Alkaline Phosphatase Kinetics Predict Metastasis among Prostate Cancer Patients Who Experience Relapse following Radical Prostatectomy

Biomed Res Int. 2018 Jun 28:2018:4727089. doi: 10.1155/2018/4727089. eCollection 2018.

Abstract

Introduction: Metastasis prostate cancer (CaP) occurs in a small fraction of patients. Improved prognostication of disease progression is a critical challenge. This study examined alkaline phosphatase velocity (APV) in predicting distant metastasis-free survival (DMFS).

Materials and methods: This retrospective cohort study examined CaP patients enrolled in the Center for Prostate Disease Research (CPDR) multicenter national database who underwent RP and experienced BCR (n=1783). BCR was defined as a PSA ≥ 0.2 ng/mL at ≥ 8 weeks post-RP, followed by at least one confirmatory PSA ≥ 0.2 ng/mL or initiation of salvage therapy. APV was computed as the slope of the linear regression line of all alkaline phosphatase (AP) values after BCR and prior to distant metastasis. APV values in the uppermost quartile were defined as "rapid" and compared to the lower three quartiles combined ("slower"). Unadjusted Kaplan Meier (KM) estimation curves and multivariable Cox proportional hazards analysis were used to examine predictors of DMFS.

Results: Of the 1783 eligible patients who experienced post-RP BCR, 701 (39.3%) had necessary AP data for APV calculation. PSA doubling time (PSADT) and APV were strongly associated (p=0.008). No differences in APV were observed across race. In KM analysis, significantly poorer DMFS was observed among the rapid versus slower APV group (Log-rank p=0.003). In multivariable analysis, a rapid APV was predictive of a twofold increased probability of DMFS (HR = 2.2; 95% CI = 1.2, 3.9; p = 0.008), controlling for key study covariates.

Conclusions: Building on previous work, this study found that rapid APV was a strong predictor of DMFS for a broader group of CaP patients, those who undergo post-RP BCR who were enrolled in a longitudinal cohort with long-term follow-up and equal health care access. APV is worth considering as a complementary clinical factor for predicting DMFS.

MeSH terms

  • Aged
  • Alkaline Phosphatase / metabolism*
  • Disease-Free Survival
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Neoplasm Metastasis*
  • Neoplasm Recurrence, Local
  • Proportional Hazards Models
  • Prostate-Specific Antigen
  • Prostatectomy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • Recurrence
  • Retrospective Studies

Substances

  • Alkaline Phosphatase
  • Prostate-Specific Antigen