Risk Factors for Prostate Cancer-Specific Mortality after Failure of Primary Therapy

After failure of primary therapy, any one of these independent risk factors can signal a patient at high risk for prostate cancer-specific mortality1:

  • Short time to biochemical recurrence
  • Rapid PSA-DT*
  • High Gleason score

* Prostate-specific antigen doubling time (PSA-DT) is the time it takes for a PSA value to double after PSA returns to measurable levels following primary therapy.

Together, these risk factors in patients with biochemical recurrence after radical prostatectomy (RP) can be a deadly combination¹

Estimated 10-Year Risk After RP–Prostate Cancer Mortality
Adapted from Freedland SJ et al. JAMA. 2005;294:433-439.

Objective

Define risk factors for prostate cancer-specific mortality (PCSM) following RP. Risk stratification tables for PCSM at 5, 10, and 15 years following biochemical recurrence after RP were developed.

Results

Patients who had the longest time to biochemical recurrence, lowest Gleason score, and longest PSA-DT were at lowest 10-year risk for PCSM.1

By contrast, the shortest time to biochemical recurrence, highest Gleason score, and shortest PSA-DT, identified patients at highest 10-year risk.1

Study Design

A retrospective analysis of patients with Stage T1b-T3 prostate cancer who underwent RP at The Johns Hopkins Hospital was reported in 1999 by Pound et al (N=1997).2 In 2005, Freedland et al conducted a follow-up study, which included the patient subset from the earlier analysis (N=5096).1,2

When faced with these patient types, what are your plans of action?
Click here for illustrative patient profiles
  • 979 (19%) experienced biochemical recurrence1
    • 379 patients with biochemical recurrence and information on PSA-DT were used to estimate the risk of prostate cancer-specific mortality (PCSM)1
  • Patients did not receive adjuvant radiation or hormonal therapy prior to biochemical recurrence1
  • Follow-up:
    • Median of 10 years following surgery1
    • Median of 6 years following biochemical recurrence1
  • 66 of 379 (17%) PCSMs1

There were wide confidence intervals around the estimates and some groups consisted of a small number of patients. This may limit the value of these data for prognostic purposes.1

The concordance index of this model using PDA-DT alone as a continuous variable to estimate time to PCSM was 0.83.1

Identification of high-risk patients can help determine which patients should be closely monitored for onset of metastatic prostate cancer.

What factors can signal increased risk of metastases after failure of primary therapy?

References: 1. Freedland SJ, Humphreys EB, Mangold LA, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294:433-439. 2. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591-1597.