Patterns of Failure in Men With Radiorecurrent Prostate Cancer: A Post Hoc Analysis of 3 Prospective Gallium 68 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Trials

Abstract

Men with radiorecurrent prostate cancer (PCa) are often not offered curative treatment due to concerns regarding occult extraprostatic disease. Prostate specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has significantly improved sensitivity for detecting extraprostatic disease compared with conventional imaging. We evaluated the patterns of PSMA-positivity in a cohort of men presenting for PSMA PET/CT to evaluate radiorecurrence. This was a post-hoc analysis of men from 3 prospective studies of PSMA PET/CT for radiorecurrent prostate cancer who had detailed clinicopathologic and treatment characteristics available and at least one positive PSMA PET/CT finding. Patterns of failure were defined as intraprostatic (including seminal vesicles) or extraprostatic (regional lymph node or distant metastatic disease with or without intraprostatic disease). Multivariable analyses (MVAs) were performed to evaluate for predictors of extraprostatic vs intraprostatic recurrence. Of the 128 patients included in this study, 17 (13%) were initially diagnosed with low-risk, 69 (54%) with intermediate-risk, and 42 (33%) with high-risk PCa. Median time since radiotherapy (RT) was 4.3 years (interquartile range [IQR], 2.7 - 7.2 years), and median PSA at time of PSMA PET/CT was 4.8 ng/mL (IQR, 2.8-10). Intraprostatic only failures were seen in 46 patients (36%), while extraprostatic failures were seen in 82 patients (64%). On MVA, greater years since RT was associated with decreased likelihood of extraprostatic recurrence (OR 0.89 [0.8 - 1.0], p=0.04) p=0.04) while increased PSA at PSMA PET/CT (OR 1.17 [1.05 - 1.29], p=0.003) and ADT use during initial treatment (OR 3.44 [1.0 - 11.85], p=0.05) were associated with extraprostatic recurrence. Nearly 1/3rd of patients with radiorecurrent disease who have identifiable disease on a PSMA PET/CT scan have intraprostatic recurrences only. Prospective studies evaluating salvage treatment approaches that integrate PSMA PET/CT imaging data are warranted.