Androgen Receptor Targeted Agents for Castration Resistant Prostate Cancer: A Review of Clinical Effectiveness and Cost-Effectiveness
Bibliographic record
Abstract
Prostate cancer is the most common cancer in men and is the fourth most common cancer in Canada. Approximately 1 in 7 men will be diagnosed with prostate cancer in their lifetime, and 1 in 27 will die from the disease., However, the age-standardized mortality rate for all stages of prostate cancer have decreased by an average of 2.9% per year, or 41.0% from 1995 to 2012., The majority (75%) of diagnosed prostate cancer are stage I or stage II (localized), and the age-standardized incidence rate of these cancer stages have decreased by 3.2% per year from 2005 to 2015. The age-standardized incidence rate of stage III and IV cancers have remained relatively unchanged.Androgen deprivation therapy (ADT) has been the mainstay treatment for metastatic prostate cancer. Current ADT approaches include surgical castration or medical castration using a gonadotropin releasing hormone agonist with or without an anti-androgen drug. Although over 80% of patients respond to ADT initially, nearly all eventually develop progressive disease following castration, a lethal stage known as metastatic castration-resistant prostate cancer (mCRPC). In 2004, docetaxel (DTX) was the first chemotherapy approved by the US Food and Drug Administration for treatment of mCRPC., Since then, five newly developed agents were approved including a second generation taxane cabazitaxel (CTX), cellular immunotherapy sipuleucel-T, radiopharmaceutical radium-223, and two androgen receptor-targeted agents (ARTA) abiraterone acetate (AA)– and enzalutamide (ENZ).,Since ARTA have been demonstrated by recent studies in improving overall survival (OS) in both chemotherapy-pretreated and chemotherapy-naive patients with mCRPC, both AA and ENZ have been approved as first-line treatment, instead of DTX.– However, some patients have rapidly progressed on ARTA treatments despite the initial clinical effectiveness. After progression on first-line ARTA, it was unclear which subsequent therapy, such as second-line chemotherapy, an alternative ARTA, or an alternative ARTA with chemotherapy in between, would improve clinical outcomes.The aim of this report is to review the comparative clinical effectiveness and cost-effectiveness of varying treatment sequences of ARTA in patients with CRPC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".