An interesting report on GU and other complications after PBRT

A new article on the WebMD web site appears under the heading “Targeted radiation may help men avoid impotence,” but it is the incidence of adverse genitourinary (GU) obstructive symptoms during and after treatment that is of greater interest to The “New” Prostate Cancer InfoLink.

The content that follows has been significantly revised since the initial posting of this commentary early on November 8, and since receipt of the abstract of the actual paper presented by Hoppe and colleagues from the University of Florida Proton Therapy Institute last week at the annual meeting of the American Society for Radiation Oncology (ASTRO).

Over the years, there have been remarkably few publications providing peer-reviewed documentation of the adverse effects of proton beam radiation therapy (PBRT) in the management of prostate cancer. The data reported by Hoppe and his colleagues are therefore of some interest, even though they come from a small cohort of relatively young men (n = 98) followed for only about 18 months post-treatment. (Fourteen of these men also received neoadjuvant or adjuvant androgen deprivation therapy.) It should also be noted that, as a presentation at a medical meeting, these data should be considered as no more than “preliminary.” They have not been subjected to rigorous peer review.

Here is a summary of the results from the original abstract:

  • All 98 patients were 55 years of age or younger.
  • The patients’ Gleason scores are not generally provided; however, 57 had low-risk disease, 29 had intermediate-risk disease, and 12 had high-risk disease.
  • The patients’ average (median) PSA level before treatment was 5.0 ng/ml (range, 0.7 to 124 ng/ml).
  • The patients’ average (median) PSA levels at 6, 12, and 18 months post-treatment were 1.5 (range, 0 to 10), 1.3 (range, 0 to 7.6), and 1.2 (range, 0 to 4.2).
  • Only 1/98 patients (1 percent) had a rising PSA at 18 months post-PBRT. (Prior to treatment, this patient had a Gleason score of 8, clinical stage T2c disease, and a PSA of 124 ng/ml. It is not clear from the abstract whether he received ADT, but it seems likely.)
  • At 6, 12, and 18 months post-treatment, the proportions of patients said to be “sexually active” were 90, 95, and 94 percent, respectively.
  • Also at 6, 12, and 18 months post-treatment, patient dissatisfaction scores are reported to be 1, 0, and 5 percent, respectively.</li>
  • The average (median) pre-treatment IIEF score of the 84 men who did not receive ADT was 24 (out of a possible maximum 25). (The IIEF is the International Index of Erectile Function — a standard method of assessing erectile quality and function.)
  • At 6, 12, and 18 months post-treatment, the average (median) IIEF scores of the 84 men who did not receive ADT were 22 (range, 9 to 25), 21 (range 5 to 25), and 18 (range 5 to 25). (In other words, the IIEF scores were dropping noticeably over time, even though the patients were said to be “sexually active.”)
  • Prior to treatment, 14/98 patients had grade 2 genitourinary (GU) obstructive symptoms such as difficulty urinating that required Rx medication.
  • During treatment, 34/98 patients (35 percent) had similar grade 2 GU obstructive symptoms.
  • At 6, 12, and 18 months post-treatment, similar grade 2 GU obstructive symptoms were observed in 16, 14, and 21 percent of patients, respectively.
  • Temporary urinary urge incontinence requiring a pad (grade 2) occurred in 3 patients during follow-up but resolved with Rx medication.
  • Gastrointestinal symptoms requiring Rx medications occurred in 10 percent of patients during treatment and in 5, 10, and 3 percent of patients at 6, 12, and 18 months of follow-up.
  • No grade 2 or higher rectal incontinence was observed.
  • 1/98 patients (1 percent) suffered serious side effects that required surgery (a transurethral recection of the prostate) at 3 months after treatment, but this patient had been receiving Rx medication for GU symptoms prior to PBRT.

This was a relatively young cohort of prostate cancer patients. Unless there were specific reasons to think otherwise, it is a cohort that one would expect to recover as well as any after their treatment. The authors’ conclusion to their abstract states that, “Young men treated with proton therapy for prostate cancer have few significant side effects in the first 18 months after treatment. Although erectile dysfunction after treatment can occur, complete impotence was rare and few were dissatisfied with their treatment choice.” However, it is clear that:

  • At 18 months after PBRT, there was a clear signal of a decline in erectile function and quality. Such a decline in potency over time is well known to occur in radiation therapy patients.
  • During PBRT, 20/98 patients (20 percent) had GU symptoms that needed therapy and that had not been present prior to treatment.
  • 3/98 patient had rectal side effects sufficiently serious to require medication.

To quote Dr. Anthony Zeitman, the president of ASTRO, with reference to the low incidence of a rising PSA at 18 months of follow-up in this paper, “That’s about all you would expect with any treatment this early on. You don’t start to see rising PSAs until 2,3,or 4 years out.” It should also be noted that “complete impotence” within 18 months after treatment would be abnormal in any series of radiation therapy patients.

The “New” Prostate Cancer InfoLink is pleased to see — finally — what seems to be a well-documented set of adverse event data from one of the new PBRT centers. The idea that PBRT is associated with virtually no side effects appears to be contradicted by these data from a series of relatively young patients. It will be interesting to see what the erectile function and other adverse effect data look like at (say) 4 years of follow-up.

5 Responses

  1. The following comment was posted before alterations were made to the original post above.

    You state: The “New” Prostate Cancer InfoLink is pleased to see — finally — what seems to be a well-documented set of adverse event data from one of the new PBRT centers.

    WTF? You’re pleased that PBRT isn’t shown as problem free? I’d think you’d be terribly disappointed that we still don’t have a “trouble free” solution! But no, you take pleasure in negative results. Yippee, hurray, THAT solution isn’t that good either! Woohoo! “We’re PLEASED.” Wow, and maybe the 4-year follow up will be even worse!

    Your attitude makes me sick.

  2. The following comment was posted before alterations were made to the original post above.

    I respectfully suggest that it may be misleading to head this post as “An interestingly HIGH …” etc. If anyone thought that proton beams totally spare the vulnerable tissues that concern erectile function and other GU matters, he was not dealing with reality. No one has shown that to be the case. So, yes, the study shows that complications do occur. However, what was concluded from this report, at least by Dr. Zietman, who has been critical in such matters, is that “the men reported a relatively low rate of erectile problems.”

    So maybe PBT is better that IMRT in this regard, but it is difficult to study such things, certainly in a comparative way, and I would not wish to express any conclusion about this myself.

    Also, as noted, with radiation, such complications increase with time, up to a certain point.

    This group was treated in a heterogeneous way, with doses between 78 and 82 cobalt gray equivalents, some by a hypofractionated routine, some not. Though not stated, I think they were probably treated by “old-fashioned” conformal beam methodology. Newer pencil beam or spot beam methods ought to be better, though that needs to be demonstrated. And there are different versions of that, too.

    The centers do PBT in different ways and it can be hard to track down just what they are doing. I had a contact at Florida who told me they were using a pencil beam method, but later I found out that it was only in selected cases. I think maybe in Bloomington, IN, they are using a pencil beam method.

  3. The following comment was posted before alterations were made to the original post above.

    Thank you Herb. You are correct. I have adjusted the headline.

    I would, however, respectfully suggest that there have been a lot of people who have not been living in the real world with regard to the possibility of any significant side effects as a consequence of PBRT.

  4. The following comment was submitted before alterations were made to the original post above.

    I, for one, never thought that PBRT was without any risks or side effects. What I was responding to was the feeling that the author was gleeful in hearing of the side effects/problems, rather than saddened that: “unfortunately, perhaps PBRT sounded too good to be true.”

    I look forward to follow up reports and studies as I am holding steady with active surveillance now. When the time comes for more intrusive intervention, I’ll re-evaluate all the available options with my doctors including PRBT, traditional and “robotic” surgery, brachytherapy, HIFU, and whatever else may be appropriate.

  5. Dear Mr. Owens:

    We apologize for inadvertently conveying the idea that we might be “gleeful” about the adverse effects of PBRT. This commentary is just one in a series of commentaries over nearly 3 years noting the distressing failure of the Loma Linda group to provide any detailed report on adverse effects of PBRT based on their 15-year experience. We consider that failure to be (at best) seriously negligent, particularly because — in the absence of such data — the Loma Linda group tacitly encouraged the dissemination of a belief in some quarters that PBRT had far fewer adverse effects than any other type of treatment.

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