Loading ...

TOPLINE:

Among patients with metastatic or very high-risk nonmetastatic prostate cancer, lower prostate-specific antigen (PSA) levels during hormone-based therapy — particularly ≤ 0.2 ng/mL — were strongly associated with improved long-term overall survival, according to a post hoc analysis of the STAMPEDE platform trial. However, the findings suggest PSA response alone may not fully capture prognosis. Disease burden continued to influence outcomes even among patients with very low PSA levels. For instance, 96-month overall survival ranged from 64.1% in low-volume metastatic disease to 44.6% in high-volume disease among patients achieving PSA ≤ 0.2 ng/mL at 24 weeks.

METHODOLOGY:

• Several analyses have demonstrated that PSA concentrations during treatment are associated with long-term outcomes, but the prognostic value of PSA in patients with very high-risk nonmetastatic disease receiving hormone therapy is less clear.
• Researchers conducted a post hoc analysis of 7129 patients with metastatic or very high-risk nonmetastatic prostate adenocarcinoma enrolled in the STAMPEDE platform trial across 126 hospitals and oncology centers in the UK and Switzerland between 2005 and 2016.
• Patients received standard of care with androgen deprivation therapy (ADT) alone or with docetaxel, or experimental approaches including ADT plus docetaxel with or without zoledronic acid, abiraterone acetate with or without enzalutamide, or prostate radiotherapy in selected metastatic disease cohorts.
• Overall, 62% of patients had metastatic disease and 38% had very high risk nonmetastatic disease.
• Landmark analyses evaluated PSA concentrations in four categories (≤ 0.2 ng/mL, > 0.2-1.0 ng/mL, > 1.0-3.0 ng/mL, and > 3.0 ng/mL) at 6, 12, and 24 weeks after treatment initiation and assessed associations with overall survival at 96 months according to metastatic volume and nodal status. Median follow-up was 9.6 years.

TAKEAWAY:

• Patients who achieved PSA ≤ 0.2 ng/mL at 6 or 12 weeks had similar 96-month overall survival rates to those achieving this threshold at 24 weeks in both metastatic disease (47.9% at 6 weeks, 50.2% at 12 weeks, 50.3% at 24 weeks) and nonmetastatic disease (77.3%, 75.7%, 78.0%, respectively).
• In metastatic disease, progressively higher PSA levels at 24 weeks were associated with progressively higher risk for prostate cancer-specific death (adjusted hazard ratio [aHR], 1.70 for PSA > 0.2-1.0 ng/mL; aHR, 2.72 for PSA > 1.0-3.0 ng/mL; and aHR, 4.72 for PSA > 3.0 ng/mL).
• Disease burden remained prognostically important even among patients with similarly low PSA levels. Patients with low-volume metastatic disease were more likely to achieve PSA ≤ 0.2 ng/mL at 24 weeks than those with high-volume disease (39.9% vs 22.6%).
• Patients allocated to abiraterone with or without enzalutamide generally had the most favorable long-term survival outcomes. Among patients receiving abiraterone who achieved PSA ≤ 0.2 ng/mL at 24 weeks, 96-month overall survival was nearly 83% in those with nonmetastatic node-negative disease compared with 79.4% in those with node-positive disease. In metastatic disease, 96-month overall survival was 64.1% in those with low-volume metastatic disease compared with 44.6% in those with high-volume disease.

IN PRACTICE:

“Metastatic volume or nodal status influence survival rates associated with on-treatment serum PSA categories, including for undetectable PSA,” the authors concluded. “PSA at 24 weeks showed strongest associations with overall survival, although a PSA concentration of 0.2 ng/mL or less at any timepoint predicted favourable outcome.” Overall, these findings could help refine prognosis and “warrant evaluation for treatment selection in clinical trials,” the researchers added. 

SOURCE:

The study, led by Mahaz Kayani, MBBS, and Gerhardt Attard, PhD, both from UCL Cancer Institute, University College London, London, England, was published online in The Lancet Oncology. 

LIMITATIONS:

The study recruited patients before widespread adoption of next-generation imaging modalities such as PET and MRI, with metastatic status determined using conventional imaging alone, which may have resulted in some patients classified as nonmetastatic actually having metastases detectable. The analysis was limited to patients who survived long enough to provide PSA measurements at specified timepoints, potentially underrepresenting individuals with particularly aggressive prostate cancer biology who progressed rapidly or died before PSA assessment. The lower limit of PSA recorded was 0.2 ng/mL, reflecting the sensitivity of clinical assays used during the accrual period, whereas recent studies suggest ultra-low PSA concentrations below 0.01 ng/mL might also have prognostic utility. Treatment options for castration-resistant prostate cancer expanded during the trial period, potentially influencing overall survival outcomes and possibly underestimating current survival rates.

DISCLOSURES:

The STAMPEDE protocol received funding from Cancer Research UK’s Clinical Research Committee, with educational grants provided by Novartis, Sanofi-Aventis, Pfizer, Janssen Pharma, Astellas, and Clovis Oncology. Sanofi-Aventis, Janssen, and Novartis supplied drugs at no cost for the trials. The Clinical Trials Unit at University College London receives core funding from the UK Medical Research Council. These analyses received support from Prostate Cancer UK and the John Black Charitable Foundation. Kayani disclosed receiving support for the manuscript from Cancer Research UK and research funding to the institution for the STAMPEDE trial from Janssen, Astellas, Novartis, Sanofi, and Clovis. Attard disclosed grants from Janssen, Astellas Pharma, Novartis, and Agilent; personal fees from multiple pharmaceutical companies; and patents for blood-based methylation markers. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.