Wednesday, April 24, 2019

Should SBRT be THE preferred treatment for intermediate risk prostate cancer?

Last year, the American Society of Radiation Oncologists (ASTRO) looked at the available evidence comparing hypofractionated radiotherapy (either 60 Gy in 20 treatments or 70 Gy in 28 treatments) to standard fractionation (78-82 Gy in 40-44 treatments), and found it was at least as good in terms of oncological outcomes and toxicity. They found strong evidence for this recommendation (see this link). There are obvious benefits for the patient in terms of convenience and cost. They stopped short of strongly endorsing ultrahypofractionated radiation therapy (usually called SBRT), which is usually completed in only 4-5 treatments. There wasn't enough published data at the time.

Since then, there have been several published clinical trials, some with randomized comparisons. Jackson et al. have now compiled the data from 38 prospective clinical trials comprising 6,116 patients treated with SBRT for localized prostate cancer. Their meta-analysis found that 5-year biochemical recurrence-free survival (bRFS) was:

  • 97% among low-risk patients
  • 92% among intermediate-risk patients
  • more studies included intermediate risk than low risk
  • not enough high-risk patients to reliably report yet
  • 95% among all patients
  • 7-year bRFS was 94%
  • bRFS increased with higher doses
  • bRFS was not affected by the use of adjuvant ADT

In terms of physician-reported toxicity, they found:

  • Acute Grade ≥3 (serious) urinary toxicity occurred in 0.5% of patients
  • Acute Grade ≥3 (serious) rectal toxicity occurred in 0.1% of patients
  • Late-term Grade ≥3 (serious) urinary toxicity occurred in 2% of patients
  • Late-term Grade ≥3 (serious) rectal toxicity occurred in 1% of patients
  • Late urinary toxicity increased with dose, rectal toxicity did not

In terms of patient-reported adverse effects of treatment:

  • Urinary and Bowel scores returned to baseline within 2 years of treatment
  • They remained at those levels with 5 years of follow up
  • Sexual scores declined gradually over time

While the authors believe that their analysis provides enough evidence that SBRT should be considered a standard of care for low and intermediate risk patients, they stop short of recommending that SBRT be considered the standard of care for patients who choose radiotherapy.  (Active Surveillance is appropriate for most low risk patients.) There is an ongoing randomized clinical trial designed to prove whether SBRT or moderately hypofractionated radiation is superior. First results are expected in 2025. The PACE trials in the UK, will compare outcomes of SBRT vs surgery (PACE A) and SBRT vs IMRT (PACE B). Early toxicity results of PACE B have been presented. Results are expected in 2021.

Thanks to Amar Kishan for allowing me to see the full text of the analysis

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