Is salvage cryotherapy really as safe and effective as some suggest?

There have been an increasing number of articles published in the recent past suggesting salvage cryotherapy as an excellent option for the treatment of men with progressive prostate cancer after failure of first-line radiation therapy.

A new paper by Wenke et al. has offered outcome data from a consecutive series of 396 men treated with salvage cryotherapy between October 1994 and August 2011). All patients had progressive prostate cancer after first-line radiation therapy or first-line cryotherapy. An additional commentary on this paper can be found on the Medscape web site.

The basic results of this study are as follows:

  • 328/396 patients had follow-up data sufficient for meaningful evaluation.
  • The average (median) time from primary therapy to disease recurrence was 55 months (range, 0.0 to 183.6 months).
  • At the time of salvage cryotherapy
    • The average (median) PSA level of the patients was 4.0 ng/ml (range, 0.1 to 112.4 ng/ml).
    • The average (median) time from primary therapy was 67.5 months (range 7.0 to 212.7 months).
  • After completion of salvage cryotherapy
    • The average (median) follow-up was 47.8 months (range 1.6 to 203.5 months).
    • The average (median) PSA nadir was 0.2 ng/ml (range, 0.01 to 70.70 ng/ml).
    • The average (median) time to PSA nadir was 2.6 months (range, 2.0 to 67.3 months).
  • During the post-salvage cryotherapy follow-up period
    • 35 patients (10.7 percent) died of prostate cancer.
    • 72 patients (22.3 percent) died of non-prostate cancer-related causes.
  • Estimated survival data at a follow-up of 5 years after salvage therapy are
    • 91 percent for prostate cancer-specific survival
    • 74 percent for overall survival
    • 63 percent for biochemical progression-free (i.e., disease-free) survival
  • Estimated survival data at a follow-up of 10 years after salvage therapy are
    • 79 percent for prostate cancer-specific survival
    • 45 percent for overall survival
    • 35 percent for biochemical progression-free survival
  • Only the nadir PSA level after salvage cryotherapy was predictive of risk for recurrence and disease-free survival in multivariate analysis.
  • Significant complications requiring further intervention “were rare” and included
    • Urethral strictures in 15 cases (4.6 percent)
    • Bladder outlet obstruction in 11 patients (3.4 percent)
    • Rectourethral or urethroperineal fistulae in 6 patients (1.8 percent)

The authors also state that:

  • 55/328 patients had focal as opposed to whole-gland salvage cryotherapy
  • Among the 55 men who had focal cryotherapy
    • The average (median) nadir PSA level was 0.44 ng/ml (range, 0.04 to 20.1 ng/ml).
    • 27/55 patients (49 percent) had a second recurrence
    • Prostate cancer-specific survival at 10 years was 83 percent.
    • Overall survival at 10 years was 81 percent
    • Biochemical recurrence-free survival at 10 years was 42 percent

It is not entirely clear from the abstract of this paper what the average age or the age-range of the patients was at the time of salvage therapy. The median age and the age range given in the abstract may refer to ages at the time of primary therapy as opposed to ages at the time of salvage therapy.

Furthermore, there is no mention of some predictable consequences of salvage cryotherapy such as incontinence and erectile dysfunction that significantly impact quality of life. It is likely that the incidence of such side effects is very high among men who have received both radiotherapy and salvage cryotherapy or primary and salvage cryotherapy.

Based on their data, the authors conclude that,

Our analysis confirms [salvage cryotherapy] as an effective treatment option for patients failing primary therapy. Patients experienced excellent survival outcome and minimal associated morbidity after [salvage cryotherapy]. Focal [salvage cryotherapy] is an efficacious treatment for properly selected patients.

The problem with this conclusion is that it simply doesn’t seem (at least to us) to be justified by the available data.

Modern focal and whole-gland salvage cryotherapy are, quite certainly, appropriate options for carefully selected men with progressive disease after first-line treatment with radiotherapy, cryotherapy, and high-intensity focused ultrasound (HIFU). However, this paper does not justify the conclusion stated above, and the authors would have been wiser to have offered some documentary evidence about appropriate patient selection based on these data than to make statements like the following (taken from the article on the Medscape web site):

Salvage treatment of the prostate with cryosurgery has been shown to be effective in many patients; it can be repeated if necessary, and rarely has side effects. We are excited to offer this therapy, as it appears to be effective and carries a favorable side effect profile.

This seems to The “New” Prostate Cancer InfoLink to be a massive over-generalization. The critical question for most of us is not whether salvage therapy can be done. It can. The key question is, “For whom is it appropriate and safe, with a high probability of a good outcome?”

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