In this edition of Clear Horizons, Comprehensive Urologic Care, Professor Xin Yao from Tianjin Medical University Cancer Institute and Hospital discusses the mechanistic and clinical differences between LHRH agonists and antagonists, as well as practical strategies for managing ADT-related adverse events to maximize both treatment efficacy and patient quality of life.Q1. Since Huggins first established the concept of androgen deprivation therapy in the 1940s, treatment has evolved into today’s era of combination ADT. Despite the emergence of many novel therapies, why does ADT remain the foundation of prostate cancer treatment?
Professor Xin Yao:
The evolution of systemic therapy for prostate cancer has always reflected advances in our understanding of the disease’s underlying biology.
In the 1940s, Huggins and colleagues first demonstrated the androgen dependence of prostate cancer, establishing ADT as the foundation of systemic treatment.
Since then, prostate cancer therapy has undergone remarkable innovation. Treatment options now extend beyond conventional ADT to include next-generation hormonal therapies, proteolysis-targeting chimeras (PROTACs) targeting the androgen receptor, antibody-drug conjugates (ADCs), and many other emerging approaches.
Despite these advances, ADT remains indispensable because it directly targets the central biological driver of prostate cancer. By consistently reducing testosterone to castrate levels, ADT continues to provide the essential therapeutic foundation upon which modern treatment strategies are built.
Q2. ADT mainly consists of LHRH agonists and LHRH antagonists, which differ in both mechanism and clinical effects. Based on your clinical experience, how would you compare their respective clinical value?
Professor Xin Yao:
During the early years of ADT, LHRH agonists represented the primary therapeutic option. As drug development progressed, LHRH antagonists were introduced, initially as injectable formulations and more recently as oral agents, further expanding treatment options.
The two drug classes differ fundamentally in their mechanisms of action.
LHRH agonists initially induce a transient testosterone surge, making preventive measures—such as concurrent androgen receptor blockade—necessary before treatment begins. For patients with rapidly progressing or advanced disease, particularly those with bone metastases, this testosterone flare may worsen urinary symptoms or precipitate skeletal-related events.
Rapid suppression of serum testosterone is therefore highly desirable, allowing earlier disease control and faster symptom relief.
The introduction of degarelix, an LHRH antagonist, represented a major milestone in ADT. By directly competing for LHRH receptors, degarelix immediately suppresses testosterone production without inducing the flare phenomenon associated with agonists. Recent improvements in LHRH antagonist formulations have also enhanced treatment convenience.
Overall, the evolution from LHRH agonists to LHRH antagonists—and the continued refinement of antagonist formulations—has provided patients with advanced prostate cancer faster disease control, improved safety, and greater convenience, ultimately enhancing quality of life.
Q3. Because ADT is typically administered long-term, patients may experience hot flashes, night sweats, fatigue, bone loss, and cardiovascular complications. How do you balance effective tumor control with maintaining quality of life in daily practice?
Professor Xin Yao:
Compared with many anticancer therapies, including chemotherapy and tyrosine kinase inhibitors (TKIs), ADT is generally well tolerated. Nevertheless, patients may still experience adverse effects such as hot flashes, night sweats, gynecomastia-related breast pain, osteoporosis, and fractures. Older patients or those with underlying cardiovascular disease may also face an increased risk of cardiovascular events.
In my view, maintaining treatment efficacy requires comprehensive, individualized management throughout the entire treatment journey.
Bone health is one area that has historically been underappreciated. Since osteoporosis is a treatment-related complication of ADT, patients should undergo regular monitoring of serum calcium and phosphate levels while receiving counseling on adequate dietary calcium intake to reduce the risk of osteoporosis and compression fractures.
Cardiovascular management is equally important. Because most prostate cancer patients are older and many have pre-existing cardiovascular disease, cardiac function should be carefully monitored throughout treatment to ensure patient safety.
Hot flashes and night sweats are among the most common ADT-related adverse effects. For patients whose disease is well controlled and clinically stable, intermittent ADT may be considered. This strategy can substantially improve quality of life without compromising oncologic outcomes, helping achieve an optimal balance between disease control and patient well-being.
Overall, although ADT is relatively safe, no treatment is completely free of risk. Comprehensive long-term management combined with individualized care is essential to maximize both cancer control and quality of life.
Q4. With advances in artificial intelligence and emerging treatment strategies, prostate cancer care is becoming increasingly personalized. How do you envision the future of androgen deprivation therapy?
Professor Xin Yao:
We are now transitioning from evidence-based medicine toward truly precision oncology. Although this journey presents many challenges, it also offers tremendous opportunities.
I believe precision treatment depends on two essential prerequisites.
First, we need a broad therapeutic arsenal encompassing drugs with diverse mechanisms of action. Only when multiple treatment options are available can therapy be tailored to each patient’s individual needs.
Second, we must develop practical precision assessment models. Across oncology, including prostate cancer, molecular classification is becoming increasingly important. Technologies such as genomic profiling and liquid biopsy are enabling more accurate prediction of treatment response.
In today’s era of big data, large clinical datasets—particularly those including patients treated with a variety of therapeutic approaches—can support the development of data-driven precision treatment models. Building these models requires comprehensive, high-quality clinical data, which explains why both professional societies and national healthcare initiatives place great emphasis on integrating and analyzing real-world clinical data.
As more innovative therapies enter clinical practice and our clinical datasets continue to grow, I believe precision and personalized treatment for prostate cancer will become increasingly achievable, ultimately providing patients with more effective and higher-quality care.
Expert Profile
Professor Xin Yao Tianjin Medical University Cancer Institute and Hospital
