Outcomes of Prostate Cancer Screening by 5α-Reductase Inhibitor Use (original) (raw)
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BMJ (Clinical research ed.), 2013
To assess the association between 5α-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk. Nationwide, population based case-control study for men diagnosed with prostate cancer in 2007-09 within the Prostate Cancer data Base Sweden 2.0. The National Prostate Cancer Register, National Patient Register, census, and Prescribed Drug Register in Sweden, from which we obtained data on 5-ARI use before date of prostate cancer diagnosis. 26,735 cases and 133,671 matched controls; five controls per case were randomly selected from matched men in the background population. 7815 men (1499 cases and 6316 controls) had been exposed to 5-ARI. 412 men had been exposed to 5-ARI before the diagnosis of a cancer with Gleason score 8-10. Risk of prostate cancer calculated as odds ratios and 95% confidence intervals by conditional logistic regression analyses. Risk of prostate cancer overall decreased with an increasing duration of exposure; men on 5-ARI tr...
Impact of 5α-Reductase Inhibitors on Men Followed by Active Surveillance for Prostate Cancer
European Urology, 2011
Background: In two large randomized controlled trials, 5a-reductase inhibitors (5-ARIs) were shown to prevent prostate cancer. No prior work had shown the effect of 5-ARIs on those already diagnosed with low-risk prostate cancer. Objective: Our aim was to determine the effect of 5-ARIs on pathologic progression in men on active surveillance. Design, setting, and participants: We conducted a single-institution retrospective cohort study comparing men taking a 5-ARI versus no 5-ARI while on active surveillance for prostate cancer. Measurements: Pathologic progression was evaluated and defined as Gleason score >6, maximum core involvement >50%, or more than three cores positive on a follow-up prostate biopsy. Kaplan-Meier analyses were conducted along with multivariable Cox proportional hazard regression modeling for predictors of pathologic progression. Results and limitations: A total of 288 men on active surveillance met the inclusion criteria. The median follow-up was 38.5 mo (interquartile range: 23.6-59.4) with 93 men (32%) experiencing pathologic progression and 96 men (33%) abandoning active surveillance. Men taking a 5-ARI experienced a lower rate of pathologic progression (18.6% vs 36.7%; p = 0.004) and were less likely to abandon active surveillance (20% vs 37.6%; p = 0.006). On multivariable Cox proportional hazards analysis, lack of 5-ARI use was most strongly associated with pathologic progression (hazard ratio: 2.91; 95% confidence interval, 1.5-5.6). The main study limitation was the retrospective design and variable duration of 5-ARI therapy. Conclusions: The 5-ARIs were associated with a significantly lower rate of pathologic progression and abandonment of active surveillance.
Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer
Canadian Urological Association Journal, 2013
Introduction: This retrospective review compares prostate-specific antigen (PSA) doubling time (DT) prior to the initiation of a 5-alpha reductase inhibitor (pre-5-ARI) to after the PSA nadir (post-nadir) has been reached for patients on active surveillance for favourable risk prostate cancer.Methods: Between 1996 and 2010, a total of 100 men with a history of 5-ARI use were captured from our active surveillancedatabase. Twenty-nine patients had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir DTs. PSADT was calculated using the general linear mixed-model method.Results: The median follow-up was 69.5 months. The median pre-5-ARI PSADT was 55.8 (range: 6-556.8) months, while the post-nadir value was 25.2 (range: 6-231) months (p = 0.0081). Six patients were reclassified after an average of 67.7 (range: 59-95) months, due to progression in PSADT (n = 2) or Gleason score (n = 4). The median pre-5-ARI and post-nadir DTs for this group were 42.3 (range: 32.4-9...
5α-Reductase inhibitors and risk of high-grade or lethal prostate cancer
JAMA internal medicine, 2014
5α-Reductase inhibitors (5ARIs) are widely used for benign prostatic hyperplasia despite controversy regarding potential risk of high-grade prostate cancer with use. Furthermore, the effect of 5ARIs on progression and prostate cancer death remains unclear. To determine the association between 5ARI use and development of high-grade or lethal prostate cancer. Prospective observational study of 38,058 men followed up for prostate cancer diagnosis and outcomes between 1996 and 2010 in the Health Professionals Follow-up Study. Use of 5ARIs between 1996 and 2010. Cox proportional hazards models were used to estimate risk of prostate cancer diagnosis or development of lethal disease with 5ARI use, adjusting for possible confounders including prostate specific antigen testing. During 448,803 person-years of follow-up, we ascertained 3681 incident prostate cancer cases. Of these, 289 were lethal (metastatic or fatal), 456 were high grade (Gleason sum [GS] 8-10), 1238 were GS 7, and 1600 were...
PharmacoEconomics, 2010
Background: Although 5-alpha reductase inhibitors (5ARIs) have demonstrated that they reduce the risk of prostate cancer (PCa), they have not demonstrated cost effectiveness in the patient populations in which they have been examined. Objective: A decision-analytic model was created to explore economic benefits from a third-party payer perspective of the use of 5ARIs in preventing PCa in men with different risk factors for developing the disease. Methods: A Markov model was developed to simulate a cohort of men annually through health states (e.g. healthy male, benign prostatic hyperplasia [BPH], PCa, PCa recurrence) over a man's lifetime. Men with risk factors were treated with a 5ARI and compared with patients given no chemoprevention. Men from the general population were examined along with higher-risk men who had been referred to a PCa centre. Baseline risk was estimated via published risk data, risk factor analyses and risk equations. Clinical efficacy, morality, costs and utilities were obtained from published literature. Outcomes of the model included number of prostate cancers, incremental costs, incremental QALYs, incremental cost per QALY and number needed to treat. Along with sensitivity and scenario analyses, a validation of outcomes was performed. All costs were valued in US,year2009values.Costswerediscountedat3US, year 2009 values. Costs were discounted at 3% per annum. Results: Men receiving 5ARIs benefited through a reduction in the number of PCas. Assuming a cost-effectiveness threshold of US,year2009values.Costswerediscountedat3US50 000 per QALY, chemoprevention with 5ARIs was cost effective ($US37 900 per QALY) in men from the general population who were aged 50 years with elevated prostate-specific antigen (PSA), and who were aged 50 years with PCa family history and elevated PSA ($US31 065 per QALY). Chemoprevention with 5ARIs was not cost effective in men aged 50 years with no additional risk factors, men aged 50 years with abnormal digital rectal examinations (DREs), and men aged 50 years with a family history ($US86 511, $US85 577 ORIGINAL RESEARCH ARTICLE
BJU international, 2017
To determine the clinical performance of the urinary prostate cancer antigen 3 (PCA3) test to predict the risk of Gleason grade re-classification amongst men receiving a 5α-reductase inhibitor (5ARI) during active surveillance (AS) for prostate cancer. Patients with low-risk prostate cancer were enrolled in a prospective Phase II study of AS complemented with prescription of a 5ARI. A repeat biopsy was taken within the first year and annually according to physician and patient preference. In all, 90 patients had urine collected after digital rectal examination of the prostate before the first repeat biopsy. The PCA3 test was performed in a blinded manner at a central laboratory. Using a PCA3-test score threshold of 35, there was a significant difference (P < 0.001) in the risk of being diagnosed with Gleason ≥7 cancer during a median of 7 years of follow-up. Adjusted Cox regression and Kaplan-Meier analyses also showed a significantly higher risk of upgrading to Gleason ≥7 during...
Do 5α-Reductase Inhibitors Alter Prostate Cancer Detection and What Are the Implications?
European Urology Supplements, 2006
The 5a-reductase inhibitors (5-ARIs) have a number of effects on benign, hyperplastic, and malignant prostate epithelium. The extent of these effects appears to differ significantly among patients, and on average, appears less than that observed with luteinising hormone-releasing hormone (LHRH) agonist therapy. Indeed, the ''characteristic changes'' observed for hormonal therapy may not be so specific after all, if such changes can also be observed in men not receiving 5-ARIs or hormonal therapy. Although prostate specimens derived from men receiving a 5-ARI need to be interpreted with care, currently little evidence supports the original contention that use of a 5-ARI can result in significant misinterpretation of Gleason grade in those with prostate cancer. Data from the Prostate Cancer Prevention Trial (PCPT) strongly suggest that the reduction in prostate volume combined with changes in the performance of prostate-specific antigen (PSA) observed with 5-ARI treatment results in an excess detection of tumours, especially high-grade lesions, compared with untreated men. The effects of 5-ARIs on PSA appear to improve the predictive value of PSA as a diagnostic test for prostate cancer, possibly by differential suppression of PSA derived from cancerous and noncancerous tissue. New analyses, under development, are seeking to examine how this increased detection affects the reduction in risk of prostate cancer observed with 5-ARI therapy during the 7 yr of the PCPT.
British Journal of Medical and Surgical Urology, 2012
There is still much debate regarding the long-term effect of 5␣reductase inhibitors (5-ARI) on the development of prostate cancer (PC). We tested the incidence of prostate cancer and the tumour Gleason grading in a non-screened population who were prescribed 5-ARIs for lower urinary tract symptoms (LUTS). Data from a prostatic biopsy database were analysed in a retrospective study, and included a period of 14 years (01/01/1997 to 01/01/2011). Those patients who were on 5-ARIs with either finasteride or dutasteride for less than 1 year were excluded. Patients who presented with LUTS and underwent diagnostic prostatic biopsies were included in this study. This patient cohort was further categorised according to their history of 5-ARIs medication. The incidence of PC in the 5-ARI treated group was 15.4% (n = 22/143), comparable to that of the untreated group (16.7%, n = 332/1990) (p = 0.7318). Mean Gleason sum score and respective grade was the same (7 = 3 + 4) (median sum score 7 (range 6-10)). Average age at the time of PC diagnosis was similar regardless of 5-ARIs treatment: 72 (range 50-84) and 73 (45-84) years for treated and untreated groups, respectively. In this retrospective study, patients treated with 5-ARIs for LUTS had similar risk in developing PC when compared to those who did not receive 5-ARIs. The Gleason sum scores for the cancers were similar in the two groups.
Role of 5 alpha-reductase inhibitors in the management of prostate cancer
Clinical Interventions in Aging, 2006
Prostate cancer is one of the most complex and enigmatic oncologic problems in medicine. It is highly prevalent, particularly in elderly males. Unfortunately, its generally protracted and variable clinical course and high association with treatment-related morbidity raise serious questions about the ideal treatment strategy for the individual patient. 5 alphareductase (5AR) inhibitors have a dramatic effect on benign prostatic disease with low toxicity. Thus, there is much interest in the potential role of 5AR inhibitors in the prevention and treatment of prostate cancer. Finasteride is the only agent that has been shown in a randomized clinical trial to decrease the risk of prostate cancer with a reduction of almost 25%. Additionally, a recent analysis of the Prostate Cancer Prevention Trial (PCPT) has found that fi nasteride improves the performance characteristics of prostate-specifi c antigen (PSA) blood test as a screening tool for prostate cancer, for both cancer detection as well as for detection of high risk disease. Finally, 5AR inhibitors have been studied as a component of multimodal therapy for all stages of prostate cancer, with the goal of improving oncologic outcomes while avoiding the toxicity of medical and surgical castration.