Reduction in prostate size prior to permanent seed prostate brachytherapy

Data from a randomized clinical trial have shown that there is more than one way to reduce the size of a man’s prostate (if such cytoreduction is needed) prior to treatment with permanent, radioactive pellets (permanent, low-dose brachytherapy) for localized prostate cancer.

Most specialists in the use of brachytherapy want their patients to have a total prostate volume of something less than about 45 cm3 prior to treatment planning and implementation of permanent, low-dose brachytherapy, and the traditional means used to accomplish this is through the use of a single 3- or 4-month injection of an LHRH agonist (such as leuprolide acetate/Lupron or goserelin acetate/Zoladex). However, use of LHRH agonists is associated with such significant short-term side effects (in many men) as hot flashes and effects on libido and sexual function.

Gaudet et al. set out to investigate whether a 3-month regimen of dutasteride (Avodart) + bicalutamide (Casodex) + tamoxifen (Nolvadex) could actually reduce the prostate volume prior to brachytherapy as effectively as an LHRH agonist — but with fewer side effects for the patients. To do this they conducted a randomized, non-inferiority trial, among men with low- and intermediate-risk prostate cancer and a prostate volume of > 50 cm3 who were scheduled for brachytherapy.The patients were randomized into or or other of two groups:

  • Group A: who were all treated with dutasteride (0. 5 mg daily) + bicalutamide (50 mg daily) + tamoxifen (10 mg daily) for 3 months.
  • Group B: who were all treated with a 3-month dose of an LHRH agonist + bicalutamide (50 mg daily) for  the first month.

Patients’ prostate volumes were all measured prior to randomization (baseline) and after treatment but prior to radioactive seed implantation. The patients were all also asked to complete two different quality of life questionnaries (the IPSS and the EPIC questionnaries) at baseline, pre-implant, and at 1, 3, 6, 12, 18, and 24 months post-treatment.

Here are the study findings:

  • A total of 60 patients were enrolled and randomized.
    • 29 patients were randomized to Group A
    • 31 patients were randomized to Group B.
  • The average (mean) relative reductions in prostate volume were
    • 31.7 ± 9.6 percent in Group A.
    • 35.5 ± 8.9 percent in Group B.
  • The mean reduction in prostate volume among patients in Group A was not inferior to the mean reduction in prostate volume among patients in Group B, but …
  • 5/29 patients (17 percent) Group A required required more than 3 months on therapy to achieve adequate volume reduction.
  • There were no statistically significant differences in IPSS scores between patients in the two groups over the entire follow-up period.
  • EPIC sexual summary scores were significantly better in Group A compared to Group B at pre-implant and at 1 and 3 months post-implant.

The authors conclude that the combination of dutasteride + bicalutamide + tamoxifen is a regimen

of non-inferior efficacy to LHRH agonist based regimens for prostate volume reduction prior to permanent implant prostate brachytherapy … has less sexual toxicity compared to LHRH agonists prior to implant and for the first 6months after implant [and] is therefore an option to be considered for prostate volume reduction prior to [permanent low-dose brachytherapy].

These data certainly appear to suggest that a dutasteride + bicalutamide regimen can be used effectively to reduce prostate volume prior to brachytherapy.

6 Responses

  1. This begs the question — why should a low/intermediate-risk man take any systemic therapy at all when there are other radiation therapies (e.g., HDR brachytherapy and SBRT) that have reported lower sexual side effects than LDR brachytherapy and don’t require smaller prostate size?

    Bicalutamide is not innocuous and does have its own sexual side effects, as does dutasteride to a lesser extent. The tamoxifen is there to prevent gynecomastia, but what about all the other potential side effects e.g., fatigue, hot flashes, metabolic changes, cardiovascular/hematological changes, etc.) associated with blocking access of testosterone into cells?

  2. Allen:

    The differences in the side effect profiles of short- and long-term bicalutamide are considerable. We are only talking about 3 months here. most of the side effects you mention would not be significantly exhibited within 3 months on bicalutamide.

    With regard to whether LDR is a good idea for a specific patient compared to other options, only a specific patient and his doctor can answer that question. LDR brachytherapy is now just one of many options for many patients, but it may still be appropriate for all sorts of reasons, potentially starting with convenience and cost.

  3. It is true of both chemical castration and anti-androgen therapy that side effects increase with duration of medication. Fatigue and libido loss occur even with short duration. Cost and convenience are compromised by having to go through months of systemic treatment just so one is eligible to get the treatment. I think patients with large prostates are better advised to look at other therapies (or active surveillance for low risk) rather than trying to make a round peg fit a square hole.

  4. Fatigue and short term ADT, also libido

    It is important to bear in mind that the ADT addressed in this article is quite short — a matter of a few months. That short duration means the impact of ADT on a variety of side-effects will be lighter.

    On my first round of long-term IADT I was not so aware of the importance of aerobic and strength exercise to counter fatigue, and my recollection is that I took more naps when I could. (I have records but have not checked them.) It is important to bear in mind that the ADT addressed in this article is quite short.

    On subsequent rounds, then aware of the importance of regular exercise to counter fatigue and other side effects of ADT, I did not experience unusual fatigue. My view is that, for those of us able to exercise, exercise effectively counters fatigue that may otherwise result from ADT, at least for many of us.

    Regarding libido, experts advise that about 10% of us receive the benefits of ADT with minimal side effects, including impact on libido. Of course the flip side is that about 90% of us do experience some impact.

    I believe that decrease of libido is a matter of degree for ADT patients, though I found it substantial, yet far from complete. Some doctors who use a lot of ADT in their practices advise use of imagery and other techniques to help preserve libido and erectile function while on ADT.

    However, the very good news is that the vast majority of us will recover from these side effects fairly quickly and nearly completely (within several months, typically) after stopping short-term ADT. For long-term ADT of 31 months for my first round, I achieved substantial recovery at about 3 months and virtually full recovery at 6 months. Published research and my own conversations with fellow ADT veterans suggest that that is typical, though there are exceptions on both sides, with men aged about 70 and older having considerably more of an issue with libido and erectile recovery.

  5. Sitemaster:

    In response to Allen, you state, “The differences in the side effect profiles of short- and long-term bicalutamide are considerable.”

    By the same token, the difference in response to short- and long-term treatment with LHRH drugs is considerable. Most men will experience little or none of the QoL side effects over the first 4 to 6 weeks. Thereafter they do ramp up slowly, but with a 90 to 120 day treatment period, they dissipate quickly too.

  6. Yes Rick … but the trial referred to above was all about whether bicalutamide + dutasteride was as effective as an LHRH agonist but had fewer side effects, and this was shown to be the case.

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