PSMA PET Validates Higher Rates of Metastatic Disease for European Association of Urology Biochemical Recurrence Risk Groups: An International Multicenter Study

Abstract

The European Association of Urology (EAU) prostate cancer guidelines panel recommends risk groups for biochemical recurrence (BCR) of prostate cancer to identify men at high risk of progression or metastatic disease. The rapidly growing availability of PSMA-directed PET imaging will impact prostate cancer staging. We determined the rates of local and metastatic disease in BCR and biochemical persistence (BCP) of prostate cancer stratified by EAU BCR risk groups and BCP. Methods: Patients with BCR or BCP were enrolled under the same prospective clinical trial protocol conducted at 3 sites (n = 1,777 [91%]: UCLA, n = 662 [NCT02940262]; University of California San Francisco, n = 508 [NCT03353740]; University of Michigan, n = 607 [NCT03396874]); 183 patients with BCP from the Universities of Essen, Bologna, and Munich were included retrospectively. Patients with BCR had to have sufficient data to determine the EAU risk score. Multivariate, binomial logistic regression models were applied to assess independent predictors of M1 disease. Results: In total, 1,960 patients were included. Post-radical prostatectomy EAU BCR low-risk, EAU BCR high-risk, and BCP groups yielded distant metastatic (M1) detection in 43 of 176 (24%), 342 of 931 (37%), and 154 of 386 (40%) patients. For postradiotherapy EAU BCR low-risk and EAU BCR high-risk groups, the M1 detection rate was 113 of 309 (37%) and 110 of 158 (70%), respectively. BCP, high-risk BCR, and higher levels of serum prostate-specific antigen were significantly associated with PSMA PET M1 disease in multivariate regression analysis. PSMA PET revealed no disease in 25% and locoregional-only disease in 33% of patients with post-radical prostatectomy or postradiotherapy EAU BCR high risk. Conclusion: Our findings support the new EAU classification; EAU BCR high-risk groups have higher rates of metastatic disease on PSMA PET than do the low-risk groups. Discordant subgroups, including metastatic disease in low-risk patients and no disease in high-risk patients, warrant inclusion of PSMA PET stage to refine risk assessment.

Keywords: EAU; PSMA; prostate cancer; prostate specific membrane antigen; risk score.

Graphical abstract

FIGURE 1.

Study flowchart. IBF = interval from primary therapy to biochemical failure; PSADT = PSA doubling time; RT = radiotherapy.

FIGURE 2.

PET disease extent in EAU BCR low-risk patients, EAU BCR high-risk patients, and BCP patients (A) and predictors of PET M1 disease (B). OR = odds ratio.