comorbidity score (HR, 7.94; 95% CI, 1.55 to 40.52; P = .01) were associated with increased ACM. PSA velocity at recurrence was associated with significantly higher risk of ACM among patients with no or minimal comorbidity (P < .001), but not moderate to severe comorbidity (P = .12).

Conclusion: Rapid PSA velocity at recurrence is significantly associated with an increased risk of ACM among patients with no or minimal comorbidity but not moderate to severe comorbidity. These findings support judicious use of salvage AST, particularly in men with moderate to severe comorbidities, where prospective surveillance protocols are needed.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Estimates of all cause mortality stratified by the prostate-specific antigen (PSA) velocity value at the time of PSA recurrence in men with no or minimal comorbidity. Statistical significance is defined as P < .025.

Fig 2.

Estimates of all cause mortality stratified by the prostate-specific antigen (PSA) velocity value at the time of PSA recurrence in men with moderate or severe comorbidity. Statistical significance is defined as P < .025.