研究等業績 - その他 - 成田　伸太郎

ニボルマブ・イピリムマブ併用療法に対して治療不応性を示す転移性腎細胞癌患者の特徴

沼倉 一幸, 畠山 真吾, 武藤 弓奈, 関根 悠哉, 蘇武 竜太, 小林 瑞貴, 笹川 甫, 嘉島 相輝, 山本 竜平, 奈良 健平, 齋藤 満, 成田 伸太郎, 大山 力, 羽渕 友則

腎癌研究会会報 ( (一社)腎癌研究会 )  ( 53 ) 49 - 49   2023年07月

当科におけるペムブロリズマブ・レンバチニブ併用療法の初期治療経験

関根 悠哉, 沼倉 一幸, 小林 瑞貴, 山本 竜平, 奈良 健平, 齋藤 満, 成田 伸太郎, 羽渕 友則

腎癌研究会会報 ( (一社)腎癌研究会 )  ( 53 ) 54 - 54   2023年07月

転移性腎細胞癌に対するニボルマブ+イピリムマブ併用療法のirAEと治療効果の関連についての検討

蘇武 竜太, 沼倉 一幸, 畠山 真吾, 関根 悠哉, 武藤 弓奈, 小林 瑞貴, 嘉島 相輝, 山本 竜平, 小泉 淳, 奈良 健平, 齋藤 満, 成田 伸太郎, 大山 力, 羽渕 友則

腎癌研究会会報 ( (一社)腎癌研究会 )  ( 53 ) 87 - 87   2023年07月

BRAF V600E変異は副腎腫瘍からのコルチゾール産生を亢進する(BRAF V600E mutation promoted excess of cortisol secretion in adrenal cortical adenoma)

沼倉 一幸, 武藤 弓奈, 杉山 志子, 小林 瑞貴, 関根 悠哉, 嘉島 相輝, 山本 竜平, 奈良 健平, 黄 明国, 齋藤 満, 成田 伸太郎, 西本 紘嗣郎, 羽渕 友則

日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 )  110回   AOP08 - 03   2023年04月

代用膀胱造設術後23年で生じた代用膀胱内小腸癌の1例

船越 佑大, 嘉島 相輝, 関根 悠哉, 小林 瑞貴, 山本 竜平, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則, 南條 博

泌尿器外科 ( 医学図書出版(株) )  36 ( 4 ) 357 - 357   2023年04月

日本人上部尿路上皮癌の大規模ゲノム解析(Large-scale genetic analysis of Upper Urinary Tract Urothelial Carcinoma in Japanese)

関根 悠哉, 岩崎 雄介, 遠藤 ミキ子, 佐野 剛視, 赤松 秀輔, 小林 恭, 中川 英刀, 沼倉 一幸, 成田 伸太郎, 桃沢 幸秀, 羽渕 友則

日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 )  110回   AOP06 - 07   2023年04月

Factors influencing warm ischemia time in robot-assisted partial nephrectomy change depending on the surgeon’s experience

Numakura K.

World Journal of Surgical Oncology ( World Journal of Surgical Oncology )  20 ( 1 ) 202 - 202   2022年12月

INTRODUCTION: Warm ischemia time (WIT) is a primary concern for robot-assisted laparoscopic partial nephrectomy (RALPN) patients because longer WIT is significantly associated with postoperative deteriorating kidney function. Tumor complexity, determined by the RENAL nephrometry score (RENAL score), can help predict surgical outcomes, but it is unclear what RENAL score and clinical factors affect WIT. This study explored the clinical factors predicting long WIT in experienced surgeon to RALPN. MATERIALS AND METHODS: In our institute, 174 RALPNs were performed between November 2013 and February 2021, of which 114 were performed by a single surgeon and included in this study. Clinical staging and the total RENAL score were determined based on preoperative CT scans. The cases were divided into three groups based on experience: period 1: 1-38, period 2: 39-76, and period 3: 77-114. The clinical factors associated with longer WIT were analyzed per period. RESULTS: The overall median tumor diameter was 32 mm, and one patient had a positive surgical margin, but there were no cancer-related deaths. In total, there were 18 complications (15.8%). Periods 2 and 3 had larger tumor diameters (p < 0.01) and worse preoperative kidney function (p = 0.029) than period 1. A RENAL L-component score of 3 was associated with longer WIT in period 3 (odds ratio: 3.900; 95% confidence interval: 1.004-15.276; p = 0.044), but the tumor diameter and the total RENAL score were not. CONCLUSIONS: A large tumor in the central lesion indicated by the RENAL L-component score was associated with increased WIT in RALPN.

DOI PubMed

Prognostic significance of pathogenic variants in BRCA1, BRCA2, ATM and PALB2 genes in men undergoing hormonal therapy for advanced prostate cancer

Kimura H.

British Journal of Cancer ( British Journal of Cancer )  127 ( 9 ) 1680 - 1690   2022年11月

BACKGROUND: The prognostic significance of germline variants in homologous recombination repair genes in advanced prostate cancer (PCa), especially with regard to hormonal therapy, remains controversial. METHODS: Germline DNA from 549 Japanese men with metastatic and/or castration-resistant PCa was sequenced for 27 cancer-predisposing genes. The associations between pathogenic variants and clinical outcomes were examined. Further, for comparison, DNA from prostate biopsy tissue samples from 80 independent patients with metastatic PCa were analysed. RESULTS: Forty-four (8%) patients carried germline pathogenic variants in one of the analysed genes. BRCA2 was most frequently altered (n = 19), followed by HOXB13 (n = 9), PALB2 (n = 5) and ATM (n = 5). Further, the BRCA1, BRCA2, PALB2 and ATM variants showed significant association with a short time to castration resistance and overall survival (hazard ratio = 1.99 and 2.36; 95% CI, 1.15-3.44 and 1.23-4.51, respectively), independent of other clinical variables. Based on log-rank tests, the time to castration resistance was also significantly short in patients with BRCA1, BRCA2, PALB2 or ATM somatic mutations and TP53 mutations. CONCLUSIONS: Germline variants in BRCA1, BRCA2, PALB2 or ATM are independent prognostic factors of the short duration of response to hormonal therapy in advanced PCa.

DOI PubMed

Cancer-specific and net overall survival in older patients with de novo metastatic prostate cancer initially treated with androgen deprivation therapy

Narita S.

International Journal of Urology ( International Journal of Urology )  29 ( 10 ) 1147 - 1154   2022年10月

OBJECTIVE: This study aimed to assess survival outcomes in older patients with de novo metastatic prostate cancer who initially received androgen deprivation therapy. METHODS: The retrospective multicenter study included 2784 men with metastatic prostate cancer who were treated with androgen deprivation therapy between 2008 and 2017. Patients were classified into <75, 75-79, and ≥80 age groups. Propensity score matching was conducted to assess the cancer-specific survival of the groups. The 5-year net overall survival of each group was derived to evaluate relative survival compared with the general population using the Pohar-Perme estimator and the 2019 Japan Life Table. RESULTS: During the follow-up (median, 34 months), 1014 patients died, of which 807 died from metastatic prostate cancer progression. Compared with the <75 group, the cancer-specific survival of the 75-79 group was similar (hazard ratio 1.07; 95% confidence interval 0.84-1.37; P = 0.580), whereas that of the ≥80 group was significantly worse (hazard ratio 1.41; 95% confidence interval 1.10-1.80; P = 0.006). The 5-year net overall survival of the <75, 75-79, and ≥80 age groups were 0.678, 0761, and 0.718, respectively. The 5-year net overall survival of patients aged ≥80 years with low- and high-volume disease were 0.893 and 0.586, respectively, which was comparable with those in patients aged <75 years (0.872 and 0.586, respectively). CONCLUSIONS: Older metastatic prostate cancer patients aged ≥80 years had poorer cancer-specific survival compared with younger patients. Conversely, 5-year net overall survival in older patients aged ≥80 years was comparable with that in younger patients aged <75 years.

DOI PubMed

Does castration status affect docetaxel-related adverse events? :Identification of risk factors for docetaxel-related adverse events in metastatic prostate cancer

Yanagisawa T.

Prostate ( Prostate )  82 ( 14 ) 1322 - 1330   2022年10月

BACKGROUND: Docetaxel-related adverse events (AEs) such as neutropenia and febrile neutropenia (FN) can be life-threatening. A previous in vivo study raised the hypothesis that the castration status affects the rate of hematologic AEs. We aimed to investigate the impact of castration status on the incidence of docetaxel-related AE in metastatic prostate cancer (mPCa) patients. METHODS: We retrospectively analyzed the records of 265 mPCa patients treated with docetaxel, comprising 92 patients with metastatic hormone-sensitive prostate cancer (mHSPC) and 173 patients with metastatic castration-resistant prostate cancer (mCRPC) between January 2015 and December 2021. Common terminology Criteria for Adverse Events (CTCAE) was applied to evaluate AEs. We analyzed the differential incidences between mHSPC and mCRPC, and risk factors of hematologic and nonhematologic AEs using a logistic regression model. RESULTS: The rate of patients who received primary prophylaxis against neutropenia was higher in those with the mHSPC compared with those with the mCRPC (7.5% vs. 33%, p < 0.001). Among the patients without primary prophylaxis, incidence rates of severe neutropenia (CTCAE ≥ Grade3) and FN were 89% and 16% in patients with mCRPC compared to 81% and 18% in those with mHSPC. Logistic regression analysis revealed that age ≥ 75 years and failure to provide primary prophylaxis were independent risk factors of severe neutropenia (odds ratio [OR]: 2.39, 95% confidential interval [CI]: 1.10-5.18 and OR: 15.8, 95% CI: 7.23-34.6, respectively). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≧ 1 was an independent risk factor of FN (OR: 2.26, 95% CI: 1.13-4.54). Castration status (mHSPC vs. mCRPC) was not associated with the risks of severe neutropenia and FN. CONCLUSIONS: Castration status did not affect the risk of severe neutropenia or FN in mPCa patients treated with docetaxel regardless of the disease state. Failure to provide primary prophylaxis and advanced patient age are independent risk factors of severe neutropenia; while patients with poor PS are more likely to develop FN. These findings may help guide the clinical decision-making for proper candidate selection of docetaxel treatment.

DOI PubMed

特集 限局性前立腺癌診療バイブル-このへんでキッチリと前立腺癌診療の"あたりまえ"を整理しよう! 〈高齢者・その他〉 高齢者限局性前立腺癌治療

成田 伸太郎

臨床泌尿器科 ( 株式会社医学書院 )  76 ( 11 ) 844 - 850   2022年10月

DOI CiNii Research

転移性腎癌におけるイピリムマブ・ニボルマブ併用療法の早期の耐性化と関連因子の検討

武藤 弓奈, 沼倉 一幸, 畠山 真吾, 関根 悠哉, 小林 瑞貴, 嘉島 相輝, 山本 竜平, 奈良 健平, 齋藤 満, 成田 伸太郎, 大山 力, 羽渕 友則

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 )  60回   P51 - 1   2022年10月

転移性腎細胞癌患者におけるニボルマブ+イピリムマブ療法と免疫関連有害事象との関連

沼倉 一幸, 小林 瑞貴, 武藤 弓奈, 関根 悠哉, 嘉島 相輝, 山本 竜平, 奈良 健平, 齋藤 満, 成田 伸太郎, 羽渕 友則

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 )  60回   O9 - 2   2022年10月

Effect of upfront intensive therapy on oncological outcomes in older patients with high tumor burden metastatic castration-sensitive prostate cancer: A multicenter retrospective study

Miura Y.

Prostate ( Prostate )  82 ( 13 ) 1304 - 1312   2022年09月

BACKGROUND: The effect of upfront intensive therapy on the prognosis of older patients with metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Thus, we assessed the impact of older age (≥75 years) on oncological outcomes in mCSPC patients with a high tumor burden. METHODS: This multicenter retrospective study included 252 patients aged ≥75 years treated with either upfront or conventional therapy between 2014 and 2021. We compared castration-resistant prostate cancer (CRPC)-free survival (FS) and overall survival (OS) between patients with androgen deprivation therapy (ADT) plus upfront intensive therapy (docetaxel [DTX] or abiraterone acetate [ABI] plus prednisolone) and conventional therapy (ADT monotherapy or ADT combined with bicalutamide). We evaluated the effect of upfront intensive therapy on prognosis by multivariable Cox regression analysis. RESULTS: The 231 patients enrolled in our study were classified in the conventional group (n = 148) or the upfront group (n = 104; DTX = 27 and ABI = 77). The upfront group had significantly prolonged CRPC-FS and OS compared with the conventional group, and this was also the case in the background-adjusted multivariable Cox regression analysis. CONCLUSION: Patients aged ≥75 years who received upfront intensive therapy had significantly longer CRPC-FS and OS compared with similar age patients treated with conventional therapy in real-world practice. The oncological benefit may not diminish in this older population.

DOI PubMed

Prevalence and risk estimation of cancer-predisposing genes for upper urinary tract urothelial carcinoma in Japanese.

Yuya Sekine, Yusuke Iwasaki, Nozomi Hakozaki, Mikiko Endo, Yoichiro Kamatani, Koichi Matsuda, Yoshinori Murakami, Takeshi Sano, Shusuke Akamatsu, Takashi Kobayashi, Hidewaki Nakagawa, Kazuyuki Numakura, Shintaro Narita, Tomonori Habuchi, Yukihide Momozawa

Japanese journal of clinical oncology   52 ( 12 ) 1441 - 1445   2022年09月

Upper urinary tract urothelial carcinoma is a rare cancer that has been associated with mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2. In addition, patients with pathogenic variants of cancer-predisposing genes such as BRCA1 and BRCA2 have been reported. However, how cancer-predisposing genes affect the risk of upper urinary tract urothelial carcinoma in the Japanese population remains unclear. Thus, we performed a case-control sequencing study of 27 cancer-predisposing genes in 208 upper urinary tract urothelial carcinoma patients and 37 727 controls. Only MSH6 and MSH2 were observed with a value of P < 0.05. However, there was no difference in the prevalence of pathogenic variants of BRCA1/2, which does not support the use of a poly adenosine diphosphate-ribose polymerase inhibitor in patients with upper urinary tract urothelial carcinoma. Only mismatch repair genes were associated with patients with upper urinary tract urothelial carcinoma, but the prevalence of pathogenic variants in mismatch repair genes was lower than that reported in previous studies from other populations.

DOI PubMed

Real-world outcomes and risk stratification in patients with metastatic castration-sensitive prostate cancer treated with upfront abiraterone acetate and docetaxel

Narita S.

International Journal of Clinical Oncology ( International Journal of Clinical Oncology )  27 ( 9 ) 1477 - 1486   2022年09月

PURPOSE: We assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies. METHODS: The medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted. RESULTS: A total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34-0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33-1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42-2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups. CONCLUSIONS: Upfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.

DOI PubMed

診断に難渋したIVC浸潤を伴う腫瘍マーカー陰性NSGCTの1例

佐々木 禎, 奈良 健平, 小泉 淳, 石田 雅則, 青山 有, 梶原 知佳, 嘉島 相輝, 山本 竜平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 9 ) 1022 - 1022   2022年09月

Carney複合に合併した難治性性索間質性腫瘍の1例

天野 賢士, 嘉島 相輝, 小泉 淳, 南條 博, 赤井 太郎, 明円 真吾, 安達 尚宣, 川村 貞文, 山本 竜平, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 安田 純, 荒井 陽一, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 9 ) 1021 - 1021   2022年09月

【新規保険収載ロボット支援手術手技を極める】ロボット支援腎尿管全摘除術

成田 伸太郎, 齋藤 満, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 9 ) 954 - 959   2022年09月

2022年の診療報酬改定でロボット支援腎尿管摘除術(Robot-assisted laparoscopic nephroureterectomy:RNU)が保険収載となった。当科の初期成績は良好で、膀胱カフ切除までの操作がPatient Cartのポジション変更なく可能であった。至適ポート位置、リンパ節郭清手技、後腹膜アプローチに関しては今後検討が必要である。(著者抄録)

細胞質内におけるコネキシン43の発現が腎細胞癌の予後に与える影響(High expression of Connexin 43 in cytoplasm relates to worse clinical outcomes in patients with renal cell carcinoma)

小林 瑞貴, 大森 泰文, 沼倉 一幸, 関根 悠哉, 武藤 弓奈, 成田 伸太郎, 羽渕 友則

日本癌学会総会記事 ( (一社)日本癌学会 )  81回   P - 3190   2022年09月