Lymph Node Metastases In Prostate Cancer Research Articles

An artificial intelligence model for detecting pathological lymph node metastasis in prostate cancer using whole slide images: a retrospective, multicentre, diagnostic study

The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P=0.023; 0.879 [0.767-0.950], P=0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P>0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P=0.041) to the level of senior pathologists (both P>0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P<0.0001;-34%, P<0.0001;-29%, P<0.0001; and-27%, P=0.00031). ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

Diagnostic capability of 18F-PSMA PET-MRI and pelvic MRI plus bone scan in treatment-naive prostate cancer: a single-center paired validating confirmatory study.

Radical prostatectomy with pelvic lymph node dissection for the treatment of high-risk localized prostate cancer (PCa) results in long-term benefits in selected patients. But insufficient sensitivity of conventional examinations which are pelvic MRI and bone scan, limits the diagnosis of bone and lymph node metastasis of PCa. This affects the surgical management strategy of a large number of patients. The purpose of this study was to investigate whether 18F-prostate-specific membrane antigen (PSMA) PET-MRI could improve the clinical detection of PCa metastases compared with the conventional pelvic MRI plus bone scan. From April 2020 to April 2023, we prospectively enroled 472 patients with histologically proven PCa in our centre, and 120 patients underwent 18F-PSMA PET-MRI, multiparametric MRI, and bone scan before laparoscopic radical prostatectomy plus lymph node dissection. The accuracy of imaging results in detecting lymph node and bone metastatic lesions was compared between PSMA PET-MRI and MRI plus bone scan. In diagnosing lymph node metastasis, PSMA PET-MRI had an area under the curve (AUC) of 0.844 (95% CI: 0.738-0.949, P < 0.001), sensitivity and specificity of 75% and 96%, which performed apparently better than MRI [AUC=0.615 (95% CI: 0.480-0.750, P =0.073)]. PSMA PET-MRI showed excellent expression in the diagnosis of bone metastases, with an AUC of 0.910 (95% CI: 0.840-0.981, P <0.001) compared to 0.700 (95% CI: 0.577-0.823, P =0.001) in bone scanning. PSMA PET-MRI also had higher sensitivity than bone scanning (90% vs. 43%), while lower specificity (92% vs. 97%). PSMA PET-MRI is superior to conventional imaging at diagnosing metastases in lymph nodes and bones in PCa and can provide a more accurate stagement.

ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer

BackgroundMetastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq.MethodsA total of 32,766 cells were obtained from four PCa tissue samples for scRNA-seq, annotated, and grouped. InferCNV, GSVA, DEG functional enrichment analysis, trajectory analysis, intercellular network evaluation, and transcription factor analysis were carried out for each cell subgroup. Furthermore, validation experiments targeting luminal cell subgroups and CXCR4 + fibroblast subgroup were performed.ResultsThe results showed that only EEF2 + and FOLH1 + luminal subgroups were present in LNM, and they appeared at the initial stage of luminal cell differentiation, which were comfirmed by verification experiments. The MYC pathway was enriched in the EEF2 + and FOLH1 + luminal subgroups, and MYC was associated with PCa LNM. Moreover, MYC did not only promote the progression of PCa, but also led to immunosuppression in TME by regulating PDL1 and CD47. The proportion of CD8 + T cells in TME and among NK cells and monocytes was lower in LNM than in the primary lesion, while the opposite was true for Th and Treg cells. Furthermore, these immune cells in TME underwent transcriptional reprogramming, including CD8 + T subgroups of CCR7 + and IL7R+, as well as M2-like monocyte subgroups expressing tumor-associated signature genes, like CCR7, SGKI, and RPL31. Furthermore, STEAP4+, ADGRF5 + and CXCR4+, and SRGNC + fibroblast subgroups were closely related to tumor progression, tumor metabolism, and immunosuppression, indicating their contributions in PCa metastasis. Meanwhile, The presence of CXCR4 + Fibroblasts in PCa was confirmed by polychromatic immunofluorescence.ConclusionsThe significant heterogeneity of luminal, immune, and interstitial cells in PCa LNM may not only directly contribute to tumor progression, but also indirectly result in TME immunosuppression, which may be the cause of metastasis in PCa and in which MYC played an role.

Inguinal Lymphadenopathy After Renal Transplantation Leading to the Diagnosis of Prostate Cancer: A Case Report

It is extremely rare for a patient with prostate cancer (PCa) to have palpable lymph nodes at the initial presentation. In fact, only 4 case reports of palpable superficial lymph nodes at the first visit led to the diagnosis of PCa. Moreover, no such cases are reported in kidney transplantation (KT) patients. A 72-year-old man who started hemodialysis due to diabetic nephropathy was referred to our hospital for a KT in 2018. Before the KT, he had a negative screen for cancer, including PCa. The postoperative course was good. He felt a lump in the left inguinal region three years after the KT. A computed tomography scan revealed abdominal and left inguinal lymphadenopathy, which was consistent with a post-transplant lymphoproliferative disorder. However, a biopsy of an inguinal lymph node revealed adenocarcinoma with positive prostate-specific antigen (PSA) staining, suggesting lymph node metastasis of PCa. The blood PSA level was 1674.23 ng/mL. A prostate biopsy was performed, the pathologic diagnosis of which was PCa, with a Gleason score of 10. In conclusion, even though the standardized incidence ratio of PCa is not known to increase in KT patients, PCa should be included in the differential diagnosis, along with the possibility of post-transplant lymphoproliferative disorder. We also suggest the importance of regular screening for malignant tumors after organ transplantation.

Transcription factor p53-mediated activation of miR-519d-3p and downregulation of E2F1 attenuates prostate cancer growth and metastasis.

Prostate cancer (PCa) is a commonly diagnosed malignancy in men. The transcription factor p53, a well-known cancer suppressor, has been extensively analyzed in the progression of many tumor types, but its involvement in PCa remains not fully understood. Hence, this study aims to explore the possible molecular mechanism underlying p53 in the growth and metastasis of PCa. Based on bioinformatics analysis findings of GEPIA and starBase databases, p53 was demonstrated to be involved in the development of PCa by transcriptionally activating microRNA-519d-3p (miR-519d-3p) expression to suppress the expression of E2F transcription factor 1 (E2F1) and CD147. In order to verify this finding, clinically-obtained PCa tumor tissues were enrolled and commercially-purchased PCa cell lines were used to detect the cell viability, cycle, and apoptosis, as well as invasion and migration by CCK-8, flow cytometry, and Transwell assays respectively. The results of clinical tissue experiments and in vitro cell experiments showed that miR-519d-3p and p53 were poorly-expressed in PCa tissues and cell lines, while E2F1 was highly-expressed. Overexpression of miR-519d-3p led to inhibited PCa cell proliferation, invasion and migration, and p53 overexpression was found to promote miR-519d-3p expression to suppress the malignant characteristics of PCa cells, while the additional E2F1 overexpression restored the malignant traits. Moreover, ChIP analysis and dual-luciferase reporter assay confirmed the interactions among p53, miR-519d-3p, and E2F1. Mechanistically, it was found that p53 transcriptionally activated miR-519d-3p to suppress E2F1 expression. Finally, the in vitro results were further validated by in vivo experiments, which showed that miR-519d-3p prevents tumorigenesis and lymph node metastasis of PCa in nude mice via negatively regulation of E2F1 and CD147. Taken together, the findings uncover that the transcription factor p53 could upregulate miR-519d-3p expression to directly suppress the expression of E2F1, thus inhibiting PCa growth and metastasis. It highlights a novel therapeutic strategy against PCa based on the p53/miR-519d-3p/E2F1 regulatory pathway.

MP60-20 DETECTION OF LYMPH NODE METASTASES USING POOLING METHOD BY ONE-STEP NUCLEIC ACID AMPLIFICATION (OSNA) ASSAY IN PROSTATE CANCER PATIENTS: PRELIMINARY RESULTS FROM A PROSPECTIVE-MULTICENTRE STUDY

MP60-20 DETECTION OF LYMPH NODE METASTASES USING POOLING METHOD BY ONE-STEP NUCLEIC ACID AMPLIFICATION (OSNA) ASSAY IN PROSTATE CANCER PATIENTS: PRELIMINARY RESULTS FROM A PROSPECTIVE-MULTICENTRE STUDY

18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is accurate for high-grade prostate cancer bone staging when compared to bone scintigraphy.

In this study, we compared 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography/computed tomography (PET/CT) and bone scintigraphy accuracies for the detection of bone metastases for primary staging in high-grade prostate cancer (PCa) patients to determine if 18F-FDG-PET/CT could be used alone as a staging modality. Men with localized high-grade PCa (n=256, Gleason 8-10, International Society of Urological Pathology [ISUP] grades 4 or 5) were imaged with bone scintigraphy and 18F-FDG-PET/CT. We compared, on a per-patient basis, the accuracy of the two imaging modalities, taking inter-modality agreement as the standard of truth (SOT). 18F-FDG-PET/CT detected at least one bone metastasis in 33 patients compared to only 26 with bone scan. Of the seven false-negative bone scintigraphies, four (57.1%) were solitary metastases (monometastatic), three (42.9%) were oligometastatic (2-4 lesions), and none were plurimetastatic (>4 lesions). Compared to SOT, 18F-FDG-PET/CT showed higher sensitivity and accuracy than bone scintigraphy (100% vs. 78.8%, and 98.7% vs. 98.2%) for the detection of skeletal lesions. 18F-FDG-PET/CT appears similar or better than conventional bone scans to assess for bone metastases in patients newly diagnosed with high-grade PCa. Since intraprostatic FDG uptake is also a biomarker for failure of radical prostatectomy and that FDG-PET/CT has been shown to be accurate in detecting PCa lymph node metastasis, FDG-PET/CT has the potential to be used as the sole preoperative staging modality in high-grade PCa.

A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer.

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l−1 with a sensitivity of 60.0% and a specificity of 67.8%. In the validation set, the optimal cutoff value showed significantly higher sensitivity than that of conventional magnetic resonance imaging (MRI) (0.619 vs 0.238, P < 0.001). The nomogram involving PMC, free prostate-specific antigen (fPSA), clinical T stage, preoperative Gleason score, and monocyte-to-lymphocyte ratio (MLR) was generated, which showed a robust predictive capacity for predicting LNM before the operation. Our results indicated that PMC as a single agent, or combined with other clinical parameters, showed a robust predictive capacity for LNM in PCa. It can be employed as a complementary factor for the decision of whether to conduct pelvic lymph node dissection.

P003 - How often is Cloquet’s node involved in prostate cancer lymph node metastasis?

P003 - How often is Cloquet’s node involved in prostate cancer lymph node metastasis?

RETRACTED: LncRNA DLX6-AS1 Promotes Malignant Phenotype and Lymph Node Metastasis in Prostate Cancer by Inducing LARGE Methylation

Long non-coding RNAs (lncRNAs) have recently become recognized as crucial players in cancer cellular events including proliferation, migration, and invasion. Herein, we investigated the potential role of lncRNA DLX6-AS1 in prostate cancer cell malignant behaviors and lymph node metastasis. A differentially expressed lncRNA DLX6-AS1 and its downstream regulatory gene (LARGE) were predicted by analysis in silico. RT-qPCR and western blot analysis results demonstrated that DLX6-AS1 was highly expressed, but LARGE was poorly expressed in prostate cancer tissues and cells. The online website indicated that DLX6-AS1 negatively targeted LARGE expression, which was validated by Pearson correlation analysis and MSP. ChIP, RIP, and RNA pull-down assays further suggested that DLX6-AS1 downregulated LARGE expression through recruitment of DNMT1 to its promoter. We induced DLX6-AS1/LARGE overexpression or knockdown to examine their effects through Edu and Transwell assays, which revealed that DLX6-AS1 overexpression accelerated proliferation, invasion, and migration of prostate cancer cells, and that overexpression of LARGE rescued these effects. Tumors xenografts studies confirmed that DLX6-AS1 promoted lymph node metastasis by regulating LARGE, as evidenced by enhanced expression of MMP-9, uPAR, and cathepsin B. In summary, DLX6-AS1 stimulated prostate cancer malignant progression and lymph node metastasis by inducing DNMT1-mediated LARGE methylation, highlighting a potential therapeutic target against prostate cancer.

384 - Correlation between the sides of positive biopsy and lymph-node metastases in prostate cancer. Are we on the right side?

384 - Correlation between the sides of positive biopsy and lymph-node metastases in prostate cancer. Are we on the right side?

Comparison of cross-sectional imaging techniques for the detection of prostate cancer lymph node metastasis: a critical review.

Conventional staging for prostate cancer (PCa) is performed for men diagnosed with unfavorable-intermediate or higher risk disease. Computed tomography (CT) of the abdomen and pelvis and whole body bone scan remains the standard of care for the detection of visceral, nodal, and bone metastasis. The implementation of the 2012 United States Preventive Services Task Force recommendation against routine prostate specific antigen (PSA) screening resulted in a rise of metastatic PCa at the time of diagnosis, emphasizing the importance of effective imaging modalities for evaluating metastatic disease. CT plays a major role in clinical staging at the time of PCa diagnosis, but multi-parametric magnetic resonance imaging (MRI) is now integrated into many prostate biopsy protocols for the detection of primary PCa, and may be a surrogate for CT for nodal staging. Current guidelines incorporate both CT and MRI as appropriate cross-sectional imaging modalities for the identification of nodal metastasis in indicated patients. There is an ongoing debate about the utility of traditional cross-sectional imaging modalities as well as advanced imaging modalities in detection of both organ-confined PCa detection and nodal involvement.

Peri-prostatic adipose tissue measurements using MRI predict prostate cancer aggressiveness in men undergoing radical prostatectomy.

To evaluate the effect of peri-prostatic adipose tissue (PPAT) measurements using preoperative MRI on the prediction of prostate cancer (PCa) aggressiveness in men undergoing radical prostatectomy (RP). We performed a retrospective study on 179 consecutive patients receiving RP from June 2016 to October 2018. Clinical characteristics were collected. PPAT measurements including peri-prostatic fat area (PPFA) and peri-prostatic fat area to prostate area (PA) ratio (PPFA/PA) were calculated by MRI. Multivariable logistic regression analysis was performed to identify independent predictors of PCa lymph node metastasis (LNM). The predictive performance was estimated through ROC curves. Nomograms were created based on the predictors. Pathologic Gleason score positively correlated with digital rectal examination (DRE), PSA, PPFA/PA, P504S, and Ki-67 (all P < 0.05). ROC curves revealed that high PPFA and high PPFA/PA were associated with LNM (both P < 0.05). Multivariate analysis revealed that high PPFA/PA, pathologic Gleason score, pT stage, and Ki-67 were independently predictive of LNM. The nomograms were created and the C-index was 0.945. PPFA/PA is an independent predictor for LNM along with Gleason score, pT stage, and Ki-67. PPFA/PA may help predict LNM in men undergoing RP, thus providing adjunctive information for therapeutic strategy and prognosis.

A CT-based radiomics model to detect prostate cancer lymph node metastases in PSMA radioguided surgery patients

PurposeIn recurrent prostate carcinoma, determination of the site of recurrence is crucial to guide personalized therapy. In contrast to prostate-specific membrane antigen (PSMA)–positron emission tomography (PET) imaging, computed tomography (CT) has only limited capacity to detect lymph node metastases (LNM). We sought to develop a CT-based radiomic model to predict LNM status using a PSMA radioguided surgery (RGS) cohort with histological confirmation of all suspected lymph nodes (LNs).MethodsEighty patients that received RGS for resection of PSMA PET/CT-positive LNMs were analyzed. Forty-seven patients (87 LNs) that received inhouse imaging were used as training cohort. Thirty-three patients (62 LNs) that received external imaging were used as testing cohort. As gold standard, histological confirmation was available for all LNs. After preprocessing, 156 radiomic features analyzing texture, shape, intensity, and local binary patterns (LBP) were extracted. The least absolute shrinkage and selection operator (radiomic models) and logistic regression (conventional parameters) were used for modeling.ResultsTexture and shape features were largely correlated to LN volume. A combined radiomic model achieved the best predictive performance with a testing-AUC of 0.95. LBP features showed the highest contribution to model performance. This model significantly outperformed all conventional CT parameters including LN short diameter (AUC 0.84), LN volume (AUC 0.80), and an expert rating (AUC 0.67). In lymph node–specific decision curve analysis, there was a clinical net benefit above LN short diameter.ConclusionThe best radiomic model outperformed conventional measures for detection of LNM demonstrating an incremental value of radiomic features.

MP62-08 PROSTATE CANCER LYMPH NODE METASTASIS: HOW OFTEN IS CLOQUET’S NODE INVOLVED?

You have accessJournal of UrologyProstate Cancer: Staging I (MP62)1 Apr 2020MP62-08 PROSTATE CANCER LYMPH NODE METASTASIS: HOW OFTEN IS CLOQUET’S NODE INVOLVED? Sarah E Apatov, Ines Rivero Belenchon*, Clauda Mercader Barrull, Natalia Picola Brau, Nicole Benfante, Samson Fine, and Karim A Touijer Sarah E ApatovSarah E Apatov More articles by this author , Ines Rivero Belenchon*Ines Rivero Belenchon* More articles by this author , Clauda Mercader BarrullClauda Mercader Barrull More articles by this author , Natalia Picola BrauNatalia Picola Brau More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Samson FineSamson Fine More articles by this author , and Karim A TouijerKarim A Touijer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000937.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Located below the inguinal ligament and anterior to Cooper’s ligament, Cloquet’s node is easily accessible and commonly dissected during pelvic lymph node dissection for prostate cancer. We hypothesize that Cloquet’s node - the junction between the deep inguinal nodes and the external iliac chain – is not part of lymphatic metastatic spread of prostate cancer. METHODS: 100 consecutive high-risk prostate cancer patients underwent laparoscopic radical prostatectomy and bilateral extended pelvic lymph node dissection (PLND). During PLND, Cloquet’s node was dissected and submitted separately to pathology as right and left Cloquet’s node. Each lymph node retrieved was cut in 3 mm slices which were separately embedded in paraffin, stained with hematoxylin and eosin, and examined microscopically. RESULTS: The median PSA was 7.3 ng/mL (IQR: 4.8 – 12.8). 81% of the patients had biopsy grade group 4 or 5 and 10% had cT3 disease. 37% of the patients had lymph node metastasis. Cloquet’s node was involved in one patient only (1%), this patient had six other lymph nodes as well. CONCLUSIONS: Cloquet’s node is rarely involved in prostate cancer. Even in high-risk prostate cancer, Cloquet’s node removal should not be the principal focus of the lymph node dissection. Source of Funding: No funding © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e948-e948 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sarah E Apatov More articles by this author Ines Rivero Belenchon* More articles by this author Clauda Mercader Barrull More articles by this author Natalia Picola Brau More articles by this author Nicole Benfante More articles by this author Samson Fine More articles by this author Karim A Touijer More articles by this author Expand All Advertisement PDF downloadLoading ...

Up-regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features, lymph node metastases and biochemical recurrence.

This study aimed to explore the association between LIM domain kinase 1 (LIMK1) expression in prostate cancer (PCa) tissues with advanced pathological features, lymph node metastases and biochemical recurrence. A total of 279 PCa specimens from patients who underwent radical prostatectomy and 50 benign prostatic hyperplasia (BPH) specimens were collected to construct tissue microarray, which were subjected to immunohistochemical staining for LIMK1 expression subsequently. Logistic and Cox regression analysis were used to evaluate the relationship between LIMK1 expression and clinicopathological features of patients with PCa. Immunohistochemical staining assay demonstrated that LIMK1 expression was significantly higher in PCa than BPH specimens (77.1% vs 26.0%; P < .001). LIMK1 expression was significantly higher in positive lymph node specimens than corresponding PCa specimens (P = .002; P < .001). Up‐regulation of LIMK1 was associated with prostate volume, prostate‐specific antigen, prostate‐specific antigen density, Gleason score, T stage, lymph node metastases, extracapsular extension and seminal vesicle invasion, and positive surgical margin. Multivariate logistic regression analysis demonstrated that LIMK1 was an independent risk factor for PCa lymph node metastasis (P < .05). Multivariate Cox regression analysis revealed that the up‐regulation of LIMK1 was an independent risk factor for biochemical recurrence. Kaplan‐Meier analysis indicated that up‐regulation LIMK1 was associated with shortened biochemical‐free survival (BFS) after radical prostatectomy (P < .001). In conclusion, LIMK1 was significantly up‐regulated in PCa and positive lymph node specimens and correlated with lymph node metastasis and shortened BFS of PCa. The underlying molecular mechanism of LIMK1 in PCa should be further evaluated.

Development and validation of hub genes for lymph node metastasis in patients with prostate cancer.

Lymph node metastasis is one of the most important independent risk factors that can negatively affect the prognosis of prostate cancer (PCa); however, the exact mechanisms have not been well studied. This study aims to better understand the underlying mechanism of lymph node metastasis in PCa by bioinformatics analysis. We analysed a total of 367 PCa cases from the cancer genome atlas database and performed weighted gene co‐expression network analysis to explore some modules related to lymph node metastasis. Gene Ontology analysis and pathway enrichment analysis were conducted for functional annotation, and a protein‐protein interaction network was built. Samples from the International Cancer Genomics Consortium database were used as a validation set. The turquoise module showed the most relevance with lymph node metastasis. Functional annotation showed that biological processes and pathways were mainly related to activation of the processes of cell cycle and mitosis. Four hub genes were selected: CKAP2L, CDCA8, ERCC6L and ARPC1A. Further validation showed that the four hub genes well‐distinguished tumour and normal tissues, and they were good biomarkers for lymph node metastasis of PCa. In conclusion, the identified hub genes facilitate our knowledge of the underlying molecular mechanism for lymph node metastasis of PCa.

Prostate Cancer Nodal Staging: Using Deep Learning to Predict 68Ga-PSMA-Positivity from CT Imaging Alone

Lymphatic spread determines treatment decisions in prostate cancer (PCa) patients. 68Ga-PSMA-PET/CT can be performed, although cost remains high and availability is limited. Therefore, computed tomography (CT) continues to be the most used modality for PCa staging. We assessed if convolutional neural networks (CNNs) can be trained to determine 68Ga-PSMA-PET/CT-lymph node status from CT alone. In 549 patients with 68Ga-PSMA PET/CT imaging, 2616 lymph nodes were segmented. Using PET as a reference standard, three CNNs were trained. Training sets balanced for infiltration status, lymph node location and additionally, masked images, were used for training. CNNs were evaluated using a separate test set and performance was compared to radiologists’ assessments and random forest classifiers. Heatmaps maps were used to identify the performance determining image regions. The CNNs performed with an Area-Under-the-Curve of 0.95 (status balanced) and 0.86 (location balanced, masked), compared to an AUC of 0.81 of experienced radiologists. Interestingly, CNNs used anatomical surroundings to increase their performance, “learning” the infiltration probabilities of anatomical locations. In conclusion, CNNs have the potential to build a well performing CT-based biomarker for lymph node metastases in PCa, with different types of class balancing strongly affecting CNN performance.

68Ga-PSMA-11 PET-Based Prostate Cancer Lymph Node Atlas Reveals Patterns of Potential Geographic Miss in Consensus Pelvic Nodal Contours

Gallium-68 prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) enables highly sensitive and specific detection of metastatic prostate cancer. We aimed to characterize patterns of prostate cancer lymph node metastasis through development of a PSMA PET-based lymph node atlas. We then compared our results to the RTOG consensus prostate cancer pelvic nodal atlas to reveal areas of potential geographic miss during radiation therapy. From December 2015 to October 2018, 378 patients were enrolled in a prospective study evaluating the use of 68Ga-PSMA-11 PET in the staging of prostate cancer. We identified 84 previously untreated prostate cancer patients in the study cohort who underwent staging 68Ga-PSMA PET demonstrating pelvic lymph node metastasis. DICOM images were exported to the commercially available deformable registration algorithm, and PET avid lymph nodes were manually contoured. Each node was categorized by laterality, location and volume. Finally, rigid and deformable image fusion was performed, and the location of involved pelvic lymph nodes was compared to the RTOG consensus prostate cancer pelvic nodal contours. We identified 242 68Ga-PSMA-11 PET avid lymph nodes with an average volume of 2.3mL (range 0.9-55.96mL). Among all patients, external iliac and internal iliac nodal basins were most often involved with avid nodes found in 60.7% and 34.5% of patients respectively. Pelvic (32.1%), common iliac (25.0%), perirectal (13.1%), and presacral (10.7%) nodal basins were also commonly involved followed by low frequency involvement of obturator, inguinal, anterior bladder, and retropubic regions (1.2% each). In total, 57 of 242 (24%) PSMA PET avid lymph nodes were located outside of RTOG consensus prostate cancer pelvic nodal contours; missed nodes were found in 37 of the 84 (44%) patients. The most common sites of geographic miss were in the proximal common iliac, distal anterior external iliac, low presacral and perirectal regions. We used 68Ga-PSMA-11 PET imaging to generate a prostate cancer lymph node atlas in previously untreated prostate cancer patients, revealing that more than 1 in 5 involved lymph nodes may be prone to geographic miss by current consensus pelvic nodal contours. These findings suggest that 68Ga-PSMA-11 PET may be used to supplement conventional target delineation. Further research may refine clinical scenarios in which extended lymph node delineation is warranted.

High body mass index predicts multiple prostate cancer lymph node metastases after radical prostatectomy and extended pelvic lymph node dissection

Our aim is to evaluate the association between body mass index (BMI) and preoperative total testosterone (TT) levels with the risk of single and multiple metastatic lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy and extended pelvic lymph node dissection. Preoperative BMI, basal levels of TT, and prostate-specific antigen (PSA) were evaluated in 361 consecutive patients undergoing radical prostatectomy with extended pelvic lymph node dissection between 2014 and 2017. Patients were grouped into either nonmetastatic, one, or more than one metastatic lymph node invasion groups. The association among clinical factors and LNI was evaluated. LNI was detected in 52 (14.4%) patients: 28 (7.8%) cases had one metastatic node and 24 (6.6%) had more than one metastatic node. In the overall study population, BMI correlated inversely with TT (r = −0.256; P < 0.0001). In patients without metastases, BMI inversely correlated with TT (r = −0.282; P < 0.0001). In patients with metastasis, this correlation was lost. In the overall study population, BMI (odds ratio [OR] = 1.268; P = 0.005) was the only independent clinical factor associated with the risk of multiple metastatic LNI compared to cases with one metastatic node. In the nonmetastatic group, TT was lower in patients with BMI >28 kg m−2 (P < 0.0001). In patients with any LNI, this association was lost (P = 0.232). The median number of positive nodes was higher in patients with BMI >28 kg m−2 (P = 0.048). In our study, overweight and obese patients had a higher risk of harboring multiple prostate cancer lymph node metastases and lower TT levels when compared to patients with normal BMI.