Editor's Note: Prostate cancer is one of the most common malignancies among men in China, and its development and progression are closely associated with androgens. Consequently, androgen deprivation therapy (ADT) remains an indispensable cornerstone throughout the prostate cancer disease continuum, from localized disease and metastatic hormone-sensitive prostate cancer to castration-resistant prostate cancer.In recent years, the emergence of novel endocrine therapies and poly(ADP-ribose) polymerase (PARP) inhibitors has shifted androgen-targeted treatment from single-pathway blockade toward combination strategies designed to enhance efficacy. Meanwhile, longer patient survival has increasingly made prostate cancer a chronic disease management challenge. Metabolic abnormalities, cardiovascular risks, and quality-of-life improvement during long-term pharmacological castration have become important clinical concerns alongside treatment efficacy.
Against this background, Oncology Frontier invited Professor Benkang Shi of Qilu Hospital of Shandong University to provide an in-depth analysis of current ADT drug classes and their characteristics, the value of combination treatment strategies, safety management during long-term therapy, and future directions, with the aim of further improving outcomes for patients with prostate cancer in China.
Oncology Frontier: First, could you explain the fundamental role of ADT in comprehensive prostate cancer management? What are the main types of ADT currently used, and what are their respective characteristics?
Professor Benkang Shi: Prostate cancer is a malignancy specific to men, and its development and progression are highly dependent on androgen signaling. As a result, ADT occupies an important position in the comprehensive treatment of prostate cancer. Whether patients are in the hormone-sensitive stage or have progressed to castration-resistant disease, ADT remains an indispensable treatment strategy.
Historically, ADT relied primarily on surgical castration, which involves removing the testes to block the main source of androgens. However, clinical research has shown that the adrenal glands retain the ability to synthesize and secrete approximately 5%–10% of androgens. Surgical castration alone therefore cannot achieve complete androgen blockade.
With a deeper understanding of the disease and advances in research, pharmacological castration has gradually become the predominant approach. ADT drugs have developed rapidly, and numerous options are now available. The main classes include luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin, leuprorelin, and triptorelin, as well as LHRH antagonists, such as degarelix. LHRH antagonists bind directly and competitively to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland, rapidly suppressing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) without causing an initial transient increase in hormone levels.
In terms of formulation, ADT drugs include injectable preparations, subcutaneous implants, microsphere formulations, and newer oral formulations. According to their drug-release intervals, they can be categorized as ultra-long-acting formulations lasting six months, long-acting formulations lasting three months, and short-acting formulations lasting one month.
In clinical practice, we need to consider multiple factors—including disease characteristics, safety, treatment adherence, and quality of life—to select the most appropriate treatment for each patient with prostate cancer.
Oncology Frontier: Prostate cancer treatment options have expanded rapidly in recent years. How do you view the overall evolution of treatment strategies, and how has the role of ADT changed?
Professor Benkang Shi: Prostate cancer can be treated using a range of approaches, including surgery, radiotherapy, chemotherapy, and pharmacological therapy. Given the strong dependence of prostate cancer on androgen signaling, pharmacological treatment, particularly androgen-targeted therapy, plays an important role throughout the disease continuum.
As mentioned earlier, prostate cancer treatment requires both androgen deprivation and the suppression of androgen synthesis or the blockade of androgen binding to its receptor, thereby inhibiting tumor growth. This has led to the development of various drugs and treatment strategies.
Overall, ADT remains a cornerstone of prostate cancer treatment. At the same time, several novel endocrine therapies have emerged in recent years, including abiraterone, which inhibits androgen synthesis, and various second-generation androgen receptor inhibitors that effectively block androgen binding to its receptor.
Consequently, clinical practice has gradually evolved from ADT monotherapy toward ADT-based combination therapy. For younger patients with highly aggressive tumors who are suitable for novel endocrine therapies, ADT is generally combined with a novel endocrine agent. In some cases, chemotherapy is also added to further enhance treatment efficacy.
Furthermore, for patients carrying BRCA mutations or other defects in homologous recombination repair (HRR) genes, PARP inhibitors offer a precision treatment option.
In short, pharmacological treatment for prostate cancer has entered an era of precision medicine and combination therapy, offering the potential to further improve both survival outcomes and quality of life.
Oncology Frontier: As survival continues to improve for patients with prostate cancer, disease management is increasingly shifting toward a chronic, whole-course care model. During long-term ADT, which safety issues should clinicians prioritize?
Professor Benkang Shi: With continued advances in cancer diagnosis and treatment, outcomes for patients with prostate cancer have improved significantly, and some patients are now entering an era of chronic disease management. Because prostate cancer predominantly affects middle-aged and older men, the potential metabolic effects of long-term treatment require particular attention.
During treatment, we need to systematically monitor and manage patients’ metabolic status, paying close attention to fluctuations in blood glucose, changes in lipid levels, calcium loss, and changes in cardiovascular function. Such comprehensive monitoring is essential to ensuring treatment safety and efficacy and, ultimately, improving patient outcomes.
Oncology Frontier: Looking ahead, what promising directions can we expect in precision treatment and the development of novel drugs for prostate cancer?
Professor Benkang Shi: Precision treatment in prostate cancer encompasses both the precise use of medications and precision surgery.
Regarding pharmacological treatment, clinicians need to develop individualized treatment plans based on each patient’s clinical characteristics, using ADT as the foundation. For example, in younger patients with high Gleason scores and relatively low PSA levels, adding novel endocrine agents and combining treatment with chemotherapy may help enhance efficacy. For patients carrying mutations in HRR genes, combining treatment with PARP inhibitors can provide a more targeted approach to tumor control.
At the same time, prostate cancer surgery has entered a new era of precision, progressing from traditional open surgery and conventional laparoscopy to robot-assisted laparoscopic surgery.
Robot-assisted intelligent surgical technologies offer exceptional precision and control. During surgery, they enable precise removal of the prostate and tumor lesions while allowing meticulous preservation of the neurovascular bundles and sphincter function. By ensuring oncologically adequate resection while preserving physiological function to the greatest extent possible, these techniques can help improve postoperative quality of life.
Professor Benkang Shi
