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Record W4413817119 · doi:10.3389/fonc.2025.1638405

Comparing the safety and efficacy of systemic therapies for high-risk biochemically recurrent hormone-sensitive prostate cancer: a network meta-analysis

2025· review· en· W4413817119 on OpenAlexaff
Armen Aprikian, Andrew Chilelli, Thomas W. McLean, Anchen F. Nasr, Arijit Ganguli, A. Serikoff, Franco Guzman, Ifigeneia Barouma, Maria Zacharioudaki, Stephen J. Freedland

Bibliographic record

VenueFrontiers in Oncology · 2025
Typereview
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsMcGill University
FundersAstellas Foundation for Research on Metabolic DisordersAstellas PharmaPfizer
KeywordsProstate cancerMedicineMeta-analysisOncologyCancerInternal medicineProstateHormone therapyHormoneBioinformaticsBiologyBreast cancer

Abstract

fetched live from OpenAlex

Introduction: Enzalutamide is the only androgen receptor pathway inhibitor approved by the United States Food and Drug Administration and the European Medicines Agency to treat high-risk biochemically recurrent non-metastatic hormone-sensitive prostate cancer. The objective of this network meta-analysis was to provide indirect evidence of the efficacy of enzalutamide relative to other therapies for biochemical recurrence after definitive therapy. Materials and Methods: We conducted a systematic literature review to identify trials that assessed the efficacy and safety of current and emerging interventions. Outcomes of interest were metastasis-free survival, overall survival, time to prostate-specific antigen progression, time to castration resistance, proportion of patients with prostate-specific antigen <0.2 ng/ml at 36 (± 4) weeks of treatment, and grade ≥3 treatment-related adverse events. Fixed- and random-effects models were run under the Bayesian framework. Results: Enzalutamide with androgen-deprivation therapy (i.e., combination therapy) demonstrated superiority over most comparators for overall survival (except androgen-deprivation therapy + docetaxel, which was similar), and over all comparators for metastasis-free survival, time to prostate-specific antigen progression, and time to castration resistance. Enzalutamide combination therapy demonstrated superiority over enzalutamide monotherapy for all efficacy outcomes, and similar performance for safety. Enzalutamide monotherapy demonstrated superiority over androgen-deprivation therapy alone and androgen-deprivation therapy + docetaxel for metastasis-free survival and time to prostate-specific antigen progression. Treatment-related adverse events were least common for androgen-deprivation therapy alone. Discussion: This network meta-analysis provides evidence that enzalutamide combination therapy provides considerable oncological benefit in high-risk biochemically recurrent non-metastatic hormone-sensitive prostate cancer, albeit with a higher risk of treatment-related adverse events.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.022
metaresearch head score (Gemma)0.037
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.022
Threshold uncertainty score0.114

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0220.037
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0120.049
Bibliometrics0.0040.004
Science and technology studies0.0000.001
Scholarly communication0.0030.001
Open science0.0020.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0040.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.070
GPT teacher head0.389
Teacher spread0.319 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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