Abstract

PurposePLND (pelvic lymph node dissection)-validated nomograms are widely accepted clinical tools to determine the necessity of PLND by predicting the metastasis of lymph nodes (LNMs) in pelvic region. However, these nomograms are in lacking of a threshold to predict the metastasis of extrareolar lymph nodes beyond pelvic region, which is not suitable for PLND. The aim of this study is to evaluate a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases beyond pelvic region in high-risk prostate cancer patients, by using 68Ga-PSMA PET/CT as a reference to determine LN metastases (LNMs).Experimental DesignWe performed a retrospective analysis of 57 high-risk treatment-naïve PC patients in a large tertiary care hospital in China who underwent 68Ga-PSMA-617 PET/CT imaging. LNMs was detected by 68Ga-PSMA-617 PET/CT and further determined by imaging follow-up after anti-androgen therapy. The pattern of LN metastatic spread of PC patients were evaluated and analyzed. The impact of 68Ga-PSMA PET/CT on clinical decisions based on three clinical PLND-validated nomograms (Briganti, Memorial Sloan Kettering Cancer Center, Winter) were evaluated by a multidisciplinary prostate cancer therapy team. The diagnostic performance and the threshold of these nomograms in predicting extrareolar LNMs metastasis were evaluated via receiver operating characteristic (ROC) curve analysis.ResultsLNMs were observed in 49.1% of the patients by 68Ga-PSMA PET/CT, among which 65.5% of LNMs were pelvic-regional and 34.5% of LNMs were observed in extrareolar sites (52.1% of these were located above the diaphragm). The Briganti, MSKCC and Winter nomograms showed that 70.2%-71.9% of the patients in this study need to receive ePLND according to the EAU and NCCN guidelines. The LN staging information obtained from 68Ga-PSMA PET/CT would have led to changes of planned management in 70.2% of these patients, including therapy modality changes in 21.1% of the patients, which were mainly due to newly detected non-regional LNMs. The thresholds of nomograms to predict non-regional LNMs were between 64% and 75%. The PC patients with a score >64% in Briganti nomogram, a score >75% in MSKCC nomogram and a score >67% in Winter nomogram were more likely to have non-regional LNMs. The AUCs (Area under curves) of the clinical nomograms (Briganti, MSKCC and Winter) in predicting non-regional LNMs were 0.816, 0.830 and 0.793, respectively.ConclusionsBy using 68Ga-PSMA PET/CT as reference of LNM, the PLND-validated clinical nomograms can not only predict regional LNMs, but also predict non-regional LNMs. The additional information from 68Ga-PSMA PET/CT may provide added benefit to nomograms-based clinical decision-making in more than two-thirds of patients for reducing unnecessary PLND. We focused on that a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases with an AUC accuracy of about 80% after optimizing the simple nomograms which may help to improve the efficiency for PC therapy significantly in clinical practice.

Highlights

  • Prostate cancer (PC) is the most commonly diagnosed malignant tumor and the second leading cause of cancer associated death in men worldwide [1]

  • This study depicted the pattern of metastatic spread by 68GaPSMA positron emission tomography computed tomography (PET/computed tomography (CT)) and demonstrated the potential benefit of this imaging modality on clinical decision-making for high-risk PC patients, especially in patients with non-regional lymph node metastases (LNMs). 68GaPSMA PET/CT can provide pattern of metastatic spread of LNMs with a higher sensitivity and specificity compared with conventional morphological imaging [34]

  • One previous study indicated that, compared with multiparametric magnetic resonance imaging (mpMRI), more LNMs can be observed by 68Ga-Prostate-specific membrane antigen (PSMA) PET/CT in 27.8% of PC patients [35]

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Summary

Introduction

Prostate cancer (PC) is the most commonly diagnosed malignant tumor and the second leading cause of cancer associated death in men worldwide [1]. The most common route of metastasis is lymphogenous spread [2], and regional lymph node metastases (LNMs) can be observed in high-risk PC patients at 19.4% [3]. To better predict the risk of regional LNMs in PC patients, multiple pelvic lymph node dissection (PLND) validated nomograms, such as the Briganti, Memorial Sloan Kettering Cancer Center (MSKCC) and Winter nomograms were created to identify optimal candidates for PLND in treatment-naïve PC patients, according to EAU (European Association of Urology) and NCCN (National Comprehensive Cancer Network) guidelines [5,6,7]. PLND should be performed in the patients with LNMs risk higher than 2% in MSKCC nomogram, 5% in Briganti nomogram or 7% in Winter nomogram [5,6,7]

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