Assessing Interlesional Tumor Response and Patient Outcomes with Sequential PSMA PET/CT in Metastatic Castration-Resistant Prostate Cancer.

The impact of heterogeneous interlesional tumor response on outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) remains unclear. We aimed to evaluate the role of prostate-specific membrane antigen (PSMA) PET/CT in assessing patient outcomes on the basis of global tumor response and interlesional tumor response. We retrospectively analyzed data for 24 patients with mCRPC treated with androgen receptor pathway inhibitors who underwent [Ga]Ga-PSMA-11 PET/CT at baseline and at weeks 4 and 12 of therapy as well as conventional imaging at baseline and week 12 of therapy. Global PET/CT response was evaluated in accordance with the European Association of Urology/European Association of Nuclear Medicine criteria, classifying patients as having progressive disease (PD) or nonprogressive disease (non-PD) (i.e., complete response, partial response, or stable disease) and was correlated with overall survival (OS), prostate-specific antigen-progression-free survival (PSA-PFS) (i.e., time from diagnosis to PSA progression or death from any cause), radiologic progression-free survival, and time to no longer clinically benefiting from treatment. For interlesional assessment, a subset of PSMA-positive lesions was extracted from each patient and compared longitudinally. Patients classified as having either interlesional progression or interlesional homogeneous response were included in the OS and PSA-PFS analyses. The median OS was 22 mo for patients with PD ( = 8) and 51 mo for those with non-PD ( = 16) (hazard ratio [HR], 28.2; < 0.0001). PSMA PET/CT-based response was significantly associated with median PSA-PFS (6.5 mo vs. not reached [NR]; HR, 20.5; = 0.0001), radiologic progression-free survival (9 mo vs. NR; HR, 12.2; = 0.002), and time to no longer clinically benefiting from treatment (12 mo vs. NR; HR, 18.6; = 0.0002) for patients with PD versus non-PD, respectively. The results were similar at week 12 and remained statistically significant. Interlesional assessment was performed for 125 PSMA-positive lesions in 20 (83%) patients. At week 12, 9 (45%) of 20 patients had interlesional progression, which was significantly associated with worse outcomes compared with patients who had an interlesional homogeneous response (median PSA-PFS, 7 mo vs. NR; HR, 19.2; < 0.0001; median OS, 16 mo vs. 52 mo; HR, 31.2; < 0.0001, respectively). Assessment of interlesional tumor response at week 12 by sequential PSMA PET/CT enabled the identification of patients with mCRPC who had worse outcomes after treatment with an androgen receptor pathway inhibitor.