A decline in prostate-specific antigen (PSA) levels following treatment with the androgen receptor inhibitor enzalutamide may effectively predict improved survival rates among patients with nonmetastatic castration-resistant prostate cancer, according to a post hoc analysis of data from the PROSPER trial published by Maha Hussain, MD, FACP, FASCO, and colleagues in The Journal of Urology.
Background
Increases in PSA may signal an increased risk that the cancer will metastasize outside of the prostate gland. In patients with nonmetastatic castration-resistant prostate cancer, rising PSA levels are often the first sign that the cancer is growing.
Maha Hussain, MD, FACP, FASCO
"Our analysis of data from the PROSPER [trial] shows a previously unappreciated relationship between changes in PSA levels and clinical outcomes in [patients] with nonmetastatic castration-resistant prostate cancer," highlighted lead study author Dr. Hussain, the Genevieve Teuton Professor of Medicine in the Division of Hematology-Oncology in the Department of Medicine as well as Deputy Director of the Genitourinary Oncology Program at the Robert H. Lurie Comprehensive Cancer Center at the Northwestern University Feinberg School of Medicine. "The findings may help us to make personalized decisions regarding clinical follow-up and imaging studies for a group of patients at high risk of prostate cancer metastases.”
PROSPER Trial and Enzalutamide’s Impact on PSA
In the analysis, the researchers examined data from the 2018 PROSPER trial—conducted by Dr. Hussain and her colleagues and published in The New England Journal of Medicine—which enrolled patients with nonmetastatic castration-resistant prostate cancer and rapidly rising PSA levels.
The PROSPER trial was designed to evaluate the effects of the novel hormonal agent enzalutamide, which works by directly blocking the androgen receptor to prevent the hormone’s encouragement of prostate cancer growth. The initial results of the PROSPER trial showed longer survival times in patients who received enzalutamide in combination with androgen-deprivation therapy.
The researchers used 12 months of follow-up data from the PROSPER trial to assess how PSA levels responded to enzalutamide. Changes in PSA levels and patient survival rates were compared among 905 patients treated with enzalutamide and 457 treated with placebo.
Most patients had sharp reductions in PSA after enzalutamide treatment—with 97% of patients who received enzalutamide demonstrating at least a 50% decrease in PSA levels. In 38% of patients, PSA levels decreased by at least 90%.
Greater Declines in PSA May Be Linked to Lower Risk of Metastases, Longer Survival
The analysis showed that the reduction in PSA levels after treatment with enzalutamide may be a strong predictor of survival rates. Median metastasis-free survival was 37 months in patients with a PSA decline of 90% or greater, compared with about 22 months in those whose PSA levels decreased by less than 50%.
The researchers also found that overall survival may also be related to a response to enzalutamide, ranging from 41 months for patients with less than a 50% decline in PSA levels to 54 months for those with a 90% decline or greater. For patients who had a 90% decline or greater as well as a PSA nadir of 0.2 ng per mL or less, the overall survival time increased to 64 months, with the median survival time not reached—meaning that longer follow-up would be needed to determine the final overall survival benefits.
Conclusions
The researchers noted that their findings may have implications not only for predicting the outcomes of enzalutamide therapy but also for personalized treatment of patients with nonmetastatic castration-resistant prostate cancer.
Dr. Hussain concluded that the findings "further underscore the value of PSA as an intermediate biomarker for treatment benefits and risks of disease progression in patients with nonmetastatic castration-resistant prostate cancer.”
Dr. Hussain and her colleagues called for further studies clarifying the dynamics of changes in PSA levels in response to enzalutamide—including the significance of reaching a PSA nadir of 0.2 ng per mL or less.
Disclosure: For full disclosures of the study authors, visit auajournals.org.
