Finasteride kan prostaatkanker voorkomen (met 24 procent blijkt uit nieuwe studie onder ruim 18.000 mannen). Maar finasteride en dutasteride, zogeheten 5A-reductaseremmers, zorgen er ook voor dat als er wel prostaatkanker ontstaat deze ernstiger van aard is dan zonder gebruik van deze middelen.
De belangrijkste reden die dr. Walsh geeft is deze:
Er is geen 5α-reductase-eiwit aanwezig in normale of kwaadaardige prostaatepitheelcellen; het 5α-reductase-eiwit bevindt zich in het stroma. Omdat hooggradige prostaatkanker (Gleason> 6) weinig stroma hebben, hebben 5-ARI's geen effect op het verminderen van de ziekte van Gleason 7-10. (ref 2)
Behandeling met een 5-ARI vermindert de productie van PSA door stromacellen in BPH. Om dit effect te corrigeren, moeten mannen die met een 5-ARI worden behandeld hun niveau gedurende de eerste 2 jaar met 2,0 vermenigvuldigen, met 2,3 voor de jaren 2 tot 7 en na jaar 7 met 2,5. (ref 3)
Als patiënten dit niet weten, moeten ze zullen zich niet realiseren dat ze mogelijk eerder een biopsie nodig hebben en de kans missen om gediagnosticeerd te worden met een geneesbare ziekte. Dit verklaart de bevindingen in deze studie. (ref 1)
Hier de referenties behorende bij zijn commentaar.
is gratis in te zien.
TO THE EDITOR:
One man in nine will receive a diagnosis of prostate cancer during his lifetime. We previously reported the results of the Prostate Cancer Prevention Trial, in which 18,882 men were randomly assigned to receive finasteride or placebo for 7 years. The study’s primary end point — the prevalence of prostate cancer during the 7 years of the trial — was met: the relative risk of prostate cancer with finasteride was 24.8% lower than the risk with placebo.1 Paradoxically, the risk of high-grade cancer (Gleason score of 7 to 10) was higher with finasteride, a finding that led to recommendations against the use of finasteride for the prevention of prostate cancer. Subsequent trials showed that finasteride improved detection of prostate cancer and high-grade prostate cancer by improving the performance characteristics of the prostate-specific antigen (PSA) test, digital rectal examination, and the prostate biopsy. These biases could explain the paradox, but the questions of whether the greater number of high-grade prostate cancers could have led to diminished survival or to an increase in prostate cancer mortality persisted.2 In 2013, we addressed the first of these questions, finding similar survival rates in the two treatment groups of the Prostate Cancer Prevention Trial.3
To address the second question, participants with a potentially valid Social Security number, whether last known to be alive or previously deceased, were submitted to the National Death Index in December 2014. Deaths from prostate cancer were reviewed by an end-point review committee. The cumulative incidence of death from prostate cancer was calculated, including all participants who underwent randomization, with deaths due to a cause other than prostate cancer classified as a competing risk. (For details, see the Supplementary Appendix, available with the full text of this letter at NEJM.org.)
Figure 1 shows the results. With 296,842 person-years of follow-up and a median follow-up of 18.4 years, of 9423 men randomized to finasteride, there were 3048 deaths of which 42 were due to prostate cancer; of 9457 randomized to placebo, there were 2979 deaths, 56 due to prostate cancer. With the small number of deaths due to prostate cancer, the 25% lower risk of death from prostate cancer with finasteride was not statistically significant.
PSA-detected prostate cancer will likely increase with recommendations to offer screening to men 55 to 65 years of age.4 Screening may reduce the risk of death from prostate cancer but often leads to the detection of prostate cancer that will remain asymptomatic during a man’s life. If indolent cancers are treated with surgery or radiation, complications, including impotence and incontinence, are common. If managed with active surveillance, up to 45% of men will ultimately receive treatment; they will also face frequent examination, repeated invasive biopsies, and anxiety.5 Finasteride is a generic agent that is used to treat lower urinary tract symptoms, prevents complications from these symptoms, and prevents prostate cancer. The early concerns regarding an association between finasteride and an increased risk of high-grade prostate cancer have not been borne out.
Phyllis J. Goodman, M.S.
Catherine M. Tangen, Dr.P.H.
Fred Hutchinson Cancer Research Center, Seattle, WA
Amy K. Darke, M.S.
M. Scott Lucia, M.D.
Leslie G. Ford, M.D.
Lori M. Minasian, M.D.
Howard L. Parnes, M.D.
Michael L. LeBlanc, Ph.D.
Ian M. Thompson, Jr., M.D.
CHRISTUS Santa Rosa Hospital Medical Center, San Antonio, TX
thompsoni@uthscsa.edu
Supported by grants (UM1 CA182883 and U10 CA37429) from the National Cancer Institute.
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
Key Points
Question Does prediagnostic 5α-reductase inhibitor use, with associated prostate-specific antigen suppression, lead to delayed diagnosis and increased risk of death from prostate cancer in a prostate specific antigen–screened population?
Findings In this population-based cohort study of 80 875 men with prostate cancer, prediagnostic 5α-reductase inhibitor users had longer time from first elevated prostate-specific antigen test result to diagnosis, higher adjusted prostate-specific antigen at diagnosis, more advanced disease at diagnosis, and worse prostate cancer–specific and all-cause mortality compared with nonusers.
Meaning Prediagnostic use of 5α-reductase inhibitors is associated with delayed prostate cancer diagnosis and increased mortality in men who underwent prostate-specific antigen screening.
Importance 5α-Reductase inhibitors (5-ARIs), commonly used to treat benign prostatic hyperplasia, reduce serum prostate-specific antigen (PSA) concentrations by 50%. The association of 5-ARIs with detection of prostate cancer in a PSA-screened population remains unclear.
Objective To test the hypothesis that prediagnostic 5-ARI use is associated with a delayed diagnosis, more advanced disease at diagnosis, and higher risk of prostate cancer–specific mortality and all-cause mortality than use of other or no PSA-decreasing drugs.
Design, Setting, and Participants This population-based cohort study linked the Veterans Affairs Informatics and Computing Infrastructure with the National Death Index to obtain patient records for 80 875 men with American Joint Committee on Cancer stage I-IV prostate cancer diagnosed from January 1, 2001, to December 31, 2015. Patients were followed up until death or December 31, 2017. Data analysis was performed from March 2018 to May 2018.
Exposures Prediagnostic 5-ARI use.
Main Outcomes and Measures The primary outcome was prostate cancer–specific mortality (PCSM). Secondary outcomes included time from first elevated PSA (defined as PSA≥4 ng/mL) to diagnostic prostate biopsy, cancer grade and stage at time of diagnosis, and all-cause mortality (ACM). Prostate-specific antigen levels for 5-ARI users were adjusted by doubling the value, consistent with previous clinical trials.
Results Median (interquartile range ) age at diagnosis was 66 (61-72) years; median follow-up was 5.90 (3.50-8.80) years. Median time from first adjusted elevated PSA to diagnosis was significantly greater for 5-ARI users than 5-ARI nonusers (3.60 [95% CI, 1.79-6.09] years vs 1.40 [95% CI, 0.38-3.27] years; P < .001) among patients with known prostate biopsy date. Median adjusted PSA at time of biopsy was significantly higher for 5-ARI users than 5-ARI non-users (13.5 ng/mL vs 6.4 ng/mL; P < .001). Patients treated with 5-ARI were more likely to have Gleason grade 8 or higher (25.2% vs 17.0%; P < .001), clinical stage T3 or higher (4.7% vs 2.9%; P < .001), node-positive (3.0% vs 1.7%; P < .001), and metastatic (6.7% vs 2.9%; P < .001) disease than 5-ARI nonusers. In a multivariable regression, patients who took 5-ARI had higher prostate cancer–specific (subdistribution hazard ratio , 1.39; 95% CI, 1.27-1.52; P < .001) and all-cause (HR, 1.10; 95% CI, 1.05-1.15; P < .001) mortality.
Conclusions and Relevance Results of this study demonstrate that prediagnostic use of 5-ARIs was associated with delayed diagnosis and worse cancer-specific outcomes in men with prostate cancer. These data highlight a continued need to raise awareness of 5-ARI-induced PSA suppression, establish clear guidelines for early prostate cancer detection, and motivate systems-based practices to facilitate optimal care for men who use 5-ARIs.
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1 Reactie op "finasteride kan prostaatkanker voorkomen (min 24 procent). Maar finasteride en dutasteride gebruik veroorzaakt wel bij eerste diagnose hogere Gleasonscores, vaker uitgezaaide ziekte en hogere specifieke sterfte aan prostaatkanker en alle oorzaken"