Cryotherapy in the treatment of high-risk, localized prostate cancer

The Cryo On-Line Data or COLD registry is a registry of data on men with prostate cancer treated by cryotherapy and supported by an unrestricted research grant from a commercial maufacturer of cryotherapy equipment. Data are held and analyzed by an independent research company under the direction of an independent physician board. We believe that the registry is limited to men treated by cryotherapy within the USA.

A recent paper by Tay et al. in the Journal of Endourology has used data from the COLD registry to look at the biochemical progression-free survival (bPFS) rates of 300 men initially diagnosed with high-grade prostate cancer and treated with whole gland cryotherapy since 2006. Biochemical progression was defined according to the Phoenix criteria (a PSA level based on the post-treatment nadir PSA value + 2 ng/ml).

Specifically, patients whose data had been entered into the COLD registry and who were eligible for evaluation in the current study had to have been diagnosed with a Gleason score of 8, 9, or 10; a PSA level of < 50 ng/ml; and a clinical stage of T1-2N0M0. Any man with a PSA level of ≥ 50 ng/ml was presumed to have micrometastatic prostate cancer and was therefore ineligible for inclusion in the current study.

Here are the core results reported by Tay and his colleagues:

  • The average (mean) age of the patients was 73.2 years and their median PSA level was 6.95 ng/ml.
  • The average (mean) follow-up time was 28.4 months (range 0.2 to 211 months), but the median follow-up time was only 18.2 months.
  • The median bPFS was 69.8 months.
  • 122/300 patients (40.6 percent) received neoadjuvant androgen deprivation therapy (ADT) but …
    • The time for which these 122 patients were on ADT is unclear.
    • For the 66 patients for whom data are available, the mean time on ADT was 5.9 months (range 1 to 48 months).
  • 47/300 patients (15.7 percent) received ADT for an undetermined time only after cryotherapy.
  • The average (mean) PSA nadir post-cryotherapy was 0.40 ± 1.14 ng/ml
  • 126/300 patients (42.0 percent) had a nadir PSA level of < 0.02 ng/ml (but it is unclear how many of these patients achieved this nadir PSA level while on or shortly after they had been on ADT).
  • The estimated rates of bPFS were
    • 77.2 percent at 2 years
    • 59.1 percent at 5 years
  • A post-treatment PSA nadir of < 0.4 ng/ml was a much stronger predictor of bPFS compared to a post-treatment PSA nadir of ≥ 0.4 ng/ml (hazard ratio  [HR] = 5.5).
  • At 12 months post-treatment, patient-reported data indicated that
    • 258/285 patients (90.5 percent) stated that they were continent.
    • 27/285 patients (9.5 percent) reported varying degrees of incontinence.
      • 15/27 had low-level leakage not requiring pads.
      • 9/27 patients were using one or two pads per day.
      • 1 man was using three or four pads per day.
      • 2 men gave no detailed information.
    • 36/218 men (16.5 percent) claimed to be sexually “potent”.
    • Only 8 of these 36 men claimed to be able to have intercourse without the use of medications or adjunct devices.
  • 29/300 men (9.7 percent) experienced urinary retention within 12 months of treatment.
    • 4/29 men required prolonged, intermittent self catheterization.
    • 6/29 men required addition forms of care.
  • 4/300 men (1.3 percent) experienced formation of a rectourethral fistula.

Tay et al. conclude that:

Cryotherapy is a viable choice for patients with high-grade, localized prostate cancer with acceptable short-term oncological and functional outcomes.

The authors are very clear that there are several limitations on their analysis of data like these from the COLD registry:

  • Average follow-up times are short.
  • Because most patients were being treated in a community setting, there was no formal, standardized study protocol.
  • This type of registry data provides useful data on trends but few data on long-term outcomes, and some important data (such as initial biopsy data and locations of tumors within the prostate) were not available.

The “New” Prostate Cancer InfoLink would generally concur with the author’s conclusion, but note that whole gland cryotherapy is associated with a very significant risk for loss of erectile/sexual function (always assuming that good erectile/sexual function was present prior to treatment). The lack of consistency about data on how many patients received ADT, when, and for how long, does make it a little difficult to ascertain the degree to which outcomes of many patients were entirely due to the effectiveness of cryotherapy in this patient cohort.

Editorial note: The “New” Prostate Cancer InfoLink thanks Dr. Kae Jack Tay of Duke University Medical Center for providing us with a full text copy of this article for review prior to comment.

3 Responses

  1. I’m taken aback by Tay et al.’s conclusion. I suppose one man’s “acceptable short-term oncological and functional outcomes,” is another man’s unacceptable. The 59% bPFS at 5 years is considerably less than what we see with brachy boost therapy in the high-risk group. The 83% impotence rate is terrible. And there is a urinary double-whammy: 10% incontinence and 10% serious urinary retention. I find the fistulas troubling as well. I can’t really see the use for cryo beyond focal treatment or salvage.

  2. Dear Allen:

    A lot of men have a high level of aversity to radiation therapy just as a lot of men have a high level of aversity to surgery. The question of which form of treatment is most appropriate for any specific individual is, at the end of the day, a matter of patient choice (if we assume that all the relevant options were presented to the patient).

    Since most of the men in this cohort seem to have been relatively elderly (mean age > 73 years), it may well be that most of them wouldn’t have been good candidates for any form of treatment that involved surgery of any type — and that would mean no brachytherapy boost either.

    To be fair to Dr. Tay and his colleagues, they state only that cryotherapy is a “viable” option for treatment of high-risk patients with “acceptable” outcome levels. They make no statement about whether it is better or worse or even comparable to other options.

  3. It seems to me that to report a median bPFS of 69 months, you would have to have followed half the participants for 69 months. But in fact half the participants were followed for 18.2 months or less. This seems like a mathematical impossibility.

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