Abstract
BackgroundThe prostate-specific membrane antigen (PSMA) is a relevant target in prostate cancer, and immunohistochemistry studies showed associations with outcome. PSMA-ligand positron emission tomography (PET) is increasingly used for primary prostate cancer staging, and the molecular imaging TNM classification (miTNM) standardizes its reporting. We aimed to investigate the potential of PET-imaging to serve as a noninvasive imaging biomarker to predict disease outcome in primary prostate cancer after radical prostatectomy (RP).MethodsIn this retrospective analysis, 186 primary prostate cancer patients treated with RP who had undergone a 68Ga-PSMA-11 PET up to three months prior to the surgery were included. Maximum standardized uptake value (SUVmax), SUVmean, tumor volume (TV) and total lesion (TL) were collected from PET-imaging. Moreover, clinicopathological information, including age, serum prostate-specific antigen (PSA) level, and pathological characteristics, was assessed for disease outcome prediction. A stage group system for PET-imaging findings based on the miTNM framework was developed.ResultsAt a median follow-up after RP of 38 months (interquartile range (IQR) 22–53), biochemical recurrence (BCR) was observed in 58 patients during the follow-up period. A significant association between a positive surgical margin and miN status (miN1 vs. miN0, odds ratio (OR): 5.428, p = 0.004) was detected. miT status (miT ≥ 3a vs. miT < 3, OR: 2.696, p = 0.003) was identified as an independent predictor for Gleason score (GS) ≥ 8. Multivariate Cox regression analysis indicated that PSA level (hazard ratio (HR): 1.024, p = 0.014), advanced GS (GS ≥ 8 vs. GS < 8, HR: 3.253, p < 0.001) and miT status (miT ≥ 3a vs. miT < 3, HR: 1.941, p = 0.035) were independent predictors for BCR. For stage I disease as determined by PET-imaging, a shorter BCR-free survival was observed in the patients with higher SUVmax (IA vs. IB stage, log-rank, p = 0.022).ConclusionPreoperative miTNM classification from 68Ga-PSMA-11 PET correlates with postoperative GS, surgical margin status and time to BCR. The association between miTNM staging and outcome proposes 68Ga-PSMA-11 PET as a novel non-invasive imaging biomarker and potentially serves for ancillary pre-treatment stratification.
Highlights
The prostate-specific membrane antigen (PSMA) is a relevant target in prostate cancer, and immu‐ nohistochemistry studies showed associations with outcome
68Ga‐PSMA‐11 positron emission tomography (PET) findings molecular imaging TNM classification (miTNM) staging and miTNM stage groups In 67.2% (n = 125) of patients, the primary tumor was classified as miT2, 90.3% (n = 168) were classified as miN0, 3.8% (n = 7) were classified as miN1, 5.9% (n = 11) were classified as miN2, and 96.2% (n = 179) were classified as miM0. 68Ga-PSMA-11 PET findings
We found that following factors were significantly associated with biochemical recurrence (BCR)-free survival in prostate cancer patients: clinical data including age (HR: 1.056, 95% confidence intervals (CI) 1.018–1.096, p = 0.004) and initial prostate-specific antigen (PSA) (HR: 1.021, 95% CI 1.007–1.035, p = 0.003); pathological data including Gleason score (GS ≥ 8 vs. GS < 8, hazard ratios (HR): 5.097, 95% CI 3.013–8.625, p < 0.001), pT stage, pN stage and surgical margin
Summary
The prostate-specific membrane antigen (PSMA) is a relevant target in prostate cancer, and immu‐ nohistochemistry studies showed associations with outcome. PSMA-ligand positron emission tomography (PET) is increasingly used for primary prostate cancer staging, and the molecular imaging TNM classification (miTNM) stand‐ ardizes its reporting. We aimed to investigate the potential of PET-imaging to serve as a noninvasive imaging bio‐ marker to predict disease outcome in primary prostate cancer after radical prostatectomy (RP). There is growing interest in identifying novel biomarkers to improve BCR prediction accuracy of prostate cancer patients after radical prostatectomy (RP). In the last few years positron emission tomography (PET) probes targeting prostate-specific membrane antigen (PSMA) has significantly improved detection and localization of disease in primary and recurrent prostate cancer [1, 10,11,12]. PSMA expression increases progressively in highergrade prostate tumor cells and metastatic lesions [15, 16]
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