EBRT + 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. Now, for the first time, to our knowledge, we have a randomized comparative trial confirming that. Morris et al. presented data from the ASCENDE-RT trial at the Genitourinary Cancers Symposium in Orlando, 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 six Canadian centers from 2002 to 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 from I-125 seeds implanted 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 percent for the LDRBT-boost group compared to 62 percent for the EBRT-only group.
  • bPFS deteriorated by about 6 percent per year for the EBRT-only group.
  • bPFS was fairly stable for the LDRBT-boost group after reaching 89 percent at 5 years.
  • After 7 years, LDRBT-boost had better bPFS than EBRT-only both among intermediate-risk men (94 vs. 80 percent), and among high-risk men (83 vs. 72 percent).
  • 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 percent for the LDRBT-boost group vs. 5 percent 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 percent 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.

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

3 Responses

  1. Particularly interesting to me since this was close to my Tx protocol Allen, although I did a little longer ADT. The results/toxicities are similar to my experience. I was high risk.

    115 Gy for the LDR boost sounds high — am I correct. I think I got less than half that. I recall sitting next to Dr. Steven Frank at a dinner one time, and when I told him I got 54 Gy as an LDR boost he corrected me in that I was reading it wrong … so perhaps I’m mistaken .

    Perhaps you can clarify …

  2. Rick D,

    Did you have I-125 implants, Pd-103 implants, or Cs-131 implants? The dose used with the lower dose rate I-125 has to be higher. Real-time intraoperative planning has also shifted toward higher doses recently. The other problem with comparisons is confusion over which measure of dose is being quoted; sometimes they quote the dose that 90% of the prostate is getting, or other dosimetry parameters.

    I’d say the 115 Gy is on the high side, but certainly not extraordinary. The CALGB 99809 (2011) study used 100 Gy of I-125 + 45 Gy EBRT; RTOG 00-19 (2012) used 108 Gy of I-125 + 45 Gy EBRT; Zelefsky et al. (2012) used 110 Gy of I-125 + 50 Gy EBRT; Merrick et al. (2006) used 108 Gy of I-125 + 45 Gy EBRT; Potters et al. (2005) used 108 Gy of I-125 + 45 Gy EBRT; Ohashi et al. (2014) used 110 Gy of I-125 + 45 Gy EBRT.

    Perhaps Dr. Frank misheard you and thought you were talking about an HDR brachy boost, or maybe he thought the 54 Gy referred to the EBRT part of the treatment.

  3. You are correct — as ever, Allen. I just pulled the file which I should have done first — and it was my confusion. I had 54 I-125 seeds planted for a total of 110 Gy; and I think I got around 42 Gy for IMRT. That makes a lot more sense!

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