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Salvage cryoablation in men with recurrent prostate cancer after first-line radiotherapy

Posted Mar 04 2011 12:00am

Two recent papers from a clinical research team at the University of Western Ontario in Canada have offered us insights into the appropriate usage of cryoablation as salvage therapy for men with progressive (recurrent) prostate cancer after first-line treatment for localized and locally advanced prostate cancer.

In the first of these two papers, Williams et al. report patient survival based on a retrospective analysis of data from a series of 187 men who received salvage cryoablation at their institution between 1995 and 2004. Nearly all of these patients (176/187; 94 percent) had sufficient data available to permit detailed follow-up over a period of up to 14 years. All except four of the patients had received first-line external beam radiation therapy; the remaining 4 had received first-line brachytherapy.

As a final note, we should observe that the paper by Williams et al. is only the second to offer data from a large cohort of salvage cryotherapy patients. It is the first such paper to offer data from a single institution, with all patients followed according to a relatively standardized protocol over time. Williams and his colleagues are careful t0 point out that different interpretations can be placed on some of these data based on the use of the ASTRO criteria or the Phoenix criteria for failure of salvage cryotherapy.

The patients were all followed with PSA levels at 3, 6, and 12 months post-salvage cryotherapy and every 6 months thereafter, and with post-salvage biopsies at 6, 12, and 24 months. PSA levels and biopsies could also be carried out if clinically indicated.

Here are the key findings of this paper:

  • Average (mean) patient follow-up was 7.46 years (range, 1 to 14 years).
  • 52/176 patients were followed for > 10 years.
  • Overall survival rates were 95 percent at 5 years, 91 percent at 8 years, and 87 percent at 10 years.
  • Metastasis-free survival rates were 87 percent at 5 years, 83 percent at 8 years, and 82 percent at 10 years.
  • Disease-free (progression-free) survival was 47 percent at 5 years, 39 percent at 8 years and 39 percent at 10 years.
  • 68/176 patients (38.6 percent) required subsequent hormone therapy after salvage cryotherapy (at a mean time period of 2,83 years post-salvage therapy).
  • Risk factors for disease recurrence were the pre-radiation therapy PSA level, the pre-salvage therapy PSA level, and the pre-salvage therapy Gleason score.
  • A PSA nadir of > 1 ng/ml after salvage cryotherapy indicated a poor prognosis; disease recurrence occurred in all such patients.
  • A PSA nadir of < 1 ng/ml after salvage cryotherapy was associated with progression-free survival in 56 percent of patients at 5 years, 46 percent of patients at 8 years, and 46 percent of patients at 10 years.

Williams et al. conclude that salvage cryotherapy is an appropriate form of treatment for patients who are either unwilling to have or inappropriate candidates for salvage surgery. Whether high-intensity focused ultrasound can offer better outcomes than this will take several years to discover.

It is regrettable that one piece of important information is not provided in the current paper: that is the time from a clear indication of the failure of first-line radiotherapy to the conduct of salvage cryotherapy. Other papers have suggested that (in general) salvage therapy after first-line radiation therapy may occur much later than salvage radiation therapy after failure of first-line surgery. It does have to be said, however, that there seems to have been no difference in the outcome of salvage cryotherapy whether it happened < 5 years or > 5 years after the initial first-line radiation therapy.

In the second of the two papers referred to above, Ng et al. have reported on the patterns of local recurrence of prostate cancer in 122 patients treated with first-line radiation therapy and subsequent salvage cryotherapy at a mean follow-up of 56 months after salvage cryotherapy. (We assume that these 122 patients are a subset of the series of 176 patients referred to above.)

We do not intend to go into this paper in as much detail as we have with the paper by Williams et al. Suffice it to say that:

  • 28/122 patients (23.1 percent) had a positive biopsy for prostate cancer after salvage cryotherapy.
  • The majority of cancer recurrences occurred in the apex of the prostate (51 percent), the base of the prostate (21.2 percent), and the seminal vesicles (18.2 percent).
  • Overall biochemical progression-free survival was 28 percent at 5 years in these 122 patients.
  • Patients with biopsy-proven cancer in the base of the prostate post-salvage cryotherapy had a biochemical progression-free survival of 0 percent at 5 years of follow-up.

The authors conclude that cancer recurrences appear to have occurred in areas of the prostate where aggressive freezing is generally avoided because of the potential risks for subsequent incontinence or a recto-urethral fistula. This may suggest that (unless further improvements in cryotherapy technique are possible), patients known to have cancer recurrence in the base of the prostate may be less appropriate candidates for salvage cryotherapy.

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