Sunday, August 28, 2016

External beam radiation therapy (EBRT) with a low dose rate brachytherapy (LDRBT) boost provides superior cancer control compared to EBRT alone.

Numerous retrospective analyses have suggested that the combination of external beam radiation therapy (EBRT) with a low dose rate brachytherapy (LDRBT) boost is highly effective in controlling prostate cancer in unfavorable risk patients. For the first time, to my knowledge, we have a randomized comparative trial confirming that. An abstract was presented at the GU Conference and there is a press release about it.

ASCENDE-RT was a randomized clinical trial among 122 intermediate and 276 high risk patients treated in 6 Canadian centers from 2002-2011. The treatment specifications were:
  • All patients received:
    • Whole pelvis EBRT of 46 GY
    • 8 months of neoadjuvant ADT + 4 months of concurrent and adjuvant ADT
  • The EBRT-only group of 200 patients received an additional 32 Gy to the prostate (total = 78 Gy)
  • The LDRBT-boost group of 198 patients received an additional boost of 115 Gy I-125 seeds in the prostate.
  • Median follow up was 6.5 years, and was as long as 9 years for 65 patients.
The researchers found:
  • After 9 years, the biochemical progression-free survival  (bPFS) was 83% for the LDRBT-boost group compared to 62% for the EBRT-only group.
  • bPFS deteriorated by about 6% per year for the EBRT-only group.
  • bPFS was fairly stable for the LDRBT-boost group after reaching 89% at 5 years.
  • After 7 years, LDRBT-boost had better bPFS than EBRT-only both among intermediate risk men (94% vs. 80%), and among high risk men (83% vs. 72%).
  • Median PSA at latest follow up was 0.02 ng/ml for the LDRBT-boost group and 0.24 ng/ml for the EBRT-only group.
  • Reflecting the long natural history of disease progression, there were no significant differences in metastasis-free survival, prostate cancer-specific survival, or overall survival. Differences may emerge with longer follow up.
The improved oncological control came at the expense of increased toxicity for the combination therapy.
  • Late term Grade 2 or higher genitourinary (GU) toxicity was higher for the LDRBT-boost group. Late term Grade 3 GU toxicity reached 19% for the LDRBT-boost group vs. 5% for the EBRT-only group.
  • Late term gastrointestinal (GI) toxicity was similarly mild for both groups
  • This early report did not include an analysis of acute toxicity, or an analysis of erectile function.
I look forward to the full analysis of the data when published. I hope they will break out the results separately for favorable and unfavorable intermediate risk patients to the extent that sample size may allow. Perhaps the favorable intermediate risk patients can be spared the extra toxicity of the LDRBT-boost treatment while still enjoying oncological control.

For the high risk patients especially, this study establishes LDRBT-boost therapy as the preferred treatment compared to EBRT-only, unless pre-existing urinary issues rule it out. It is unclear whether the 12 months of ADT and the whole-pelvis radiation would be necessary for all patients.

In an earlier randomized clinical trial (Sathya et al.), high dose rate brachytherapy (HDRBT) boost was shown to reduce the biochemical and clinical failure rate by 50% compared to EBRT-only (66 Gy). Other randomized clinical trials of HDRBT-boost (Hoskin et al., Guix et al.) also found that the boost improved outcomes. It is unclear whether boost with HDRBT, LDRBT, or treatment with SBRT alone will eventually emerge as the preferred treatment for unfavorable risk patients, or whether it will make a difference.

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