Dr Spratt on Uncertainties Regarding Treatment Intensification in High-Risk Prostate Cancer

Daniel Spratt, MD, professor, Department of Radiation Oncology, School of Medicine, member, Developmental Therapeutics Program, Case Comprehensive Cancer Center, Case Western Reserve University, discusses ongoing debate and unanswered questions regarding the optimal use of intensified treatment approaches in high-risk prostate cancer.

The addition of abiraterone acetate (Zytiga) to androgen deprivation therapy (ADT) in patients with high-risk prostate cancer present with a lack of clear criterion for patient selection amidst the evolving landscape of diagnostic treatment modalities, Spratt begins. For example, the phase 2/3 STAMPEDE trial (NCT00268476) is often cited as evidence showing benefit with this approach; however, the patient population included in this study may not fully represent patients with high-risk localized prostate cancer who are seen in current clinical practice, Spratt explains.

In the STAMPEDE trial, patients without metastatic disease had exceptionally high prostate-specific antigen (PSA) levels, which may not reflect the current standard of care, especially with the advent of prostate-specific maturation agent (PSMA)–PET imaging, Spratt reports. Spratt notes that contemporary patients with similar PSA levels are more likely to have nodal or distant metastases. Consequently, there is uncertainty regarding which patients truly benefit from treatment intensification with abiraterone, he says.

Defining clear criteria for patient selection remains a challenge, Spratt continues. Although some institutions may adhere strictly to the criteria outlined in trials like STAMPEDE, others may adopt a more nuanced approach considering additional factors such as MRI findings and biomarkers like PSMA-PET, Spratt says. This variability in interpretation further complicates decision-making, he emphasizes.

Given the ongoing uncertainty emergence of alternative biomarkers and treatment strategies, caution should be employed when using abiraterone in this setting, Spratt states. Ongoing trials like the phase 3 ATLAS trial (NCT02531516) investigating apalutamide plus a GnRH agonist, and the phase 3 ENZARAD trial (NCT02446444) of enzalutamide (Xtandi) plus adjuvant ADT and radiotherapy, may provide valuable insights into the efficacy of different treatment approaches in high-risk localized prostate cancer, he notes. Until conclusive evidence is available, individualized decision-making based on patient characteristics and available data remains essential to optimize outcomes in this patient population, Spratt concludes.