Evidence map›Paper›PMID 27322462›Full record

Trial reportEBioMedicine2016

Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

Jeri Kim, John W Davis, Eric A Klein, Cristina Magi-Galluzzi, Yair Lotan, John F Ward, Louis L Pisters, Joseph W Basler, Curtis A Pettaway, Andrew Stephenson and 15 more

Open access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Histopathology of Prostate Cancer.Cold Spring Harbor perspectives in medicine · 2017
    Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 7 institutions in 1 country.

Jeri KimDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jekim@mdanderson.org.
John W DavisDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Eric A KleinGlickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Cristina Magi-GalluzziDepartment of Anatomic Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Yair LotanDepartment of Urology, The University of Texas Southwestern Medical School, Dallas, TX 75390, USA.
John F WardDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Louis L PistersDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Joseph W BaslerDepartment of Urology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Curtis A PettawayDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Andrew StephensonGlickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Elsa M Li Ning TapiaDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Eleni EfstathiouDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xuemei WangDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Kim-Anh DoDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Jack LeeDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ivan P GorlovDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lana A VornikGeisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.
Ashraful M HoqueDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ina N ProkhorovaDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Howard L ParnesDivision of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA.
Scott M LippmanMoores Cancer Center, University of California, San Diego, San Diego, CA 92093, USA.
Ian M ThompsonDepartment of Urology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Powel H BrownDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Christopher J LogothetisDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Patricia TroncosoDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
The University of Texas MD Anderson Cancer Center · USCleveland Clinic · USThe University of Texas Health Science Center at San Antonio · USDartmouth College · USNational Cancer Institute · USThe University of Texas Southwestern Medical Center · USUniversity of California San Diego · US

Funding

Targeting Tumor Microenvironment-Induced Therapy Resistance in Prostate Cancer Bone MetastasisP50CA140388 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI THOMPSON, TIMOTHY CHARLES · 2009 to 2022
$23.4M
PHASE I and II CLINICAL TRIALS OF CHEMOPREVENTIVE AGENTS-261035159-261035159N01CN035159 · CN · UNIVERSITY OF TEXAS M D ANDER · PI LIPPMAN, SCOTT M. · 2004 to 2006
–
NCI NIH HHS N01 CN035159NCI NIH HHS P50 CA140388
6 · The paper itself

Abstract

backgroundIn the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride.

methodsFrom 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5mg finasteride or placebo daily in a double-blind study during the 4-6weeks preceding prostatectomy. As the primary end point, the expression of a predefined molecular signature (ERβ, UBE2C, SRD5A2, and VEGF) differentiating high- and low-grade tumors in Gleason grade (GG) 3 areas of finasteride-exposed tumors from those in GG3 areas of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy, was compared. We also determined androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to evaluate the effects of finasteride on the expression of its downstream target, cell proliferation, and apoptosis, respectively. The expression of these markers was also compared across grades between and within treatment groups. Logistic regression was used to assess the expression of markers.

findingsWe found that the predetermined molecular signature did not distinguish GG3 from GG4 areas in the placebo group. However, AR expression was significantly lower in the GG4 areas of the finasteride group than in those of the placebo group. Within the finasteride group, AR expression was also lower in GG4 than in GG3 areas, but not significantly. Expression of cleaved caspase 3 was significantly increased in both GG3 and GG4 areas in the finasteride group compared to the placebo group, although it was lower in GG4 than in GG3 areas in both groups.

interpretationWe showed that finasteride's effect on apoptosis and AR expression is tumor grade dependent after short-term intervention. This may explain finasteride's selective suppression of low-grade tumors observed in the PCPT.

Indexed as

Administration, OralAgedApoptosisBiomarkers, TumorCell ProliferationDouble-Blind MethodFinasterideHumansLogistic ModelsMaleMiddle AgedNeoplasm GradingProstatic NeoplasmsReceptors, AndrogenTreatment OutcomeAR protein, humanBiomarkers, TumorFinasterideReceptors, Androgen5α-reductase inhibitorsBiomarkersCancer preventionFinasterideProstate cancer

Identifiers

PMID27322462
PMCPMC4909608
OpenAlexW2330716506

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.