Biochemical recurrence (BCR) after radical prostatectomy occurs in up to one-third of patients and increases the risk of metastasis and prostate cancer-specific mortality. While androgen deprivation therapy (ADT) remains a foundational approach, its routine use in low- and intermediate-risk BCR raises concerns regarding overtreatment and long-term quality-of-life (QOL) impairment. This review summarizes contemporary testosterone-sparing treatment (TST) strategies for BCR, including patient selection frameworks, emerging therapeutics, and evolving imaging modalities.
Advances in multifactorial risk stratification-including genomic classifiers and artificial intelligence (AI)-driven models-are reshaping treatment decision-making and may help identify patients unlikely to benefit from ADT. PSMA-PET has redefined disease staging and is increasingly used to guide salvage radiation therapy and metastasis-directed therapy. Several emerging TST strategies-including enzalutamide monotherapy, salvage radiation without ADT, metastasis-directed therapy, salvage lymph node dissection, radioligand therapy, and structured lifestyle interventions-demonstrate potential to delay or avoid hormonal therapy. Early evidence suggests select patients can maintain cancer control while avoiding testosterone suppression and its associated toxicities. BCR represents a heterogeneous clinical state, requiring individualized management strategies that balance oncologic efficacy with long-term survivorship concerns. Testosterone-sparing approaches may provide safe alternatives to ADT in appropriately selected patients. Ongoing work to validate predictive biomarkers and integrate AI-derived decision tools is expected to refine patient selection as emerging clinical trials mature.
Current oncology reports. 2026 Mar 31*** epublish ***
Faris Najdawi, Rashid K Sayyid, Thomas Ahlering, David I Lee, Ryan W Dobbs, Mohammed Shahait
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., Department of Urology, University of California at Irvine, Irvine, CA, USA. .