Two pivotal randomized controlled trials (RCTs) demonstrate that abiraterone acetate + prednisone (AAP) combined with androgen deprivation therapy (ADT) significantly extends the survival of men with metastatic hormone-sensitive prostate cancer (mHSPC) compared with ADT alone. Their subgroup analyses indicate that the survival benefit is significant for younger men but not older men. We aimed to assess whether publication of the RCTs was associated with differential real-world AAP utilization by age groups.
Using TriNetX electronic medical records data collected from 43 healthcare organizations across the United States, we performed a difference-in-differences event study among men with newly diagnosed mHSPC observed from June 2014 to June 2019. Eligible subjects were identified based on a comprehensive published algorithm. We analyzed the change in utilization rate of AAP before versus after publication of the RCTs among men aged <70 years versus ≥70 years, adjusting for demographic factors and clinical conditions.
Our study included 6,888 men with newly diagnosed mHSPC with 12,738 observations, of whom 46% were aged <70 years. The prepublication trends of AAP utilization were similar between the age groups, whereas publication of the RCTs was associated with a 3.5% higher adjusted uptake rate of AAP among younger men (95% CI, 1.2%-5.8%) relative to older men. This estimate reflects an uptake rate nearly 3 times higher than would have been expected had younger men followed the same utilization trends as older men. The estimates remained consistent throughout the postpublication period.
Our study suggests that publication of the RCTs was associated with faster uptake of AAP among younger versus older men with newly diagnosed mHSPC, despite the absence of clinical guidance for differential treatment selection. This finding highlights the importance of confirmatory studies among older men, considering the uncertainties of subgroup analyses in RCTs.

BACKGROUND: The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy (ADT) in combination with apalutamide and enzalutamide, a new generation of androgen receptor antagonists, as first-line therapy. A decrease in prostate-specific antigen (PSA) levels may occur in the early stages of novel hormonal therapy; however, radionuclide bone imaging may suggest disease progression. During follow-up, PSA, radionuclide bone imaging, and prostate-specific membrane antigen (PSMA) positron emission tomography - computed tomography (PET-CT) are needed for systematic evaluation.
METHODS: We admitted a 56-year-old male patient with metastatic hormone-sensitive prostate cancer. Initial radionuclide bone imaging, magnetic resonance imaging (MRI), and PSMA PET-CT showed prostate cancer with multiple bone metastases. Ultrasound-guided needle biopsy of the prostate revealed a poorly differentiated adenocarcinoma of the prostate with a Gleason score: 5+4 = 9. The final diagnosis was a prostate adenocarcinoma (T4N1M1). ADT with novel hormonal therapy (goseraline sustained-release implant 3.6 mg monthly and apalutamide 240 mg daily) was commenced. Three months later, radionuclide bone imaging and MRI revealed advanced bone metastasis. However, PSMA PET-CT examination showed a significant reduction in PSMA aggregation on the bone, indicating improved bone metastases. Considering that progressive decrease in the presenting lumbar pain, treatment strategies were considered to be effective.
CONCLUSIONS: ADT using novel hormonal therapy is effective for treating patients with prostate adenocarcinoma. Careful evaluation must precede treatment plan changes.