For very high-risk patients, EBRT + BT is superior to surgery or EBRT only (redux)

In August last year, Kishan et al. showed a preliminary analysis of oncological outcomes among patients diagnosed with Gleason score 9 and 10 and treated with brachy boost therapy (EBRT + BT), external beam radiation therapy alone (EBRT), or surgery (see this link). Because of the limited sample size, some of the differences were not large enough to be statistically significant.

Kishan et al. have now expanded their analysis to include 1,001 patients treated between 2000 and 2013, who were treated at several of the top institutions in the US: UCLA, Fox Chase, Cleveland Clinic, Mt. Sinai, and Wheeling Hospital. So far, only an abstract of the study has been posted. The full data will be presented at the Genitorunary Cancers Symposium in Orlando, later this week.

The patient characteristics were as follows:

  • 324 were treated with radical prostatectomy (RP).
  • 347 were treated with EBRT only.
  • 330 were treated with EBRT + BT (BT was either low dose rate or high dose rate).
  • All patients were Gleason 9 or 10 on biopsy.

Treatment specs

  • Among the RP patients, 40 percent had adjuvant or salvage radiation therapy.
  • Among radiation therapy patients, 90 percent had adjuvant ADT
  • Median dose of EBRT was 78 Gy.
    • Adjuvant ADT continued for a median of 18 months.
  • Median equivalent dose of EBRT + BT was 90 Gy.
    • Adjuvant ADT continued for a median of 12 months.

Oncologic Outcomes

After median follow-up periods of 4.8, 6.4, and 5.1 years for EBRT, EBRT  + BT and RP, respectively, the oncologic outcomes were as follows:

  • The 10-year rates of distant metastases were
    • 39.9 percent for RP
    • 34.2 percent for EBRT
    • 19.7 percent for EBRT + BT
    • Differences between EBRT + BT and the two others were statistically significant.
  • The 10-year rates of prostate cancer-specific mortality (PCSM) were
    • 20.3 percent for RP
    • 25.2 percent for EBRT
    • 14.1 percent for EBRT + BT
    • Differences between EBRT + BT and the two others were statistically significant.

The authors conclude that:

Extremely dose-escalated radiotherapy offered improved systemic control and reduced PCSM when compared with either EBRT or RP. Notably, this was achieved despite a significantly shorter median duration of ADT than in the EBRT arm. 

Prostate cancer-specific mortality rates were cut in half by combining EBRT with a BT boost. While this does not prove causality, only a randomized clinical trial can do that, it is highly suggestive that escalated dose can provide lasting cures. There may be good reasons why some high-risk patients may have to forgo brachy boost therapy in favor of high dose EBRT or RP with adjuvant EBRT, but for most, brachy boost therapy with ADT will probably be the best choice.

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

8 Responses

  1. These are amazing results for all three types of treatment. Frankly, I find them hard to believe. Since Gleason 9-10 frequently includes EPE, SVI, and positive margins, which usually result in fast biochemical recurrence, as well as distant metastases, how do this data square with the need for more treatment including advanced hormone therapy, chemotherapy, etc., upon recurrence, with their reported inability to cure this disease?


  2. Good commentary.

    One of the maddening things about these studies us how long it takes for results to be analyzed and have an effect on routine clinical practice.

    Enough evidence has accumulated already regarding use of Casodex as adjuvant treatment immediately after prostatectomy for high-risk cancer to recommend its use, at least according to my take on the data. Same with its use during subsequent salvage radiation treatment.

    That 40℅ figure for combined use of surgery and salvage radiation treatment for Gleason 9 and 10 cancers is really discouraging and for me calls into question the whole rationale of administering them with “curative intent”.

    Check out an article entitled “Hit the primary: a paradigm shift in the treatment of metastatic prostate cancer” by Arcangeli et al. (in Critical Reviews in Oncology/Hematology. 2016;97:231-237) for additional food for thought on this question.

  3. Excellent study … very helpful to support group leaders as a reference! Tx for bringing our attention to this, Alan.

  4. I think and hope Boost was the right choice for me. I got EBRT + HDR + 3 years ADT in Uppsala but was offered only EBRT or RP without a word about ADT, in Amsterdam. I had PSA of 31 and Gleason 4 + 4. This post supports my move from Nederland to Sweden, where I got the trimodal treatment.

  5. Brachytherapy/BT followed by external beam radiation therapy/EBRT has been a protocol of radiation oncologist Michael Dattoli for years. EBRT followed by BT has been a protocol of radiation oncologist Frank Critz for years.

  6. There is zero surprise to me that any combination therapy in high-risk cases performs better than any monotherapy. This historic relevance has been proven time and again. …

  7. Sadly, a recent analysis of the National Cancer Database showed that utilization of brachy boost therapy for high-risk patients has declined precipitously from 28% in 2004 to 11% in 2013.

    If a patient sees anyone other than the first urologist, he often only sees a single radiation oncologist who only informs him about IMRT. In most parts of the US, there is a dearth of experienced brachytherapists.

  8. It is almost 2020 and I am reading this again. Still thinking about the dearth of brachytherapists. Now, the lack of information given by urologists as stated here is a moral failing. The urologists should admit that the BBT cannot be given using their resources and those generally available. Let the patient decide about going elsewhere, where treatment is available. I did, by consulting with doctors in Sweden and on their advice letting them treat me.

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