In this review, we examined the evolving role of testosterone-sparing treatment strategies in the management of BCR, with a focus on emerging technologies, patient selection, and the expanding therapeutic landscape.
Why This Matters
Androgen deprivation therapy (ADT) has long been a cornerstone in the management of BCR prostate cancer. However, the adverse effects of testosterone suppression are substantial and well established, including impacts on metabolic health, bone density, cardiovascular risk, cognitive function, and overall quality of life (QOL).
As our understanding of BCR biology improves, it is increasingly clear that not all patients benefit equally from early or prolonged ADT. For a subset of individuals, the harms of treatment may outweigh the oncologic benefit.
Risk Stratification and Testosterone-Sparing Treatment Strategies
Traditional clinicopathologic factors remain highly informative in prognosis, but novel technologies are quickly reshaping this landscape. PSMA-PET imaging, genomic classifiers, and artificial intelligence (AI)-based models have each shown promise in prognostic insight and enhancing risk prediction.
Additionally, there is a growing body of evidence supporting ADT-free management approaches for carefully selected patients with BCR. Strategies discussed include:
- Active surveillance in carefully selected low-risk patients
- Salvage radiation therapy without ADT
- Metastasis-directed therapy in oligorecurrent disease
- Salvage nodal interventions
- Androgen receptor-targeted monotherapy
Clinical Implications, Limitations, and Future Direction
Importantly, this is not an argument against ADT in patients who clearly benefit from it, such as those with high-risk features. Rather, it is a call for more selective use in addition to refined risk stratification models.
Many of the emerging tools discussed, including genomic classifiers, AI-based models, and radionuclide therapy, need further prospective validation. Additionally, high-level evidence comparing testosterone-sparing strategies with standard ADT-based approaches remains limited.
Undeniably, the financial impact of ADT use on patients and the entire healthcare system should be considered, though it may be difficult to comprehensively calculate, given the systemic and long-term effects. Additionally, ensuring access to these new technologies across all patient populations, regardless of financial or geographic constraints, must be prioritized. And a strategy to ensure diffusion of these management strategies among both academic and community providers is imperative.
Conclusion
Biochemical recurrence after radical prostatectomy represents a spectrum of disease that requires risk-stratification and individualized management.
Testosterone-sparing treatment strategies are increasingly supported by novel diagnostic and therapeutic options. Our hope is that this review helps shift the conversation from reflexive ADT treatment escalation to risk-adapted care that balances oncologic benefit with survivorship.
Written by: Faris Najdawi,1 Rashid K. Sayyid,2 Thomas Ahlering,3 David I. Lee,3 Ryan W. Dobbs,1 Mohammed Shahait3
- Division of Urology, Cook County Health and Hospitals System, Chicago, IL, USA.
- Department of Urology, University of Arizona, Tucson, AZ, USA.
- Department of Urology, University of California at Irvine, Irvine, CA, USA.