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Background <p>Novel hormonal therapies (NHTs) have substantially improved outcomes in prostate cancer across multiple disease states. However, their hepatic safety remains clinically relevant because treatment is often prolonged and may be combined with androgen-deprivation therapy, corticosteroids, or chemotherapy. We performed a systematic review and meta-analysis to quantify the risk of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations associated with NHT-based therapy.</p> Methods <p>This study was conducted in accordance with PRISMA guidelines. Randomized controlled trials comparing NHT-containing regimens with control regimens in patients with prostate cancer were eligible if they reported extractable ALT and/or AST adverse-event data. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for four prespecified outcomes: all-grade ALT elevation, grade ≥ 3 ALT elevation, all-grade AST elevation, and grade ≥ 3 AST elevation.</p> Results <p>Ten randomized studies reported in 11 publications were included, involving 10,173 participants treated with abiraterone, enzalutamide, darolutamide, or abiraterone plus enzalutamide combination regimens. Compared with controls, NHT-based therapy significantly increased the risk of all-grade ALT elevation (RR 1.49, 95% CI 1.12–2.00; I<sup>2</sup> = 82.8%), grade ≥ 3 ALT elevation (RR 5.91, 95% CI 2.86–12.20; I<sup>2</sup> = 67.5%), all-grade AST elevation (RR 1.58, 95% CI 1.02–2.45; I<sup>2</sup> = 84.5%), and grade ≥ 3 AST elevation (RR 3.32, 95% CI 2.13–5.18; I<sup>2</sup> = 0%). Subgroup analyses suggested that the hepatic safety signal was more evident for abiraterone-containing and abiraterone plus enzalutamide combination regimens, whereas estimates for enzalutamide and darolutamide varied across outcomes and should be interpreted cautiously because of the limited number of available comparisons.</p> Conclusions <p>NHT-based therapy for prostate cancer was associated with an increased risk of hepatic enzyme abnormalities, particularly severe ALT elevation. The hepatic safety signal appeared more evident for abiraterone-containing and combination regimens, whereas drug-specific estimates for enzalutamide and darolutamide remained limited. Because this analysis focused on laboratory-defined ALT and AST elevations, careful liver function monitoring remains warranted during NHT-based therapy, especially in patients receiving abiraterone-containing or prolonged combination regimens.</p>

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Exploring the relationship between potential hepatotoxicity and novel hormonal therapies in prostate cancer: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Liang Ma,
  • Liwei Fan,
  • Xiaoli Luo,
  • Zhuangcheng Huang,
  • Jiacheng Dai,
  • Yuejun Wu,
  • Wenhua Zhang

摘要

Background

Novel hormonal therapies (NHTs) have substantially improved outcomes in prostate cancer across multiple disease states. However, their hepatic safety remains clinically relevant because treatment is often prolonged and may be combined with androgen-deprivation therapy, corticosteroids, or chemotherapy. We performed a systematic review and meta-analysis to quantify the risk of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations associated with NHT-based therapy.

Methods

This study was conducted in accordance with PRISMA guidelines. Randomized controlled trials comparing NHT-containing regimens with control regimens in patients with prostate cancer were eligible if they reported extractable ALT and/or AST adverse-event data. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for four prespecified outcomes: all-grade ALT elevation, grade ≥ 3 ALT elevation, all-grade AST elevation, and grade ≥ 3 AST elevation.

Results

Ten randomized studies reported in 11 publications were included, involving 10,173 participants treated with abiraterone, enzalutamide, darolutamide, or abiraterone plus enzalutamide combination regimens. Compared with controls, NHT-based therapy significantly increased the risk of all-grade ALT elevation (RR 1.49, 95% CI 1.12–2.00; I2 = 82.8%), grade ≥ 3 ALT elevation (RR 5.91, 95% CI 2.86–12.20; I2 = 67.5%), all-grade AST elevation (RR 1.58, 95% CI 1.02–2.45; I2 = 84.5%), and grade ≥ 3 AST elevation (RR 3.32, 95% CI 2.13–5.18; I2 = 0%). Subgroup analyses suggested that the hepatic safety signal was more evident for abiraterone-containing and abiraterone plus enzalutamide combination regimens, whereas estimates for enzalutamide and darolutamide varied across outcomes and should be interpreted cautiously because of the limited number of available comparisons.

Conclusions

NHT-based therapy for prostate cancer was associated with an increased risk of hepatic enzyme abnormalities, particularly severe ALT elevation. The hepatic safety signal appeared more evident for abiraterone-containing and combination regimens, whereas drug-specific estimates for enzalutamide and darolutamide remained limited. Because this analysis focused on laboratory-defined ALT and AST elevations, careful liver function monitoring remains warranted during NHT-based therapy, especially in patients receiving abiraterone-containing or prolonged combination regimens.