STAMPEDE Analysis Links Low On-Treatment PSA to Better Survival in Advanced Prostate Cancer

Lower prostate-specific antigen (PSA) levels during hormone-based therapy were strongly associated with improved long-term overall survival among patients with metastatic or very high-risk nonmetastatic prostate cancer in a post hoc analysis of the STAMPEDE platform trial. However, the findings suggest PSA response alone may not fully capture prognosis, because disease burden continued to influence outcomes even among patients with very low PSA levels.

Researchers conducted a post hoc analysis of 7129 patients with metastatic or very high-risk nonmetastatic prostate adenocarcinoma enrolled in STAMPEDE 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. Median follow-up was 9.6 years.

Landmark analyses evaluated PSA concentrations in four categories 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. 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, with adjusted hazard ratios of 1.70 for PSA > 0.2-1.0 ng/mL, 2.72 for PSA > 1.0-3.0 ng/mL, and 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%). Among patients achieving PSA ≤ 0.2 ng/mL at 24 weeks, 96-month overall survival ranged from 64.1% in low-volume metastatic disease to 44.6% in high-volume disease.

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.

The analysis was published online in The Lancet Oncology. Limitations included recruitment before widespread adoption of next-generation imaging modalities such as PET and MRI, metastatic status determined using conventional imaging alone, and an analysis limited to patients who survived long enough to provide PSA measurements at specified timepoints. The lower limit of PSA recorded was 0.2 ng/mL, and treatment options for castration-resistant prostate cancer expanded during the trial period, potentially influencing overall survival outcomes.