Editor’s Note: The 14th Shanghai Urologic Oncology Academic Conference and the Annual Meeting of the Chinese Anti-Cancer Association Male Reproductive System Tumor Committee (CACA-GO) took place from December 6–8,2024 in Shanghai. The conference invited several internationally renowned experts in urologic oncology for academic lectures and surgical demonstrations.Dr. Stephen Freedland from Cedars-Sinai Medical Center in the United States delivered two impactful presentations titled “EMBARK and Something Related to BCR” and “Race and Prostate Cancer – Access to Care vs. Biology or Both?” In an interview with Urology Frontier, Dr. Freedland further discussed the latest progress in the treatment of biochemical recurrence (BCR) in prostate cancer and topics related to racial disparities in healthcare.

Urology Frontier: In the EMBARK study, both enzalutamide monotherapy and its combination with androgen deprivation therapy (ADT) demonstrated metastasis-free survival (MFS) benefits over ADT alone. Additionally, treatment could be paused when PSA levels dropped below 0.2 ng/ml by week 36. How do you design endocrine therapy regimens for BCR patients in clinical practice (monotherapy with next-generation hormonal therapy [NHT] or combined with ADT), and when do you decide to stop treatment?

• Dr. Stephen Freedland:These questions highlight the key insights we gained from the EMBARK study and how we apply them in clinical practice. Let me explain using two patient scenarios:

One patient was at high risk for biochemical recurrence but refused any treatment. However, understanding the tumor’s progression and the need for intervention, he opted for combination therapy after thorough discussions, as it offered the possibility of a longer treatment-free interval.

Another patient, although 80 years old, prioritized preserving his sexual function. This led us to choose monotherapy, given its lesser impact on sexual health.

Ultimately, treatment decisions must be individualized. In our practice, if patients respond well to therapy, we typically stop treatment after nine months. Although some advocate for continuous monotherapy due to better tolerance, studies suggest that treatment efficacy can be sustained even after stopping. Translating clinical data into patient care requires carefully balancing these subtle differences.

Urology Frontier: Salvage radiotherapy (SRT) is also a treatment option for BCR. How do you compare the value or differences between radiotherapy and novel endocrine therapies for BCR?

• Dr. Stephen Freedland:This is an excellent question. Comparing salvage radiotherapy and systemic therapy isn’t straightforward. If a patient is suitable for salvage radiotherapy, they should absolutely receive it.

However, for high-risk BCR, salvage radiotherapy isn’t always effective. Therefore, it’s not a matter of choosing one over the other but rather determining the sequence of interventions. Salvage radiotherapy should be prioritized, and if it fails, systemic treatments like those evaluated in the EMBARK study become the next step.

Urology Frontier: Beyond PSA, what role do PSMA-PET scans or other biomarkers play in guiding treatment decisions and monitoring BCR?

• Dr. Stephen Freedland:The EMBARK study was designed during a period when PSA levels and traditional imaging were the primary assessment tools. Today, PSMA-PET imaging provides valuable additional information.

Data from UCLA show that 85% of patients meeting the EMBARK criteria had detectable disease on PSMA-PET scans—45% with metastatic disease and 40% with local or regional disease. This information guides treatment strategies. For example, in postoperative patients who failed standard pelvic radiotherapy, enzalutamide can improve outcomes.

Moreover, combining systemic therapy with stereotactic body radiotherapy (SBRT) targeting metastases could potentially extend treatment-free intervals. However, it’s important to note that 15% of patients died from prostate cancer before PSMA-PET scans turned positive. Waiting for scan confirmation isn’t always feasible since early intervention could be critical for better outcomes.

Urology Frontier: In your clinical practice, you must have treated prostate cancer patients from diverse racial backgrounds. Are there significant racial differences in prostate cancer, especially concerning BCR or other stages?

• Dr. Stephen Freedland:This is a very important topic. In the United States, Black patients are more likely to develop prostate cancer and have higher mortality rates. In contrast, Asian patients have a lower incidence and generally better prognoses.

Interestingly, Hispanic patients exhibit a higher incidence but tend to have better overall outcomes, a paradox that warrants further research. Studies have shown that Black patients respond better to novel endocrine therapies.

However, disparities in healthcare access, insurance coverage, and socioeconomic factors significantly influence these outcomes. Race is often viewed as a social construct reflecting broader social determinants of health. When provided with equal care, the survival differences across racial groups diminish. The key is ensuring all patients have equitable access to high-quality care and treatment.

Dr. Stephen J. Freedland

• Professor of Urology, Cedars-Sinai Medical Center, USA
• Director, Center for Integrated Research in Cancer and Lifestyle, Cedars-Sinai Medical Center
• Author of over 700 academic publications
• Editorial Board Member and Peer Reviewer for top medical journals, including The Lancet, New England Journal of Medicine, JAMA, Cancer, Nature Communications, Urology, Lancet Oncology, British Journal of Cancer, European Journal of Cancer, American Journal of Epidemiology, and Annals of Oncology.