Prazosin used to manage LUTS in men with prostate cancer reduces risk of biochemical relapse following radiotherapy

Hart J1, Spencer B1, McDermott C2, Chess-Williams R2, Sellers D2, Christie D1, Anoopkumar-Dukie S1

Research Type

Clinical

Abstract Category

Pharmacology

Abstract 527
Open Discussion ePosters
Scientific Open Discussion ePoster Session 28
Friday 31st August 2018
12:50 - 12:55 (ePoster Station 4)
Exhibition Hall
Pharmacology Male Retrospective Study Voiding Dysfunction
1. Griffith University, 2. Bond University
Presenter
S

Shailendra Anoopkumar-Dukie

Links

Poster

Abstract

Hypothesis / aims of study
Alpha1-adrenceptor antagonists are commonly used to manage  lower urinary tract symptoms (LUTS) experienced by  men receiving  radiotherapy for localised prostate cancer.  There is evidence that some alpha1-adrenoceptor antagonists such as prazosin, reduce the incidence of prostate cancer and increase apoptosis in the prostate compared to unexposed men [1, 2].  Several  in vitro  studies  have also demonstrated cytotoxic actions of quinazoline alpha1-adrenceptor antagonists in prostate cancer cell lines, an effects that is independent of alpha-adrenoceptor blockade [3].  These cytotoxic actions are not observed with the non-quinazoline antagonist tamsulosin.   The potential dual LUTS and anti-cancer actions of these antagonists may be particularly beneficial in men treated with radiotherapy for localised prostate cancer. The  aim of this study was to determine if the quinazoline alpha1-adrenceptor antagonist prazosin and the non-quinazoline  antagonist tamsulosin  delay time to biochemical relapse and influence recurrence in men with prostate who have received radiotherapy as part of their treatment regimen.
Study design, materials and methods
We retrospectively evaluated data from 303 men  with histologically proven adenocarcinoma of the prostate who received radiotherapy  between 1998 and 2017. The medical records database was first refined to identify patients who had been treated with either prazosin (n=147) or tamsulosin (n=72), while men naive to  alpha1-ADR antagonists were used as a control (n=84) group for comparison.  Baseline demographic characteristics including age at diagnosis, Gleason score, tumour staging and any treatment modalities were collected. PSA values were recorded periodically from diagnosis up to 120 months (10 years) if available. Two primary outcomes were evaluated including relapse rates (%) at two and five years and  time to biochemical relapse (months). Recurrence free survival (%) was also calculated using Kaplan Meier curves.
Results
The number of prostate cancer patients who experienced biochemical relapse at both the two and five-year points was significantly lower in the prazosin group  (2.7%, 8.8%; p<0.01) when compared to the control (22.6%, 34.5%) and tamsulosin (15.2%, 25.0%) groups. Kaplan Meier survival analysis demonstrated that the recurrence free survival was strikingly higher in the prazosin group and median survival was significantly extended (Figure 1). Men taking prazosin to manage LUTS had a 3.9 times lower relative risk of biochemical relapse when compared to control. Difference in time to biochemical relapse was not significant altered by prazosin or tamsulosin  (p=0.1258), despite this the use of tamsulosin and prazosin extended recurrence free survival by 13.15 and 9.21 months respectively.
Interpretation of results
Exposure  to the quinazoline alpha1-ADR antagonist prazosin, reduces the risk of prostate cancer recurrence and delays time to biochemical relapse. Although tamsulosin delayed time to biochemical relapse, there was no effect on two and five-year relapse rates.
Concluding message
These findings indicate that use of prazosin to manage LUTS in men with prostate cancer may also improve treatment outcomes by reducing the risk of biochemical relapse.  This was not true of the non-quinazoline tamsulosin. To our knowledge, this is the first study to provide an argument for the use prazosin in  the treatment of prostate cancer as an adjunct treatment option.
Figure 1
References
  1. Kyprianou N, Litvak JP, Borkowski A, Alexander R, Jacobs SC. Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia. J Urol. 1998 Jun;159(6):1810-5.
  2. Harris AM, Warner BW, Wilson JM, Becker A, Rowland RG, Conner W, Lane M, Kimbler K, Durbin EB, Baron AT, Kyprianou N. Effect of alpha1-adrenoceptor antagonist exposure on prostate cancer incidence: an observational cohort study. J Urol. 2007 Nov;178(5):2176-80
  3. Benning CM1, Kyprianou N. Quinazoline-derived alpha1-adrenoceptor antagonists induce prostate cancer cell apoptosis via an alpha1-adrenoceptor-independent action. Cancer Res. 2002 Jan 15;62(2):597-602
Disclosures
<span class="text-strong">Funding</span> Quality Use of Medicine Network, Griffith University <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> Greenslopes Human Research Ethics Committee <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> No