Hypofractionation –- no long-term effect on quality of life

Reducing the number of radiation treatments but giving a slightly higher dose of radiation at each visit (“hypofractionation”) had no long-term differential effect on patients’ urinary, rectal, or sexual quality of life, according to a study from Fox Chase Cancer Center that was presented the other day at the annual meeting of the American Society for Radiation Oncology (ASTRO). These findings complement their 2013 report of of equivalent rates of cancer control from the two treatment schedules.

Between 2002 and 2006, the research team randomly assigned 303 patients to either hypofractionation or conventional fractionation:

  • Hypofractionation: 70.2 Gy in 26 fractions (2.7 Gy per fraction)
  • Conventional fractionation: 76 Gy in 38 fractions (2.0 Gy per fraction)
  • High-risk patients received long-term adjuvant ADT; some intermediate-risk patients received short-term ADT (there were no low risk patients).
  • Mean age was 67 years in both groups.
  • Patients evaluated their quality of life using the EPIC and IPSS questionnaires.

The findings that were presented at ASTRO or included in in a Medscape article about it were:

  • Urinary irritative symptoms declined by less than the amount considered to be minimally clinically detectable at both 3 years and 5 years, and were not different between the two groups.
  • Urinary continence symptoms declined by 7 percent at 3 years and by 9 percent at 5 years in the hypofractionated group. Compared to the conventionally fractionated group, it was significantly different at 3 years but not significantly different at 5 years.
  • Patients with poor baseline genitourinary function had worse quality of life outcomes with hypofractionated radiation than with conventionally fractionated radiation.
  • Bowel symptoms declined by less than the amount considered to be minimally clinically detectable at both 3 years and 5 years, and were not different between the two groups.
  • Sexual function declined by a clinically detectable degree at both 3 years and 5 years, but was not different between the two groups.
  • Baseline function was an important predictor of long-term quality of life outcomes.

These findings echo the results just reported from the CHHiP trial in the UK. While caution is warranted among men with poor baseline urinary, rectal, and sexual function, these two studies provide strong Level 1 evidence that hypofractionated radiation is not inferior to conventionally fractionated radiation. Most patients should be able to complete primary IMRT treatments in about 5 weeks rather than 8 weeks, and at considerably reduced cost.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

3 Responses

  1. Nice Study of MILD Hypofractionation, but Some Concern with Urinary Incontinence Results (looking for interpretive help)

    Thanks for finding and sharing this interesting study, Allen. I have questions and several comments/concerns.

    First question: Would you mind confirming that the 72.2 Gy in the hypofractionated group is bioequivalent to the 76 Gy in the conventional IMRT group? (I’m confident that it is based on Fox Chase’s reputation.) Of course, the Fox Chase team were researching a mild form of hypofractionation, reducing the sessions by just 12 instead of by 33, which would have been the reduction using the most interesting form of hypofractionation that is getting a lot of play today, in other words, delivering the total dose in just five sessions.

    That brings us to a second point: Fox Chase. Allen, Sitemaster, I and others who have followed radiation for some time know that Fox Chase Cancer Center in Philadelphia has an excellent reputation for radiation therapy. That’s worth putting on the record for those who may be less familiar with the territory.

    As someone who had to choose a form of radiation therapy in 2013 (TomoTherapy, 78 Gy with pelvic boost of 46 Gy), I have been following the hypofractionation story pretty closely. I’m impressed with reports of effectiveness in controlling cancer at the meaningful point of 5-year median follow-up, and the report here is reassuring at the 5-year point about most side effects, with one possible prominent exception: urinary incontinence! I’d like to focus on that.

    For urinary incontinence, at baseline (prior to treatment) the men in the hypofractionated group were somewhat better off, though both groups were doing pretty well. However, as the graph in one of the links shows, urinary incontinence was more than twice as great in the hypofractionated group at the 5-year point. Moreover, for the hypofractionated group there appears to be a steady decline in urinary continence with one interruption of short-term improvement between 3 and 4 years; with that exception the decline appears to be rather steep and continuing through the 5-year point, suggesting further decline in coming years. In contrast, the graph for the conventionally treated group (the 76 Gy/38 sessions) looks like an inverted bathtub line (temporary improvement from 6 months through 3 years), with the urinary incontinence score at 60 months just slightly inferior to the score at 6 months, and with the curve for incontinence both much shallower overall and with a much more gradual rate of declining continence through the 5-year point than for the hypofractionated group.

    On the other hand, while the decline in urinary continence appears substantially greater and more concerning for the hypofractionated group, understanding the scoring used in the EPIC survey instrument may put the results for both groups in a more favorable perspective. It’s possible that both groups are doing very well with urinary continence, as is typical with external beam radiation therapy, and that the differences apparent in the graph do not amount to much. Here’s my shot at this as an amateur who is unfamiliar with the EPIC survey, after checking this site for EPIC:

    EPIC’s scale for urinary continence has a question in each of four areas: leaks over the past 4 weeks; urinary control over the past 4 weeks; diapers per day; and how big a problem urinary incontinence poses. It looks to me as if the scale runs from 0 to 100 (e.g., 1 leak/4 weeks = 0, 2 leaks = 25, 3 leaks = 50, etc.), with responses for the four areas averaged. While the score in the graph at 5 years is nearly minus 4 for the conventional group and about minus 9 for the hypofractionated group, that would put both groups above zero concern but well to the good side of the least burdensome level (1 leak in the past 4 weeks; occasional lack of control in the past 4 weeks; use of 1 diaper per day; and a “very small” urinary continence problem overall. If this is the case, then I would concur that Fox Chase has made a good case on effectiveness and side effect grounds for this mild form of hypofractionation at the meaningful 5-year point.

    I’m hoping one of us is able to confirm or clarify my hack at the EPIC scoring.

  2. The BED for the hypofractionated schedule is about 10% higher than the normally fractionated schedule in terms of cancer control, but they are identical in their effect on urinary tract tissue. None of the conclusions necessarily apply to SBRT, which entails a different treatment process.

    Perhaps I should have explained that the EPIC categories that are lumped together as “urinary incontinence” may not mean what most people mean by the term. As you say, it may include patient perception of any leaking or dribbling, as well as any pad use. The decline was large enough to be noticeable, but were not very large. The fact that they were not significantly different between the two groups at 5 years may speak to common age-related declines.

  3. Thanks Allen.

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