Dataset Information

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.

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 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 < .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.

Conclusions and relevance

These findings suggest that PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.

SUBMITTER: Xiang M

PROVIDER: S-EPMC8669522 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ContextIn December 2020, the US Food and Drug Administration approved a 68Ga-labeled prostate-specific membrane antigen ligand (68Ga-PSMA-11) for positron emission tomography (PET) in patients with suspected prostate cancer (PCa) metastasis who are candidates for initial definitive therapy. 68Ga-PSMA PET is increasingly performed for these patients and is usually combined with computed tomography (CT). In recent years, 68Ga-PSMA PET has been combined with high-resolution magnetic resonance imaging (MRI), which is beneficial for T staging and may further enhance the staging of primary PCa.ObjectiveTo compare the diagnostic accuracy of 68Ga-PSMA PET/MRI with 68Ga-PSMA PET/CT for staging of primary PCa.Evidence acquisitionA comprehensive literature search was performed using Embase, PubMed/Medline, Web of Science, Cochrane Library, and Google Scholar up to June 24, 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the QUADAS-2 tool.Evidence synthesisThe search identified 2632 articles, of which 27 were included. The diagnostic accuracy of 68Ga-PSMA PET/MRI, measured as the pooled natural logarithm of diagnostic odds ratio (lnDOR), was 2.27 (95% confidence interval [CI] 1.21-3.32) for detection of extracapsular extension (ECE), 3.50 (95% CI 2.14-4.86) for seminal vesicle invasion (SVI), and 4.73 (95% CI 2.93-6.52) for lymph node metastasis (LNM). For 68Ga-PSMA PET/CT, the analysis showed lnDOR of 2.45 (95% CI 0.75-4.14), 2.94 (95% CI 2.26-3.63), and 2.42 (95% CI 2.07-2.78) for detection of ECE, SVI, and LNM, respectively. The overall risk of bias and applicability concerns were assessed as moderate and low, respectively.Conclusions68Ga-PSMA PET/MRI shows high diagnostic accuracy equivalent to that of 68Ga-PSMA PET/CT for detection of ECE, SVI, and LNM in staging of PCa. There is an urgent need for direct comparison of the two diagnostic tests in future research.Patient summaryThe use of radioactively labeled molecules that bind to prostate-specific membrane antigen (68Ga-PSMA) for positron emission tomography (PET) scans combined with either computed tomography (CT) or magnetic resonance imaging (MRI) is increasing for prostate cancer diagnosis. There is a need for direct comparison of the two tests to demonstrate the benefit of 68Ga-PSMA PET/MRI for determining tumor stage in prostate cancer.Take home messageAfter the recent US Food and Drug Administration approval of 68Ga-labeled prostate-specific membrane antigen ligand (68Ga-PSMA) positron emission tomography (PET) for staging of primary prostate cancer (PCa), it is expected that the use of this imaging modality will increase rapidly. Our review of the literature shows that 68Ga-PSMA PET/magnetic resonance imaging has high diagnostic accuracy equivalent to that of 68Ga-PSMA PET/computed tomography in primary PCa staging. There is an urgent need for direct head-to-head comparison of the two diagnostic tests in future research.

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