AUA report and update no. 3: Sunday, April 26, 2009

The following four reports address some other interesting papers and posters presented at the AUA today.

Blumberg et al. (abstract no. 261) reported the results of a retrospective analysis of the different outcomes of men treated with LHRH agonist therapy for advanced prostate cancer using three differing treatment rationales:

  • Calender-based treatment, in which the patients is simply dosed on a regular basis that depends on the dose of drug delivered.
  • Intermittent therapy, in which the patient vcomes on and off drug dedpending on present PSA levels
  • Testosterone level-based treatment, in which the dosing is tailored to the patient’s testosterone level, which is regularly assessed.

The study, which evaluated data from 1,617 patients treated between 2003 and 2006, clearly showed that of the 692 patients who received LHRH monotherapy and met other study criteria, the relative risk of treatment failure was lowest for men receiving testosterone-based dosing (hazard ratio = 0.65) compared to the men treated on a calendar basis. In the case of men treated with intermittent therapy, there was a trend toward reduced risk for treatment failure (HR = 0.80)

A study by Boorjian et al. (abstract no. 471) was a retrospective analysis of data from 3,651 men who received a radical prostatectomy at the Mayo Clinic between 1990 and 2006, and who were found to have a positive surgical margin post-surgery.

After conducting a detailed reanalysis of data from these patients, Boorjian and his colleagues were able to show that the presence of a positive surgical margin:

  • Did increase the risk for biochemical recurrernce and local disease recurrence
  • Did not independently increase risk for systemic progression, caner-specific survival, or overall survival.

They suggest that these data need to be taken into account when considering the value of adjuvant therapy of men with positive surgical margins post-surgery, given the potential adverse effects (and the costs) of secondary therapies.

Lee et al. (abstract no. 488) have reassessed the validity of Epstein’s criteria as providing an accurate predictor of clinically insignificat prostate cancer. (Epstein’s criteria defined clincially insignificant prostate cancer as being a cancer with a PSA density of < 0.15 ng/ml, < 3 positive biopsy cores, ≤ 50 percent of any single core being involved, and a Gleason score ≤ 6.)

Lee and his colleagues looked at data from 268 men with a biopsy Gleason score of 6, all of whom received the biopsy and a subsequent radical prostatectomy at the Cleveland Clinic between October 1999 and January 2007. They then used the available data to evaluate the ability of Epstein’s criteria to predict insignificant cancer using two slightly different definitions of “insignificant.”

The bottom line was that Epstein’s criteria did not provide a sufficiently accurate means to predict clinically insignificant prostate cancer or patients suitable for inclusion in  active surveillance protocols based on this patient population. The authors suggest that Epstein’s criteria can accurately identify men in which definitive surgical therapy can offer to cure prostate cancer. Howeever, they also state their belief that we need better markers to identify patients likley to have truly clinicaly insignificant disease.

The last paper we shall comment on from today’s sessions was one by Greene et al. (abstract no. 495).

Greene and her colleagues at the University of California at San Francisco screened 366 men diagnosed with prostate cancer between 1998 and 2007, and placed on their active surveillance protocol. They were looking for men who had at least 6 months of follow-up,a minimum of six cores taken at the time of their initial diagnostic biopsy, and at least two subsequent biopsies. They were able to identify 62 patients who met these criteria.

The authors then looked at the Gleason scores of these men at each biopsy to identify changes in Gleason score over time. A patient was considered to have a Gleason score upgrade if his Gleason score at repeat biopsy  was higher than the initial Gleason score on biopsy and was at least 7 or higher.

The results of the study were as follows:

  • 62 percent of the men had a PSA of ≤ 6 ng/ml at diagnosis.
  • All 67 men had a biopsy Gleason score of ≤ 6.
  • 94 percent of the men had a biopsy Gleason score of 6.
  • 83 percent of the men had < 33 percent of their biopsy cores involved at the ntime of diagnosis.
  • 66 percent of the emn were diagnosed as cT1 and 91 poercent were classified as low risk
  • Mean age at diagnosis was 62 years.
  • Mean follow-up was 56.6 months.
  • 6 patients were upgraded at their second biopsy.
  • Of this group of 6 patients, no one was further upgraded but 2 patients were downgraded at their third biopsy.
  • Of the men who showed no change in grade at the time of their second biopsy, 10 were upgraded on their third biopsy, 51 showed no change, and no men were downgraded.

The authors conclude that men on active surveilance may show variation in their Gleason scores on multiple biopsies, but they state further that, “The change in Gleason grade on serial biopsy does not always represent a trend in disease behavior and must be interpreted cautiously.”

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