Chris H.‐M. Wong, Ivan C.‐H. Ko, David K.‐W. Leung, Brian Siu, Cheuk‐K. K. Cheng, Yung‐Y. J. Lim, Hiu T. Mok, Chun‐F. B. Kwok, Cheuk Y. Tang, Steven C.‐H. Leung, Peter K.‐F. Chiu, Jeremy Y.‐C. Teoh, Chi F. Ng
IntroductionIn de novo metastatic hormone‐sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real‐world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes.MethodsA prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6‐months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders.FindingsA total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression‐free survival (HR = 0.56; 95%CI = 0.34–0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26–0.97; p = 0.036), and cancer‐specific survival (HR = 0.43; 95%CI = 0.19–0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis.ConclusionOur analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real‐world setting, providing valuable information for patient counselling and potentially guiding future trial design.
{"title":"Deep PSA response and extended time‐to‐nadir as robust predictors of survival in Asian patients with de novo metastatic hormone‐sensitive prostate cancer receiving upfront intensified treatment","authors":"Chris H.‐M. Wong, Ivan C.‐H. Ko, David K.‐W. Leung, Brian Siu, Cheuk‐K. K. Cheng, Yung‐Y. J. Lim, Hiu T. Mok, Chun‐F. B. Kwok, Cheuk Y. Tang, Steven C.‐H. Leung, Peter K.‐F. Chiu, Jeremy Y.‐C. Teoh, Chi F. Ng","doi":"10.1002/pros.24797","DOIUrl":"https://doi.org/10.1002/pros.24797","url":null,"abstract":"IntroductionIn de novo metastatic hormone‐sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real‐world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes.MethodsA prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6‐months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders.FindingsA total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression‐free survival (HR = 0.56; 95%CI = 0.34–0.91; <jats:italic>p</jats:italic> = 0.019), overall survival (HR = 0.50; 95%CI = 0.26–0.97; <jats:italic>p</jats:italic> = 0.036), and cancer‐specific survival (HR = 0.43; 95%CI = 0.19–0.99; <jats:italic>p</jats:italic> = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis.ConclusionOur analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real‐world setting, providing valuable information for patient counselling and potentially guiding future trial design.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriela N C De Jesus,Veronica Pereira,Prasanta Karak,Emily Shearier
BACKGROUNDProstate-specific membrane antigen (PSMA) Positron emission tomography/computed tomography (PET/CT) has become a crucial imaging modality for the staging of patients with prostate cancer. The purpose of this study is to retrospectively determine the frequency, anatomical distribution, and clinical-pathologic correlates of extra-nodal and extra-osseous metastatic prostate cancer detected on PSMA PET/CT.METHODSAll available 650 PSMA PET/CT performed in patients with biopsy-proved prostate cancer in our institution between September 2021 and December 2023 were reviewed for the presence of extra-nodal and extra-osseous metastatic disease (M1C disease). Thirty-four patients with M1C disease were identified.RESULTSThe most frequent sites of visceral/soft tissue metastases were the lungs (58.8%), liver (23.5%) and adrenal glands (20.6%). 75% of patients with lung metastases detected on PSMA PET/CT had concurrent intrathoracic lymph node involvement. A higher frequency of patients with M1C disease (55.9%) had a high Gleason score. The median prostate-specific antigen (PSA) level at the time of the PSMA scan was 20.16 ng/mL. There was a statistically significant association between PSA level and osseous disease (p = 0.004), as well as PSA level and nodal disease (p = 0.008). While a large number of patients had concurrent osseous and nodal disease (82.4% and 79.4%, respectively), no visceral/soft tissue sites demonstrated a significant association with the presence of osseous or nodal involvement.CONCLUSIONSGiven the increasing utilization of PSMA PET/CT, increased knowledge of the location and pattern of distribution of visceral/soft tissue metastatic sites is crucial not only for staging but also to better understand patterns of therapeutic response. We identified the lungs, liver and adrenal glands as the most common visceral/soft tissue metastatic sites from prostate cancer. We found that higher PSA levels at the time of PSMA PET/CT imaging were positively associated with concurrent osseous and nodal involvement.
{"title":"A single-center retrospective review of metastatic prostate cancer on PSMA position emission tomography/computed tomography: Beyond lymph nodes and bones.","authors":"Gabriela N C De Jesus,Veronica Pereira,Prasanta Karak,Emily Shearier","doi":"10.1002/pros.24795","DOIUrl":"https://doi.org/10.1002/pros.24795","url":null,"abstract":"BACKGROUNDProstate-specific membrane antigen (PSMA) Positron emission tomography/computed tomography (PET/CT) has become a crucial imaging modality for the staging of patients with prostate cancer. The purpose of this study is to retrospectively determine the frequency, anatomical distribution, and clinical-pathologic correlates of extra-nodal and extra-osseous metastatic prostate cancer detected on PSMA PET/CT.METHODSAll available 650 PSMA PET/CT performed in patients with biopsy-proved prostate cancer in our institution between September 2021 and December 2023 were reviewed for the presence of extra-nodal and extra-osseous metastatic disease (M1C disease). Thirty-four patients with M1C disease were identified.RESULTSThe most frequent sites of visceral/soft tissue metastases were the lungs (58.8%), liver (23.5%) and adrenal glands (20.6%). 75% of patients with lung metastases detected on PSMA PET/CT had concurrent intrathoracic lymph node involvement. A higher frequency of patients with M1C disease (55.9%) had a high Gleason score. The median prostate-specific antigen (PSA) level at the time of the PSMA scan was 20.16 ng/mL. There was a statistically significant association between PSA level and osseous disease (p = 0.004), as well as PSA level and nodal disease (p = 0.008). While a large number of patients had concurrent osseous and nodal disease (82.4% and 79.4%, respectively), no visceral/soft tissue sites demonstrated a significant association with the presence of osseous or nodal involvement.CONCLUSIONSGiven the increasing utilization of PSMA PET/CT, increased knowledge of the location and pattern of distribution of visceral/soft tissue metastatic sites is crucial not only for staging but also to better understand patterns of therapeutic response. We identified the lungs, liver and adrenal glands as the most common visceral/soft tissue metastatic sites from prostate cancer. We found that higher PSA levels at the time of PSMA PET/CT imaging were positively associated with concurrent osseous and nodal involvement.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PurposeThis study was to construct a nomogram utilizing shear wave elastography and assess its efficacy in detecting clinically significant prostate cancer (csPCa).Methods290 elderly people with suspected PCa who received prostate biopsy and shear wave elastography (SWE) imaging were respectively registered from April 2022 to December 2023. The elderly participants were stratified into two groups: those with csPCa and those without csPCa, which encompassed cases of clinically insignificant prostate cancer (cisPCa) and non‐prostate cancer tissue, as determined by pathology findings. The LASSO algorithm, known as the least absolute shrinkage and selection operator, was utilized to identify features. Logistic regression analysis was utilized to establish models. Receiver operating characteristic (ROC) and calibration curves were utilized to evaluate the discriminatory ability of the nomogram. Bootstrap (1000 bootstrap iterations) was employed for internal validation and comparison with two models. A decision curve and a clinical impact curve were employed to assess the clinical usefulness.ResultsOur nomogram, which contained Emean, ΔEmean, prostate volume, prostate‐specific antigen density (PSAD), and transrectal ultrasound (TRUS), showed better discrimination (AUC = 0.89; 95% CI: 0.83−0.94), compared to the clinical model without SWE parameters (p = 0.0007). Its accuracy, sensitivity and specificity were 0.83, 0.89 and 0.78, respectively. Based on the analysis of decision curve, the thresholds ranged from 5% to 90%. According to our nomogram, biopsying patients at a 20% probability threshold resulted in a 25% reduction in biopsies without missing any csPCa. The clinical impact curve demonstrated that the nomogram's predicted outcome is closer to the observed outcome when the probability threshold reaches 20% or greater.ConclusionOur nomogram demonstrates efficacy in identifying elderly individuals with clinically significant prostate cancer, thereby facilitating informed clinical decision‐making based on diagnostic outcomes and potential clinical benefits.
{"title":"Predicting clinically significant prostate cancer in elderly patients: A nomogram approach with shear wave elastography","authors":"Xiang Liu, Jia Zhu, Meng‐Qi Shi, Yong‐Sheng Pan, Xin‐Yu Cao, Zhong‐Xin Zhang","doi":"10.1002/pros.24789","DOIUrl":"https://doi.org/10.1002/pros.24789","url":null,"abstract":"PurposeThis study was to construct a nomogram utilizing shear wave elastography and assess its efficacy in detecting clinically significant prostate cancer (csPCa).Methods290 elderly people with suspected PCa who received prostate biopsy and shear wave elastography (SWE) imaging were respectively registered from April 2022 to December 2023. The elderly participants were stratified into two groups: those with csPCa and those without csPCa, which encompassed cases of clinically insignificant prostate cancer (cisPCa) and non‐prostate cancer tissue, as determined by pathology findings. The LASSO algorithm, known as the least absolute shrinkage and selection operator, was utilized to identify features. Logistic regression analysis was utilized to establish models. Receiver operating characteristic (ROC) and calibration curves were utilized to evaluate the discriminatory ability of the nomogram. Bootstrap (1000 bootstrap iterations) was employed for internal validation and comparison with two models. A decision curve and a clinical impact curve were employed to assess the clinical usefulness.ResultsOur nomogram, which contained Emean, ΔEmean, prostate volume, prostate‐specific antigen density (PSAD), and transrectal ultrasound (TRUS), showed better discrimination (AUC = 0.89; 95% CI: 0.83−0.94), compared to the clinical model without SWE parameters (<jats:italic>p</jats:italic> = 0.0007). Its accuracy, sensitivity and specificity were 0.83, 0.89 and 0.78, respectively. Based on the analysis of decision curve, the thresholds ranged from 5% to 90%. According to our nomogram, biopsying patients at a 20% probability threshold resulted in a 25% reduction in biopsies without missing any csPCa. The clinical impact curve demonstrated that the nomogram's predicted outcome is closer to the observed outcome when the probability threshold reaches 20% or greater.ConclusionOur nomogram demonstrates efficacy in identifying elderly individuals with clinically significant prostate cancer, thereby facilitating informed clinical decision‐making based on diagnostic outcomes and potential clinical benefits.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Boiarsky, Alok K. Tewari, Doga C. Gulhan, Ziad Bakouny, Guruprasad Ananda, Hunter Savignano, Gitanjali Lakshminarayanan, Heather M. McClure, Rebecca Silver, Toni K. Choueiri, Mary‐Ellen Taplin, Peter J. Park, Jacob E. Berchuck
BackgroundThe PARP inhibitor (PARPi) olaparib is approved for homologous recombination repair (HRR) gene‐altered metastatic castration‐resistant prostate cancer (mCRPC). However, there is significant heterogeneity in response to PARPi in patients with mCRPC. Better clinical biomarkers are needed to identify patients likely to benefit from PARPi.MethodsPatients with prostate adenocarcinoma and panel sequencing at Dana‐Farber Cancer Institute were identified. Mutational signature analysis was performed using SigMA to characterize tumors as HRR deficient (HRD). The validity of SigMA to identify patients likely to benefit from olaparib was compared to the current FDA label (presence of a deleterious alteration in one of 14 HRR genes).Results546 patients were identified, of which 34% were HRD. Among patients with HRR gene alterations, only patients with BRCA2 two‐copy loss (2CL) were more likely to be HRD compared to patients without HRR gene alterations (74% vs 31%; P = 9.1 × 10‐7). 28 patients with mCRPC received olaparib, of which 13 were HRD and 9 had BRCA2 2CL. SigMA improved upon the current FDA label for predicting PSA50 (sensitivity: 100% vs 90%; specificity: 83% vs 44%; PPV: 77% vs 47%; NPV: 100% vs 89%) and rPFS > 6 months (sensitivity: both 92%; specificity: 93% vs 53%; PPV: 92% vs 63%; NPV: 93% vs 89%). On multivariate analysis, incorporating prognostic clinical factors and HR gene alterations, SigMA‐predicted HRD independently associated with improved PSA‐PFS (HR = 0.086, p = 0.00082) and rPFS (HR = 0.078, p = 0.0070).ConclusionsSigMA‐predicted HRD may better identify patients likely to benefit from olaparib as compared to the current FDA label. Larger studies are needed for further validation.
背景PARP抑制剂（PARPi）奥拉帕利被批准用于治疗同源重组修复（HRR）基因改变的转移性去势抵抗性前列腺癌（mCRPC）。然而，mCRPC 患者对 PARPi 的反应存在明显的异质性。我们需要更好的临床生物标志物来识别可能从 PARPi 中获益的患者。使用 SigMA 进行突变特征分析，将肿瘤定性为 HRR 缺乏（HRD）。将 SigMA 识别可能从奥拉帕利获益的患者的有效性与当前的 FDA 标签（14 个 HRR 基因之一存在有害改变）进行了比较。在有HRR基因改变的患者中，只有BRCA2双拷贝缺失（2CL）患者比没有HRR基因改变的患者更有可能是HRD（74% vs 31%; P = 9.1 × 10-7）。28例mCRPC患者接受了奥拉帕利治疗，其中13例为HRD，9例为BRCA2 2CL。在预测PSA50（灵敏度：100% vs 90%；特异性：83% vs 44%；PPV：77% vs 47%；NPV：100% vs 89%）和rPFS > 6个月（灵敏度：均为92%；特异性：93% vs 53%；PPV：92% vs 63%；NPV：93% vs 89%）方面，SigMA比目前的FDA标签有所改进。结论与目前的 FDA 标签相比，SigMA 预测的 HRD 可以更好地识别可能从奥拉帕利获益的患者。需要更大规模的研究来进一步验证。
{"title":"A panel‐based mutational signature of homologous recombination deficiency associates with response to PARP inhibition in metastatic castration‐resistant prostate cancer","authors":"Daniel Boiarsky, Alok K. Tewari, Doga C. Gulhan, Ziad Bakouny, Guruprasad Ananda, Hunter Savignano, Gitanjali Lakshminarayanan, Heather M. McClure, Rebecca Silver, Toni K. Choueiri, Mary‐Ellen Taplin, Peter J. Park, Jacob E. Berchuck","doi":"10.1002/pros.24788","DOIUrl":"https://doi.org/10.1002/pros.24788","url":null,"abstract":"BackgroundThe PARP inhibitor (PARPi) olaparib is approved for homologous recombination repair (HRR) gene‐altered metastatic castration‐resistant prostate cancer (mCRPC). However, there is significant heterogeneity in response to PARPi in patients with mCRPC. Better clinical biomarkers are needed to identify patients likely to benefit from PARPi.MethodsPatients with prostate adenocarcinoma and panel sequencing at Dana‐Farber Cancer Institute were identified. Mutational signature analysis was performed using SigMA to characterize tumors as HRR deficient (HRD). The validity of SigMA to identify patients likely to benefit from olaparib was compared to the current FDA label (presence of a deleterious alteration in one of 14 HRR genes).Results546 patients were identified, of which 34% were HRD. Among patients with HRR gene alterations, only patients with <jats:italic>BRCA2</jats:italic> two‐copy loss (2CL) were more likely to be HRD compared to patients without HRR gene alterations (74% vs 31%; <jats:italic>P</jats:italic> = 9.1 × 10<jats:sup>‐7</jats:sup>). 28 patients with mCRPC received olaparib, of which 13 were HRD and 9 had <jats:italic>BRCA2</jats:italic> 2CL. SigMA improved upon the current FDA label for predicting PSA50 (sensitivity: 100% vs 90%; specificity: 83% vs 44%; PPV: 77% vs 47%; NPV: 100% vs 89%) and rPFS > 6 months (sensitivity: both 92%; specificity: 93% vs 53%; PPV: 92% vs 63%; NPV: 93% vs 89%). On multivariate analysis, incorporating prognostic clinical factors and HR gene alterations, SigMA‐predicted HRD independently associated with improved PSA‐PFS (HR = 0.086, <jats:italic>p</jats:italic> = 0.00082) and rPFS (HR = 0.078, <jats:italic>p</jats:italic> = 0.0070).ConclusionsSigMA‐predicted HRD may better identify patients likely to benefit from olaparib as compared to the current FDA label. Larger studies are needed for further validation.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Responses to queries concerning \"Performance of large language models on benign prostatic hyperplasia frequently asked questions\".","authors":"YuNing Zhang, JianQiao Zhou","doi":"10.1002/pros.24748","DOIUrl":"https://doi.org/10.1002/pros.24748","url":null,"abstract":"","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"5 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140969107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lawrence Karsh, Shawn Du, Jinghua He, Dexter Waters, Erik Muser, Neal Shore
BackgroundLimited real‐world evidence exists on the long‐term clinical outcomes of patients with localized prostate cancer (LPC) who received external beam radiation therapy (EBRT) as the initial treatment. This study evaluated clinical outcomes of US patients with high‐risk LPC (HR‐LPC) and low/intermediate‐risk LPC (LIR‐LPC) who received EBRT.MethodsThis retrospective study using Surveillance, Epidemiology, and End Results‐Medicare linked data from 2012 to 2019 included patients ≥ 65 years old who received EBRT as initial therapy. Baseline patient characteristics were summarized, metastasis‐free survival (MFS), overall survival, and time to initiation of advanced prostate cancer treatment were compared using Kaplan−Meier (KM) and adjusted Cox proportional hazard (PH) models. 5‐year survival probabilities stratified by race/ethnicity (non‐Hispanic [NH] White, NH Black, NH Asian, and Hispanic) were assessed.ResultsOf 11,313 eligible patients, 41% (n = 4600) had HR‐LPC and 59% (n = 6713) had LIR‐LPC. Patient characteristics for both groups were comparable, with mean age at EBRT initiation > 70 years, 86% white, and mean follow‐up time >40 months. More patients in the HR‐LPC than LIR‐LPC groups (78% vs 34%) had concurrent androgen deprivation therapy use and for a longer duration (median 10.4 months vs. 7.4 months). A higher proportion of HR‐LPC patients developed metastasis, died, or received advanced prostate cancer treatment. Adjusted Cox PH survival analyses showed significantly (p < 0.0001) higher risk of mortality (hazard ratios [HR], 1.57 [1.38, 2.34]), metastasis or death (HR, 1.97 [1.78, 2.17]), and advanced prostate cancer therapy use (HR, 2.57 [2.11, 3.14]) for HR‐LPC than LIR‐LPC patients. Within 5 years after the initial EBRT treatment, 18%−26% of patients with HR‐LPC are expected to have died or developed metastasis. The 5‐year MFS rate in the HR‐LPC group was lower than the LIR‐LPC group across all racial/ethnic subgroups. NH Black patients with HR‐LPC had the highest all‐cause mortality rate and lowest rate of receiving advanced prostate cancer treatment, compared to other racial/ethnic subgroups.ConclusionsThis real‐world study of clinical outcomes in patients with LPC treated with EBRT suggests substantial disease burden in patients with HR‐LPC and highlights the need for additional treatment strategies to improve clinical outcomes in patients with HR‐LPC.
{"title":"Differences in real‐world outcomes by risk classification for localized prostate cancer patients after radiation therapy","authors":"Lawrence Karsh, Shawn Du, Jinghua He, Dexter Waters, Erik Muser, Neal Shore","doi":"10.1002/pros.24720","DOIUrl":"https://doi.org/10.1002/pros.24720","url":null,"abstract":"BackgroundLimited real‐world evidence exists on the long‐term clinical outcomes of patients with localized prostate cancer (LPC) who received external beam radiation therapy (EBRT) as the initial treatment. This study evaluated clinical outcomes of US patients with high‐risk LPC (HR‐LPC) and low/intermediate‐risk LPC (LIR‐LPC) who received EBRT.MethodsThis retrospective study using Surveillance, Epidemiology, and End Results‐Medicare linked data from 2012 to 2019 included patients ≥ 65 years old who received EBRT as initial therapy. Baseline patient characteristics were summarized, metastasis‐free survival (MFS), overall survival, and time to initiation of advanced prostate cancer treatment were compared using Kaplan−Meier (KM) and adjusted Cox proportional hazard (PH) models. 5‐year survival probabilities stratified by race/ethnicity (non‐Hispanic [NH] White, NH Black, NH Asian, and Hispanic) were assessed.ResultsOf 11,313 eligible patients, 41% (<jats:italic>n</jats:italic> = 4600) had HR‐LPC and 59% (<jats:italic>n</jats:italic> = 6713) had LIR‐LPC. Patient characteristics for both groups were comparable, with mean age at EBRT initiation > 70 years, 86% white, and mean follow‐up time >40 months. More patients in the HR‐LPC than LIR‐LPC groups (78% vs 34%) had concurrent androgen deprivation therapy use and for a longer duration (median 10.4 months vs. 7.4 months). A higher proportion of HR‐LPC patients developed metastasis, died, or received advanced prostate cancer treatment. Adjusted Cox PH survival analyses showed significantly (<jats:italic>p</jats:italic> < 0.0001) higher risk of mortality (hazard ratios [HR], 1.57 [1.38, 2.34]), metastasis or death (HR, 1.97 [1.78, 2.17]), and advanced prostate cancer therapy use (HR, 2.57 [2.11, 3.14]) for HR‐LPC than LIR‐LPC patients. Within 5 years after the initial EBRT treatment, 18%−26% of patients with HR‐LPC are expected to have died or developed metastasis. The 5‐year MFS rate in the HR‐LPC group was lower than the LIR‐LPC group across all racial/ethnic subgroups. NH Black patients with HR‐LPC had the highest all‐cause mortality rate and lowest rate of receiving advanced prostate cancer treatment, compared to other racial/ethnic subgroups.ConclusionsThis real‐world study of clinical outcomes in patients with LPC treated with EBRT suggests substantial disease burden in patients with HR‐LPC and highlights the need for additional treatment strategies to improve clinical outcomes in patients with HR‐LPC.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"106 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea K. Miyahira, Sophia C. Kamran, Tamara Jamaspishvili, Catherine H. Marshall, Kara N. Maxwell, Abhijit Parolia, Nicholas A. Zorko, Kenneth J. Pienta, Howard R. Soule
IntroductionThe 2023 Coffey‐Holden Prostate Cancer Academy (CHPCA) Meeting, themed “Disrupting Prostate Cancer Research: Challenge Accepted,” was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from June 22 to 25, 2023.MethodsThe 2023 marked the 10th Annual CHPCA Meeting, a discussion‐oriented scientific think‐tank conference convened annually by the Prostate Cancer Foundation, which centers on innovative and emerging research topics deemed pivotal for advancing critical unmet needs in prostate cancer research and clinical care. The 2023 CHPCA Meeting was attended by 81 academic investigators and included 40 talks across 8 sessions.ResultsThe central topic areas covered at the meeting included: targeting transcription factor neo‐enhancesomes in cancer, AR as a pro‐differentiation and oncogenic transcription factor, why few are cured with androgen deprivation therapy and how to change dogma to cure metastatic prostate cancer without castration, reducing prostate cancer morbidity and mortality with genetics, opportunities for radiation to enhance therapeutic benefit in oligometastatic prostate cancer, novel immunotherapeutic approaches, and the new era of artificial intelligence‐driven precision medicine.DiscussionThis article provides an overview of the scientific presentations delivered at the 2023 CHPCA Meeting, such that this knowledge can help in facilitating the advancement of prostate cancer research worldwide.
{"title":"Disrupting prostate cancer research: Challenge accepted; report from the 2023 Coffey‐Holden Prostate Cancer Academy Meeting","authors":"Andrea K. Miyahira, Sophia C. Kamran, Tamara Jamaspishvili, Catherine H. Marshall, Kara N. Maxwell, Abhijit Parolia, Nicholas A. Zorko, Kenneth J. Pienta, Howard R. Soule","doi":"10.1002/pros.24721","DOIUrl":"https://doi.org/10.1002/pros.24721","url":null,"abstract":"IntroductionThe 2023 Coffey‐Holden Prostate Cancer Academy (CHPCA) Meeting, themed “Disrupting Prostate Cancer Research: Challenge Accepted,” was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from June 22 to 25, 2023.MethodsThe 2023 marked the 10th Annual CHPCA Meeting, a discussion‐oriented scientific think‐tank conference convened annually by the Prostate Cancer Foundation, which centers on innovative and emerging research topics deemed pivotal for advancing critical unmet needs in prostate cancer research and clinical care. The 2023 CHPCA Meeting was attended by 81 academic investigators and included 40 talks across 8 sessions.ResultsThe central topic areas covered at the meeting included: targeting transcription factor neo‐enhancesomes in cancer, AR as a pro‐differentiation and oncogenic transcription factor, why few are cured with androgen deprivation therapy and how to change dogma to cure metastatic prostate cancer without castration, reducing prostate cancer morbidity and mortality with genetics, opportunities for radiation to enhance therapeutic benefit in oligometastatic prostate cancer, novel immunotherapeutic approaches, and the new era of artificial intelligence‐driven precision medicine.DiscussionThis article provides an overview of the scientific presentations delivered at the 2023 CHPCA Meeting, such that this knowledge can help in facilitating the advancement of prostate cancer research worldwide.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diane E. Peters, Michael Brownlee, Donna Layne‐Colon, Barbara S. Slusher
BackgroundProstate‐specific membrane antigen (PSMA) is a biomarker and therapeutic target of high relevance in prostate cancer. Although upregulated PSMA expression is a well‐documented feature of prostatic neoplasia in both humans and canids, to date humans are the only species known to express PSMA basally in the prostate. Thus, traditional laboratory animal species have limited utility for studying PSMA biology in the prostate or for predicting efficacy or toxicity of PSMA‐targeted agents.MethodsPSMA expression in human, macaque, and marmoset prostates was determined by immunohistochemistry, employing an antibody with validated cross‐species reactivity in a PSMA‐positive control tissue; kidney.ResultsWe newly discover that the common marmoset endogenously expresses PSMA in non‐diseased prostate, similar to humans, and thus may be a valuable preclinical model for researchers studying PSMA.
{"title":"Discovery of PSMA in the prostate of the common marmoset (Callithrix jacchus)","authors":"Diane E. Peters, Michael Brownlee, Donna Layne‐Colon, Barbara S. Slusher","doi":"10.1002/pros.24722","DOIUrl":"https://doi.org/10.1002/pros.24722","url":null,"abstract":"BackgroundProstate‐specific membrane antigen (PSMA) is a biomarker and therapeutic target of high relevance in prostate cancer. Although upregulated PSMA expression is a well‐documented feature of prostatic neoplasia in both humans and canids, to date humans are the only species known to express PSMA basally in the prostate. Thus, traditional laboratory animal species have limited utility for studying PSMA biology in the prostate or for predicting efficacy or toxicity of PSMA‐targeted agents.MethodsPSMA expression in human, macaque, and marmoset prostates was determined by immunohistochemistry, employing an antibody with validated cross‐species reactivity in a PSMA‐positive control tissue; kidney.ResultsWe newly discover that the common marmoset endogenously expresses PSMA in non‐diseased prostate, similar to humans, and thus may be a valuable preclinical model for researchers studying PSMA.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amy M Nguyen, Gebra Cuyun Carter, Lesley-Ann Miller Wilson, Steven Canfield
OBJECTIVES Descriptive study focusing on real-world utilization and characteristics of men with prostate cancer tested with the 17-gene Genomic Prostate Score® (GPS™) assay by linking administrative claims and electronic health record (EHR) data with GPS results. METHODS This retrospective, observational cohort study (January 1, 2013 to December 31, 2020) included men aged 40-80 years with localized prostate cancer claims, continuous enrollment in Optum's Integrated Claims data set, ≥1 day of EHR clinical activity, and a GPS result. Men were classified as undergoing definitive therapy (DT) (prostatectomy, radiation, or focal therapy) or active surveillance (AS). AS and DT distribution were analyzed across GPS results, National Comprehensive Cancer Network® (NCCN®) risk, and race. Costs were assessed 6 months after the first GPS result (index); clinical outcomes and AS persistence were assessed during the variable follow-up. All variables were analyzed descriptively. RESULTS Of 834 men, 650 (77.9%) underwent AS and 184 (22.1%) DT. Most men had Quan-Charlson comorbidity scores of 1-2 and a tumor stage of T1c (index). The most common Gleason patterns were 3 + 3 (79.6%) (AS cohort) and 3 + 4 (55.9%) (DT cohort). The mean (standard deviation) GPS results at index were 23.2 (11.3) (AS) and 30.9 (12.9) (DT). AS decreased with increasing GPS result and NCCN risk. Differences between races were minimal. Total costs were substantially higher in the DT cohort. CONCLUSIONS Most men with GPS-tested localized prostate cancer underwent AS, indicating the GPS result can inform clinical management. Decreasing AS with increasing GPS result and NCCN risk suggests the GPS complements NCCN risk stratification.
{"title":"Real-world utilization, patient characteristics, and treatment patterns among men with localized prostate cancer tested with the 17-gene genomic prostate score® (GPSTM) assay.","authors":"Amy M Nguyen, Gebra Cuyun Carter, Lesley-Ann Miller Wilson, Steven Canfield","doi":"10.1002/pros.24709","DOIUrl":"https://doi.org/10.1002/pros.24709","url":null,"abstract":"OBJECTIVES\u0000Descriptive study focusing on real-world utilization and characteristics of men with prostate cancer tested with the 17-gene Genomic Prostate Score® (GPS™) assay by linking administrative claims and electronic health record (EHR) data with GPS results.\u0000\u0000\u0000METHODS\u0000This retrospective, observational cohort study (January 1, 2013 to December 31, 2020) included men aged 40-80 years with localized prostate cancer claims, continuous enrollment in Optum's Integrated Claims data set, ≥1 day of EHR clinical activity, and a GPS result. Men were classified as undergoing definitive therapy (DT) (prostatectomy, radiation, or focal therapy) or active surveillance (AS). AS and DT distribution were analyzed across GPS results, National Comprehensive Cancer Network® (NCCN®) risk, and race. Costs were assessed 6 months after the first GPS result (index); clinical outcomes and AS persistence were assessed during the variable follow-up. All variables were analyzed descriptively.\u0000\u0000\u0000RESULTS\u0000Of 834 men, 650 (77.9%) underwent AS and 184 (22.1%) DT. Most men had Quan-Charlson comorbidity scores of 1-2 and a tumor stage of T1c (index). The most common Gleason patterns were 3 + 3 (79.6%) (AS cohort) and 3 + 4 (55.9%) (DT cohort). The mean (standard deviation) GPS results at index were 23.2 (11.3) (AS) and 30.9 (12.9) (DT). AS decreased with increasing GPS result and NCCN risk. Differences between races were minimal. Total costs were substantially higher in the DT cohort.\u0000\u0000\u0000CONCLUSIONS\u0000Most men with GPS-tested localized prostate cancer underwent AS, indicating the GPS result can inform clinical management. Decreasing AS with increasing GPS result and NCCN risk suggests the GPS complements NCCN risk stratification.","PeriodicalId":501684,"journal":{"name":"The Prostate","volume":"20 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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