Effectiveness and safety of two forms of salvage therapy for patients with radio-recurrent prostate cancer

Two new papers address the utility of different types of salvage therapy for men with apparently localized, recurrent prostate cancer after first-line radiation therapy: the first paper reviews available data on outcomes after salvage radical prostatectomy (SRP); the second offers data from a small, recent series of men treated with salvage cryotherapy (SCT) using third-generation cryotechnology.

The first point to be made about the appropriate treatment of patients with recurrent but apparently localized prostate cancer after first-line radiation is that there is no established type of treatment that is considered to be any sort of “gold standard.” A variety of different types of salvage treatments are in routine use today and range from SRP and SCT to the application of high-intensity focused ultrasound, repeat radiation, and of course various forms of hormonal intervention.

Chade et al. have published a systematic review of the published data on the use of SRP after careful identification and selection of 40 primary papers on this topic published between 1980 and June 2011. Their findings can be summarized as follows:

  • In earlier articles from this series of papers
    • Positive surgical margins were found in 43 to 70 percent of patients.
    • Pathologically organ-confined disease was found in 22 to 53 percent of patients.
  • In more recent articles from the series
    • Positive surgical margins were found in 0 to 36 percent of patients.
    • Pathologically organ-confined disease was found in 44 to 73 percent of patients.
  • The probability of biochemical recurrence-free survival ranged from 47 to 82 percent at 5 years and from 28 to 53 percent at 10 years, respectively.
  • The probability of prostate cancer-specific survival ranged from 70 to 83 percent at 10 years of follow-up.
  • The probability of overall survival ranged from 54 to 89 percent at 10 years of follow-up.
  • PSA and biopsy-based Gleason scores immediately prior to SRP were the strongest prognostic risk factors for organ-confined disease, progression-free survival, and cancer-specific survival.
  • All standard surgical techniques (open, laparoscopic, and robot assisted) appeared to be feasible in the hands of experienced surgeons.
  • Major complications (modified Clavien classification grade 3 to 5) ranged from 0 to 25 percent of patients in different cohorts.
  • The two most common complications were anastomotic stricture (in between 7 and 41 percent of patients ) and rectal injury (in between 0 and 28 percent).
  • With the exception of anastomotic stricture, most complications occurred with lower frequency in more recent patient series.
  • 50 to 91 percent of patients had erectile dysfunction prior to SRP.
  • 80 to 100 percent of patients had erectile dysfuntion after SRP.
  • 21 to 90 percent of men had significant urinary incontinence after SRP.

The authors conclude that carefully selected men with confirmed, localized, radiation-recurrent prostate cancer can be treated with SRP and and receive “durable cancer control” with an acceptable level of surgical morbidity but a variable level of functional recovery.

By contrast, Phillipou et al. have described the outcomes of a series of 19 men defined as having prostate cancer recurrence after first-line radiation therapy (based on a positive prostate biopsy). These men were all treated with SCT using third-generation equipment between February 2006 and August 2008. Failure of SCT was defined according to the Phoenix criteria (nadir PSA + 0.2 ng/ml).

Phillipou and his colleagues report the following results:

  • Average (mean) age of patients at cryotherapy was 69.2 years
  • Average (mean) time from radiotherapy to cryotherapy was 72.3 months.
  • Patient characteristics prior to cryotherapy included
    • A mean PSA level of 6.84 ng/ml
    • A median Gleason score of 7
  • The mean follow-up period after cryotherapy was 33.3 months.
  • The 2-year biochemical disease-free survival rate was 58 percent.
  • The median PSA nadir after cryotherapy was 0.20 ng/ml (range, 0.005 to 8.260 ng/ml).
  • No procedure-related or cancer-related deaths occurred.
  • Complications included urinary incontinence (in 10.5 percent of patients), erectile dysfunction (in 89 percent), and fistula formation (in 5.3 percent).

The authors suggest that the rates of biochemical response observed in this series of men support the use of third-generation cryotechnology as a salvage procedure for radio-recurrent prostate cancer.

The “New” Prostate Cancer InfoLink notes that the follow-up for the cryotherapy series is relatively short by comparison with the 5- and 10-year data that are available for the various surgical series, and it is open to question whether the cancer outcomes are therefore as good as the outcomes that can now be provided after SRP by highly experienced surgeons. On the other hand, the complication rates of SCT as compared to be SRP appear to be lower (with the clear exception of erectile dysfunction).

It seems clear that neither SRP nor SCT can offer an ideal form of definitive salvage treatment for most men with radio-recurrent, localized prostate cancer. On the other hand, no other form of salvage therapy is known to offer any better option as yet.

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