PBRT as a form of salvage radiation therapy after cryotherapy and HIFU


A new paper in “the Red Journal” prvides some information about the potential of proton beam radiation therapy (PBRT) as a salvage therapy in men who have failed either cryotherapy or first-line high-intensity focused ultrasound (HIFU) as first-line therapy for localized prostate cancer.

Whether the patients in question were ever good candidates for either cryotherapy or HIFU is not something we can answer on the basis of this paper, but it is certainly the case that there are going to be patients who have local recurrences after cryotherapy and after HIFU. What this paper tells us is that salvage PBRT is an option for selected patients previously treated with cryotherapy and HIFU. Whether it is “the best” option is not necessarily so cut and dried.

Holtzman et al. reviewed data from 21 consecutive patients treated with salvage PBRT at the University of Florida Proton Therapy Institute between 2007 and 2014. All 21 patients has exhibited a local recurrence of their prostate cancer after either first-line cryotherapy (n = 12) or first-line HIFU (n = 9). The patients were all treated with a median dose of 74 Gy. Eight of the patients also received androgen deprivation therapy (ADT) along with their radiation therapy.

Here are the key study findings:

  • Average (median) follow-up was 37 months (range, 6 to 95 months).
  • The 3-year biochemical progression-free survival (bPFS) rate was 77 percent.
  • The 3-year grade 3 toxicity rate was 17 percent (but 2/21 patients had pre-existing grade 3 gen iturinary toxicities from their first-line therapies).
  • Bowel summary, urinary incontinence, and urinary obstructive quality of life scores declined after 1 year of follow-up, but only the bowel quality of life score at 1 year of follow-up met the minimally important difference threshold.

The authors conclude that PBRT

achieved a high rate of bPFS with acceptable toxicity and minimal changes in [quality of life scores] compared with baseline [pre-PBRT] functions.

They are also careful to note that the study size is small, follow-up is short, and that early results suggest that outcomes with PBRT for salvage after cryotherapy and HIFU failure are inferior to outcomes with PBRT given as first-line therapy with respect to disease control, toxicity, and quality of life.

What is also not clear, of course, is whether these patients might have done just as well with other forms of salvage therapy. For example, it seems likely that all of the HIFU patients would have been eligible for a repeat HIFU, and that all of the patients would have been eligible for salvage radiation using other forms of radiation therapy. We are not aware of any form of salvage therapy that can offer the same quality of outcome when used as a salvage treatment as compared to the outcome available when it is used as a first-line therapy, so the fact that this is true for PBRT is hardly surprising.

3 Responses

  1. Empirically, proton would seem to be the wrong approach for this class of patients. One has to presume that the earlier failure of the tight-focus techniques (cryo or HIFU) was possibly attributable in part to imaging which didn’t accurately indicate where the tumor was (or where all the tumors were). Logically, salvage radiation treatment should therefore include deeper and broader penetration by the beam (unless the new imaging is better, more precise and more trustworthy than the old, which could certainly be the case after 3 years). The main selling point of proton therapy is its greater precision and reduced penetration, seemingly the opposite of what is called for in these cases. Whacking the prostate with wider and deeper photon IMRT would seem to have a better chance of cooking bits of cancer hiding in the ducts, lymph nodes and other crannies.

  2. KenB:

    Most failures after ablation are local-only failures within the prostate, so it’s appropriate to attempt salvage on the prostate only. In the present study, the patients were confirmed to have local recurrence. If the first-line therapy was focal or hemi-gland ablation, it’s expected that there will be retreatment with ablation in many (about 20 to 30% for HIFU or cryotherapy). If the first-line therapy was whole gland, ablative retreatment is impossible on previously ablated tissue, so they have to turn to salvage using radiation or surgery.

  3. Allen (and KneB):

    It is my understanding that for a man who has had first-line, whole-gland HIFU and then a has an elevated PSA confirmed to be due to the continued presence of localized prostate cancer, the HIUFU can be repeated at least once and sometimes more than once. That is not the case for cryotherapy. However, for HIFU repeat treatment is not limited to men who had focal or hemi-gland ablation as their first-line treatment.

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