Impact of PSMA PET staging on initial treatment in newly diagnosed prostate cancer: An emulated randomized controlled trial.

Abstract

350 Background: Prostate-specific membrane antigen (PSMA) PET/CT has become a common initial staging modality for localized prostate cancer due to its increased sensitivity and specificity over conventional staging. However, the causal impact of widespread PSMA staging on initial prostate cancer treatments has not been described. Methods: We used electronic medical record data from a national, diverse health system (Veterans Health Administration) to emulate a randomized controlled trial in which patients with newly diagnosed conventionally localized unfavorable intermediate, high, and very high-risk prostate cancer were allocated to either upfront PSMA staging or conventional imaging with technetium-99 bone scan and pelvic CT or MRI. Primary outcomes included the use of any androgen deprivation therapy (ADT), advanced androgen receptor pathway inhibitors (ARPIs), radiotherapy, and radical prostatectomy assessed in the year after diagnosis. We used the cloning, censoring, and weighting technique to estimate the causal effect of PSMA staging, controlling for potential confounders. In exploratory analyses, we extracted radiographic stage from PSMA reports using a natural language processing algorithm and assessed the influence of PSMA findings (N0M0, N1M0, or M1) on treatment patterns. Results: 9,049 patients met criteria for inclusion in the emulated trial, of whom 35% underwent PSMA staging and 46% underwent bone scan. In the emulated trial, PSMA staging was associated with higher rates of any ADT usage relative to conventional staging (adjusted hazard ratio [aHR] 1.26, 95% confidence interval [CI] 1.19-1.44), higher ARPI usage (aHR 1.52, 95% CI 1.33-1.78), lower prostatectomy usage (aHR 0.69, 95% CI 0.56-0.83), and no effect on radiotherapy usage (aHR 1.10, 95% CI 0.99-1.25). Compared to patients with PSMA N0M0, ARPI usage was higher in patients with N1M0 (aHR 6.87, 95% CI 5.41-8.73) and M1 (aHR 10.13, 95% CI 8.16-1.2.58). Patients with N1M0 or M1 disease were less likely to undergo prostatectomy compared to N0M0. Similar patterns were seen in subgroup analyses within risk groups. Conclusions: In this emulated randomized trial, PSMA staging of localized prostate cancer was associated with increased rates of any ADT and ARPI use and lower rates of prostatectomy relative to conventional staging. The implications of these treatment changes on oncologic outcomes require further study.