Impact of PSMA PET Staging on Initial Treatment in Newly Diagnosed Prostate Cancer

Prostate-specific membrane antigen (PSMA) PET/CT has become a common staging modality for newly diagnosed high-risk and unfavorable intermediate-risk prostate cancer after showing improved sensitivity and specificity compared with conventional imaging in clinical trials. We aimed to assess the causal impact of PSMA PET staging on initial treatment selection in real-world practice. Methods: We used observational data from the U.S. Veterans Health Administration to emulate a randomized controlled trial in which patients with newly diagnosed, unfavorable intermediate-, high-, and very-high-risk prostate cancer from January 2022 to December 2023 would have been randomized to undergo either upfront ¹⁸F- or ⁶⁸Ga-PSMA PET staging or conventional imaging (^99mTc bone scan and pelvic CT or MRI). Outcomes of interest included use of frontline androgen deprivation therapy (ADT), second-generation androgen receptor pathway inhibitors (ARPIs), radiotherapy, and radical prostatectomy. Weighted univariable Cox regression was performed to assess the effect of treatment group on each outcome, and 95% CIs were generated from 1,000 bootstrap replicates. Results: In total, 9,049 patients met the criteria for inclusion. PSMA PET staging was associated with higher rates of any ADT use relative to conventional staging (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.19-1.44), higher rates of ARPI use (aHR, 1.52; 95% CI, 1.33-1.78), lower rates of prostatectomy (aHR, 0.69; 95% CI, 0.56-0.83), and no significant effect on the use of radiotherapy (aHR, 1.10; 95% CI, 0.99-1.25). Compared with patients with PSMA stage N0M0, ARPI use was more common in patients with PSMA stage N1M0 (aHR, 6.87; 95% CI, 5.41-8.73) and PSMA stage M1 (aHR, 10.13; 95% CI, 8.16-1.2.58). Patients with PSMA N1M0 disease were much less likely to undergo prostatectomy compared with PSMA N0M0. Conclusion: PSMA PET staging may be leading to fewer prostatectomies and higher use rates of ADT and ARPIs in the Veterans Health Administration.