Patterns of Failure in Men With Radiorecurrent Prostate Cancer: A Post-Hoc Analysis of Two Prospective Ga-68-PSMA PET/CT Imaging Trials

Abstract

<h3>Purpose/Objective(s)</h3> The advent of novel nuclear medicine imaging modalities, such as prostate specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), has significantly impacted the ability to localize disease in patients with biochemically recurrent prostate cancer (PCa). However, the topography of recurrence in men with radiorecurrent disease remains poorly understood. <h3>Materials/Methods</h3> This was a <b>post-hoc</b> analysis of men from two prospective studies of PSMA PET/CT for radiorecurrent prostate cancer, previously treated with definitive radiotherapy (RT), who had detailed clinicopathologic and treatment characteristics available and at least one PSMA PET/CT finding. Patterns of failure were defined as local-only (intraprostatic or seminal vesicle), nodal (regional lymph node with or without local failure), and distant (with or without local or nodal failures). Univariable multinomial logistic regression (UVA) was performed to evaluate predictors of nodal or distant recurrence vs. local only, and subsequent multivariable analyses (MVAs) were conducted including only variables with <i>P</i> < 0.1 on UVA. Variables evaluated included years since radiation, post-radiation nadir PSA, PSA at time of PSMA, initial disease features (cT stage, iPSA, Gleason grade group), and treatment variables (type of radiation, use of ADT, use of whole pelvis radiotherapy). <h3>Results</h3> There were 118 patients included in this study. Of these 118 patients, 17 (14%) were initially diagnosed with low-risk, 61 (52%) with intermediate-risk, and 40 (34%) with high-risk PCa. Median time since RT was 4.4 years (interquartile range [IQR], 2.5-7.4 years), and median PSA at time of PSMA was 4.9 ng/mL (IQR, 2.7-9.6). Local only failures were seen in 47 patients (40%), regional failures (without distant failures) in 23 patients (19%), and distant failures in 48 patients (41%). On UVA, higher iPSA and higher PSA at time of PSMA were associated with regional recurrence, while shorter interval from RT, higher Gleason grade, higher initial PSA, and higher PSA at time of PSMA were associated with distant disease. On MVA, only PSA at time of PSMA remained significant for distant recurrence (<i>P</i> = 0.003) and trended toward significance for regional recurrence (<i>P</i> = 0.07). <h3>Conclusion</h3> Nearly 40% of patients with radiorecurrent prostate cancer have local-only recurrences on PSMA imaging, while another 40% have distant disease. PSA at the time of PSMA imaging is a significant predictor of distant recurrence. Prospective studies evaluating salvage treatment approaches that integrate PSMA imaging data are warranted, and imaging at a lower PSA threshold should be considered.