Evidence map›Paper›PMID 33755225›Full record

ArticleThe Prostate2021

Targeting backdoor androgen synthesis through AKR1C3 inhibition: A presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer.

Laura S Graham, Lawrence D True, Roman Gulati, George R Schade, Jonathan Wright, Petros Grivas, Todd Yezefski, Katie Nega, Katerina Alexander, Wen-Min Hou and 11 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Prostate, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 4 institutions in 1 country.

Laura S GrahamDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.ORCID 0000-0003-4371-572X
Lawrence D TrueDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Roman GulatiClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
George R SchadeDepartment of Urology, University of Washington, Seattle, Washington, USA.
Jonathan WrightDepartment of Urology, University of Washington, Seattle, Washington, USA.
Petros GrivasDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Todd YezefskiDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Katie NegaDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Katerina AlexanderClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Wen-Min HouClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Evan Y YuDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Bruce MontgomeryDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Elahe A MostaghelDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Alvin A MatsumotoGeriatric Research Education and Clinical Care, VA Puget Sound Health Care System, Seattle, Washington, USA.
Brett MarckGeriatric Research Education and Clinical Care, VA Puget Sound Health Care System, Seattle, Washington, USA.
Nima SharifiGenitourinary Malignancies Research Center, Cleveland Clinic, Cleveland, Ohio, USA.
William J EllisDepartment of Urology, University of Washington, Seattle, Washington, USA.
Nicholas P RederDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Daniel W LinDepartment of Urology, University of Washington, Seattle, Washington, USA.
Peter S NelsonDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Michael T SchweizerDivision of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA.
University of Washington · USFred Hutch Cancer Center · USVA Puget Sound Health Care System · USCleveland Clinic · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0M
TRAINING IN CANCER BIOLOGY &TRANSPLANTATIONT32CA009515 · NCI · UNIVERSITY OF WASHINGTON · PI NANCY ELLEN DAVIDSON, Effie W Petersdorf · 1985 to 2026
$16.2M
Statistical modeling to support population and translational cancer researchR50CA221836 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Roman Gulati · 2017 to 2026
$2.0M
NCI NIH HHS P01 CA163227NCI NIH HHS P30 CA015704NCI NIH HHS P50 CA097186NCI NIH HHS R50 CA221836NCI NIH HHS T32 CA009515
6 · The paper itself

Abstract

backgroundLocalized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP).

methodsThis was an open label, single-site, Phase II neoadjuvant trial in men with high to very-high-risk PC, as defined by NCCN criteria. Patients received 12 weeks of apalutamide (Apa), abiraterone acetate plus prednisone (AAP), degarelix, and Indo followed by RP. Primary objective was to determine the pathologic complete response (pCR) rate. Secondary objectives included minimal residual disease (MRD) rate, defined as residual cancer burden (RCB) ≤ 0.25cm

resultsTwenty patients were evaluable for the primary endpoint. Baseline median prostate-specific antigen (PSA) was 10.1 ng/ml, 4 (20%) patients had Gleason grade group (GG) 4 disease and 16 had GG 5 disease. At RP, 1 (5%) patient had pCR and 6 (30%) had MRD. Therapy was well tolerated. Over a median follow-up of 23.8 months, 1 of 7 (14%) men with pathologic response and 6 of 13 (46%) men without pathologic response had a PSA relapse. There was no association between prostate hormone levels or HSD3B1 genotype with pathologic response.

conclusionsIn men with high-risk PC, pCR rates remained low even with combinatorial AR-directed therapy, although rates of MRD were higher. Ongoing follow-up is needed to validate clinical outcomes of men who achieve MRD.

Indexed as

Neoadjuvant TherapyProstatectomyAbiraterone AcetateAgedAldo-Keto Reductase Family 1 Member C3Androgen AntagonistsAntineoplastic Agents, HormonalHumansMaleMiddle AgedProstatic NeoplasmsThiohydantoinsTreatment OutcomeAbiraterone AcetateAldo-Keto Reductase Family 1 Member C3Androgen AntagonistsAntineoplastic Agents, HormonalapalutamideThiohydantoinsabiraterone acetateandrogen deprivation therapyapalutamideindomethacinprostatectomy

Identifiers

PMID33755225
PMCPMC8044035
OpenAlexW3137537012

What OpenQuestion holds

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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.