Biochemical recurrence among pT2 patients with a positive surgical margin post-surgery

A new paper by a group of German researchers and clinicians has provided us with expanded insight into risk for biochemical recurrence for men with organ-confined prostate cancer and a positive surgical margin based on their post-surgical pathology report.

Karl et al. conducted a retrospective, multi-center analysis based on data from 956 men, all of whom were given a radical prostatectomy for treatment of organ-confined prostate cancer between 1994 and 2009, and who were found to have pT2R1N0 or pT2R1Nx prostate cancer post-surgery. (The R1 designation means that there was a positive surgical margin.) It is important to note that

  • All pathological specimens were re-examined as part of the study based on a standardized and well-defined protocol, to ensure that all patients did indeed conform to the same pathological standards.
  • None of the patients in this study received any type of neoadjuvant or adjuvant treatment (i.e., no radiation therapy and no androgen deprivation therapy) prior to a formal biochemical recurrence.

The authors’ goal was to be able to predict risk for biochemical recurrence by monitoring the natural history of prostate cancer in this cohort of pT2R1 patients.

Here are their core findings:

  • Average (mean) post-surgical follow-up was 48 months.
  • Overall, 25.4  percent of patients (243/956) exhibited biochemical recurrence during the follow-up period.
  • Based on multivariate analysis, only the patients’ post-surgical Gleason scores were significant in predicting risk for biochemical recurrence.
  • For men with a pathologic Gleason score of 6
    • The median time to biochemical recurrence was not reached during the follow-up period.
    • 5-year biochemical recurrence-free survival was 82 percent.
  • For men with a pathologic Gleason score of 3 + 4 = 7
    • The median time to biochemical recurrence was 127 months.
    • 5-year biochemical recurrence-free survival was 72 percent.
  • For men with a pathologic Gleason score of 4 + 3 = 7
    • The median time to biochemical recurrence was 56 months.
    • 5-year biochemical recurrence-free survival was 54 percent.
  • For men with a pathologic Gleason score of 8 to 10
    • The median time to biochemical recurrence was 27 months.
    • 5-year biochemical recurrence-free survival was 32 percent.

Although the retrospective nature of this analysis is clearly a study limitation, these data may be helpful to clinicians and their patients in making decisions about risk for and timing of biochemical recurrence among men with pT2R1 prostate cancer after initial surgery, and therefore in making decisions about the possible value of adjuvant as opposed to salvage radiation or other forms of salvage therapy.

At least in this study cohort, among patients with pT2R1 disease, the short-term (i.e., 5-year) risk for a biochemical recurrence is clearly far lower for men with a pathologic Gleason score of 3 + 3 = 6 or 3 + 4 = 7 than it is for men with pathologic Gleason scores of 4 + 3 = 7 and higher.

One Response

  1. Thank you as always for reporting this, which highlights the importance of the pathologic Gleason score.

    This seems consistent with earlier findings, especially those by the Stephen Freedland team from Johns Hopkins (as of 2005) about the severity of recurrence, where a cut point of reaching a PSA of 2.0 by 36 months after surgery was an important differentiator, along with Gleason (less than 8 or 8 and greater) and PSA doubling time (PSADT). The median times to recurrence in this German study for the GS 4+3=7 and higher patients are clearly in the ballpark of the Johns Hopkins findings, as is the Gleason scoring.

    These John Hopkins results were updated, with a much larger number of patients and longer follow-up, by Antonarakis et al., which boiled down the factors to assess severity of recurrence to PSADT and Gleason score. They considered these variables: age, race, preoperative PSA, clinical stage, Gleason score, extraprostatic extension, seminal vesicle invasion, lymph node involvement, surgical margin status, time to biochemical recurrence and PSADT, but just the two mentioned (PSADT and Gleason score) survived their multivariate analysis as independent predictors. The earlier factor involving time to recurrence dissolved, probably because it was not independent of PSADT, as the authors comment. It’s important to keep in mind that these patients were winnowed from a larger base by excluding patients who had adjuvant or salvage therapy, which adjuvant/salvage therapy included ADT as I recall it based on presentations I have attended.

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