Editor's Note: Prostate cancer is one of the most common malignancies in men, with endocrine therapy being a standard treatment approach. However, it often comes with some side effects. Recently, the 31st Annual Urology Conference, hosted by the Chinese Medical Association and the Chinese Urological Association (CUA), was held from September 19-22, 2024, at the Tianjin National Convention Center. Following the event, Urology Frontier invited Dr. Qiang Wei from West China Hospital, Sichuan University to share insights on the latest advancements in endocrine therapy for prostate cancer, side effect management, and the future research directions of his team.

Urology Frontier: What are the unmet clinical needs for prostate cancer patients in China?

Dr. Qiang Wei: In recent years, the incidence of prostate cancer has been rapidly increasing in China, with a higher proportion of late-stage diagnoses and a higher mortality rate compared to developed countries like the U.S. and Europe. This highlights significant unmet needs throughout the management of prostate cancer:

First, early diagnosis is crucial. The high proportion of late-stage prostate cancer cases contributes to the higher mortality rate in China. Early diagnosis and treatment can give most patients a chance at curative treatment and potentially achieve remission.

Second, challenges during endocrine therapy must not be overlooked. Patients often transition from the hormone-sensitive phase to the hormone-resistant phase, which is inevitable, though the timeframe can vary. Maintaining sensitivity to endocrine therapy and extending the effective duration of treatment are critical challenges that need to be addressed.

Finally, once advanced prostate cancer progresses to the metastatic castration-resistant stage, it significantly impacts patients’ quality of life and survival. Identifying treatments that effectively extend survival and improve quality of life is another urgent need.

Urology Frontier: In recent years, what do you consider to be the major breakthroughs in endocrine therapy for prostate cancer?

Dr. Qiang Wei: The most significant breakthroughs in prostate cancer endocrine therapy have been in the area of precision medicine. The androgen deprivation therapy (ADT) approach, which targets the androgen pathway, has been widely adopted in clinical practice. However, many patients eventually develop castration resistance after undergoing ADT for some time, limiting the effectiveness of treatment. Recently, with a deeper understanding of genetic mutations and new therapeutic targets, multiple new strategies have emerged to address androgen receptor pathway mutations and resistance to ADT. These include novel androgen synthesis inhibitors, androgen receptor antagonists targeting new mutations, and androgen receptor degraders. We are optimistic that these treatment strategies will provide better survival outcomes for patients.

For prostate cancer patients with DNA repair gene mutations, precision therapy using PARP inhibitors is available. Recently, three major clinical trials have reported results on the combination of PARP inhibitors with novel endocrine therapies for metastatic castration-resistant prostate cancer (mCRPC), including the PROpel study (olaparib plus abiraterone), TALAPRO-2 study (talazoparib plus enzalutamide), and the MAGNITUDE study (niraparib plus abiraterone). These studies demonstrated that first-line treatment with PARP inhibitors combined with novel endocrine therapies significantly improved radiographic progression-free survival (rPFS) and even overall survival (OS), earning recommendations in major clinical guidelines.

Urology Frontier: What side effects of endocrine therapy for prostate cancer should be closely monitored?

Dr. Qiang Wei: Endocrine therapy is typically a long-term process, with most patients requiring ADT throughout both hormone-sensitive and hormone-resistant stages. Unfortunately, such treatments inevitably lead to a range of side effects, with osteoporosis and cardiovascular events being the most common. For patients who develop osteoporosis, we recommend regular bone density monitoring and proper supplementation with calcium and vitamin D, while encouraging outdoor physical activity to promote calcium absorption and slow bone loss. Additionally, cardiovascular side effects must be carefully managed, with comprehensive evaluations and individualized management strategies developed for each patient.

Urology Frontier: What are the future research directions for your team regarding prostate cancer?

Dr. Qiang Wei: Our team is committed to the in-depth study of prostate tissue inflammation and related diseases. In the field of translational medicine, the West China urology team continues to explore innovative approaches, aiming to effectively translate basic research findings into clinical applications, and we will continue to deepen this focus in the future.

Recently, we have paid particular attention to environmental pollutants, especially endocrine disruptors, and their impact on the development and progression of prostate cancer.

We are also investigating the effects of androgen deprivation therapy on the immune system. While ADT can effectively treat prostate cancer, it may also have complex effects on the patient’s immune system. Given that prostate cancer is often considered an “immunologically cold tumor” due to its poor response to immunotherapy, we hope to identify the key factors responsible for this and determine how to convert the “cold tumor” microenvironment into a “hot tumor” that responds well to immunotherapy. This exploration holds significant scientific value and could lead to more effective treatment strategies for prostate cancer patients.

Dr. Qiang Wei: Professor, Chief Physician, PhD Supervisor Director, Urologic Disease Center, West China Hospital of Sichuan University Deputy Director, Urology Branch, Chinese Medical Association Vice President, Urology Branch, Chinese Medical Doctor Association Vice Chair, Prostate and Renal Cancer Committee, Chinese Society of Clinical Oncology (CSCO) Vice Chair, Male Reproductive Tumor Committee, Chinese Anti-Cancer Association Director, Sichuan Province Kidney and Urological Disease Clinical Research Center President, Sichuan Provincial Surgical Robot Physicians Branch Chair, Urologic Oncology Branch, Sichuan Anti-Cancer Association Chair, Urology Branch, Chengdu Medical Association Recipient of the CUA “Golden Cystoscope Award,” Wu Jieping Urology Award, and Global Chinese Urology Lifetime Achievement Award