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

(updated)

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

The advantages for the patient are large: fewer visits than the conventional 38-44 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 4 or 5. 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 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. reported the acute toxicity results of the PACE-B RCT in the UK at the Genitourinary Conference of ASCO. 844 men with favorable risk prostate cancer were randomized to get SBRT (414 men) or conventionally fractionated/moderately hypofractionated  IMRT - "CFMHRT" (430 men). The qualifications were:

• localized, favorable risk prostate cancer (Gleason score ≤ 3+4, 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 1-2 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% for SBRT vs 12% for CFMHRT - difference was not statistically significant
• urinary: 23% for SBRT vs 27% for CFMRT - difference was not statistically significant

(Update 9/14/22)

Tree et al. reported the late-term toxicity results of the PACE-B RCT.

At 24 months post-treatment, the worst late-term grade 2 or higher toxicity (RTOG* criteria) was:

• rectal: 2% for SBRT vs 3% for CFMHRT - difference was not statistically significant
• Using CTCAE 4.0* criteria, patients treated on the CyberKnife platform had less toxicity (1%) vs CFMRT (4%) and were better off than patients treated with other linacs (5%)
• urinary: 3% for SBRT vs 2% for CFMRT - difference was not statistically significant
• CTCAE 4.0* urinary toxicity was worse vs. RTOG* urinary toxicity: 12% for SBRT vs 7% for CFMRT
• Patients treated on the CyberKnife platform had no difference in toxicity (6%) vs CFMRT (7%) and were much better off than patients treated in 5 treatments with other linacs (17%)
• Patient-evaluated (EPIC*) moderate/severe urinary bother was worse for SBRT (10%) than for CFMRT (5%)
• Grade 3 toxicity was <1% in all groups
• There was no difference in erectile dysfunction

By 24 months post-treatment, the cumulative incidence of late-term grade 2 or higher toxicity (RTOG* criteria) was:

• rectal: 8% for SBRT vs 8% for CFMHRT - difference was not statistically significant
• CTCAE 4.0* rectal toxicity was worse vs. RTOG* rectal toxicity: 12% for SBRT vs 12% for CFMRT
• urinary: 18% for SBRT vs 11% for CFMRT - difference was statistically significant
• CTCAE 4.0* urinary toxicity was worse vs. RTOG* urinary toxicity: 32% for SBRT vs 20% for CFMRT
• Increased urinary frequency was the type of urinary toxicity most often reported: 10% for SBRT vs 5% for CFMRT

*RTOG and CTCAE 4.0 have different criteria for physicians to evaluate toxicity. EPIC-26 is a questionnaire that patients fill out.

Patients treated on appropriate platforms in high-volume centers had equal or better outcomes. Toxicity was low.

 

(updated 9/30/23) After a median follow-up of 6 years of 874 predominantly (91%) intermediate-risk patients across 38 centers in the UK and Canada, van As et al. reported:

• 95% and 96% were free of biochemical (PSA) failure for SBRT and conventionally fractionated radiotherapy, respectively.
• Grade 2 or worse urinary toxicity was 5.5% and 3.2% (not significantly different) for SBRT and conventionally fractionated radiotherapy, respectively.
• Only 1 patient in each cohort had Grade 2 or worse rectal toxicity.

Poon et al. reported the one year late-term toxicity results of a RCT in Hong Kong. 64 low- and intermediate-risk patients were randomized to get SBRT (31 patients) or conventionally fractionated IMRT - "CFIMRT" (33 patients). The qualifications were: 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% for SBRT vs 84% for CFIMRT - significantly different
• urinary grade 1 (mild) or higher: 93% 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.