The natural history of biochemical recurrence after surgery

It has been well understood for years that biochemical recurrence (BCR) after radical prostatectomy does not always translate into systemic progression or necessarily lead to prostate cancer metastasis and death. The “natural history” of BCR is actually very variable.

With the benefit of being able to work from an institutional registry at the Mayo Clinic that includes data on 14,632 men who were given an open, radical retropubic prostatectomy (RRP) between 1990 and 2006, Boorjian et al. were able to identify 2,426 men with BCR (based on a PSA level ≥ 0.4 ng/ml) who received no form of neoadjuvant or adjuvant therapy before or immediately after their initial surgery. They wanted to be able to use data from these patients to evaluate long-term clinical outcomes after BCR and to determine predictors of disease progression and mortality in these men.

The researchers grouped the patients into quartiles according to time from RRP to BCR as follows:

  • Group A: BCR less than 1.2 years after RRP
  • Group B: BCR within 1.2 to 3.1 years after RRP
  • Group C: BCR within 3.1 to 5.9 years after RRP
  • Group D: BCR more than 5.9 years after RRP

Survival after BCR was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression models were used to analyze clinicopathologic variables associated with systemic progression and death from PCa.

Here are the results of their analysis:

  • Average (median) overall follow-up was 11.5 years after RRP and 6.6 years after BCR.
  • Average (median) systemic progression-free survival (PFS) and prostate cancer-specific survival (CSS) had not been reached after 15 years of follow-up post-BCR.
  • Prostate cancer-specific mortality at 10 years after BCR occurred in 9.9 percent for Group A, 9.3 percent for Group B, 7.8 percent for Group C, and 4.7 percent for Group D.
  • On multivariate analysis, time from RRP to BCR was not significantly associated with either the risk of systemic progression (p = 0.50) or the risk of prostate cancer-specific mortality (p =0.81).
  • Older patient age, increased pathologic Gleason score, advanced tumor stage, and rapid PSA doubling time predicted systemic progression and death from prostate cancer.

This study has a number of limitations above and beyond the fact that it is a retrospective analysis. These limitations include the use of differing forms of salvage therapy and the inclusion in this database of relatively few patients with positive lymph nodes at the time of surgery.

What is clear from this study, however, is that less than 10 percent of the men who had a BCR went on to experience systemic progression and death from prostate cancer.

Boorjian and his colleagues conclude their study by noting that, “The decision to institute secondary therapies must balance the risk of disease progression with the cost and morbidity of treatment, independent of time from RRP to BCR.” In other word, the tendency to rush into second-line therapy the second that any patient’s PSA exceeds 0.2 or 0.4 ng/ml needs to be tempered by a careful assessment of that patient’s real risk for progressive, systemic disease over the next 15 years.

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