Abstract
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 riskstratification tools. DESIGN, SETTING, AND PARTICIPANTS This cohort study included patients diagnosed with highrisk 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 probabilitywas significantly prognostic of all clinical end points, with 8-year C indicesof 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 < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95%CI, 0.66-0.71] vs STAR-CAP, 0.65 [95%CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95%CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95%CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E2138550 |
| Journal | JAMA network open |
| Volume | 4 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 13 2021 |
Funding
Conflict of Interest Disclosures: Dr Savjani reported receiving grants from Varian Medical Systems Research outside the submitted work. Dr Karnes reported delivering an advisory lecture for Telix/Lanteus outside the submitted work. Dr Tosoian reported be cofounder of and holding equity in LynxDx. Dr Trock reported receiving grants from Myriad Genetics and MDxHealth to their institution outside the submitted work. Dr Spratt reported receiving personal fees from Janssen Pharmaceuticals, AstraZeneca, Boston Scientific, and Varian outside the submitted work. Dr Song reported receiving grants from Candel Therapeutics, Bayer, Celgene, BioProtect, Allegheny Health Network, and the National Cancer Institute outside the submitted work. Dr Ross reported receiving personal fees from GenomeDx, Bayer, Astellas, Pfizer, Myovant, and Blue Earth outside the submitted work. Dr Boutros reported serving on the scientific advisory boards of Sage Bionetworks, BioSymetrics, Intersect Diagnostics outside the submitted work. Dr Nickols reported receiving grants from Lantheus during the conduct of the study; receiving grants from Janssen Pharmaceuticals and Bayer outside the submitted work; and receiving personal fees from Oncolinea outside the submitted work. Dr Rettig reported consulting for Amgen, Ambrx, and Roivant; serving as speaker for Bayer and Johnson & Johnson; receiving nonfinancial support from Merck and Novartis outside the submitted work; and having a patent pending for androgen receptor inhibitors. Dr Tward reported serving on the advisory board of Blue Earth Diagnostics during the conduct of the study and receiving grants from Bayer and Myriad Genetics outside the submitted work. Dr Steinberg reported receiving honoraria from Viewray outside the submitted work. Dr Tilki reported receiving personal fees from AAA/Novartis, Apogepha, AstraZeneca, Exact Sciences, Ipsen, Roche, Takeda, and mIR Scientific outside the submitted work. Dr Czernin
ASJC Scopus subject areas
- General Medicine
