Risk for GU side effects higher after SBRT than after IMRT?

A recent, retrospective analysis of Medicare data suggests that men who have first-line stereotactic body radiation therapy (SBRT) are at somewhat higher risk for genitourinary (GU) side effects than men who select intensity-moduated radiation therapy (IMRT). However, it should be immediately noted that the paper’s authors have also noted that

Despite our finding of increased toxicity, it is still possible that SBRT may be preferable to IMRT for both insurers and patients.

and that

as radiation therapy techniques improve, and as practitioners become more experienced with SBRT, the comparison between SBRT and IMRT is a moving target.

In other words, we need to be careful not to over-react to an initial finding like this that is based on retrospective analysis of  Medicare claims data from patients treated between 2008 and 2011 (when relatively few clinicians had extensive experience of using the CyberKnife or other technology to deliver SBRT).

The study by Yu et al. appears in a recent issue of the Journal of Clinical Oncology along with editorial comment by D’Amico. It is also discussed in a recent issue of The ASCO Post. Here is the core information from the study:

  • All patients were Medicare beneficiaries (age ≥ 66 years) who received SBRT or IMRT as primary treatment for prostate cancer from 2008 to 2011.
    • There were 1,335 SBRT patients
    • Each SBRT patient was matched to two IMRT patients (i.e., 2,670 IMRT patients in total) with similar follow-up (6, 12, or 24 months).
  • The mean treatment costs were
    • $13,645 for SBRT
    • $21,023 for IMRT
  • At 6 months after initiation of treatment
    • 15.6 percent of of SBRT patients experienced GU toxicity
    • 12.6 percent of IMRT patients experienced GU toxicity
    • The odds ratio (OR) = 1.29, and this is a statistically significant difference (P = 0.009)
  • At 24 months after initiation of treatment
    • 43.9 percent of SBRT patients experienced GU toxicity
    • 36.3 percent of IMRT patients experienced GU toxicity
    • OR = 1.38, and this is a statistically significant difference (P = 0.001)
  • The increase in GU toxicity was due to claims indicative of urethritis, urinary incontinence, and/or obstruction.

Now it has to be said that it would not be entirely surprising to find a slight increase in risk for GU side effects among men treated with SBRT as compared to men treated with IMRT. The SBRT patients are getting fewer but significantly higher individual doses of radiation therapy. Certainly in the relatively early days (the “learning curve” period) of use of SBRT, there was inevitably going to be a process of experience building for radiation oncologists as they started to treat patients with this technique.

D’Amico, in his editorial comments, refers to the findings by Yu et al. as constituting “a concerning but testable hypothesis.” The “New” Prostate Cancer InfoLink would tend to agree with that characterization. There is an ongoing, prospective, randomized clinical trial in Europe that is designed to compare IMRT and SBRT directly as first-line options for radiation therapy, and we will know more about this issue in due course. In the meantime, patients considering SBRT as their first-line option for treatment of prostate cancer should be aware of the data reported by Yu et al. and at least discuss their with their doctors.

5 Responses

  1. I think that two of the more serious drawbacks of Yu’s study, as mentioned in his discussion, is that the Medicare database does not include grade data, and, as you said, the analysis includes the early years of SBRT when many ROs were on the early part of their learning curve.

    I looked a little deeper into some data on grade of toxicity. For those who are unfamiliar with the RTOG grading system, Grade 1 is mild, Grade 2 is what I would call annoying (e.g., getting up to pee more than twice a night), Grade 3 is serious, requiring medical intervention, and Grade 4 is life-threatening. The Medicare database treats a visit to the doctor for a problem that is resolved by a prescription for Flomax the same as a visit to the ER for catheterization for urinary retention. Research studies often don’t bother reporting Grade 1 events, but I found a couple. I looked at the late term urinary morbidity by grade as reported for high dose IMRT (81 Gy) by Alicikus et al. at Memorial Sloan Kettering and compared it to the QOL results reported by Bhattasali et al. at Georgetown after 2 years.

    Georgetown reports for their patients 2 years after SBRT: 26% Grade 1 late urinary symptoms, 17% Grade 2 urinary symptoms, 1% Grade 3, and no Grade 4 symptoms. For IMRT, MSK reports late term urinary toxicities of 23% Grade 1, 9% Grade 2, and 5% Grade 3. So at Georgetown (SBRT), 44% of patients had a reported visit to their doctor, while at MSK (IMRT), 37% saw their doctor with a urinary complaint — 16% less for IMRT. Yet IMRT had 5 times as high a rate of serious (Grade 3) urinary complaints.

    Incidentally, Alan Katz reports much lower toxicity rates, perhaps related to his longer experience and his lower SBRT dose rates.

    The Georgetown study shows the typical SBRT pattern of an immediate drop in GU and GI EPIC scores followed by a gradual return to baseline. Based on this, I would expect to see Medicare claims for SBRT reduced over time. Perhaps Yu et al., in a follow-up, will be able to track SBRT patient claims per physician over time.

    My other question is … Are ROs who are relatively new to a procedure (as many were in 2008-2011) more likely to refer their patients to a urologist with even minor complaints? Maybe this occurs in the same way that new mothers are more likely to call pediatricians when their first baby sneezes, while by the third or fourth child, they seldom would.

    I think Yu et al. raise good questions about the relative costs of IMRT vs SBRT and whether the large cost difference justifies what may be a minor increase in low grade symptoms. I also agree with D’Amico that the RCTs now in the works will be dispositive.

  2. Mike, can you explain what type of “side effects” you are referrring to?

  3. Jim Wickstrom:

    It’s hard to tell exactly but they include “urethritis, urethral strictures, urinary incontinence,” and urinary tract obstructions.

  4. I have a friend who apparently needs a “dilation” … that be a solution to any of those side effects?

  5. I think your friend probably requires a “dilatation” as opposed to a “dilation”. A dilatation of the urethra is a relatively minor surgical intervention designed to expand the diameter of the urethra at a point of constriction — a urethral stricture (most commonly after surgery, but it can occur as a consequence of other procedures too).

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