RALP as a first-line treatment for high-risk, localized and locally advanced prostate cancer


In light of the publication this week of data by Warde et al. on external beam radiation therapy + lifelong total androgen deprivation (ADT) as a first-line treatment for high-risk, localized and locally advanced prostate cancer (click here for commentary), it is interesting to note an article from another research group outlining experience with a very different strategy.

Connolly et al. have conducted a retrospective analysis of data from their series of nearly 1,500 men treated with robot-assisted laparoscopic prostatectomy (RALP) between December 2003 and September 2010. From within this series of patients, they were able to identify 160 patients who met one or more of the National Comprehensive Cancer Network (NCCN) criteria for high-risk disease:

  • A PSA level of > 20 ng/ml
  • A clinical stage of cT3-4
  • A biopsy-based Gleason score of  ≥ 8

Such patients are therefore comparable to those enrolled by Warde et al. in their randomized, controlled trial.

Connolly et al. defined treatment failure in their retrospective analysis of these 160 patients as follows:

  • A biochemical recurrence of ≥ 0.2 ng/ml indicated failure of RALP monotherapy
  • Overall treatment failure was characterized by
    • Either a rising PSA level after salvage radiation therapy
    • Or the need to initiate ADT

Analysis of outcomes data from this series of patients showed the following:

  • The average age of the patients (mean ± standard deviation) was 63.1 ± 6.3 years.
  • The average (median) PSA level at diagnosis was 9.95 ng/ml.
  • Post-surgical analysis of prostatectomy specimens showed that
    • 65/160 men (41 percent) had Gleason 8-10 cancers.
    • 96/160 men (60 percent) had extracapsular disease (pathologic stage ≥ pT3).
    • 36/160 men (23 percent) had evidence of  seminal vesicle invasion.
    • 64/160 men (40 percent) were downgraded after prostatectomy (as compared to their biopsy-based Gleason score).
    • 29/169 men (18 percent) were upgraded after prostatectomy (as compared to their biopsy-based Gleason score).
    • 5/160 men (3 percent) were downstaged to pT2 disease after prostatectomy compared to their original clinical stage.
    • 68/160 men (43 percent) were upstaged after prostatectomy compared to their original clinical stage.
  • 61/160 patients (38 percent) showed positive surgical margins.
  • At a median follow-up of 26.2 months
    • 2/160 men had died (of non-cancer-related causes).
    • The overall survival rate was 98.8 percent.
    • The prostate cancer-specific survival rate was 100 percent.
    • Biochemical recurrence post-RALP had occurred in 53/160 men (33 percent).
    • RALP has been followed by salvage radiation therapy alone in 24/160 men (15 percent).
    • RALP has been followed by salvage radiation therapy + ADT  or by ADT alone in 19/160 men (12 percent).
    • The overall 2-year and 3-year treatment failure rates were 31 and 41 percent, respectively.
    • The pre-treatment serum PSA level was the only independent predictor of overall treatment failure (hazard ratio [HR] = 1.02, P= 0.001).
    • The clinical stage (HR =1.22, P= 0.058) and the number of positive biopsy cores on transrectal biopsy (HR = 1.06, P = 0.057) both showed a strong trend as independent predictors of overall treatment failure.

By comparison with the data presented by Warde et al., let us be clear that:

  • This Australian study is only a retrospective analysis, not a randomized, controlled clinical trial.
  • The patients have been followed for an average of only 2.6 years (as compared to 6.0 years for the patients in the study by Warde et al.)
  • No data are provided on the quality of life of patients after RALP and relevant follow-up therapy.
  • Most of these patients were diagnosed much later than those treated by Warde et al.

On the other hand, at a median 2.6 years of follow-up, there had been no prostate cancer-specific deaths, and 107/160 patients (67 percent) were still in complete remission with a PSA level < 0.2 ng/ml.

This study appears to continue to suggest that first-line radical prostatectomy is a valid therapeutic option for at least some men with high-risk and locally advanced prostate cancer. Longer-term follow-up from this and other case series would certainly help to clarify the potential of this treatment strategy, which does have the benefit of significantly delaying the use of long-term ADT, with its extensive side effects. Whether it may be possible to identify which men are more appropriate for first-line surgery and which for first-line radiation + ADT is not evident at this time.

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