Baseline Nodal Status on 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Intermediate- to High-risk Prostate Cancer Is Prognostic for Treatment Failure: Follow-up of the proPSMA Trial.

Background and objective: There is uncertainty regarding the clinical significance of ⁶⁸Ga-PSMA-11 positron emission tomography (PET) computed tomography (CT) findings in men with prostate cancer. In this prespecified objective of the proPSMA study, we report the prognostic value of PET-defined nodal involvement.

Methods: Men with intermediate- to high-risk prostate cancer (grade group 3-5, prostate-specific antigen [PSA] ≥20 ng/ml, or clinical stage ≥T3) underwent ⁶⁸Ga-PSMA-11 PET-CT or CT and bone scanning as first- or second-line imaging. Patients without distant metastatic disease (miM0) in either arm were stratified by prostate-specific membrane antigen (PSMA) PET-CT negative (miN0) or positive (miN1) regional nodal status and followed for up to 54 mo. Treatment failure was defined as biochemical failure, commencement of salvage therapy, or development of distant metastatic disease. Freedom from treatment failure (FFTF) was plotted on Kaplan-Meier curves for patients with miN0 and miN1 cancer based on PET-CT and CT/bone scan classification. Cox proportional hazards were used to derive a hazard ratio (HR) for FFTF.

Key findings and limitations: A total of 302 patients were randomised at ten sites. Of them, 294 underwent a PSMA PET-CT. In all, 251 patients with miM0 disease were included in this analysis. Patients were treated with curative-intent surgery or radiotherapy ± androgen deprivation. FFTF was greater in the PSMA PET-CT miN0M0 group than in the miN1M0 group (HR 2.1 [95% confidence interval {CI} 1.2-3.7], p = 0.01). CT/bone scan-defined N0M0 versus N1M0 was not prognostic for FFTF (HR 0.6, 95% CI 0.1-2.4, p = 0.45). In a multivariate analysis, PSMA PET-CT miN1M0 versus miN0M0 remained prognostic after adjusting for PSA, Gleason grade group, and age (HR 2.0, 95% CI 1.10-3.64, p = 0.007).

Conclusions and clinical implications: PSMA PET-CT regional nodal staging at baseline is prognostic for medium-term oncological outcomes, identifying patients at a higher risk of treatment failure.

Patient summary: Men with prostate cancer who have cancer in their nearby lymph nodes observed on a prostate-specific membrane antigen positron emission tomography scan have poorer outcomes than men who have no nearby lymph node involvement.