Pub Date : 2023-12-01DOI: 10.1016/j.prnil.2023.09.001
Taeyoung Park, Philip Gu, Chang-Hee Kim, Kwang Taek Kim, Kyung Jin Chung, Tea Beom Kim, Han Jung, Sang Jin Yoon, Jin Kyu Oh
Background
Artificial intelligence (AI) is changing our life, including the medical field. Repeated machine learning using big data made various fields more predictable and accurate. In medicine, IBM Watson for Oncology (WFO), trained by Memorial Slone Kettering Cancer Center (MSKCC), was first introduced and applied in 14 countries worldwide.
Our study was designed to assess the feasibility of WFO in actual clinical practice. We aimed to investigate the concordance rate between WFO and multidisciplinary tumor board (MTB) in Urologic cancer patients.
Materials and methods
We reviewed retrospectively collected data for consecutive patients who underwent WFO and MTB simultaneously in the diagnosis of urologic malignancy before determining further treatment between August 2017 and September 2020. We compared the recommendation of the AI system, WFO (IBM Watson Health, Cambridge, MA), with the opinion of MTB for further managing all patients diagnosed with urologic malignancies such as prostate, bladder, and kidney cancer.
Results
A total of 55 patients were enrolled in our study. The number of patients with prostate cancer was 48. The number of bladder and kidney cancer patients was 5 and 2, respectively. The overall concordance rate between WFO and MTB was 92.7%. Three patients could not suggest proper treatment options using WFO, and the recommended choice of WFO was not feasible in the Korean Health Insurance Review and Assessment Service.
Conclusions
The decision of WFO showed a high concordance rate with a multidisciplinary tumor board for urologic oncology. However, some recommendations of WFO were not feasible in actual practice, and WFO still has some points to improve and modify. Interestingly, applying WFO is likely to facilitate a multidisciplinary team approach.
{"title":"Artificial intelligence in urologic oncology: the actual clinical practice results of IBM Watson for Oncology in South Korea","authors":"Taeyoung Park, Philip Gu, Chang-Hee Kim, Kwang Taek Kim, Kyung Jin Chung, Tea Beom Kim, Han Jung, Sang Jin Yoon, Jin Kyu Oh","doi":"10.1016/j.prnil.2023.09.001","DOIUrl":"10.1016/j.prnil.2023.09.001","url":null,"abstract":"<div><h3>Background</h3><p>Artificial intelligence (AI) is changing our life, including the medical field. Repeated machine learning using big data made various fields more predictable and accurate. In medicine, IBM Watson for Oncology (WFO), trained by Memorial Slone Kettering Cancer Center (MSKCC), was first introduced and applied in 14 countries worldwide.</p><p>Our study was designed to assess the feasibility of WFO in actual clinical practice. We aimed to investigate the concordance rate between WFO and multidisciplinary tumor board (MTB) in Urologic cancer patients.</p></div><div><h3>Materials and methods</h3><p>We reviewed retrospectively collected data for consecutive patients who underwent WFO and MTB simultaneously in the diagnosis of urologic malignancy before determining further treatment between August 2017 and September 2020. We compared the recommendation of the AI system, WFO (IBM Watson Health, Cambridge, MA), with the opinion of MTB for further managing all patients diagnosed with urologic malignancies such as prostate, bladder, and kidney cancer.</p></div><div><h3>Results</h3><p>A total of 55 patients were enrolled in our study. The number of patients with prostate cancer was 48. The number of bladder and kidney cancer patients was 5 and 2, respectively. The overall concordance rate between WFO and MTB was 92.7%. Three patients could not suggest proper treatment options using WFO, and the recommended choice of WFO was not feasible in the Korean Health Insurance Review and Assessment Service.</p></div><div><h3>Conclusions</h3><p>The decision of WFO showed a high concordance rate with a multidisciplinary tumor board for urologic oncology. However, some recommendations of WFO were not feasible in actual practice, and WFO still has some points to improve and modify. Interestingly, applying WFO is likely to facilitate a multidisciplinary team approach.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 4","pages":"Pages 218-221"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2287888223000405/pdfft?md5=d079b9c289366d335716651a6ca34640&pid=1-s2.0-S2287888223000405-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135889550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.prnil.2023.07.002
Tae Hoon Lee , Hongryull Pyo , Gyu Sang Yoo , Hyun Moo Lee , Seong Soo Jeon , Seong Il Seo , Byong Chang Jeong , Hwang Gyun Jeon , Hyun Hwan Sung , Minyong Kang , Wan Song , Jae Hoon Chung , Bong Kyung Bae , Won Park
Background
This study aimed to evaluate the treatment outcomes and define the prostate-specific antigen (PSA) kinetics as potential prognostic factors in patients with intermediate- or high-risk localized prostate cancer (PCa) who underwent moderately hypofractionated radiation therapy.
Methods
The study retrospectively reviewed the medical records of 149 patients with intermediate- or high-risk localized PCa who underwent definitive radiation therapy (70 Gy in 28 fractions) without androgen deprivation therapy. Clinical outcomes were analyzed based on risk stratification (favorable-intermediate, unfavorable-intermediate, and high-risk). The biochemical failure rate (BFR) and clinical failure rate (CFR) were stratified based on the PSA nadir and the time to the PSA nadir to identify the prognostic effect of PSA kinetics. Acute and late genitourinary and gastrointestinal adverse events were analyzed.
Results
Significant differences were observed in the BFR and CFR according to risk stratification. No recurrence was observed in the favorable intermediate-risk group. The 7-year BFR and CFR for the unfavorable intermediate-risk and high-risk groups were 19.2% and 9.8%, and 31.1% and 25.3%, respectively. Patients with a PSA nadir >0.33 ng/mL or a time to the PSA nadir <36 months had a significantly greater BFR and CFR. The crude rate of grade 3 late adverse events was 3.4% (genitourinary: 0.7%; gastrointestinal: 2.7%). No grade 4–5 adverse event was reported.
Conclusion
A significant difference in clinical outcomes was observed according to risk stratification. The PSA nadir and time to the PSA nadir were strongly associated with the BFR and CFR. Therefore, PSA kinetics during follow-up are important for predicting prognosis.
{"title":"Prostate-specific antigen kinetics in hypofractionated radiation therapy alone for intermediate- and high-risk localized prostate cancer","authors":"Tae Hoon Lee , Hongryull Pyo , Gyu Sang Yoo , Hyun Moo Lee , Seong Soo Jeon , Seong Il Seo , Byong Chang Jeong , Hwang Gyun Jeon , Hyun Hwan Sung , Minyong Kang , Wan Song , Jae Hoon Chung , Bong Kyung Bae , Won Park","doi":"10.1016/j.prnil.2023.07.002","DOIUrl":"10.1016/j.prnil.2023.07.002","url":null,"abstract":"<div><h3>Background</h3><p>This study aimed to evaluate the treatment outcomes and define the prostate-specific antigen (PSA) kinetics as potential prognostic factors in patients with intermediate- or high-risk localized prostate cancer (PCa) who underwent moderately hypofractionated radiation therapy.</p></div><div><h3>Methods</h3><p>The study retrospectively reviewed the medical records of 149 patients with intermediate- or high-risk localized PCa who underwent definitive radiation therapy (70 Gy in 28 fractions) without androgen deprivation therapy. Clinical outcomes were analyzed based on risk stratification (favorable-intermediate, unfavorable-intermediate, and high-risk). The biochemical failure rate (BFR) and clinical failure rate (CFR) were stratified based on the PSA nadir and the time to the PSA nadir to identify the prognostic effect of PSA kinetics. Acute and late genitourinary and gastrointestinal adverse events were analyzed.</p></div><div><h3>Results</h3><p>Significant differences were observed in the BFR and CFR according to risk stratification. No recurrence was observed in the favorable intermediate-risk group. The 7-year BFR and CFR for the unfavorable intermediate-risk and high-risk groups were 19.2% and 9.8%, and 31.1% and 25.3%, respectively. Patients with a PSA nadir >0.33 ng/mL or a time to the PSA nadir <36 months had a significantly greater BFR and CFR. The crude rate of grade 3 late adverse events was 3.4% (genitourinary: 0.7%; gastrointestinal: 2.7%). No grade 4–5 adverse event was reported.</p></div><div><h3>Conclusion</h3><p>A significant difference in clinical outcomes was observed according to risk stratification. The PSA nadir and time to the PSA nadir were strongly associated with the BFR and CFR. Therefore, PSA kinetics during follow-up are important for predicting prognosis.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 173-179"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/97/c1/main.PMC10513905.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41102283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.prnil.2023.02.001
Dong Jin Park , Se Yun Kwon , Young Jin Seo , Hye Jin Byun , Kyung Seop Lee
Background
This study aimed to determine the relationship between resistive indices (RIs) and changes in prostate size after medical treatment in patients with benign prostatic hyperplasia (BPH).
Methods
A total of 86 patients with BPH were included in the study, excluding 42 patients with a total prostate volume (TPV) of <30 cc or taking α1-adrenergic blockers and 5α-reductase inhibitors (5ARI) before study participation. Therefore, the data for 44 patients were analyzed. All patients were treated with α1-adrenergic blockers and 5ARIs. The variables examined were prostate-specific antigen, International Prostate Symptom Score, quality of life score, maximal urinary flow rate, residual urine volume, TPV, transition zone volume, and RIs of the urethral artery and left and right capsular arteries. These variables were assessed at baseline and after 3 and 6 months of treatment.
Results
The mean TPV was 43.5 ± 10.9 and decreased to 35.2 ± 11.5 and 33.9 ± 9.8 after 3 and 6 months of treatment, respectively (p < 0.001). The mean RI of the urethral artery, right capsular artery, and left capsular artery at pretreatment did not decrease significantly. However, comparing the baseline with 3-month data, TPV at 3 months/TPV at baseline was significantly correlated with RI changes in the left capsular artery (r = 758; P < 0.001).
Conclusion
In patients with BPH, α1-adrenergic blocker and 5ARI medications for 3 and 6 months did not result in a significant reduction in the RI of the urethral artery and both capsular arteries. Larger scale, prospective studies are needed to evaluate the relationship between TPV and RI reductions.
{"title":"Changes of resistance indices after medication in benign prostatic hyperplasia: a prospective study","authors":"Dong Jin Park , Se Yun Kwon , Young Jin Seo , Hye Jin Byun , Kyung Seop Lee","doi":"10.1016/j.prnil.2023.02.001","DOIUrl":"10.1016/j.prnil.2023.02.001","url":null,"abstract":"<div><h3>Background</h3><p>This study aimed to determine the relationship between resistive indices (RIs) and changes in prostate size after medical treatment in patients with benign prostatic hyperplasia (BPH).</p></div><div><h3>Methods</h3><p>A total of 86 patients with BPH were included in the study, excluding 42 patients with a total prostate volume (TPV) of <30 cc or taking α1-adrenergic blockers and 5α-reductase inhibitors (5ARI) before study participation. Therefore, the data for 44 patients were analyzed. All patients were treated with α1-adrenergic blockers and 5ARIs. The variables examined were prostate-specific antigen, International Prostate Symptom Score, quality of life score, maximal urinary flow rate, residual urine volume, TPV, transition zone volume, and RIs of the urethral artery and left and right capsular arteries. These variables were assessed at baseline and after 3 and 6 months of treatment.</p></div><div><h3>Results</h3><p>The mean TPV was 43.5 ± 10.9 and decreased to 35.2 ± 11.5 and 33.9 ± 9.8 after 3 and 6 months of treatment, respectively (<em>p</em> < 0.001). The mean RI of the urethral artery, right capsular artery, and left capsular artery at pretreatment did not decrease significantly. However, comparing the baseline with 3-month data, TPV at 3 months/TPV at baseline was significantly correlated with RI changes in the left capsular artery (r = 758; <em>P</em> < 0.001).</p></div><div><h3>Conclusion</h3><p>In patients with BPH, α1-adrenergic blocker and 5ARI medications for 3 and 6 months did not result in a significant reduction in the RI of the urethral artery and both capsular arteries. Larger scale, prospective studies are needed to evaluate the relationship between TPV and RI reductions.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 139-144"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41131742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.prnil.2023.07.001
Jae Yeon Kim , Seong Soo Jeon , Jae Hoon Chung , Seung Soo Lee , Sung-Woo Park
Background
To develop a customized prostate biopsy indication using prostate health index density (PHID) combined with multiparametric magnetic resonance imaging (mpMRI) and assess the reliability of the PHID cutoff value in external populations.
Methods
A total of 521 cognitive MRI/ultrasonography fusion prostate biopsies and biomarker tests for prostate-specific antigen (PSA), free PSA, and PHI were performed after mpMRI. The predictive value for clinically significant prostate cancer (csPCa; Gleason score≥7) of PSA derivatives was examined using the ROC curve. We developed a new biopsy indication utilizing a PHID cutoff based on the Prostate Image-Reporting and Data System (PI-RADS) score, which was externally validated.
Results
The combination of PHID and mpMRI (AUC = 0.884) demonstrated the highest predictive ability for csPCa, although PHID (AUC = 0.843) and PI-RADS (AUC = 0.806) individually also showed a high diagnostic value. When a PHID cutoff of 0.75 was used in men with PI-RADS 3 lesions, the negative predictive value of csPCa was 100%, and approximately half of the biopsies could be safely avoided.
Conclusion
Compared to PHID or PI-RADS scores alone, the combination of PHID and PI-RADS scores increased the accuracy of csPCa detection and the number of cases in which biopsy could be avoided. In men with PI-RADS 3 lesions, the optimal PHID cutoff ≥0.75 can prevent half of the unnecessary biopsies without missing csPCa. In men with PI-RADS 4-5 lesions, biopsies are warranted regardless of PHID values because csPCa could be accompanied by low PHID.
{"title":"How to avoid prostate biopsy in men with Prostate Image-Reporting and Data System 3 lesion? Development and external validation of new biopsy indication using prostate health index density","authors":"Jae Yeon Kim , Seong Soo Jeon , Jae Hoon Chung , Seung Soo Lee , Sung-Woo Park","doi":"10.1016/j.prnil.2023.07.001","DOIUrl":"10.1016/j.prnil.2023.07.001","url":null,"abstract":"<div><h3>Background</h3><p>To develop a customized prostate biopsy indication using prostate health index density (PHID) combined with multiparametric magnetic resonance imaging (mpMRI) and assess the reliability of the PHID cutoff value in external populations.</p></div><div><h3>Methods</h3><p>A total of 521 cognitive MRI/ultrasonography fusion prostate biopsies and biomarker tests for prostate-specific antigen (PSA), free PSA, and PHI were performed after mpMRI. The predictive value for clinically significant prostate cancer (csPCa; Gleason score≥7) of PSA derivatives was examined using the ROC curve. We developed a new biopsy indication utilizing a PHID cutoff based on the Prostate Image-Reporting and Data System (PI-RADS) score, which was externally validated.</p></div><div><h3>Results</h3><p>The combination of PHID and mpMRI (AUC = 0.884) demonstrated the highest predictive ability for csPCa, although PHID (AUC = 0.843) and PI-RADS (AUC = 0.806) individually also showed a high diagnostic value. When a PHID cutoff of 0.75 was used in men with PI-RADS 3 lesions, the negative predictive value of csPCa was 100%, and approximately half of the biopsies could be safely avoided.</p></div><div><h3>Conclusion</h3><p>Compared to PHID or PI-RADS scores alone, the combination of PHID and PI-RADS scores increased the accuracy of csPCa detection and the number of cases in which biopsy could be avoided. In men with PI-RADS 3 lesions, the optimal PHID cutoff ≥0.75 can prevent half of the unnecessary biopsies without missing csPCa. In men with PI-RADS 4-5 lesions, biopsies are warranted regardless of PHID values because csPCa could be accompanied by low PHID.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 167-172"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/c1/main.PMC10513902.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salvage radiation therapy (SRT) is standard treatment for patients after radical prostatectomy (RP). However, the optimal timing of SRT remains to be elucidated.
Material and methods
We retrospectively reviewed 133 prostate cancer (PCa) patients who underwent SRT for biochemical recurrence after RP. Disease progression was defined as repeated prostate-specific antigen (PSA) level more than 0.2 ng/mL, greater than the post-SRT nadir or radiographic progression. A receiver operating characteristic curve analysis was used to identify the optimal pre-SRT PSA level for predicting progression after SRT. Cox regression analyses were performed to elucidate the association between clinicopathologic characteristics and disease progression.
Results
Fifty-one PCa patients (38.4%) experienced disease progression after SRT. The optimal cutoff value of the pre-SRT PSA for predicting disease progression was 0.44 ng/mL. In multivariable analysis, pre-SRT PSA >0.44 ng/mL was a significant independent predictor of post-SRT disease progression [hazard ratio (HR): 2.02, P = 0.02]. Although the pre-SRT PSA >0.44 ng/mL did not maintain its independent association with disease progression in the multivariable analysis of patients with adverse pathology (HR: 1.63, P = 0.22), PSA within 4 weeks after RP as a continuous variable was significantly associated with disease progression (HR: 1.19, P = 0.04)
Conclusions
Our results highlight that in PCa patients who undergo RP, SRT should be performed before their PSA reaches 0.44 ng/mL. In patients with adverse pathology disease, a high PSA level within the 4 weeks after RP might identify those who are likely to have disease progression, and these patients might require systemic therapy.
{"title":"Predictive factors for disease progression after salvage radiation therapy in biochemical recurrent patients treated by radical prostatectomy","authors":"Koichi Aikawa , Shoji Kimura , Fumihiko Urabe , Kosuke Iwatani , Kojiro Tashiro , Atsuhiko Ochi , Hirokazu Abe , Manabu Aoki , Takahiro Kimura","doi":"10.1016/j.prnil.2023.04.001","DOIUrl":"10.1016/j.prnil.2023.04.001","url":null,"abstract":"<div><h3>Objective</h3><p>Salvage radiation therapy (SRT) is standard treatment for patients after radical prostatectomy (RP). However, the optimal timing of SRT remains to be elucidated.</p></div><div><h3>Material and methods</h3><p>We retrospectively reviewed 133 prostate cancer (PCa) patients who underwent SRT for biochemical recurrence after RP. Disease progression was defined as repeated prostate-specific antigen (PSA) level more than 0.2 ng/mL, greater than the post-SRT nadir or radiographic progression. A receiver operating characteristic curve analysis was used to identify the optimal pre-SRT PSA level for predicting progression after SRT. Cox regression analyses were performed to elucidate the association between clinicopathologic characteristics and disease progression.</p></div><div><h3>Results</h3><p>Fifty-one PCa patients (38.4%) experienced disease progression after SRT. The optimal cutoff value of the pre-SRT PSA for predicting disease progression was 0.44 ng/mL. In multivariable analysis, pre-SRT PSA >0.44 ng/mL was a significant independent predictor of post-SRT disease progression [hazard ratio (HR): 2.02, <em>P</em> = 0.02]. Although the pre-SRT PSA >0.44 ng/mL did not maintain its independent association with disease progression in the multivariable analysis of patients with adverse pathology (HR: 1.63, <em>P</em> = 0.22), PSA within 4 weeks after RP as a continuous variable was significantly associated with disease progression (HR: 1.19, <em>P</em> = 0.04)</p></div><div><h3>Conclusions</h3><p>Our results highlight that in PCa patients who undergo RP, SRT should be performed before their PSA reaches 0.44 ng/mL. In patients with adverse pathology disease, a high PSA level within the 4 weeks after RP might identify those who are likely to have disease progression, and these patients might require systemic therapy.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 145-149"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/6f/main.PMC10513901.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.prnil.2023.06.002
Anveshika Manoj , Mohammad K. Ahmad , Gautam Prasad , Durgesh Kumar , Abbas A. Mahdi , Manoj Kumar
Background
Owing to the heterogeneous nature of prostate cancer (PCa) and errors in the characterization of the disease, researchers have been trying to unveil molecular biomarkers like microRNA (miRNA) as diagnostic markers. The purpose of our study is to demonstrate the precision of a panel of miRNAs as biomarkers with diagnostic potential for risk stratification.
Materials and methods
The present study demonstrates the comparative expression profiles of miRNA-141,-1290,-100, and -335 in both tissue and serum, including Benign Prostate Hyperplasia (BPH) and PCa, with healthy volunteers. Firstly, we demonstrate the expression of all miRNAs in the discovery cohort, including metastasis and benign tissue, and later validate their non-invasive diagnostic potential in BPH and PCa with healthy volunteers. MiRNA was isolated from tissue and serum to be quantified by RT-PCR and analyzed for biomarker potential by receiver operating characteristic (ROC) curve analysis, followed by targetome analysis of each miRNA.
Results
Among the non-invasive miRNA assessed, it was seen that miRNA 141 (P = 0.0003) and miRNA 1290 (P < 0.0001) are oncogenic with significantly higher expression, while miRNA 100 (P = 0.0002) and miRNA 335 are tumor suppressor, in PCa as compared to controls. While for BPH, miRNA 141 (P = 0.003) and miRNA 335 (P = 0.0002) were found to be significantly oncogenic and tumor suppressors, respectively. The analysis of the ROC curve of panel miRNAs (miRNA-141,-1290, and -100) portrayed a significant area under the curve with greater sensitivity and specificity. Moreover, in-silico prediction of their respective targetomes represents their extensive involvement in PCa progression and various other cascades that aid in PCa networks.
Conclusions
To the best of our knowledge, we are going to report for the first time this panel of miRNA that can be used to accurately and efficiently diagnose BPH and PCa patients from healthy males.
{"title":"Screening and validation of novel serum panel of microRNA in stratification of prostate cancer","authors":"Anveshika Manoj , Mohammad K. Ahmad , Gautam Prasad , Durgesh Kumar , Abbas A. Mahdi , Manoj Kumar","doi":"10.1016/j.prnil.2023.06.002","DOIUrl":"10.1016/j.prnil.2023.06.002","url":null,"abstract":"<div><h3>Background</h3><p>Owing to the heterogeneous nature of prostate cancer (PCa) and errors in the characterization of the disease, researchers have been trying to unveil molecular biomarkers like microRNA (miRNA) as diagnostic markers. The purpose of our study is to demonstrate the precision of a panel of miRNAs as biomarkers with diagnostic potential for risk stratification.</p></div><div><h3>Materials and methods</h3><p>The present study demonstrates the comparative expression profiles of miRNA-141,-1290,-100, and -335 in both tissue and serum, including Benign Prostate Hyperplasia (BPH) and PCa, with healthy volunteers. Firstly, we demonstrate the expression of all miRNAs in the discovery cohort, including metastasis and benign tissue, and later validate their non-invasive diagnostic potential in BPH and PCa with healthy volunteers. MiRNA was isolated from tissue and serum to be quantified by RT-PCR and analyzed for biomarker potential by receiver operating characteristic (ROC) curve analysis, followed by targetome analysis of each miRNA.</p></div><div><h3>Results</h3><p>Among the non-invasive miRNA assessed, it was seen that miRNA 141 (<em>P</em> = 0.0003) and miRNA 1290 (<em>P</em> < 0.0001) are oncogenic with significantly higher expression, while miRNA 100 (<em>P</em> = 0.0002) and miRNA 335 are tumor suppressor, in PCa as compared to controls. While for BPH, miRNA 141 (<em>P</em> = 0.003) and miRNA 335 (<em>P</em> = 0.0002) were found to be significantly oncogenic and tumor suppressors, respectively. The analysis of the ROC curve of panel miRNAs (miRNA-141,-1290, and -100) portrayed a significant area under the curve with greater sensitivity and specificity. Moreover, in-silico prediction of their respective targetomes represents their extensive involvement in PCa progression and various other cascades that aid in PCa networks.</p></div><div><h3>Conclusions</h3><p>To the best of our knowledge, we are going to report for the first time this panel of miRNA that can be used to accurately and efficiently diagnose BPH and PCa patients from healthy males.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 150-158"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/95/main.PMC10513910.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41144527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To investigate the role of urine spermine and spermine risk score in predicting prostate cancer (PCa) diagnoses in combination with multiparametric magnetic resonance imaging (mpMRI).
Methods
Three hundred forty seven consecutive men with elevated prostate-specific antigen (PSA) with mpMRI examination were prospectively enrolled in this study. In 265 patients with PSA levels between 4 and20 ng/ml, pre-biopsy urine samples were analyzed for spermine levels with ultra-high performance liquid chromatography (UPLC-MS/MS). Transperineal image-guided prostate biopsies with 16-18 cores were performed. Logistic regressions were used to form different models for the prediction of the PCa, and the performances were compared using the area under the curve (AUC).
Results
The median serum PSA level and prostate volume were 7.4 ng/mL and 33.9 mL, respectively. PCa and high-grade PCa (ISUP group ≥2, HGPCa) were diagnosed in 66.0% (175/265) and 132/265 (49.8%) cases, respectively. The urine spermine levels were significantly lower in men with PCa (0.87 vs. 2.20, P < 0.001). Multivariate analyses showed that age, PSA, PV, urine spermine level, and Prostate Imaging Reporting and Data System (PI-RADS) findings were independent predictors for PCa. The Spermine Risk Score is a multivariable model including PSA, age, prostate volume, and urine spermine. Adding the Spermine Risk Score to PI-RADS improved the AUC from 0.73 to 0.86 in PCa and from 0.72 to 0.83 in high grade PCa (HGPCa) prediction (both P < 0.001). At 90% sensitivity for HGPCa prediction using Spermine Risk Score, 31.1% of unnecessary biopsies could be avoided. In men with equivocal MRI PI-RADS score 3, the AUC for HGPCa prediction was 0.58, 0.79, and 0.87 for PSA, PSA density, and Spermine Risk Score, respectively.
Conclusion
Urine Spermine Risk Score, including mpMRI could accurately identify men at high risk of HGPCa and reduce unnecessary prostate biopsies. Spermine Risk Score could more accurately predict HGPCa than PSA density in men with MRI showing equivocal PI-RADS 3 lesions.
{"title":"Urine spermine and multiparametric magnetic resonance imaging for prediction of prostate cancer in Japanese men","authors":"Shuji Isotani , Peter Ka-Fung Chiu , Takeshi Ashizawa , Yan-Ho Fung , Takeshi Ieda , Toshiyuki China , Haruna Kawano , Fumitaka Shimizu , Masayoshi Nagata , Yuki Nakagawa , Satoru Muto , Ka-Leung Wong , Chi-Fai Ng , Shigeo Horie","doi":"10.1016/j.prnil.2023.07.003","DOIUrl":"10.1016/j.prnil.2023.07.003","url":null,"abstract":"<div><h3>Objectives</h3><p>To investigate the role of urine spermine and spermine risk score in predicting prostate cancer (PCa) diagnoses in combination with multiparametric magnetic resonance imaging (mpMRI).</p></div><div><h3>Methods</h3><p>Three hundred forty seven consecutive men with elevated prostate-specific antigen (PSA) with mpMRI examination were prospectively enrolled in this study. In 265 patients with PSA levels between 4 and20 ng/ml, pre-biopsy urine samples were analyzed for spermine levels with ultra-high performance liquid chromatography (UPLC-MS/MS). Transperineal image-guided prostate biopsies with 16-18 cores were performed. Logistic regressions were used to form different models for the prediction of the PCa, and the performances were compared using the area under the curve (AUC).</p></div><div><h3>Results</h3><p>The median serum PSA level and prostate volume were 7.4 ng/mL and 33.9 mL, respectively. PCa and high-grade PCa (ISUP group ≥2, HGPCa) were diagnosed in 66.0% (175/265) and 132/265 (49.8%) cases, respectively. The urine spermine levels were significantly lower in men with PCa (0.87 vs. 2.20, <em>P</em> < 0.001). Multivariate analyses showed that age, PSA, PV, urine spermine level, and Prostate Imaging Reporting and Data System (PI-RADS) findings were independent predictors for PCa. The Spermine Risk Score is a multivariable model including PSA, age, prostate volume, and urine spermine. Adding the Spermine Risk Score to PI-RADS improved the AUC from 0.73 to 0.86 in PCa and from 0.72 to 0.83 in high grade PCa (HGPCa) prediction (both <em>P</em> < 0.001). At 90% sensitivity for HGPCa prediction using Spermine Risk Score, 31.1% of unnecessary biopsies could be avoided. In men with equivocal MRI PI-RADS score 3, the AUC for HGPCa prediction was 0.58, 0.79, and 0.87 for PSA, PSA density, and Spermine Risk Score, respectively.</p></div><div><h3>Conclusion</h3><p>Urine Spermine Risk Score, including mpMRI could accurately identify men at high risk of HGPCa and reduce unnecessary prostate biopsies. Spermine Risk Score could more accurately predict HGPCa than PSA density in men with MRI showing equivocal PI-RADS 3 lesions.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 180-185"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/d4/main.PMC10513900.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41177969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.prnil.2023.06.003
Yong Seong Lee , Seong Hwan Kim , Jong Hyun Tae , In Ho Chang , Tae-Hyoung Kim , Soon Chul Myung , Myoungsuk Kim , Tuan Thanh Nguyen , Joongwon Choi , Jung Hoon Kim , Jin Wook Kim , Se Young Choi
Background
Multiple oral chemotherapeutic agents for metastatic hormone-sensitive prostate cancer (mHSPC) have been developed for conjugated use with conventional androgen deprivation therapy (ADT). Several randomized controlled trials (RCTs) report significant benefits in mHSPC patients. Therefore, we compared overall survival (OS) and progression-free survival (PFS) benefits among considerable mHSPC oral chemotherapeutic agents.
Materials and methods
We investigated mHSPC treatment efficacy through a systematic RCT-trial literature review (PubMed, Embase, Web of Science, the Cochrane Library, and Scopus). Two reviewers independently screened, extracted data, and assessed bias risk in duplicate.
Results
We identified 18 RCTs (n = 13,509). Concerning OS, ADT + abiraterone, ADT + abiraterone + docetaxel, ADT + apalutamide, ADT + bicalutamide, ADT + darolutamide + docetaxel, ADT + enzalutamide, ADT + orteronel, and ADT + rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT + bicalutamide, nilutamide, flutamide, ADT + bicalutamide + palbociclib, and ADT + nilutamide. ADT + docetaxel with androgen receptor targeted agent (ARTA) triplet therapy was not among the top three treatments determined through ranking analysis.
Conclusions
Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT + docetaxel SOC. Even so, ADT + docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.
背景:多种治疗转移性激素敏感性前列腺癌症(mHSPC)的口服化疗剂已被开发用于与传统雄激素剥夺疗法(ADT)联合使用。一些随机对照试验(RCT)报告了对mHSPC患者的显著益处。因此,我们比较了大量mHSPC口服化疗药物的总生存期(OS)和无进展生存期(PFS)益处。材料和方法:我们通过系统的随机对照试验文献综述(PubMed、Embase、Web of Science、Cochrane Library和Scopus)研究了mHSPC的治疗效果。两名评审员对数据进行了独立筛选、提取,并对偏倚风险进行了评估,一式两份。结果:我们确定了18个随机对照试验(n=13509)。在OS方面,ADT+阿比特龙、ADT+abiraterone+多西他赛、ADT+apalutamide、ADT+-bicalutamide、ADT+Tarlutamide+docetaxel、ADT+cenzalutamide,ADT+orteronel和ADT+rezvilutamide比标准护理(SOC)更有效。比较PFS,大多数治疗比SOC更有效,不包括ADT+bicalutamide、尼鲁他胺、氟他胺、ADT+bicalutamide+palbociclib和ADT+nilutamide。ADT+多西他赛联合雄激素受体靶向剂(ARTA)三联疗法不在通过排名分析确定的前三种治疗方法之列。结论:新的口服化疗药物联合治疗必须取代目前的ADT单药治疗和ADT+多西他赛SOC。尽管如此,ADT+多西他赛联合ARTA三联疗法仍然不是最佳的mHSPC治疗方法,需要进一步研究。
{"title":"Oral chemotherapeutic agents in metastatic hormone-sensitive prostate cancer: A network meta-analysis of randomized controlled trials","authors":"Yong Seong Lee , Seong Hwan Kim , Jong Hyun Tae , In Ho Chang , Tae-Hyoung Kim , Soon Chul Myung , Myoungsuk Kim , Tuan Thanh Nguyen , Joongwon Choi , Jung Hoon Kim , Jin Wook Kim , Se Young Choi","doi":"10.1016/j.prnil.2023.06.003","DOIUrl":"10.1016/j.prnil.2023.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Multiple oral chemotherapeutic agents for metastatic hormone-sensitive prostate cancer (mHSPC) have been developed for conjugated use with conventional androgen deprivation therapy (ADT). Several randomized controlled trials (RCTs) report significant benefits in mHSPC patients. Therefore, we compared overall survival (OS) and progression-free survival (PFS) benefits among considerable mHSPC oral chemotherapeutic agents.</p></div><div><h3>Materials and methods</h3><p>We investigated mHSPC treatment efficacy through a systematic RCT-trial literature review (PubMed, Embase, Web of Science, the Cochrane Library, and Scopus). Two reviewers independently screened, extracted data, and assessed bias risk in duplicate.</p></div><div><h3>Results</h3><p>We identified 18 RCTs (<em>n</em> = 13,509). Concerning OS, ADT + abiraterone, ADT + abiraterone + docetaxel, ADT + apalutamide, ADT + bicalutamide, ADT + darolutamide + docetaxel, ADT + enzalutamide, ADT + orteronel, and ADT + rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT + bicalutamide, nilutamide, flutamide, ADT + bicalutamide + palbociclib, and ADT + nilutamide. ADT + docetaxel with androgen receptor targeted agent (ARTA) triplet therapy was not among the top three treatments determined through ranking analysis.</p></div><div><h3>Conclusions</h3><p>Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT + docetaxel SOC. Even so, ADT + docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 159-166"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/14/63/main.PMC10513908.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41169685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.prnil.2022.12.001
Gyoohwan Jung , Jung Kwon Kim , Jong Jin Oh , Sangchul Lee , Seok-Soo Byun , Sung Kyu Hong , Hakmin Lee
Background
We compared the clinical outcomes of robot-assisted radical prostatectomy (RARP) and partial gland ablation (PGA) using high-intensity focused ultrasound (HIFU) in localized prostate cancer.
Methods
We analyzed 3,859 patients who had undergone RARP and PGA using HIFU. According to the propensity score for each treatment, 137 patients after PGA were matched to 3,722 patients after RARP at a 1:4 ratio using the nearest neighbor method.
Results
The matched cohort comprised 685 subjects (RARP, 548; PGA, 137), with a median follow-up period of 22 months. Treatment failures were identified in 13.9% and 9.1% of patients in the PGA and RARP groups, respectively, after a median follow-up of 36 months postoperatively. Kaplan–Meier analyses revealed significantly longer failure-free (P < 0.001) and salvage-free survival (P = 0.003) in the RARP group than in the PGA group. There was no significant difference in the postoperative urinary symptom score (P = 0.748), but the postoperative erectile function score was significantly higher in the PGA group (P < 0.001). The rate of urinary incontinence (any pad) was significantly lower in the PGA group than that in the RARP group (P < 0.001). Postoperative complications were more frequent in the PGA group (P = 0.003); however, there was no significant difference in high-grade complications (≥3) (P = 0.467).
Conclusion
PGA using HIFU showed statistically inferior oncological outcomes compared with RARP for failure-free survival and salvage-free survival. However, functional outcomes regarding postoperative incontinence and erectile dysfunction were more favorable in the PGA group.
{"title":"Partial gland ablation using high-intensity focused ultrasound versus robot-assisted radical prostatectomy: a propensity score-matched study","authors":"Gyoohwan Jung , Jung Kwon Kim , Jong Jin Oh , Sangchul Lee , Seok-Soo Byun , Sung Kyu Hong , Hakmin Lee","doi":"10.1016/j.prnil.2022.12.001","DOIUrl":"10.1016/j.prnil.2022.12.001","url":null,"abstract":"<div><h3>Background</h3><p>We compared the clinical outcomes of robot-assisted radical prostatectomy (RARP) and partial gland ablation (PGA) using high-intensity focused ultrasound (HIFU) in localized prostate cancer.</p></div><div><h3>Methods</h3><p>We analyzed 3,859 patients who had undergone RARP and PGA using HIFU. According to the propensity score for each treatment, 137 patients after PGA were matched to 3,722 patients after RARP at a 1:4 ratio using the nearest neighbor method.</p></div><div><h3>Results</h3><p>The matched cohort comprised 685 subjects (RARP, 548; PGA, 137), with a median follow-up period of 22 months. Treatment failures were identified in 13.9% and 9.1% of patients in the PGA and RARP groups, respectively, after a median follow-up of 36 months postoperatively. Kaplan–Meier analyses revealed significantly longer failure-free (<em>P</em> < 0.001) and salvage-free survival (<em>P</em> = 0.003) in the RARP group than in the PGA group. There was no significant difference in the postoperative urinary symptom score (<em>P</em> = 0.748), but the postoperative erectile function score was significantly higher in the PGA group (<em>P</em> < 0.001). The rate of urinary incontinence (any pad) was significantly lower in the PGA group than that in the RARP group (<em>P</em> < 0.001). Postoperative complications were more frequent in the PGA group (<em>P</em> = 0.003); however, there was no significant difference in high-grade complications (≥3) (<em>P</em> = 0.467).</p></div><div><h3>Conclusion</h3><p>PGA using HIFU showed statistically inferior oncological outcomes compared with RARP for failure-free survival and salvage-free survival. However, functional outcomes regarding postoperative incontinence and erectile dysfunction were more favorable in the PGA group.</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 134-138"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/a1/main.PMC10513903.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.prnil.2023.01.004
Nobumichi Tanaka
Around 40 years have passed since a modern low-dose-rate (LDR) brachytherapy for prostate cancer was introduced. LDR brachytherapy has become one of the definitive treatment options besides radical prostatectomy (RP) and external beam radiation therapy (EBRT). LDR brachytherapy has several advantages over EBRT such as a higher prescribed dose to the prostate gland while avoiding unnecessary irradiation of organs at risk, a precipitous dose gradient, a brief treatment time, and a short hospital stay. Previous reports revealed that the long-term oncologic outcomes of LDR brachytherapy are superior to those of EBRT. The oncologic outcomes of low- to intermediate-risk patients are equivalent to those of RP using the recurrence definition of surgery of prostate specific antigen (PSA) >0.2 ng/mL, while the oncologic outcomes of LDR brachytherapy as tri-modality (combined EBRT and androgen deprivation therapy) for high-risk patients is superior to that of RP using the recurrence definition of surgery. In respect of toxicity, urinary disorders such as urgency and frequency are often observed after the acute phase of treatment, but these events usually resolve, while the quality of life of urinary continence is well preserved for a long time. Erectile function decreases yearly, but is relatively preserved compared to RP. In conclusion, the most noteworthy strength of LDR brachytherapy for low- to intermediate-risk patients is the “brief treatment time” that provides long recurrence-free survival, while that for high-risk patients who received LDR brachytherapy (tri-modality) is “excellent disease control.”
{"title":"The oncologic and safety outcomes of low-dose-rate brachytherapy for the treatment of prostate cancer","authors":"Nobumichi Tanaka","doi":"10.1016/j.prnil.2023.01.004","DOIUrl":"10.1016/j.prnil.2023.01.004","url":null,"abstract":"<div><p>Around 40 years have passed since a modern low-dose-rate (LDR) brachytherapy for prostate cancer was introduced. LDR brachytherapy has become one of the definitive treatment options besides radical prostatectomy (RP) and external beam radiation therapy (EBRT). LDR brachytherapy has several advantages over EBRT such as a higher prescribed dose to the prostate gland while avoiding unnecessary irradiation of organs at risk, a precipitous dose gradient, a brief treatment time, and a short hospital stay. Previous reports revealed that the long-term oncologic outcomes of LDR brachytherapy are superior to those of EBRT. The oncologic outcomes of low- to intermediate-risk patients are equivalent to those of RP using the recurrence definition of surgery of prostate specific antigen (PSA) >0.2 ng/mL, while the oncologic outcomes of LDR brachytherapy as tri-modality (combined EBRT and androgen deprivation therapy) for high-risk patients is superior to that of RP using the recurrence definition of surgery. In respect of toxicity, urinary disorders such as urgency and frequency are often observed after the acute phase of treatment, but these events usually resolve, while the quality of life of urinary continence is well preserved for a long time. Erectile function decreases yearly, but is relatively preserved compared to RP. In conclusion, the most noteworthy strength of LDR brachytherapy for low- to intermediate-risk patients is the “brief treatment time” that provides long recurrence-free survival, while that for high-risk patients who received LDR brachytherapy (tri-modality) is “excellent disease control.”</p></div>","PeriodicalId":20845,"journal":{"name":"Prostate International","volume":"11 3","pages":"Pages 127-133"},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/0b/main.PMC10513906.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}