Effects of prazosin + radiation therapy on recurrence-free survival


The following was brought to our attention by Arthur as a consequence of a question posed on Ask Arthur by a reader within the past 24 hours.

At the International Continence Society (ICS) annual meeting in August this year, a group of Australian researchers (Hart et al.) presented what seems to be a thought-provoking poster on the effects of a drug called prazosin (Minipress) when used in combination with radiation therapy in the first-line treatment of localized prostate cancer (see here for the abstract of the poster). This is not a meeting where one would have been looking for a paper like this if one was a radiation oncologist interested in the management of prostate cancer.

There are some data to suggest that some drugs known as alpha-blockers, often used to maintain urinary function during and immediately after radiation therapy in the treatment of localized prostate cancer, may also have some additional impact on the prostate cancer itself. However, as far as we know this effect has never been formally tested in clinical trials.

What Hart et al. report are data from a retrospective review of the use of two specific alpha-blockers — prazosin and tamsulosin — in 303 men being treated with radiotherapy for localized prostate cancer between 1998 and 2017. The patients included:

  • 147/303 (48.5 percent) who received radiotherapy + prazosin
  • 72/303 (23.8 percent) who received radiotherapy + tamsulosin
  • 84/303 (27.7 percent) controls, who received neither prazosin nor tamulosin

The patients had all been followed with serial PSA tests for up to 10 years.

What Hart et al. report are the following findings:

  • Patients treated with prazosin + radiation therapy had a significantly lower rate of biochemical disease recurrence than patients treated with tamsulosin + radiation therapy or the controls (treated with radiation therapy alone); see the Kaplan-Meier plots on the actual poster.
    • For the prazosin group
      • Biochemical recurrence at 2 years was observed in 4/147 patients (2.7 percent)
      • Biochemical recurrence at 5 years was observed in 13/147 patients (8.8 percent)
    • For the tamsulosin group
      • Biochemical recurrence at 2 years was observed in 11/72 patients (15.2 percent)
      • Biochemical recurrence at 5 years was observed in 18/72 patients (25.0 percent)
    • For the control group
      • Biochemical recurrence at 2 years was observed in 19/84 patients (22.6 percent)
      • Biochemical recurrence at 5 years was observed in 29/84 patients (34.5 percent)
  • Prazosin patients demonstrated a 3.9 times lower relative risk of biochemical recurrence compared to the controls.
  • Prazosin and tamsulosin extended recurrence-free survival by 9.2 and 13.3 months, respectively
  • Patients treated with prazosin + radiation therapy had much lower PSA velocities (PSAVs) over time than patients in the other two groups
    • For the prazosin patiens, PSAV = 0.306 ng/ml/yr
    • For the tamsulosin patients, PSAV = 3.363 ng/ml/yr
    • For the control group, PSAV = 2.980 ng/ml/yr

What are we to make of these data?

So the first thing that we have to be clear about is that all retrospective data like this have to be treated with caution. They are “hypothesis-generating” and not “practice-changing”. Furthermore, the cohort represents only about 16 patients a year over a 19-year-long period during which the treatment of localized prostate cancer using various forms of radiotherapy has changed significantly.

On the other hand, these data are clearly thought-provoking (as previously indicated), and one would like to think that they might lead to at least a small, randomized Phase II trial in a well-defined group of patients with clinically significant prostate cancer scheduled for radiation therapy, with half the patients being treated with radiation + tamsulosin and the other half being treated with radiation + prazosin.

We would also hope that the authors of this poster will be writing up these initial data for publication in a relatively widely read journal where it would be seen by the radiation oncology community (as opposed to a journal on incontinence).

3 Responses

  1. Thank you for this interesting information.

    You are probably referring to tamsulosin, not tamulosin.

  2. Thank you for posting this. This is the first time I’ve seen anything about an interaction effect between radiation and alpha-blockers. I have several files about alpha-blockers and prostate cancers that interested readers may wish to read. See:

    https://onlinelibrary.wiley.com/doi/full/10.1111/iju.12156
    http://cancerpreventionresearch.aacrjournals.org/content/4/1/87.long
    https://onlinelibrary.wiley.com/doi/full/10.1111/iju.12175
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2274914/
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325211/

    Definitely worth further study!

  3. Thank you Richard. Duly fixed. I never could type very well!

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