The Role of α-Blockers in the Management of Lower Urinary Tract Symptoms in Prostate Cancer Patients Treated With Radiation Therapy

Crawford, E. David; Kavanagh, Brian D.

doi:10.1097/01.coc.0000225412.24750.4c

Cited by 17 publications

(10 citation statements)

References 56 publications

(50 reference statements)

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“…58 Animal studies have shown that the ventral prostates of rats treated with the α-adrenergic receptor agonist phenylephirine are affected by interstitial fibrosis, inflammation, neoangiogenesis, and de novo synthesis of collagen (suggestive of a desmoplastic reaction). 59 Conversely, other studies have shown that the ventral prostates of adult Wistar rats treated with the α-adrenergic receptor antagonist doxazosin contain increased levels of collagen and collagen fibrils compared with untreated controls.…”

Section: Therapeutic Targeting Of Fibrosismentioning

confidence: 99%

Prostatic fibrosis, lower urinary tract symptoms, and BPH

2013

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Lower urinary tract symptoms (LUTS)—constituting a spectrum disorder that encompasses weak stream, nocturia, and sensations of incomplete emptying and intermittent or hesitant urination—are indicative of lower urinary tract dysfunction (LUTD). LUTD is a progressive disease that can lead to bladder dysfunction if left untreated or treated ineffectively. Sequelae include urinary retention, recurrent UTI, bladder calculi, and, eventually, renal impairment. LUTD involving the prostate is associated with both ageing and inflammation. Tissue inflammation resulting from ageing, infection, or other inflammatory disease processes (for example, type 2 diabetes mellitus) is epidemiologically associated with the subsequent development of tissue fibrosis in multiple organ systems, including the prostate. Recent studies show that tissue fibrosis in the lower urinary tract is associated with LUTD, and suggest that fibrosis might be a previously unrecognized pathobiology that contributes to LUTD. Thus, antifibrotic therapeutic agents should be considered as a new approach to efficaciously treating men with LUTD, especially those who don’t experience durable responses to 5α-reductase inhibitors or α-adrenergic receptor antagonists.

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Section: Therapeutic Targeting Of Fibrosismentioning

confidence: 99%

Prostatic fibrosis, lower urinary tract symptoms, and BPH

2013

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“…Radiation therapy decreases gland size and may relieve symptoms but can also exacerbate obstructive and irritative symptoms [8,9]. α-Blockers, 5α-reductase inhibitors and anticholinergics are used in the management of LUTS in patients with benign prostatic conditions [10] and also less commonly to alleviate symptoms in patients with PrCa undergoing radiotherapy [11]. …”

Section: Introductionmentioning

confidence: 99%

Degarelix versus Goserelin (+ Antiandrogen Flare Protection) in the Relief of Lower Urinary Tract Symptoms Secondary to Prostate Cancer: Results from a Phase IIIb Study (NCT00831233)

et al. 2012

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Introduction: No studies to date have assessed the efficacy/tolerability of degarelix in the relief of lower urinary tract symptoms (LUTS) secondary to prostate cancer (PrCa). Methods: Patients were randomised to degarelix 240/80 mg or goserelin 3.6 mg + bicalutamide flare protection (G+B); both treatments were administered for 3 months. The primary endpoint was change in International Prostate Symptom Score (IPSS) at week 12 compared with baseline. Results: This study was stopped early due to recruitment difficulties. 40 patients received treatment (degarelix n = 27; G+B n = 13); most had locally advanced disease and were highly symptomatic. Degarelix was non-inferior to G+B in reducing IPSS at week 12 in the full analysis set (p = 0.20); the significantly larger IPSS reduction in the per-protocol analysis (p = 0.04) was suggestive of superior reductions with degarelix. Significantly more degarelix patients had improved quality of life (IPSS question) at week 12 (85 vs. 46%; p = 0.01). Mean prostate size reductions at week 12 were 42 versus 25% for patients receiving degarelix versus G+B, respectively (p = 0.04; post hoc analysis). Most adverse events were mild/moderate; more degarelix patients experienced injection site reactions whereas more G+B patients had urinary tract infections/cystitis. Conclusion: In 40 men with predominantly locally advanced PrCa and highly symptomatic LUTS, degarelix was at least non-inferior to G+B in reducing IPSS at week 12.

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“…Also, we were unable to control for alpha-blocker usage. Our use of patient-subjective IPSS warranted addressing the potential influence of pretreatment alpha-blocker therapy, given that alpha-blocker therapy does not affect prostate volume and is a routine consideration during radiotherapy, 26 – 28 but investigating alpha-blocker effects was not a primary aim in this study. Therefore, an inherent analytic weakness is our lack of differentiation between types of pretreatment alpha-blocking medication, ie, prophylactic, symptomatic, or chronic.…”

Section: Discussionmentioning

confidence: 99%

Effect of pretreatment prostate volume on urinary quality of life following intensity-modulated radiation therapy for localized prostate cancer

Chevli¹,

Narayanan²,

Rambarran³

et al. 2013

RRU

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BackgroundThe aim of this study was to describe the effect of pretreatment prostate volume on urinary quality of life after intensity-modulated radiation therapy (IMRT) for clinically localized prostate cancer.MethodsA total of 368 men treated with prostate IMRT (77.4–81 Gy) were stratified into three gland volume groups, ie, <30 g (group 1), 30–60 g (group 2), and >60 g (group 3). Post-IMRT urinary function was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 genitourinary guidelines at one year post-IMRT, and surveyed by the International Prostate Symptom Score (IPSS) before treatment, and then at one month and one year post-IMRT.ResultsLate (one year post-IMRT) CTCAE version 4.0 genitourinary toxicity occurred in 11/368 (3.0%) men, but was not severe (grade ≥ 3); total toxicity was similar between the prostate volume groups (P = 0.86). Continuous prostate volume neither correlated with (P = 0.50) nor predicted late genitourinary toxicity (univariate odds ratio 0.99, 95% confidence interval 0.96–1.02). The total IPSS cohort, group 1 (<30 g) and 2 (30–60 g), showed a similar IPSS trend of elevation from pretreatment baseline to one month post-IMRT (each P < 0.01), then a reduction to baseline at one year (each P < 0.01). Group 3 (>60 g) had the highest pretreatment IPSS, but uniquely showed a better urinary symptom trend than the smaller volume groups, with similar IPSS from baseline to one month post-IMRT (P = 0.88) and improved post-treatment IPSS from baseline at one year (P = 0.003).ConclusionPretreatment prostate volume and initial IPSS scores were not associated with increased late genitourinary toxicity after IMRT in our series. Patients with smaller prostates had an initial increase in urinary symptoms, but returned to baseline at one year. Larger prostate glands (>60 g) had comparatively worse pretreatment symptoms, but at one year showed an overall improvement in IPSS versus baseline.

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The Role of α-Blockers in the Management of Lower Urinary Tract Symptoms in Prostate Cancer Patients Treated With Radiation Therapy

Abstract: Basic and clinical science studies as well as clinical guidelines relevant for LUTS secondary to RT suggest that the routine use of alpha1-adrenoreceptor antagonists should be considered in patients treated with RT, either prophylactically or at the earliest sign of LUTS.

Cited by 17 publications

References 56 publications

Prostatic fibrosis, lower urinary tract symptoms, and BPH

Prostatic fibrosis, lower urinary tract symptoms, and BPH

Degarelix versus Goserelin (+ Antiandrogen Flare Protection) in the Relief of Lower Urinary Tract Symptoms Secondary to Prostate Cancer: Results from a Phase IIIb Study (NCT00831233)

Effect of pretreatment prostate volume on urinary quality of life following intensity-modulated radiation therapy for localized prostate cancer

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