SBRT has non-inferior acute and late-term toxicity vs IMRT in two randomized clinical trials


In October 2018, the American Society of Radiation Oncologists (ASTRO) strongly endorsed moderately hypofractionated IMRT (20 or 28 treatments) for primary radiation treatment (see this link). Since then, there has been another publication of a randomized clinical trial with 10 years of follow-up (see this link).

The advantages for the patient are large: fewer visits than the conventional 38 to 44 treatments, with a concomitant reduction in costs. Because there is now convincing proof that this can be accomplished without an increase in side effects and without loss of oncological effectiveness, there is no reason why any patient would suffer through the conventional regimen. The remaining question is whether the number of treatments (or fractions) can be reduced even further to only about four or five. This kind of extreme hypofractionation is called stereotactic body radiation therapy or SBRT. This requires proof.

We have seen the results of a Scandinavian randomized clinical trial (RCT) that found that urinary, rectal, and sexual side effects were not inferior with extreme hypofractionation (see this link), and that the oncological outcomes were about the same too (see this link).

Now two more RCTs have shown that the toxicity of SBRT is no worse than and possibly better than moderately hypofractionated or conventionally fractionated IMRT.

Van As et al. just reported the acute toxicity results of the PACE-B RCT in the UK at the ASCO Genitourinary Symposium in San Francisco. A total of 844 men with favorable-risk prostate cancer were randomized to treatment with SBRT (414 men) or conventionally fractionated/moderately hypofractionated IMRT — “CFMHRT” (430 men). The qualifications were:

  • Localized, favorable-risk prostate cancer (Gleason score ≤ 3 + 4, clinical stage T1 or T2, PSA ≤ 20 ng/ml)
  • Unsuitable for surgery or preferring radiation

The two groups were similar. The treatments were:

  • SBRT: 36.25 Gy in 5 fractions over 1 to 2 weeks
  • CFMHRT: 78 Gy in 39 fractions (conventional) or 62 Gy in 20 fractions (moderately hypofractionated)
  • ADT was not permitted

At 12 weeks post-treatment, acute grade 2 or higher toxicity was:

  • Rectal: 10 percent for SBRT vs 12 percent for CFMHRT — difference was not statistically significant
  • Urinary: 23 percent for SBRT vs 27 percent for CFMRT — difference was not statistically significant

At the same meeting, Poon et al. reported the 1-year late-term toxicity results of a RCT in Hong Kong. A total of 64 low- and intermediate-risk patients were randomized to get SBRT (31 patients) or conventionally fractionated IMRT — “CFIMRT” (33 patients). The qualifications were: clinical stage T1 or T2, Gleason score ≤ 7, and PSA < 20 ng/ml.

The treatments were:

  • SBRT: 36.25 Gy in 5 fractions over 2 weeks
  • IMRT: 76 Gy in 38 fractions
  • Intermediate-risk patients could optionally have ADT before their radiation.

At 1 year post-treatment:

  • One grade 3 (serious) urinary side effect was reported in each arm
  • Rectal grade 1 (mild) or higher: 64 percent for SBRT vs 84 percent for CFIMRT — significantly different
  • Urinary grade 1 (mild) or higher: 93 percent for SBRT vs 100% for CFIMRT — not significantly different

It is too early to assess if there are any differences in oncological outcomes in these two RCTs.

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

3 Responses

  1. I find it rather ironic that this trial concluded that, “SBRT was non-inferior to moderately hypofractionated IMRT.” Putting the cart before the horse?

    The increasing acceptance of “moderately hypofractionated IMRT” followed the demonstrated advantages of SBRT over conventional IMRT. One can only conclude that there apparently has been a strong bias on the part of radiation oncologists invested in IMRT to resist the evidence of the advantages to patients of SBRT. The best face one can put on it is that IMRT radiation oncologists are are very conservative about accepting changes to long-established protocols. However, one must also wonder if an influencing factor is that perhaps there is an advantage in retaining income from reducing reimbursement for 40+ radiotherapy sessions to 20 to 28 rather than the SBRT reimbursement for only five sessions. Hmmm ….

  2. Allen, thanks for your continued informative reporting on SBRT.

    Regarding the Poon study, the extremely high proportion of patients in both arms that reported mild or higher late side effects is surprising. Generally side effects are reported as grade 2, at least,or higher, and likely the percentages would have been far lower had they done so. To me, Grade 2 or higher is a much more meaningful measure.

    Also, re Poon, effectiveness results will likely be much diluted due to the proportion of low-risk patients in the pool.

  3. Jon:

    Moderately hypofractionated IMRT has more convincing data to support it (based on about eight large, randomized clinical trials) and has been strongly endorsed by ASTRO. Perhaps, as results from randomized trials like these accumulate, ASTRO will give SBRT a strong endorsement too. Anecdotally, I’ve been hearing from more and more patients who are getting at least moderate hypofractionation.

    Jim:

    Yes — I agree. The problem with Grade 1 (mild) is that they are common and patients usually expect them and don’t bother their doctors by reporting them, so Grade 0 + Grade 1 should probably be lumped together. Patient-reported outcomes on validated questionnaires are still better because they don’t rely on the patient to spontaneously call their doctors every time they get up a few times a night to pee, and for doctors to record every call.

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