Editor’s Note: Bipolar Androgen Therapy (BAT) is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC) that significantly reduces prostate-specific antigen (PSA) levels in some patients, improves their quality of life, and restores sensitivity to castration treatments. This therapy has shown great potential in the treatment of mCRPC patients. On January 6, 2024, the “2024 Beijing Urological Tumors Youth Forum,” co-hosted by the Beijing Cancer Fighting Association’s Young Committee for Urological Malignancies and the Beijing Medical Award Foundation, was successfully held in Beijing. Professor Ming Liu, Head of Urology at Beijing Hospital, delivered an insightful presentation titled “Early Experiences with Sequential Bipolar Androgen Therapy Combined with PD-1 Treatment in mCRPC,” and discussed the concept and progress of BAT in an interview with “Oncology Frontier.”
Oncology Frontier : Could you explain the concept and theoretical basis of Bipolar Androgen Therapy (BAT)?
Professor Ming Liu : The foundational treatment for prostate cancer (PCa) is castration therapy, which aims to reduce testosterone levels in the body as much as possible (ideally to less than 20ng/dL) using various methods, such as orchiectomy or GnRHa drugs. This destroys the tumor cells’ dependence on hormones, thus inhibiting tumor progression. Unlike traditional castration therapy for prostate cancer, the concept of BAT involves administering superphysiological doses of androgens when the tumor becomes tolerant to low testosterone levels, rapidly increasing testosterone, and then quickly suppressing it again. This shock therapy can restore the tumor’s sensitivity to endocrine treatment. The specific mechanisms of BAT are not yet fully understood, but studies have shown that BAT can lead to adaptive upregulation of androgen receptor (AR) gene expression that has become tolerant, DNA breaks, and correction of some resistant gene mutations, thus restoring treatment efficacy. Therefore, BAT is receiving increasing attention from researchers.
Oncology Frontier : Could you share some updates on current research into BAT followed by NHT (Novel Hormone Therapy) for treating mCRPC?
Professor Ming Liu : Bipolar Androgen Therapy has a history of over a decade with several studies conducted early on. To date, the two most significant studies are the TRANSFORMER and RESTORE studies, which have been published in international journals. These studies confirm that for patients who have failed treatments with drugs like Abiraterone and Enzalutamide, starting with BAT and then moving to NHT after progression can achieve notable results in terms of PSA50 and progression-free survival (PFS). This treatment model has proven to be more effective than starting with NHT followed by sequential BAT.
Oncology Frontier : At this conference, you introduced a new combined treatment protocol, BAT followed by NHT plus PD-1 monoclonal antibody for mCRPC. Could you share some of the experiences with this treatment?
Professor Ming Liu : We are currently conducting a clinical study on BAT at Beijing Hospital, which is one of the first of its kind in China. Our protocol targets mCRPC patients who have already developed resistance to initial novel hormone therapies. After two cycles of BAT, patients are treated with Rucaparib combined with PD-1 therapy. Our preliminary results show that 60% of the patients experienced a reduction of more than 50% in PSA (PSA50), and 50% achieved radiological remission. Considering these patients are at advanced stages of mCRPC, achieving such results is significant, demonstrating a promising future for BAT in clinical applications.
Oncology Frontier : What do you see as future directions for research on BAT? What should clinicians keep in mind in clinical practice?
Professor Ming Liu : Currently, BAT research is still in the clinical trial phase, and there are many unresolved issues, including the timing of BAT intervention, dose selection, patient selection, treatment cycles, sequencing of drugs, and whether sequential or combined therapy is more effective. We still don’t have clear answers. However, it’s evident that bipolar androgen therapy has a promising future, as it could benefit many patients. Prostate cancer is a complex disease, and traditional castration treatments may need further development and refinement.
Director of Urology, Beijing Hospital, Chief Physician
Professor at Peking University Health Science Center, Doctoral Supervisor
Doctoral Supervisor, Peking Union Medical College
Standing Committee Member of the Urology Branch of the Chinese Medical Association, Leader of the Urological Male Engineering Group
Committee Member of the Tumor Group, Basic Science Group, and International Exchange Committee of the Urology Branch of the Chinese Medical Association, Deputy Leader of the Minimally Invasive Group of the Urinary and Male Genital Tumors Professional Committee of the China Anti-Cancer Association
Standing Committee and Secretary
-General of the Beijing Medical Association Urology Branch
International Review Expert of the NCCN Prostate Cancer Guidelines
Deputy Group Leader of the “Chinese Prostate Hyperplasia Diagnosis and Treatment Guidelines”
