Jeffrey M. Spier, MD, on the evidence for reduced-dose enzalutamide

In this video, Jeffrey M. Spier, MD, discusses real-world evidence on reduced-dose enzalutamide (Xtandi) for advanced prostate cancer, including its potential to preserve clinical benefit while minimizing toxicity, and outlines monitoring strategies to assess treatment effectiveness and tolerability. Spier is a urologist at Rio Grande Urology in El Paso, Texas.

Spier notes that available retrospective studies suggest dose reduction may preserve prostate-specific antigen (PSA) responses and disease control without substantial differences in progression-free survival (PFS) or overall survival (OS).¹ However, he emphasizes that the evidence remains limited and that prospective studies are needed to better establish the effects of dose reduction on clinical outcomes. He also highlights the importance of distinguishing between starting treatment at a lower dose and reducing the dose after treatment initiation, noting that the reported benefits appear more closely associated with dose reduction to manage toxicity. Clinicians should also consider potential confounding factors, including the use of reduced doses in older or more frail patients.

Regarding treatment monitoring, Spier recommends structured follow-up to evaluate whether patients maintain disease control after an androgen receptor pathway inhibitor (ARPI) dose reduction. He describes assessing PSA levels approximately 1 month after the dose change, confirming castrate testosterone levels, and obtaining additional imaging when clinically indicated. A 3-month follow-up should include repeat PSA testing and other laboratory assessments, such as liver function tests. He also emphasizes the value of consistently evaluating patients' experiences and treatment tolerability using validated assessment tools to help guide subsequent treatment decisions.

Spier underscores that dose reduction should not necessarily be viewed as a permanent change in treatment intensity. Ongoing assessment can help clinicians determine whether patients continue to benefit from a reduced dose and whether further adjustments are warranted.

As he explains, “If they're able to tolerate the full dose, then I think the discussion of reescalation is important as well.” This approach highlights the importance of individualizing treatment based on tolerability while continuing to evaluate disease control and considering dose reescalation when appropriate.

REFERENCE

1. Oliva M, Boitano M, Carbone A, et al. Efficacy and toxicity of low-doses versus standard-dose enzalutamide in advanced prostate cancer: a real-world study with implications for cancer prevention/interception. BMC Cancer. 2025;26(1):115.doi: 10.1186/s12885-025-15396-y