首页 > 最新文献

Prostate最新文献

英文 中文
The prognostic role of pan-immune inflammation value in patients with metastatic castration resistance prostate cancer treated with Lutetium-177 (177Lu)-PSMA-617. 接受镥-177 (177Lu)-PSMA-617 治疗的转移性去势抵抗性前列腺癌患者泛免疫炎症值的预后作用。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-09-29 DOI: 10.1002/pros.24804
Satı Coskun Yazgan, Emre Yekeduz, Mine Araz, Hatice Bolek, N Ozlem Kucuk, Yuksel Urun

Background: Pan-immune inflammation value (PIV) is a newly defined biomarker that includes whole cellular components that are indicators of systemic inflammation in complete blood count (CBC), easily accessible and has the potential to reflect both the body's immune response and systemic inflammation status. This study evaluated the pretreatment PIV for its prognostic impact on overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (177Lu)-PSMA-617.

Methods: The PIV was based on the earliest CBC obtained within 1 month before treatment initiation. Patients were categorized into low and high PIV groups based on the median pretreatment PIV, and the relationship between OS and PIV groups was assessed by multivariable analysis.

Results: A total of 43 patients with mCRPC treated with (177Lu)-PSMA-617 were included. The median OS was longer in the low PIV group (15.1 months [95% confidence interval [CI] 10.6-19.5]) than in the high PIV group (4.2 months [95% CI 1.7-6.6]) (p < 0.001). In multivariable analysis, high PIV (hazard ratio [HR]: 4.3, 95% CI 1.194-15.93, p = 0.026) and high Eastern Cooperative Oncology Group performance score (HR: 7.05, 95% CI 1.48-33.46, p = 0.014) were associated with shorter OS.

Conclusion: This study showed that pretreatment PIV might be a prognostic factor in patients with mCRPC treated with (177Lu)-PSMA-617.

背景:泛免疫炎症值(PIV)是一种新定义的生物标志物,它包括全血细胞计数(CBC)中作为全身炎症指标的全细胞成分,易于获得,并有可能同时反映机体的免疫反应和全身炎症状态。本研究评估了接受镥-177(177Lu)-PSMA-617 治疗的转移性去势抵抗性前列腺癌(mCRPC)患者治疗前的 PIV 对总生存期(OS)的预后影响:PIV基于治疗开始前1个月内最早获得的全血细胞计数。根据治疗前PIV的中位数将患者分为低PIV组和高PIV组,并通过多变量分析评估OS与PIV组之间的关系:共纳入43例接受(177Lu)-PSMA-617治疗的mCRPC患者。低PIV组的中位OS(15.1个月[95% 置信区间[CI] 10.6-19.5])长于高PIV组(4.2个月[95% CI 1.7-6.6]):本研究表明,对于接受(177Lu)-PSMA-617治疗的mCRPC患者来说,治疗前PIV可能是一个预后因素。
{"title":"The prognostic role of pan-immune inflammation value in patients with metastatic castration resistance prostate cancer treated with Lutetium-177 (<sup>177</sup>Lu)-PSMA-617.","authors":"Satı Coskun Yazgan, Emre Yekeduz, Mine Araz, Hatice Bolek, N Ozlem Kucuk, Yuksel Urun","doi":"10.1002/pros.24804","DOIUrl":"10.1002/pros.24804","url":null,"abstract":"<p><strong>Background: </strong>Pan-immune inflammation value (PIV) is a newly defined biomarker that includes whole cellular components that are indicators of systemic inflammation in complete blood count (CBC), easily accessible and has the potential to reflect both the body's immune response and systemic inflammation status. This study evaluated the pretreatment PIV for its prognostic impact on overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (<sup>177</sup>Lu)-PSMA-617.</p><p><strong>Methods: </strong>The PIV was based on the earliest CBC obtained within 1 month before treatment initiation. Patients were categorized into low and high PIV groups based on the median pretreatment PIV, and the relationship between OS and PIV groups was assessed by multivariable analysis.</p><p><strong>Results: </strong>A total of 43 patients with mCRPC treated with (<sup>177</sup>Lu)-PSMA-617 were included. The median OS was longer in the low PIV group (15.1 months [95% confidence interval [CI] 10.6-19.5]) than in the high PIV group (4.2 months [95% CI 1.7-6.6]) (p < 0.001). In multivariable analysis, high PIV (hazard ratio [HR]: 4.3, 95% CI 1.194-15.93, p = 0.026) and high Eastern Cooperative Oncology Group performance score (HR: 7.05, 95% CI 1.48-33.46, p = 0.014) were associated with shorter OS.</p><p><strong>Conclusion: </strong>This study showed that pretreatment PIV might be a prognostic factor in patients with mCRPC treated with (<sup>177</sup>Lu)-PSMA-617.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"90-96"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prostate cancer focal therapy: surgeon experience influences oncological results. 前列腺癌病灶治疗:外科医生的经验影响肿瘤结果。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-09-26 DOI: 10.1002/pros.24800
Claudio Bovolenta Murta, José Pontes Júnior, Pedro Humberto Felix de Souza Filho, Paulo Cezar de Godoy Júnior, Felipe Guimarães Pugliesi, Kayann Reda El Hayek, Fábio Pescarmona Gallucci, Giuliano Betoni Guglielmetti, Joaquim Francisco de Almeida Claro

Introduction: Characterization of the index lesion of prostate cancer (PCa) has facilitated the development of focal therapy to reduce complications caused by radical treatments. In the present study, we sought to identify factors associated with the oncological results of focal therapy for PCa.

Methods: Between April 2017 and February 2020, 123 PCa patients received focal therapy performed with high-intensity focused ultrasound (HIFU). The patients presented unilateral localized disease, PSA < 20 ng/dl, clinical stage T1-T2, ISUP grade 1-3, and more than 10 years of life expectancy. Five certified surgeons with different levels of experience performed the procedures and were divided into groups #1 and #2 (>30 HIFUs performed) and #3 (10-15 HIFUs performed each). All patients were prospectively followed and underwent surveillance biopsy 1 year post-treatment. The primary endpoint was radical treatment, and secondary endpoints included focal therapy failure and in-field recurrence. Univariate and multivariate logistic regression were used to detect associations between clinical and procedure variables and the endpoints.

Results: The median follow-up was 54.3 months, with a mean age of 64.4 years. The mean PSA was 6.6 ng/dl; 59.3% of patients had intermediate-risk disease, and the remaining had low-risk. During follow-up, 29 (23.6%) patients required radical treatment (external beam radiation therapy), 37 (30.1%) experienced treatment failure, and 26 (21.1%) had an in-field recurrence with an ISUP grade of ≥2. Radical treatment in the follow-up was associated with patients treated by surgeons in group #3 and with elevated post-HIFU PSA concentrations. Baseline PSA concentrations, group #3 surgeons, and post-HIFU PSA concentrations were associated with treatment failure. In-field positive biopsies were associated with baseline and post-HIFU PSA concentrations. Furthermore, patients treated by surgeons in group #3 were independently associated with radical treatment and focal therapy failure.

Conclusion: Focal therapy with HIFU has acceptable oncological outcomes in the medium term, and the surgeon's experience and technique are independently associated with the need for subsequent radical treatment and focal therapy failure.

前言:对前列腺癌(PCa)病灶的特征描述促进了病灶治疗的发展,从而减少了根治性治疗引起的并发症。在本研究中,我们试图找出与PCa病灶治疗的肿瘤学结果相关的因素:2017年4月至2020年2月期间,123名PCa患者接受了高强度聚焦超声(HIFU)病灶治疗。这些患者均为单侧局部病变,PSA为30个HIFU,#3为10-15个HIFU。所有患者均接受了前瞻性随访,并在治疗后 1 年接受了监测活检。主要终点是根治性治疗,次要终点包括病灶治疗失败和现场复发。采用单变量和多变量逻辑回归检测临床和手术变量与终点之间的关联:中位随访时间为 54.3 个月,平均年龄为 64.4 岁。平均 PSA 为 6.6 ng/dl;59.3% 的患者为中危,其余为低危。在随访期间,29 名患者(23.6%)需要接受根治性治疗(体外放射治疗),37 名患者(30.1%)治疗失败,26 名患者(21.1%)现场复发且 ISUP 等级≥2。随访中的根治性治疗与 3 号组外科医生治疗的患者以及 HIFU 后 PSA 浓度升高有关。基线PSA浓度、3号组外科医生和HIFU术后PSA浓度与治疗失败有关。现场阳性活检与基线和 HIFU 后 PSA 浓度有关。此外,由3号组外科医生治疗的患者与根治性治疗和病灶治疗失败有独立关联:结论:使用HIFU进行病灶治疗在中期内具有可接受的肿瘤治疗效果,外科医生的经验和技术与后续根治性治疗的需要和病灶治疗失败有独立关联。
{"title":"Prostate cancer focal therapy: surgeon experience influences oncological results.","authors":"Claudio Bovolenta Murta, José Pontes Júnior, Pedro Humberto Felix de Souza Filho, Paulo Cezar de Godoy Júnior, Felipe Guimarães Pugliesi, Kayann Reda El Hayek, Fábio Pescarmona Gallucci, Giuliano Betoni Guglielmetti, Joaquim Francisco de Almeida Claro","doi":"10.1002/pros.24800","DOIUrl":"10.1002/pros.24800","url":null,"abstract":"<p><strong>Introduction: </strong>Characterization of the index lesion of prostate cancer (PCa) has facilitated the development of focal therapy to reduce complications caused by radical treatments. In the present study, we sought to identify factors associated with the oncological results of focal therapy for PCa.</p><p><strong>Methods: </strong>Between April 2017 and February 2020, 123 PCa patients received focal therapy performed with high-intensity focused ultrasound (HIFU). The patients presented unilateral localized disease, PSA < 20 ng/dl, clinical stage T1-T2, ISUP grade 1-3, and more than 10 years of life expectancy. Five certified surgeons with different levels of experience performed the procedures and were divided into groups #1 and #2 (>30 HIFUs performed) and #3 (10-15 HIFUs performed each). All patients were prospectively followed and underwent surveillance biopsy 1 year post-treatment. The primary endpoint was radical treatment, and secondary endpoints included focal therapy failure and in-field recurrence. Univariate and multivariate logistic regression were used to detect associations between clinical and procedure variables and the endpoints.</p><p><strong>Results: </strong>The median follow-up was 54.3 months, with a mean age of 64.4 years. The mean PSA was 6.6 ng/dl; 59.3% of patients had intermediate-risk disease, and the remaining had low-risk. During follow-up, 29 (23.6%) patients required radical treatment (external beam radiation therapy), 37 (30.1%) experienced treatment failure, and 26 (21.1%) had an in-field recurrence with an ISUP grade of ≥2. Radical treatment in the follow-up was associated with patients treated by surgeons in group #3 and with elevated post-HIFU PSA concentrations. Baseline PSA concentrations, group #3 surgeons, and post-HIFU PSA concentrations were associated with treatment failure. In-field positive biopsies were associated with baseline and post-HIFU PSA concentrations. Furthermore, patients treated by surgeons in group #3 were independently associated with radical treatment and focal therapy failure.</p><p><strong>Conclusion: </strong>Focal therapy with HIFU has acceptable oncological outcomes in the medium term, and the surgeon's experience and technique are independently associated with the need for subsequent radical treatment and focal therapy failure.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"58-64"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Size and SUVmax define the contribution of nodal metastases to PSA in oligorecurrent prostate cancer. 尺寸和 SUVmax 可确定结节转移对少发前列腺癌 PSA 的影响。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-10-09 DOI: 10.1002/pros.24806
Fabian Falkenbach, Marie-Lena Schmalhofer, Zhe Tian, Giovanni Mazzucato, Pierre I Karakiewicz, Markus Graefen, Sophie Knipper, Lars Budäus, Daniel Koehler, Tobias Maurer

Background: To evaluate how prostate-specific antigen (PSA) levels decrease after removal of isolated prostate cancer (PCa) nodal metastases in relation to their diameter/volume ("PSA-density of PCa-metastases") and maximum standardized uptake value (SUVmax).

Methods: A total of 83 consecutive patients with solitary nodal recurrence after radical prostatectomy who underwent prostate-specific membrane antigen-radioguided salvage surgery were retrospectively analyzed. Using multivariable linear regression models, the PSA-decrease after removal of each PCa-metastases (=PSA-contribution of each PCa-metastases) was correlated with the long axis diameter/estimated volume and the SUVmax of each removed metastasis. Sizes were measured by imaging and histopathologic examination.

Results: A total of 83 patients were included with a median (interquartile range [IQR]) PSA-decrease of 0.56 [0.22, 1.31] ng/mL after salvage surgery. The median [IQR] long axis diameters in imaging and histopathological examination were 8.0 [6.0, 11.0] mm and 8.4 [5.5, 11.1] mm, respectively. The median [IQR] estimated volumes were 0.13 [0.05, 0.32] cc (imaging) and 0.05 [0.02, 0.17] cc (pathology). In multivariable linear regression analyses, the estimated PSA-contribution ([95% confidence interval [CI]) of each millimeter of long axis diameter was 0.09 [0.03, 0.14] ng/mL (imaging) or 0.08 [0.03, 0.12] ng/mL (histology). The minimum diameter for biochemical recurrence (PSA ≥ 0.2 ng/mL) was >2.2 mm (imaging) or >2.5 mm (histology). The estimated PSA-contribution [95% CI] of each cc cancer volume was 1.23 [0.51, 1.94] ng/mL (imaging) or 1.46 [0.40, 2.52] ng/mL (histology). SUVmax as surrogate parameter for tissue composition was associated with increased PSA-contribution of PCa-metastases (+0.03-0.05 ng/mL per unit increase).

Conclusions: The diameter/volume and SUVmax of metastatic tissue correlate with its contribution to PSA levels. Therefore, very small metastases may produce too little PSA for biochemical recurrence.

背景:目的:评估切除孤立的前列腺癌(PCa)结节转移灶后,前列腺特异性抗原(PSA)水平的下降与其直径/体积("PSA-PCa-转移灶密度")和最大标准化摄取值(SUVmax)的关系:对83例前列腺癌根治术后单发结节复发、接受前列腺特异性膜抗原放射引导挽救手术的患者进行了回顾性分析。利用多变量线性回归模型,将每个 PCa 转移灶切除后的 PSA 下降(=每个 PCa 转移灶的 PSA 贡献)与每个切除转移灶的长轴直径/估计体积和 SUVmax 相关联。尺寸通过影像学和组织病理学检查进行测量:共有 83 名患者接受了抢救性手术,术后 PSA 下降的中位数(四分位数间距 [IQR])为 0.56 [0.22, 1.31] ng/mL。成像和组织病理学检查的长轴直径中位数[IQR]分别为8.0 [6.0, 11.0]毫米和8.4 [5.5, 11.1]毫米。估计体积的中位数[IQR]分别为 0.13 [0.05, 0.32] cc(成像)和 0.05 [0.02, 0.17] cc(病理)。在多变量线性回归分析中,长轴直径每毫米的PSA贡献率([95%置信区间[CI])估计为0.09 [0.03, 0.14] ng/mL(造影)或0.08 [0.03, 0.12] ng/mL(组织学)。生化复发(PSA ≥ 0.2 ng/mL)的最小直径为>2.2 mm(成像)或>2.5 mm(组织学)。每毫升癌症体积的 PSA 贡献估计值 [95% CI] 为 1.23 [0.51, 1.94] 纳克/毫升(成像)或 1.46 [0.40, 2.52] 纳克/毫升(组织学)。作为组织成分替代参数的SUVmax与PCa转移灶的PSA贡献率增加有关(每增加一个单位,PSA贡献率增加0.03-0.05纳克/毫升):结论:转移组织的直径/体积和SUVmax与其对PSA水平的贡献相关。结论:转移组织的直径/体积和 SUVmax 与其对 PSA 水平的贡献相关,因此,非常小的转移灶产生的 PSA 可能太少,无法导致生化复发。
{"title":"Size and SUV<sub>max</sub> define the contribution of nodal metastases to PSA in oligorecurrent prostate cancer.","authors":"Fabian Falkenbach, Marie-Lena Schmalhofer, Zhe Tian, Giovanni Mazzucato, Pierre I Karakiewicz, Markus Graefen, Sophie Knipper, Lars Budäus, Daniel Koehler, Tobias Maurer","doi":"10.1002/pros.24806","DOIUrl":"10.1002/pros.24806","url":null,"abstract":"<p><strong>Background: </strong>To evaluate how prostate-specific antigen (PSA) levels decrease after removal of isolated prostate cancer (PCa) nodal metastases in relation to their diameter/volume (\"PSA-density of PCa-metastases\") and maximum standardized uptake value (SUV<sub>max</sub>).</p><p><strong>Methods: </strong>A total of 83 consecutive patients with solitary nodal recurrence after radical prostatectomy who underwent prostate-specific membrane antigen-radioguided salvage surgery were retrospectively analyzed. Using multivariable linear regression models, the PSA-decrease after removal of each PCa-metastases (=PSA-contribution of each PCa-metastases) was correlated with the long axis diameter/estimated volume and the SUV<sub>max</sub> of each removed metastasis. Sizes were measured by imaging and histopathologic examination.</p><p><strong>Results: </strong>A total of 83 patients were included with a median (interquartile range [IQR]) PSA-decrease of 0.56 [0.22, 1.31] ng/mL after salvage surgery. The median [IQR] long axis diameters in imaging and histopathological examination were 8.0 [6.0, 11.0] mm and 8.4 [5.5, 11.1] mm, respectively. The median [IQR] estimated volumes were 0.13 [0.05, 0.32] cc (imaging) and 0.05 [0.02, 0.17] cc (pathology). In multivariable linear regression analyses, the estimated PSA-contribution ([95% confidence interval [CI]) of each millimeter of long axis diameter was 0.09 [0.03, 0.14] ng/mL (imaging) or 0.08 [0.03, 0.12] ng/mL (histology). The minimum diameter for biochemical recurrence (PSA ≥ 0.2 ng/mL) was >2.2 mm (imaging) or >2.5 mm (histology). The estimated PSA-contribution [95% CI] of each cc cancer volume was 1.23 [0.51, 1.94] ng/mL (imaging) or 1.46 [0.40, 2.52] ng/mL (histology). SUV<sub>max</sub> as surrogate parameter for tissue composition was associated with increased PSA-contribution of PCa-metastases (+0.03-0.05 ng/mL per unit increase).</p><p><strong>Conclusions: </strong>The diameter/volume and SUV<sub>max</sub> of metastatic tissue correlate with its contribution to PSA levels. Therefore, very small metastases may produce too little PSA for biochemical recurrence.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"105-111"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dose modification in enzalutamide and abiraterone plus prednisolone for castration-resistant prostate cancer: A subanalysis from the ENABLE study for PCa. 恩杂鲁胺和阿比特龙加泼尼松龙治疗阉割耐药前列腺癌的剂量调整:PCaENABLE研究的子分析。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-09-20 DOI: 10.1002/pros.24796
Nobumichi Tanaka, Kouji Izumi, Yasushi Nakai, Takashi Shima, Yuki Kato, Koji Mita, Manabu Kamiyama, Shogo Inoue, Seiji Hoshi, Takehiko Okamura, Yuko Yoshio, Hideki Enokida, Ippei Chikazawa, Noriyasu Kawai, Kohei Hashimoto, Takashi Fukagai, Kazuyoshi Shigehara, Shizuko Takahara, Atsushi Mizokami

Background: A head-to-head comparison between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) revealed similar survival benefits for castration-resistant prostate cancer (CRPC) in the ENABLE study for PCa. Considering that a dose reduction of ENZ and ABI has demonstrated sufficient inhibitory ability of androgen receptor (AR) signaling, we analyzed the efficacy of modified doses of these agents in the ENABLE study for PCa.

Methods: This investigator-initiated, multicenter, randomized controlled trial that was conducted in Japan analyzed the prespecified survival endpoints, prostate-specific antigen (PSA) response rate ( ≥50% decline from baseline), and safety profile in patients treated with modified doses (ENZ ≤ 120 mg/day, ABI ≤ 750 mg/day) compared with those treated with a standard dose (ENZ 160 mg/day, ABI 1000 mg/day) as a starting dose.

Results: In total, 92 patients in each arm were treated and analyzed; 16 patients were treated with a modified dose in both the ENZ and ABI arms, respectively. Moreover, 32 patients treated with modified doses showed a significantly better time to PSA progression (TTPP) and overall survival (OS) compared with the 152 patients treated with a standard dose (HR 0.47, 95%CI 0.27-0.83, p = 0.0379, and HR 0.35, 95%CI 0.19-0.63, p = 0.0162). Despite a significantly longer TTPP in the modified ABI group than in the standard ABI group (HR 0.29, 95%CI 0.14-0.62, p = 0.0248), no significant difference was observed in the TTPP between the modified and standard ENZ groups (p = 0.5366). Furthermore, similar adverse event rates and grades were observed in each treatment dose group.

Conclusions: The modified doses of ABI showed better TTPP than the standard dose of ABI and may be a potential treatment option for CRPC patients; however, its mechanism is still unclear, although its ability to suppress AR signaling is equivalent to that of a standard dose.

背景:在治疗前列腺癌的ENABLE研究中,恩杂鲁胺(ENZ)和阿比特龙加泼尼松龙(ABI)的头对头比较显示,对阉割耐药前列腺癌(CRPC)的生存获益相似。考虑到减少 ENZ 和 ABI 的剂量已显示出对雄激素受体(AR)信号转导有足够的抑制能力,我们分析了在 PCa 的ENABLE 研究中这些药物调整剂量的疗效:这项由研究者发起、在日本进行的多中心随机对照试验分析了预设的生存终点、前列腺特异性抗原(PSA)应答率(与基线相比下降≥50%)以及改良剂量(ENZ≤120毫克/天,ABI≤750毫克/天)与标准剂量(ENZ 160毫克/天,ABI 1000毫克/天)作为起始剂量的患者的安全性:每个治疗组共有 92 名患者接受了治疗和分析;在 ENZ 和 ABI 治疗组中,分别有 16 名患者接受了调整剂量的治疗。此外,与接受标准剂量治疗的152名患者相比,接受改良剂量治疗的32名患者的PSA进展时间(TTPP)和总生存期(OS)明显更长(HR 0.47,95%CI 0.27-0.83,p = 0.0379;HR 0.35,95%CI 0.19-0.63,p = 0.0162)。尽管改良 ABI 组的 TTPP 明显长于标准 ABI 组(HR 0.29,95%CI 0.14-0.62,p = 0.0248),但改良 ENZ 组和标准 ENZ 组的 TTPP 并无明显差异(p = 0.5366)。此外,各治疗剂量组的不良事件发生率和等级相似:结论:改良剂量的ABI比标准剂量的ABI显示出更好的TTPP,可能是CRPC患者的一种潜在治疗选择;然而,尽管其抑制AR信号转导的能力与标准剂量相当,但其机制仍不清楚。
{"title":"Dose modification in enzalutamide and abiraterone plus prednisolone for castration-resistant prostate cancer: A subanalysis from the ENABLE study for PCa.","authors":"Nobumichi Tanaka, Kouji Izumi, Yasushi Nakai, Takashi Shima, Yuki Kato, Koji Mita, Manabu Kamiyama, Shogo Inoue, Seiji Hoshi, Takehiko Okamura, Yuko Yoshio, Hideki Enokida, Ippei Chikazawa, Noriyasu Kawai, Kohei Hashimoto, Takashi Fukagai, Kazuyoshi Shigehara, Shizuko Takahara, Atsushi Mizokami","doi":"10.1002/pros.24796","DOIUrl":"10.1002/pros.24796","url":null,"abstract":"<p><strong>Background: </strong>A head-to-head comparison between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) revealed similar survival benefits for castration-resistant prostate cancer (CRPC) in the ENABLE study for PCa. Considering that a dose reduction of ENZ and ABI has demonstrated sufficient inhibitory ability of androgen receptor (AR) signaling, we analyzed the efficacy of modified doses of these agents in the ENABLE study for PCa.</p><p><strong>Methods: </strong>This investigator-initiated, multicenter, randomized controlled trial that was conducted in Japan analyzed the prespecified survival endpoints, prostate-specific antigen (PSA) response rate ( ≥50% decline from baseline), and safety profile in patients treated with modified doses (ENZ ≤ 120 mg/day, ABI ≤ 750 mg/day) compared with those treated with a standard dose (ENZ 160 mg/day, ABI 1000 mg/day) as a starting dose.</p><p><strong>Results: </strong>In total, 92 patients in each arm were treated and analyzed; 16 patients were treated with a modified dose in both the ENZ and ABI arms, respectively. Moreover, 32 patients treated with modified doses showed a significantly better time to PSA progression (TTPP) and overall survival (OS) compared with the 152 patients treated with a standard dose (HR 0.47, 95%CI 0.27-0.83, p = 0.0379, and HR 0.35, 95%CI 0.19-0.63, p = 0.0162). Despite a significantly longer TTPP in the modified ABI group than in the standard ABI group (HR 0.29, 95%CI 0.14-0.62, p = 0.0248), no significant difference was observed in the TTPP between the modified and standard ENZ groups (p = 0.5366). Furthermore, similar adverse event rates and grades were observed in each treatment dose group.</p><p><strong>Conclusions: </strong>The modified doses of ABI showed better TTPP than the standard dose of ABI and may be a potential treatment option for CRPC patients; however, its mechanism is still unclear, although its ability to suppress AR signaling is equivalent to that of a standard dose.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"21-29"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Head-to-head comparison of GA-68 PSMA PET/CT and multiparametric MRI findings with postoperative results in preoperative locoregional staging and localization of prostate cancer. GA-68 PSMA PET/CT 和多参数磁共振成像结果与前列腺癌术前局部分期和定位的术后结果的头对头比较。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-09-30 DOI: 10.1002/pros.24799
Mustafa Dinckal, Kasim Emre Ergun, Mustafa Serdar Kalemci, Ezgi Guler, Recep Tokac, Süleyman Ordu, Nahit Ogut, Semiha Ozgul, Ozgur Sanli, Sait Sen, Burak Turna

Background: Accurate staging of prostate cancer (PCa) is essential for determining the appropriate treatment and predicting outcomes. This study is comparing the effectiveness of Gallium-68 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (Ga-68 PSMA PET/CT) and multiparametric MRI (mpMRI) in preoperative locoregional staging and localizing PCa.

Methods: A retrospective analysis was conducted on 78 patients who underwent both mpMRI and Ga-68 PSMA PET/CT scans before surgery. The imaging was reviewed by radiologists and nuclear medicine specialists and compared with the final histopathology, which was reviewed by an experienced uropathologist.

Results: mpMRI demonstrated higher sensitivity in detecting extraprostatic extension (EPE) and bladder neck invasion (BNI) compared to Ga-68 PSMA PET/CT (83% vs. 44% and 29% vs. 17%, respectively). Conversely, Ga-68 PSMA PET/CT showed higher sensitivity in detecting seminal vesicle invasion (SVI) and lymph node metastasis (LNM) (75% vs. 55% and 50% vs. 30%, respectively). When both methods were combined, sensitivity increased in detecting both EPE and SVI. The index tumor localization in mpMRI and Ga-68 PSMA PET/CT was found to be in complete agreement with histopathological findings at 36.4% and 41.8%, respectively. When both imaging methods were combined, the agreement with histopathology in predicting index tumor localization reached 72.1%.

Conclusion: Both mpMRI and Ga-68 PSMA PET/CT provide valuable and complementary information for tumor localization and locoregional staging. While mpMRI showed higher sensitivity in detecting EPE, Ga-68 PSMA PET/CT demonstrated superior performance in detecting LNM and SVI. The combined use of these imaging modalities enhance accuracy of index tumor localizations.

背景:前列腺癌(PCa)的准确分期对于确定适当的治疗方法和预测预后至关重要。本研究比较了镓-68前列腺特异性膜抗原正电子发射断层扫描/计算机断层扫描(Ga-68 PSMA PET/CT)和多参数磁共振成像(mpMRI)在PCa术前局部分期和定位中的有效性:方法:对术前同时接受mpMRI和Ga-68 PSMA PET/CT扫描的78例患者进行了回顾性分析。结果:与Ga-68 PSMA PET/CT相比,mpMRI在检测膀胱外扩展(EPE)和膀胱颈侵犯(BNI)方面表现出更高的灵敏度(分别为83%对44%和29%对17%)。相反,Ga-68 PSMA PET/CT 在检测精囊侵犯(SVI)和淋巴结转移(LNM)方面显示出更高的灵敏度(分别为 75% 对 55% 和 50% 对 30%)。当两种方法结合使用时,检测 EPE 和 SVI 的灵敏度均有所提高。mpMRI和Ga-68 PSMA PET/CT的肿瘤定位指数与组织病理学结果完全一致,分别为36.4%和41.8%。当两种成像方法结合使用时,在预测肿瘤定位指数方面与组织病理学的一致性达到72.1%:结论:mpMRI和Ga-68 PSMA PET/CT都能为肿瘤定位和局部区域分期提供有价值的互补信息。mpMRI在检测EPE方面表现出更高的灵敏度,而Ga-68 PSMA PET/CT在检测LNM和SVI方面表现出更优越的性能。联合使用这些成像模式可提高肿瘤定位指标的准确性。
{"title":"Head-to-head comparison of GA-68 PSMA PET/CT and multiparametric MRI findings with postoperative results in preoperative locoregional staging and localization of prostate cancer.","authors":"Mustafa Dinckal, Kasim Emre Ergun, Mustafa Serdar Kalemci, Ezgi Guler, Recep Tokac, Süleyman Ordu, Nahit Ogut, Semiha Ozgul, Ozgur Sanli, Sait Sen, Burak Turna","doi":"10.1002/pros.24799","DOIUrl":"10.1002/pros.24799","url":null,"abstract":"<p><strong>Background: </strong>Accurate staging of prostate cancer (PCa) is essential for determining the appropriate treatment and predicting outcomes. This study is comparing the effectiveness of Gallium-68 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (Ga-68 PSMA PET/CT) and multiparametric MRI (mpMRI) in preoperative locoregional staging and localizing PCa.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 78 patients who underwent both mpMRI and Ga-68 PSMA PET/CT scans before surgery. The imaging was reviewed by radiologists and nuclear medicine specialists and compared with the final histopathology, which was reviewed by an experienced uropathologist.</p><p><strong>Results: </strong>mpMRI demonstrated higher sensitivity in detecting extraprostatic extension (EPE) and bladder neck invasion (BNI) compared to Ga-68 PSMA PET/CT (83% vs. 44% and 29% vs. 17%, respectively). Conversely, Ga-68 PSMA PET/CT showed higher sensitivity in detecting seminal vesicle invasion (SVI) and lymph node metastasis (LNM) (75% vs. 55% and 50% vs. 30%, respectively). When both methods were combined, sensitivity increased in detecting both EPE and SVI. The index tumor localization in mpMRI and Ga-68 PSMA PET/CT was found to be in complete agreement with histopathological findings at 36.4% and 41.8%, respectively. When both imaging methods were combined, the agreement with histopathology in predicting index tumor localization reached 72.1%.</p><p><strong>Conclusion: </strong>Both mpMRI and Ga-68 PSMA PET/CT provide valuable and complementary information for tumor localization and locoregional staging. While mpMRI showed higher sensitivity in detecting EPE, Ga-68 PSMA PET/CT demonstrated superior performance in detecting LNM and SVI. The combined use of these imaging modalities enhance accuracy of index tumor localizations.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"48-57"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Machine learning and explainable artificial intelligence to predict pathologic stage in men with localized prostate cancer. 用机器学习和可解释人工智能预测局部前列腺癌男性患者的病理分期。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-10-13 DOI: 10.1002/pros.24793
Hemal Semwal, Colton Ladbury, Ali Sabbagh, Osama Mohamad, Derya Tilki, Arya Amini, Jeffrey Wong, Yun Rose Li, Scott Glaser, Bertram Yuh, Savita Dandapani

Background: Though several nomograms exist, machine learning (ML) approaches might improve prediction of pathologic stage in patients with prostate cancer. To develop ML models to predict pathologic stage that outperform existing nomograms that use readily available clinicopathologic variables.

Methods: Patients with prostate adenocarcinoma who underwent surgery were identified in the National Cancer Database. Seven ML models were trained to predict organ-confined (OC) disease, extracapsular extension, seminal vesicle invasion (SVI), and lymph node involvement (LNI). Model performance was measured using area under the curve (AUC) on a holdout testing data set. Clinical utility was evaluated using decision curve analysis (DCA). Performance metrics were confirmed on an external validation data set.

Results: The ML-based extreme gradient boosted trees model achieved the best performance with an AUC of 0.744, 0.749, 0.816, 0.811 for the OC, ECE, SVI, and LNI models, respectively. The MSK nomograms achieved an AUC of 0.708, 0.742, 0.806, 0.802 for the OC, ECE, SVI, and LNI models, respectively. These models also performed the best on DCA. Findings were consistent on both a holdout internal validation data set as well as an external validation data set.

Conclusions: Our ML models better predicted pathologic stage relative to existing nomograms at predicting pathologic stage. Accurate prediction of pathologic stage can help oncologists and patients determine optimal definitive treatment options for patients with prostate cancer.

背景:尽管存在多种提名图,但机器学习(ML)方法可能会改善对前列腺癌患者病理分期的预测。目的:开发预测病理分期的 ML 模型,使其优于现有的使用现成临床病理变量的提名图:方法:从国家癌症数据库中找出接受手术的前列腺腺癌患者。我们训练了七个 ML 模型来预测器官封闭(OC)疾病、囊外扩展、精囊侵犯(SVI)和淋巴结受累(LNI)。模型的性能是通过保留测试数据集上的曲线下面积(AUC)来衡量的。临床实用性通过决策曲线分析(DCA)进行评估。在外部验证数据集上确认了性能指标:基于 ML 的极梯度增强树模型性能最佳,OC、ECE、SVI 和 LNI 模型的 AUC 分别为 0.744、0.749、0.816 和 0.811。MSK提名图的OC、ECE、SVI和LNI模型的AUC分别为0.708、0.742、0.806和0.802。这些模型在 DCA 上的表现也最好。这些结果在保留的内部验证数据集和外部验证数据集上都是一致的:结论:在预测病理分期方面,我们的 ML 模型比现有的提名图更能预测病理分期。准确预测病理分期有助于肿瘤学家和患者确定前列腺癌患者的最佳明确治疗方案。
{"title":"Machine learning and explainable artificial intelligence to predict pathologic stage in men with localized prostate cancer.","authors":"Hemal Semwal, Colton Ladbury, Ali Sabbagh, Osama Mohamad, Derya Tilki, Arya Amini, Jeffrey Wong, Yun Rose Li, Scott Glaser, Bertram Yuh, Savita Dandapani","doi":"10.1002/pros.24793","DOIUrl":"10.1002/pros.24793","url":null,"abstract":"<p><strong>Background: </strong>Though several nomograms exist, machine learning (ML) approaches might improve prediction of pathologic stage in patients with prostate cancer. To develop ML models to predict pathologic stage that outperform existing nomograms that use readily available clinicopathologic variables.</p><p><strong>Methods: </strong>Patients with prostate adenocarcinoma who underwent surgery were identified in the National Cancer Database. Seven ML models were trained to predict organ-confined (OC) disease, extracapsular extension, seminal vesicle invasion (SVI), and lymph node involvement (LNI). Model performance was measured using area under the curve (AUC) on a holdout testing data set. Clinical utility was evaluated using decision curve analysis (DCA). Performance metrics were confirmed on an external validation data set.</p><p><strong>Results: </strong>The ML-based extreme gradient boosted trees model achieved the best performance with an AUC of 0.744, 0.749, 0.816, 0.811 for the OC, ECE, SVI, and LNI models, respectively. The MSK nomograms achieved an AUC of 0.708, 0.742, 0.806, 0.802 for the OC, ECE, SVI, and LNI models, respectively. These models also performed the best on DCA. Findings were consistent on both a holdout internal validation data set as well as an external validation data set.</p><p><strong>Conclusions: </strong>Our ML models better predicted pathologic stage relative to existing nomograms at predicting pathologic stage. Accurate prediction of pathologic stage can help oncologists and patients determine optimal definitive treatment options for patients with prostate cancer.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"3-12"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is prostatic adenocarcinoma detectable by urine cytology-A multicenter retrospective review. 尿液细胞学能否检测出前列腺腺癌--多中心回顾性研究。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-10-14 DOI: 10.1002/pros.24805
Cheuk-Yin Tang, Joshua J X Li, Ka Long Leung, Hei Yuet Ma, Joanna K M Ng, Ryan T L Yan, Jeremy Y Teoh, Christopher J VandenBussche, Gary M Tse

Introduction: Urine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma.

Methods: Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed. Clinicopathological parameters-tumor grade, stage, histologic features, and preanalytical factors-prostate-specific antigen (PSA) level and lesion size, were retrieved and compared with cytologic diagnoses.

Results: In total, 2115 urine cytology specimens from 1119 patients were retrieved. The atypia (or above/C3+) and suspicious (or above/C4+) rates were 19.48% and 3.36%. Bilobar and extracapsular involvement, lymphovascular invasion, Gleason score, and International Society of Urological Pathology grade were associated with a positive urine diagnosis (p < 0.05). The atypia (C3+) and suspicious (C4+) rates of urine cytology in patients with a PSA level of ≤4.0 ng/mL was paradoxically higher (p < 0.01), but PSA levels correlated positively with urine diagnosis at higher cutoffs (>10, >20, >50, >100 ng/mL). All these factors remained significant on multivariate analysis (p < 0.05), including a negative correlation with low-PSA (≤4.0 ng/mL, p = 0.001) and positive correlation with high-PSA (>20 ng/mL, p = 0.020). Lesion size and multifocality were not associated with urine cytology diagnosis (p > 0.05).

Conclusion: Urine cytology showed low sensitivity in detection of prostatic adenocarcinoma. Detection rates were largely positively correlated with PSA levels but not for lesion size nor multifocality, limiting its clinical utility.

导言:尿液细胞学是诊断尿路上皮病变的可靠方法,但尿液细胞学对前列腺腺癌的检出率数据有限。本研究进行了一项多中心回顾性研究,以明确尿液细胞学在前列腺腺癌诊断中的临床作用:方法:研究人员回顾了 20 多年来三家机构对组织学证实为前列腺腺癌的下尿路细胞学标本进行的细胞学诊断。检索临床病理参数--肿瘤分级、分期、组织学特征以及分析前因素--前列腺特异性抗原(PSA)水平和病灶大小,并与细胞学诊断结果进行比较:共检索到 1119 名患者的 2115 份尿液细胞学标本。不典型(或以上/C3+)和可疑(或以上/C4+)率分别为 19.48% 和 3.36%。双叶和囊外受累、淋巴管侵犯、格里森评分和国际泌尿病理学会分级与尿液诊断阳性相关(p 10、>20、>50、>100 ng/mL)。所有这些因素在多变量分析中仍有意义(p 20 ng/mL,p = 0.020)。病灶大小和多发性与尿液细胞学诊断无关(P > 0.05):结论:尿液细胞学检测前列腺腺癌的灵敏度较低。结论:尿液细胞学检测前列腺腺癌的灵敏度较低,检测率与 PSA 水平呈显著正相关,但与病变大小和多灶性无关,因此限制了其临床应用。
{"title":"Is prostatic adenocarcinoma detectable by urine cytology-A multicenter retrospective review.","authors":"Cheuk-Yin Tang, Joshua J X Li, Ka Long Leung, Hei Yuet Ma, Joanna K M Ng, Ryan T L Yan, Jeremy Y Teoh, Christopher J VandenBussche, Gary M Tse","doi":"10.1002/pros.24805","DOIUrl":"10.1002/pros.24805","url":null,"abstract":"<p><strong>Introduction: </strong>Urine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma.</p><p><strong>Methods: </strong>Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed. Clinicopathological parameters-tumor grade, stage, histologic features, and preanalytical factors-prostate-specific antigen (PSA) level and lesion size, were retrieved and compared with cytologic diagnoses.</p><p><strong>Results: </strong>In total, 2115 urine cytology specimens from 1119 patients were retrieved. The atypia (or above/C3+) and suspicious (or above/C4+) rates were 19.48% and 3.36%. Bilobar and extracapsular involvement, lymphovascular invasion, Gleason score, and International Society of Urological Pathology grade were associated with a positive urine diagnosis (p < 0.05). The atypia (C3+) and suspicious (C4+) rates of urine cytology in patients with a PSA level of ≤4.0 ng/mL was paradoxically higher (p < 0.01), but PSA levels correlated positively with urine diagnosis at higher cutoffs (>10, >20, >50, >100 ng/mL). All these factors remained significant on multivariate analysis (p < 0.05), including a negative correlation with low-PSA (≤4.0 ng/mL, p = 0.001) and positive correlation with high-PSA (>20 ng/mL, p = 0.020). Lesion size and multifocality were not associated with urine cytology diagnosis (p > 0.05).</p><p><strong>Conclusion: </strong>Urine cytology showed low sensitivity in detection of prostatic adenocarcinoma. Detection rates were largely positively correlated with PSA levels but not for lesion size nor multifocality, limiting its clinical utility.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"97-104"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic model for second progression-free survival and overall survival in patients with high-risk metastatic hormone-sensitive prostate cancer treated with abiraterone acetate and androgen deprivation therapy. 采用醋酸阿比特龙和雄激素剥夺疗法治疗高风险转移性激素敏感性前列腺癌患者第二次无进展生存期和总生存期的预后模型。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-09-30 DOI: 10.1002/pros.24802
Shintaro Narita, Takafumi Yanagisawa, Shingo Hatakeyama, Kenichi Hata, Kazutoshi Fujita, Takashi Ueda, Toshikazu Tanaka, Shinya Maita, Shuji Chiba, Hiromi Sato, Yuya Sekine, Mizuki Kobayashi, Soki Kashima, Ryohei Yamamoto, Kazuyuki Numakura, Mitsuru Saito, Koichiro Takayama, Katsumi Okane, Toshiya Ishida, Yohei Horikawa, Teruaki Kumazawa, Jiro Shimoda, Ikuya Iwabuchi, Takehiro Suzuki, Osamu Ukimura, Takahiro Kimura, Chikara Ohyama, Kyoko Nomura, Tomonori Habuchi

Background: To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI).

Methods: This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts.

Results: The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively.

Conclusions: Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials.

背景:为接受醋酸阿比特龙(ABI)前期治疗的高危转移性激素敏感性前列腺癌(mHSPC)患者开发并验证一个预后风险模型:这项回顾性多中心研究涉及233名接受前期ABI治疗的高危mHSPC患者,由三个学术中心共同开发。该模型由282名患者组成的独立队列进行了外部验证。为了确定第二次无进展生存期(PFS2)的独立预后因素并建立最佳拟合模型,该模型采用了考克斯比例危险回归法,并遵循阿凯克信息准则。根据风险评分将患者分为三组。根据发现队列和验证队列中的风险组别对PFS2和总生存期(OS)进行评估:中位年龄为72岁(51-89岁),中位随访时间为27个月。与PFS2相关的独立因素包括:东部合作肿瘤学组(Eastern Cooperative Oncology Group)表现状态≥2、原发性Gleason评分5、疾病范围评分≥3或肝转移、乳酸脱氢酶>220 U/L。良好风险组、中等风险组和不良风险组的中位 PFS2 分别为未达到、43 个月和 16 个月。低风险组的中位 OS 为 29 个月,而高风险组和中风险组均未达到这一目标。高危、中危和低危组的两年生存率分别为 94.5%、80.1% 和 60.3%。验证队列证实了风险模型与PFS2和OS的关系。高危组中位PFS2和OS分别为21个月和32个月:我们的预后模型包括五个临床因素,对采用ADT加ABI治疗的高危mHSPC患者的护理和治疗选择很有帮助。该模型可提供更准确的信息,指导治疗决策,或在未来的临床试验中对患者进行分类。
{"title":"Prognostic model for second progression-free survival and overall survival in patients with high-risk metastatic hormone-sensitive prostate cancer treated with abiraterone acetate and androgen deprivation therapy.","authors":"Shintaro Narita, Takafumi Yanagisawa, Shingo Hatakeyama, Kenichi Hata, Kazutoshi Fujita, Takashi Ueda, Toshikazu Tanaka, Shinya Maita, Shuji Chiba, Hiromi Sato, Yuya Sekine, Mizuki Kobayashi, Soki Kashima, Ryohei Yamamoto, Kazuyuki Numakura, Mitsuru Saito, Koichiro Takayama, Katsumi Okane, Toshiya Ishida, Yohei Horikawa, Teruaki Kumazawa, Jiro Shimoda, Ikuya Iwabuchi, Takehiro Suzuki, Osamu Ukimura, Takahiro Kimura, Chikara Ohyama, Kyoko Nomura, Tomonori Habuchi","doi":"10.1002/pros.24802","DOIUrl":"10.1002/pros.24802","url":null,"abstract":"<p><strong>Background: </strong>To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI).</p><p><strong>Methods: </strong>This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts.</p><p><strong>Results: </strong>The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively.</p><p><strong>Conclusions: </strong>Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"73-81"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bipolar androgen therapy for treatment of metastatic castration-resistant prostate cancer: A case series. 双极雄激素疗法治疗转移性耐受性前列腺癌:病例系列。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-09-22 DOI: 10.1002/pros.24798
Elizabeth U Tran, Eric Royz, Kyra Yamamoto, Samantha Marley, Alexander Song, Elizabeth Pan, Aaron M Lee, Daniel Herchenhorn, Sam Denmeade, Emmanuel S Antonarakis, Mark Markowski, Rana R McKay

Introduction: Advanced prostate cancer treatment has improved with androgen receptor signaling inhibitors (ARPI), yet many patients develop metastatic castration-resistant prostate cancer (mCRPC), characterized by sustained androgen receptor (AR) signaling. Bipolar androgen therapy (BAT) introduces supraphysiologic testosterone levels to inhibit tumor growth, offering novel treatment for mCRPC by exploiting AR-dependent mechanisms.

Case presentations: Case 1: A 53-year-old man with mCRPC, post multiple systemic therapies, initiated BAT and pembrolizumab, achieving PSA reduction and improved quality of life before progression. The patient exhibited AR amplification, which may have contributed to favorable response to BAT. Case 2: A 73-year-old man with recurrent prostate cancer, stable on ADT and abiraterone, experienced PSA decline with BAT to an undetectable level, maintaining stability post-therapy discontinuation. Case 3: A 73-year-old man with metastatic prostate cancer, initially resistant to enzalutamide, achieved clinical benefit and disease control with BAT, although he did not meet PSA response criteria, patient had remarkable response upon enzalutamide rechallenge. Case 4: A 90-year-old man with localized prostate cancer, refractory to multiple treatments, experienced symptom relief and PSA reduction with BAT before progression.

Conclusion: BAT represents a promising treatment strategy for mCRPC. This case series underscores BAT's potential to induce significant clinical and biochemical responses, resensitize tumors to ARPIs, and improve patients' quality of life. Despite eventual progression in some cases, BAT offers a period of disease control. Further research is needed to optimize patient selection and understand the molecular determinants of BAT responsiveness.

简介:雄激素受体信号转导抑制剂(ARPI)改善了晚期前列腺癌的治疗,但仍有许多患者发展为以持续雄激素受体(AR)信号转导为特征的转移性阉割耐药前列腺癌(mCRPC)。双极雄激素疗法(BAT)引入了超生理水平的睾酮来抑制肿瘤生长,通过利用AR依赖机制为mCRPC提供了新的治疗方法:病例 1:一名 53 岁的男性 mCRPC 患者在接受多种系统治疗后,开始接受 BAT 和 pembrolizumab 治疗,在病情恶化前实现了 PSA 降低并改善了生活质量。该患者表现出AR扩增,这可能是对BAT产生良好反应的原因之一。病例 2:一名 73 岁的男性前列腺癌复发患者,ADT 和阿比特龙治疗后病情稳定,BAT 治疗后 PSA 下降到检测不到的水平,停药后病情保持稳定。病例 3:一名 73 岁的转移性前列腺癌患者,起初对恩杂鲁胺耐药,使用 BAT 后取得了临床疗效并控制了病情,虽然未达到 PSA 反应标准,但患者在再次使用恩杂鲁胺后反应显著。病例 4:一名 90 岁的男性患者患有局部前列腺癌,对多种治疗方法均无效,在病情恶化前使用 BAT 后症状缓解,PSA 降低:结论:BAT 是治疗 mCRPC 的一种前景广阔的治疗策略。本系列病例强调了 BAT 在诱导显著的临床和生化反应、使肿瘤对 ARPIs 再敏感以及改善患者生活质量方面的潜力。尽管某些病例最终会出现进展,但 BAT 仍能使疾病得到一段时间的控制。要优化患者选择并了解 BAT 反应性的分子决定因素,还需要进一步的研究。
{"title":"Bipolar androgen therapy for treatment of metastatic castration-resistant prostate cancer: A case series.","authors":"Elizabeth U Tran, Eric Royz, Kyra Yamamoto, Samantha Marley, Alexander Song, Elizabeth Pan, Aaron M Lee, Daniel Herchenhorn, Sam Denmeade, Emmanuel S Antonarakis, Mark Markowski, Rana R McKay","doi":"10.1002/pros.24798","DOIUrl":"10.1002/pros.24798","url":null,"abstract":"<p><strong>Introduction: </strong>Advanced prostate cancer treatment has improved with androgen receptor signaling inhibitors (ARPI), yet many patients develop metastatic castration-resistant prostate cancer (mCRPC), characterized by sustained androgen receptor (AR) signaling. Bipolar androgen therapy (BAT) introduces supraphysiologic testosterone levels to inhibit tumor growth, offering novel treatment for mCRPC by exploiting AR-dependent mechanisms.</p><p><strong>Case presentations: </strong>Case 1: A 53-year-old man with mCRPC, post multiple systemic therapies, initiated BAT and pembrolizumab, achieving PSA reduction and improved quality of life before progression. The patient exhibited AR amplification, which may have contributed to favorable response to BAT. Case 2: A 73-year-old man with recurrent prostate cancer, stable on ADT and abiraterone, experienced PSA decline with BAT to an undetectable level, maintaining stability post-therapy discontinuation. Case 3: A 73-year-old man with metastatic prostate cancer, initially resistant to enzalutamide, achieved clinical benefit and disease control with BAT, although he did not meet PSA response criteria, patient had remarkable response upon enzalutamide rechallenge. Case 4: A 90-year-old man with localized prostate cancer, refractory to multiple treatments, experienced symptom relief and PSA reduction with BAT before progression.</p><p><strong>Conclusion: </strong>BAT represents a promising treatment strategy for mCRPC. This case series underscores BAT's potential to induce significant clinical and biochemical responses, resensitize tumors to ARPIs, and improve patients' quality of life. Despite eventual progression in some cases, BAT offers a period of disease control. Further research is needed to optimize patient selection and understand the molecular determinants of BAT responsiveness.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"40-47"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of race with incidence, characteristics, and mortality from incidental prostate cancer: Analysis of two North American contemporary cohorts. 种族与偶发前列腺癌的发病率、特征和死亡率的关系:对两个北美当代队列的分析。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-01 Epub Date: 2024-10-28 DOI: 10.1002/pros.24803
Marco Finati, Chase Morrison, Alex Stephens, Giuseppe Chiarelli, Giuseppe Ottone Cirulli, Shane Tinsley, Matthew Davis, Akshay Sood, Nicolò Buffi, Giovanni Lughezzani, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Gian Maria Busetto, Carlo Bettocchi, Craig Rogers, Giuseppe Carrieri, Firas Abdollah

Background: Non-Hispanic Black (NHB) men are at higher risk both for incidence and mortality from prostate cancer (PCa) compared to Non-Hispanic White (NHW) men, but these findings arise from biopsy-detected PCa reports. We aimed to compare the incidence, subsequent management and cancer-specific mortality (CSM) of incidental PCa among NHB and NHW men, using two different North American cohorts.

Methods: The Surveillance, Epidemiology and End-Result (SEER: 2004-2017) and our institutional Henry Ford Health (HFH: 1995-2022) databases were queried to identify men diagnosed with incidental PCa. Cumulative incidence estimates were used to calculate CSM differences between NHB and NHW men. Competing-risk multivariable regression analysis tested the impact of race on CSM, after accounting for all available covariates.

Results: A total of 418 and 6,124 incidental PCa cases were recorded in HFH and SEER database respectively. No pathological differences were observed between NHB and NHW men in both the cohorts, except for prostate-specific antigen (PSA) value at diagnosis, which was higher in NHB men. At 10-years, the CSM rates were 5.5% vs 7.2% in our cohort and 8.6% vs 10.3% in the SEER cohort for NHW and NHB men, respectively (all Gray's test p-value > 0.05). At multivariable, race was not an independent predictor of CSM in our HFH cohort (HR: 1.46, 95% CI: 0.57-3.71, p = 0.6). In the SEER cohort, NHB men were 34% less likely to die from PCa from 1 year to the next (95% CI: 0.49-0.90, p = 0.008), when compared with NHW men.

Conclusions: In the comparison of incidental PCa findings between NHB and NHW men, both groups had similar pathological characteristic and survival outcomes. These findings are different from the 'conventional' screening-detected PCa and suggest that racial differences have minimal to no adverse effects on PCa-specific mortality after incidental diagnosis.

背景:与非西班牙裔白人(NHW)男性相比,非西班牙裔黑人(NHB)男性患前列腺癌(PCa)的风险和死亡率都更高,但这些研究结果都是通过活检发现的PCa报告得出的。我们的目的是利用两个不同的北美队列,比较非西班牙裔白种人和非西班牙裔白种人中偶发 PCa 的发病率、后续处理和癌症特异性死亡率(CSM):方法:我们查询了监测、流行病学和最终结果数据库(SEER:2004-2017 年)和本机构的亨利福特健康数据库(HFH:1995-2022 年),以确定诊断为偶发性 PCa 的男性。累积发病率估计值用于计算NHB和NHW男性之间的CSM差异。在考虑了所有可用的协变量后,竞争风险多变量回归分析检验了种族对CSM的影响:HFH和SEER数据库分别记录了418例和6124例偶发性PCa病例。除了确诊时的前列腺特异性抗原(PSA)值在非华裔男性中较高外,这两个队列中的非华裔男性和非华裔男性在病理学上没有差异。10年后,我们队列中的NHW和NHB男性的CSM率分别为5.5%对7.2%,SEER队列中的CSM率分别为8.6%对10.3%(所有格雷氏检验P值均大于0.05)。在我们的 HFH 队列中,种族不是 CSM 的独立预测因素(HR:1.46,95% CI:0.57-3.71,P = 0.6)。在SEER队列中,与NHW男性相比,NHB男性在一年内死于PCa的可能性降低了34%(95% CI:0.49-0.90,P = 0.008):结论:在对NHB和NHW男性偶然发现的PCa进行比较时,两组男性的病理特征和生存结果相似。这些发现与 "传统 "筛查发现的 PCa 不同,表明种族差异对偶然诊断后 PCa 特异性死亡率的不利影响很小,甚至没有。
{"title":"Association of race with incidence, characteristics, and mortality from incidental prostate cancer: Analysis of two North American contemporary cohorts.","authors":"Marco Finati, Chase Morrison, Alex Stephens, Giuseppe Chiarelli, Giuseppe Ottone Cirulli, Shane Tinsley, Matthew Davis, Akshay Sood, Nicolò Buffi, Giovanni Lughezzani, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Gian Maria Busetto, Carlo Bettocchi, Craig Rogers, Giuseppe Carrieri, Firas Abdollah","doi":"10.1002/pros.24803","DOIUrl":"10.1002/pros.24803","url":null,"abstract":"<p><strong>Background: </strong>Non-Hispanic Black (NHB) men are at higher risk both for incidence and mortality from prostate cancer (PCa) compared to Non-Hispanic White (NHW) men, but these findings arise from biopsy-detected PCa reports. We aimed to compare the incidence, subsequent management and cancer-specific mortality (CSM) of incidental PCa among NHB and NHW men, using two different North American cohorts.</p><p><strong>Methods: </strong>The Surveillance, Epidemiology and End-Result (SEER: 2004-2017) and our institutional Henry Ford Health (HFH: 1995-2022) databases were queried to identify men diagnosed with incidental PCa. Cumulative incidence estimates were used to calculate CSM differences between NHB and NHW men. Competing-risk multivariable regression analysis tested the impact of race on CSM, after accounting for all available covariates.</p><p><strong>Results: </strong>A total of 418 and 6,124 incidental PCa cases were recorded in HFH and SEER database respectively. No pathological differences were observed between NHB and NHW men in both the cohorts, except for prostate-specific antigen (PSA) value at diagnosis, which was higher in NHB men. At 10-years, the CSM rates were 5.5% vs 7.2% in our cohort and 8.6% vs 10.3% in the SEER cohort for NHW and NHB men, respectively (all Gray's test p-value > 0.05). At multivariable, race was not an independent predictor of CSM in our HFH cohort (HR: 1.46, 95% CI: 0.57-3.71, p = 0.6). In the SEER cohort, NHB men were 34% less likely to die from PCa from 1 year to the next (95% CI: 0.49-0.90, p = 0.008), when compared with NHW men.</p><p><strong>Conclusions: </strong>In the comparison of incidental PCa findings between NHB and NHW men, both groups had similar pathological characteristic and survival outcomes. These findings are different from the 'conventional' screening-detected PCa and suggest that racial differences have minimal to no adverse effects on PCa-specific mortality after incidental diagnosis.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"82-89"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Prostate
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1