Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography–Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer

Key Points Question Is previously occult, nonlocalized (regional or metastatic) disease detected on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) associated with clinically significant outcomes in patients with high-risk and very high-risk prostate cancer? Findings In this cohort study of 5275 patients, a nomogram estimative of an individual’s risk of nonlocalized disease on PSMA PET/CT was significantly associated with long-term outcomes, including distant metastasis and prostate cancer–specific mortality. The nomogram performed favorably compared with other risk-stratification tools. Meaning These findings suggest that previously occult disease may be associated with outcomes in this patient population.
This cohort study evaluates the prognostic significance of a nomogram that models an individual’s risk of nonlocalized upstaging on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and compares its performance with existing risk-stratification tools.
Importance Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. Objectives To evaluate the prognostic significance of a nomogram that models an individual’s risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools. Design, Setting, and Participants This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. Exposures Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. Main Outcomes and Measures PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer–specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. Results Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P