The advent of PSMA-PET has improved sensitivity and specificity in staging prostate cancer, particularly in intermediate- and high-risk disease. This has created uncertainty in the management of patients with PSMA-positive but conventionally negative pelvic lymphadenopathy (i.e., \<1 cm in smallest diameter). This study evaluates outcomes of enhanced androgen deprivation therapy (ADT) with abiraterone and prednisone compared to standard ADT, both in combination with radiation therapy, in patients with prostate cancer and PSMA-positive but conventionally negative pelvic lymphadenopathy. A total of 140 eligible participants will be randomized to receive either enhanced ADT with abiraterone and prednisone or standard ADT, both with concurrent radiation therapy. Participants will be followed for 5 years after completion of ADT to assess outcomes. The primary objective is to determine whether enhanced ADT improves 5-year failure-free survival compared to standard ADT. Secondary objectives include evaluation of toxicity, quality of life, biochemical progression-free survival, cancer-specific survival, overall survival, and metastasis-free survival. Exploratory objectives include evaluation of tumor growth and regression rates using PSA values and assessment of the relationship between treatment outcomes and blood-based heme oxygenase-1 (HO-1) levels.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
Standard hormone therapy used for prostate cancer treatment
Abiraterone administered as part of enhanced androgen deprivation therapy
Prednisone administered in combination with abiraterone
Radiation therapy administered per protocol to the prostate and/or pelvic lymph nodes
University of Nebraska Medical Center
Omaha, Nebraska, United States
RECRUITING5-year failure-free survival rate
Determine the impact of enhanced ADT with abiraterone/prednisone versus standard ADT on the 5-year failure-free survival of patients with PSMA-positive conventionally negative pelvic lymphadenopathy (i.e. \<1cm in smallest diameter).
Time frame: From randomization up to 5 years
Toxicity in both arms from 3 months to 2 years post-ADT.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: From 3 months to 2 years post-ADT
Evaluate and compare patient-reported symptom outcomes in both arms from 3 months to 2 years post-ADT. (IPSS)
Using IPSS (International Prostate Symptom Score). The quality-of-life measures will be summarized using descriptive statistics at each time point collected as n, mean, SD, median, minimum, and maximum. The IPSS score ranges from 0 to 35, with higher scores indicating worse urinary symptoms.
Time frame: From 3 months to 2 Years post-ADT
Evaluate and compare patient-reported symptom outcomes in both arms from 3 months to 2 years post-ADT. (FACT-P)
Using FACT-P (Functional Assessment of Cancer Therapy-Prostate.) The quality of life measures will be summarized using descriptive statistics at each time point collected as n, mean, SD, median, minimum, and maximum. The FACT-P score ranges from0 to 156, with higher scores indicating better quality of life.
Time frame: From 3 months to 2 Years post-ADT
Evaluate local progression-free survival (i.e., failure-free survival excluding biochemical failure).
Evaluate progression-free survival (i.e., failure-free survival excluding biochemical failure). Progression-free survival will be estimated with the Kaplan-Meier method and will be compared between treatment arms with the log-rank test. The 5-year survival rates will be estimated with a 95% confidence interval. Time to local failure is defined as time since randomization to disease progression within the intact prostate. Regional, metastases, and deaths are treated as competing events.
Time frame: From randomization up to 5 years
Evaluate locoregional progression-free survival (i.e., failure-free survival excluding biochemical failure).
Evaluate progression-free survival (i.e., failure-free survival excluding biochemical failure). Progression-free survival will be estimated with the Kaplan-Meier method and will be compared between treatment arms with the log-rank test. The 5-year survival rates will be estimated with a 95% confidence interval. Time to locoregional failure is defined as time since randomization to disease progression within the pelvis and pelvic lymph nodes. Metastases and deaths are treated as competing events.
Time frame: From randomization up to 5 years
Evaluate 5-year overall survival
Overall survival will be estimated with the Kaplan-Meier method and will be compared between treatment arms with the log-rank test. The 5-year survival rates will be estimated with a 95% confidence interval. Overall survival is defined as the time since the date of randomization to the date of death or last follow-up.
Time frame: From randomization up to 5 years
Evaluate 5-year cancer-specific survival
Cumulative incidence methods will be used to estimate 5-year rates (with 95% CI) of LC, LRC, and DM while accounting for death as a competing event. Cancer-specific survival is defined as time since the date of randomization to the date of death due to cancer diagnosis or treatment or last follow-up. Deaths due to other causes are treated as competing events.
Time frame: From randomization up to 5 years
Evaluate 5-year metastasis-free survival.
Time to distant metastasis is defined as time since date of randomization to distant metastases in para-aortic lymph nodes and distant organs or last follow-up. Locoregional failures and deaths are treated as competing events.
Time frame: From randomization up to 5 years
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