Androgen Deprivation Therapy on Bone Mineral Density Change in Prostate Cancer Patients
- Conditions
- Prostatic Neoplasms
- Interventions
- Drug: Maximum androgen blockade
- Registration Number
- NCT04248621
- Lead Sponsor
- Wonju Severance Christian Hospital
- Brief Summary
Androgen deprivation therapy (ADT) is a mainstay of prostate cancer treatment to improve overall survival for intermediate- and high-risk localized disease as well as metastatic disease. While ADT improves survival, it can cause significant morbidity and a decrement in quality of life. In particular, ADT is associated with decrease in bone mineral density (BMD) and increased risk of fracture.
Although current guidelines recommend continuous androgen deprivation therapy (CAD) as standard therapy for high-risk disease, there has been increasing recognition of adverse effects from CAD. Since 1986, intermittent androgen deprivation therapy (IAD) as alternative therapeutic strategy for prostate cancer has been proposed to delay development of castration resistance and to reduce the side effects of ADT.
While both CAD and IAD are commonly used in real clinical practice, no prior study examined BMD change after CAD or IAD, and assessed whether bone loss would recover during off-treatment of IAD. The investigators therefore determine the rate of change in BMD induced by ADT (CAD versus IAD) in men with prostate cancer.
- Detailed Description
Objective: To determine the rate of bone mass loss induced by two therapeutic strategies of ADT (CAD versus IAD) in men with prostate cancer.
Design, setting, and participants: the investigators will perform randomized, open label clinical trial. Men aged over 50 yrs old with prostate cancer (localized, locally advanced, metastatic prostate cancer) who are treated with primary ADT for newly diagnosed prostate cancer or salvage ADT at biochemical recurrence following radical prostatectomy will be included.
Participants will be randomly assigned to one of the following treatment arms:
Arm 1 (CAD): ADT without any discontinuation during study period (12 months).
Arm 2 (IAD): ADT for the first 6 months of study period, if the prostate-specific antigen (PSA) reaches its nadir (\< 4 ng/dL) and serum testosterone reaches castration level (\< 50 ng/dL).
Outcomes:
Primary outcome: change of L-spine total BMD. Secondary outcomes: change of femur neck BMD, incidence rate of osteoporosis, risk of 10 year major osteoporotic fracture, quality of life based on Expanded Prostate Cancer Index (EPIC) questionnaire.
Timing of outcome measurement: at baseline and up to 12 months after randomization.
Statistical analyses: student's t test for continuous outcomes and Fisher's exact or chi-square test for dichotomous outcomes.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 164
Men aged over 50 yrs old with histologically diagnosed prostate cancer (localized, locally advanced, metastatic prostate cancer) who are treated with primary ADT for newly diagnosed prostate cancer or salvage ADT at biochemical recurrence following radical prostatectomy. .
- men with double primary malignancies,
- men who have been treated with ADT or other drug therapy such as denosumab, bisphosphonate or steroid,
- men with osteoporosis at baseline (T-score ≤ -2.5),
- men with a known bone disease,
- men with poor performance status (i.e. Eastern Cooperative Oncology Group performance status 4),
- men with life expectancy < 12 months,
- men with increased serum PSA levels (≥ 4 ng/dL) or testosterone levels (≥ 50 ng/dL) even after 6 month ADT,
- men who are not able to understand trial information or informed consent,
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intermittent Androgen Deprivation Maximum androgen blockade ADT including luteinizing hormone-releasing hormone (LHRH) agonist and antagonist, antiandrogen, or maximum androgen blockade (MAB) should be withdrawn after 6 months of ADT, if the prostate-specific antigen (PSA) reaches its nadir (\< 4 ng/dL) and serum testosterone reaches castration level (\< 50 ng/dL). Continuous Androgen Deprivation Maximum androgen blockade ADT including LHRH agonist and antagonist, antiandrogen, or MAB without any discontinuation during study period. Intermittent Androgen Deprivation Goserelin ADT including luteinizing hormone-releasing hormone (LHRH) agonist and antagonist, antiandrogen, or maximum androgen blockade (MAB) should be withdrawn after 6 months of ADT, if the prostate-specific antigen (PSA) reaches its nadir (\< 4 ng/dL) and serum testosterone reaches castration level (\< 50 ng/dL). Intermittent Androgen Deprivation Degarelix ADT including luteinizing hormone-releasing hormone (LHRH) agonist and antagonist, antiandrogen, or maximum androgen blockade (MAB) should be withdrawn after 6 months of ADT, if the prostate-specific antigen (PSA) reaches its nadir (\< 4 ng/dL) and serum testosterone reaches castration level (\< 50 ng/dL). Intermittent Androgen Deprivation Bicalutamide ADT including luteinizing hormone-releasing hormone (LHRH) agonist and antagonist, antiandrogen, or maximum androgen blockade (MAB) should be withdrawn after 6 months of ADT, if the prostate-specific antigen (PSA) reaches its nadir (\< 4 ng/dL) and serum testosterone reaches castration level (\< 50 ng/dL). Intermittent Androgen Deprivation Triptorelin ADT including luteinizing hormone-releasing hormone (LHRH) agonist and antagonist, antiandrogen, or maximum androgen blockade (MAB) should be withdrawn after 6 months of ADT, if the prostate-specific antigen (PSA) reaches its nadir (\< 4 ng/dL) and serum testosterone reaches castration level (\< 50 ng/dL). Intermittent Androgen Deprivation Leuprorelin ADT including luteinizing hormone-releasing hormone (LHRH) agonist and antagonist, antiandrogen, or maximum androgen blockade (MAB) should be withdrawn after 6 months of ADT, if the prostate-specific antigen (PSA) reaches its nadir (\< 4 ng/dL) and serum testosterone reaches castration level (\< 50 ng/dL). Intermittent Androgen Deprivation Flutamide ADT including luteinizing hormone-releasing hormone (LHRH) agonist and antagonist, antiandrogen, or maximum androgen blockade (MAB) should be withdrawn after 6 months of ADT, if the prostate-specific antigen (PSA) reaches its nadir (\< 4 ng/dL) and serum testosterone reaches castration level (\< 50 ng/dL). Continuous Androgen Deprivation Triptorelin ADT including LHRH agonist and antagonist, antiandrogen, or MAB without any discontinuation during study period. Continuous Androgen Deprivation Leuprorelin ADT including LHRH agonist and antagonist, antiandrogen, or MAB without any discontinuation during study period. Continuous Androgen Deprivation Goserelin ADT including LHRH agonist and antagonist, antiandrogen, or MAB without any discontinuation during study period. Continuous Androgen Deprivation Degarelix ADT including LHRH agonist and antagonist, antiandrogen, or MAB without any discontinuation during study period. Continuous Androgen Deprivation Bicalutamide ADT including LHRH agonist and antagonist, antiandrogen, or MAB without any discontinuation during study period. Continuous Androgen Deprivation Flutamide ADT including LHRH agonist and antagonist, antiandrogen, or MAB without any discontinuation during study period.
- Primary Outcome Measures
Name Time Method Change of L-spine total BMD At baseline and 12 months Measured by bone densitometry
- Secondary Outcome Measures
Name Time Method Osteoporosis At 12 months Defined as newly diagnosed osteoporosis based on T-score (≤ -2.5)
Change of femur neck BMD At baseline and 12 months Measured by bone densitometry
Risk of 10 year major osteoporotic fracture At 12 months Estimated by Fracture Risk Assessment Tool (FRAX®, available at www.sheffield.ac.uk/FRAX)
Quality of life after treatment At baseline and 12 months Measured by EPIC questionnaire
Trial Locations
- Locations (10)
Department of Urology, Chonnam National University, School of Medicine
🇰🇷Gwangju, Korea, Republic of
Department of Urology, Kyungpook National University, School of Medicine
🇰🇷Daegu, Korea, Republic of
Department of Urology, Eulji University, College of Medicine
🇰🇷Daejeon, Korea, Republic of
Department of Urology, Yonsei University Wonju College of Medicine
🇰🇷Wonju, Korea, Republic of
Department of Urology, Yeungnam University, College of Medicine
🇰🇷Daegu, Korea, Republic of
Department of Urology, Chungbuk National University, College of Medicine
🇰🇷Cheongju, Korea, Republic of
Department of Urology, Konyang University, College of Medicine,
🇰🇷Daejeon, Korea, Republic of
Department of Urology, Wonkwang University, School of Medicine
🇰🇷Iksan, Korea, Republic of
Department of Urology,Jeonbuk National University Medical School
🇰🇷Jeonju, Korea, Republic of
Department of Urology, Pusan National University, School of Medicine
🇰🇷Pusan, Korea, Republic of