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Updated: Aug 26, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A systematic review and meta-analysis on non-metastatic castration resistant prostate cancer: The radiation
Gianluca Ingrosso1, Marta Bottero2, Carlotta Becherini3
1Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia, Italy.
Abstract:
Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic option is androgen deprivation: despite initial response rates, a progression to a state of castration resistance is observed in most of the patients. In the present article, we conducted a systematic review and meta-analysis of all clinical trials assessing treatment for nmCRPC with next-generation androgen receptor inhibitors. We performed a review and meta-analysis of phase III randomized controlled trials comparing new agents (apalutamide, enzalutamide, darolutamide) with placebo as control arm, in the setting of nmCRPC. Patients treated with next-generation ARIs had a 26% reduction in the risk of death compared with placebo; compared with other ARIs, darolutamide had the lowest rate of grade 3 and 4 AEs and the lowest therapy discontinuation rate due to any grade AEs. This meta-analysis shows that treatment with new ARIs is safe and significantly reduces the risk of death and of metastasis onset in nmCRPC patients. Under way studies on new biomarkers such as genomic classifiers will probably allow the stratification in more specific subsets of disease. New imaging modalities such as PSMA-PET have shown greater sensibility and specificity than conventional imaging in metastases detection. All patients were randomized in a 2:1 fashion, with a total of 2,694 who underwent next-generation ARIs (806 apalutamide, 955 darolutamide, 933 enzalutamide) and 1,423 in the placebo arm.
Insights
Next-generation androgen receptor inhibitors significantly reduce the risk of death and metastasis in non-metastatic castration-resistant prostate cancer (nmCRPC). Darolutamide showed favorable safety and tolerability profiles compared to other agents.
Area of Science:
- Oncology
- Pharmacology
Background:
- Prostate cancer is a leading cause of cancer mortality in men.
- Castration resistance develops in most patients after radical treatment failure.
- Androgen deprivation therapy is a primary option, but resistance is common.
Approach:
- Systematic review and meta-analysis of Phase III randomized controlled trials.
- Assessed next-generation androgen receptor inhibitors (ARIs) including apalutamide, enzalutamide, and darolutamide versus placebo in nmCRPC.
- Included 2,694 patients on next-generation ARIs and 1,423 on placebo.
Key Points:
- Next-generation ARIs reduced the risk of death by 26% compared to placebo.
- Darolutamide demonstrated the lowest rates of severe adverse events (grade 3-4) and treatment discontinuation.
- Treatment with new ARIs is safe and effective for nmCRPC patients.
Conclusions:
- Next-generation ARIs significantly reduce mortality and metastasis risk in nmCRPC.
- Darolutamide offers a favorable safety and tolerability profile.
- Future research focusing on biomarkers and advanced imaging will enhance treatment stratification and detection.
