In a post hoc analysis reported in The Lancet Oncology, Kayani et al found that on-treatment prostate-specific antigen (PSA) level was associated with overall survival in patients with metastatic or very high-risk nonmetastatic prostate adenocarcinoma from five phase III trials in the STAMPEDE platform protocol.
Study Details
The analysis used data from patients in the five randomized trials enrolled at sites in Switzerland and the United Kingdom. Patients were randomly assigned to standard of care (androgen-deprivation therapy [ADT] alone or with docetaxel) or to one of five experimental treatment groups: ADT plus docetaxel with or without zoledronic acid, ADT plus abiraterone acetate with or without enzalutamide, or ADT plus prostate radiotherapy (only in patients with metastatic disease). Data were used to perform landmark analyses testing associations of on-treatment PSA with overall survival.
Key Findings
The analysis included 7,129 patients from the STAMPEDE platform, recruited between October 2005 and September 2016; 4,438 had metastatic disease and 2,691 had very high-risk nonmetastatic disease.
A PSA concentration of 0.2 ng/mL or less was less frequent at 6 or 12 weeks than at 24 weeks, but no difference in survival rates was observed with PSA at this threshold at these time points.
Survival rates according to on-treatment PSA subcategories (≤ 0.2 ng/mL, > 0.2 to 1.0 ng/mL, > 1.0 to 3.0 ng/mL, and > 3.0 ng/mL) differed according to metastatic volume and by nodal status in those with nonmetastatic disease.
The longest survival was observed in patients who had received abiraterone with or without enzalutamide. Among patients with metastatic disease in the abiraterone with or without enzalutamide group who had PSA of 0.2 ng/mL or less at 24 weeks, 96-month overall survival in those with low-volume metastatic disease (64.1%, 95% confidence interval [CI] = 57.8%–69.8%) was higher than in those with high-volume metastatic disease (44.6%, 95% CI = 37.1%–51.9%). Both rates were lower than those observed in patients with nonmetastatic, node-positive disease (79.4%, 95% CI = 73.8%–83.9%), with the highest rates observed in patients with nonmetastatic, node-negative disease (82.8%, 95% CI = 78.7%–86.1%).
The investigators concluded: “Metastatic volume or nodal status influences survival rates associated with on-treatment serum PSA categories, including for undetectable PSA. Radiological features and serum PSA could be combined to better predict survival. 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. These findings could inform prognosis and warrant evaluation for treatment selection in clinical trials.”
Gerhardt Attard, PhD, of UCL Cancer Institute, University College London, London, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Cancer Research UK, Prostate Cancer UK, and others. For full disclosures of the study authors, visit thelancet.com.
