Trial-reported arthralgia of androgen deprivation therapy plus androgen receptor signaling inhibitors in prostate cancer: evidence from phase III randomized trials
6 affiliations
- 1Department of Pharmacy, The First Hospital of Jiaxing, First Affiliated Hospital of Jiaxing University, Jiaxing, 314001 China
- 2Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008 China
- 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 China
- 4The First Affiliated Hospital of Shantou University Medical College, Medical College of Shantou University, Shantou, 515041 China
- 5Department of Laboratory, Shantou Central Hospital, Shantou, Guangdong 515031 China
- 6Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, 410219 China
Abstract
Androgen receptor signaling inhibitors (ARSIs) are widely used in prostate cancer. However, their association with arthralgia remains incompletely explored. This systematic review and meta-analysis evaluated the risk of all-grade and grade ≥ 3 arthralgia in patients with prostate cancer related to ARSIs. PubMed, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched to identify phase III randomized controlled trials comparing ARSI-based treatment with placebo or standard care without a second-generation ARSI. The primary outcomes were risk ratios (RRs) for all-grade and grade ≥ 3 arthralgia. Pooled estimates were calculated using a random-effects model with restricted maximum likelihood estimation and Hartung-Knapp adjustment. Subgroup analyses were performed according to individual ARSI agent and disease setting. A total of 13 phase III randomized controlled trials involving 11,751 patients were included. ARSI treatment was associated with a significantly increased risk of all-grade arthralgia compared with control treatment (RR 1.26, 95% CI 1.06–1.48), with moderate heterogeneity. In drug-specific subgroup analyses, increased all-grade arthralgia risk was observed with abiraterone (RR 1.21, 95% CI 1.12–1.31), enzalutamide (RR 1.31, 95% CI 1.00–1.72), and apalutamide (RR 2.42, 95% CI 1.70–3.45), whereas darolutamide was not associated with an increased risk (RR 1.00, 95% CI 0.81–1.22). For grade ≥ 3 arthralgia, ARSI treatment was not associated with a significant increase in risk (RR 1.13, 95% CI 0.68–1.90). In conclusion, ARSI therapy was associated with an increased risk of all-grade arthralgia but not grade ≥ 3 arthralgia. These findings may inform pre-treatment counseling and early monitoring of arthralgia during ARSI therapy, although the analysis of grade ≥ 3 arthralgia should be interpreted cautiously because severe events were rare.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16636-5.
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BibTeX
@article{han2026trialreported,
title = {{Trial-reported arthralgia of androgen deprivation therapy plus androgen receptor signaling inhibitors in prostate cancer: evidence from phase III randomized trials}},
author = {Zhenping Han and Jing Tian and Zhuangcheng Huang and Yuesu Cai and Meihua Bao and Jiayang He and Xuejing Si and Bin Shen and Yahua Wang},
journal = {BMC Cancer},
year = {2026},
month = jul,
doi = {10.1186/s12885-026-16636-5},
url = {https://doi.org/10.1186/s12885-026-16636-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Trial-reported arthralgia of androgen deprivation therapy plus androgen receptor signaling inhibitors in prostate cancer: evidence from phase III randomized trials
AU - Zhenping Han
AU - Jing Tian
AU - Zhuangcheng Huang
AU - Yuesu Cai
AU - Meihua Bao
AU - Jiayang He
AU - Xuejing Si
AU - Bin Shen
AU - Yahua Wang
PY - 2026
DA - 2026/07/30
JO - BMC Cancer
DO - 10.1186/s12885-026-16636-5
UR - https://doi.org/10.1186/s12885-026-16636-5
AB - Androgen receptor signaling inhibitors (ARSIs) are widely used in prostate cancer. However, their association with arthralgia remains incompletely explored. This systematic review and meta-analysis evaluated the risk of all-grade and grade ≥ 3 arthralgia in patients with prostate cancer related to ARSIs. PubMed, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched to identify phase III randomized controlled trials comparing ARSI-based treatment with placebo or standard care without a second-generation ARSI. The primary outcomes were risk ratios (RRs) for all-grade and grade ≥ 3 arthralgia. Pooled estimates were calculated using a random-effects model with restricted maximum likelihood estimation and Hartung-Knapp adjustment. Subgroup analyses were performed according to individual ARSI agent and disease setting. A total of 13 phase III randomized controlled trials involving 11,751 patients were included. ARSI treatment was associated with a significantly increased risk of all-grade arthralgia compared with control treatment (RR 1.26, 95% CI 1.06–1.48), with moderate heterogeneity. In drug-specific subgroup analyses, increased all-grade arthralgia risk was observed with abiraterone (RR 1.21, 95% CI 1.12–1.31), enzalutamide (RR 1.31, 95% CI 1.00–1.72), and apalutamide (RR 2.42, 95% CI 1.70–3.45), whereas darolutamide was not associated with an increased risk (RR 1.00, 95% CI 0.81–1.22). For grade ≥ 3 arthralgia, ARSI treatment was not associated with a significant increase in risk (RR 1.13, 95% CI 0.68–1.90). In conclusion, ARSI therapy was associated with an increased risk of all-grade arthralgia but not grade ≥ 3 arthralgia. These findings may inform pre-treatment counseling and early monitoring of arthralgia during ARSI therapy, although the analysis of grade ≥ 3 arthralgia should be interpreted cautiously because severe events were rare. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16636-5.
SN - 1471-2407
ER -