Natural history of progression of patients with biochemical (PSA) relapse following radical prostatectomy: Update

Reviewer: Neha Vapiwala, MD
Last Modified: May 31, 2003

Presenter: M. A. Eisenberger
Presenter's Affiliation: Johns Hopkins University (JHU)
Type of Session: Scientific


    Post-prostatectomy patients demonstrating biochemical evidence of prostate cancer recurrence have been previously studied with regards to the natural history of disease progression. The original report from Pound et al. (JAMA 281:1591, 1999) looked at 315 pts with evidence of biochemical recurrence (PSA > 0.2) after prostate surgery and established the following factors as critical in defining progression risk and outcome: time to biochemical relapse, PSA doubling time (PSADT)following relapse, and prostatectomy Gleason score. Specifically, time to biochemical relapse of >2 yrs, PSADT of < 10 mos, and pathologic Gleason score 5-7 were all favorable outcome predictors. However, the final outcomes data were admittedly limited by the short follow-up, inadequate sample sizes for subgroup analysis and incomplete laboratory information. This study is an update of the original results with significantly longer follow-up in order to more clearly assess the true natural history of these patients as well as the critical determinants involved.

Materials and Methods

  • 1,997 post-radical prostatectomy pts treated at JHU between 1982-2003 were followed for evidence of biochemical relapse
  • PSA levels drawn every 3 mos for first year, then every 6 mos for second year, then yearly
  • Yearly bone scans to document any disease spread
  • Only pts receiving no androgen deprivation therapy included in analysis
  • Endpoint was progression-free survival
  • Subset analysis performed based on time to relapse, PSADT and Gleason score


  • 329 pts with biochemical progression (PSA > 0.2 ng/mL) post-prostatectomy but no androgen deprivation until development of distant metastases - 227 pts with Gleason 5-7 - 102 pts with Gleason 8-10
  • At median follow-up 5 yrs, 76% of pts alive and 44% of pts developing metastatic diseas
  • Median actuarial time from biochemical to metastatic progression of 7.5 yrs
  • Median actuarial time from development of metastases to death of 6.5 yrs
  • Time to relapse following surgery of >2 yrs, PSADT < 10 mos and Gleason score 5-7 were all significant predictors for development of distant disease.

Author's Conclusions

  • Probability of metastasis-free survival can be estimated through the use of certain clinical and pathologic parameters.
  • Natural history of pts with biochemical relapse post-prostatectomy indicate longer progression free survival when time to relpase is > 2 yrs form surgery, PSADT is < or = 10 mos, and Gleason score is 5-7 vs. 8-10.
  • "Good-risk" pts, as defined by the above categories, appear to have long progression-free survival.

Clinical/Scientific Implications

    The natural course of disease progression in post-prostatectomy pts with biochemical relapse has helped to determine the critical determinants of outcome in these groups. With the establishment of PSADT as a significant factor for progression-free survival, there arises the potential of using doubling time as a surrogate for outcome in biochemically relapsed prostate cancer. Together with the established prognostic value of time to relapse and pathologic Gleason score, a useful algorithm may be devised. Such an algorithm could then form the basis for clinical management decisions, for patient assessment post-treatment, and for the design of new clinical trials in this area.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.