研究等業績 - その他 - 羽渕 友則
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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.
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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.
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Yagishita H.
International Journal of Molecular Sciences ( International Journal of Molecular Sciences ) 23 ( 19 ) 2022年10月
The purpose of this study was to evaluate the effects of NR1I2 (7635G>A and 8055C>T) and ABCB1 (1236C>T, 2677G>T/A, and 3435C>T) genetic polymorphisms on everolimus pharmacokinetics in 98 Japanese renal transplant patients. On day 15 after everolimus administration, blood samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after administration. The dose-adjusted area under the blood concentration-time curve (AUC0-12) of everolimus was significantly lower in patients with the NR1I2 8055C/C genotype than in those with other genotypes (p = 0.022) and was significantly higher in male patients than female patients (p = 0.045). Significant correlations between the dose-adjusted AUC0-12 of everolimus and age (p = 0.001), aspartate transaminase (p = 0.001), and alanine transaminase (p = 0.005) were found. In multivariate analysis, aging (p = 0.008) and higher alanine transaminase levels (p = 0.032) were independently predictive of a higher dose-adjusted everolimus AUC0-12. Aging and hepatic dysfunction in patients may need to be considered when evaluating dose reductions in everolimus. In renal transplant patients, management using everolimus blood concentrations after administration may be more important than analysis of NR1I2 8055C>T polymorphism before administration.
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長期フォロー腎移植患者CNI血中濃度が与えるde novo DSA発生への影響
藤山 信弘, 齋藤 満, 山本 竜平, 提箸 隆一郎, 齋藤 拓郎, 青山 有, 沼倉 一幸, 羽渕 友則
日本腎臓病薬物療法学会誌 ( 日本腎臓病薬物療法学会 ) 11 ( 特別号 ) S162 - S162 2022年10月
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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.
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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 ( 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.
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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.
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Furukawa J.
International Journal of Urology ( International Journal of Urology ) 29 ( 9 ) 1038 - 1045 2022年09月
OBJECTIVES: Robot-assisted partial nephrectomy is widely performed for small renal masses, achieving excellent perioperative and intermediate oncological outcomes. However, long-term oncological, functional, and quality of life outcomes after robot-assisted partial nephrectomy remain unclear. In this study, we aimed to evaluate quality of life at 1 year and oncological and functional outcomes of robot-assisted partial nephrectomy after a minimum follow-up of 5 years. METHODS: Personal, perioperative, postoperative, functional, oncological, and quality of life data were evaluated. The EQ-5D-5L tool, which incorporates health profiles and a EuroQol Visual Analog Scale, was used to assess quality of life preoperatively and 365 days postoperatively. Regarding oncological and functional outcomes, overall survival, recurrence-free survival, and changes in estimated glomerular filtration rate were calculated. RESULTS: There were few changes in levels between the two time points for all EQ-5D dimensions. The mean change in EQ-5D-5L was 0.020 (95% confidence interval 0.006-0.033, P = 0.006), and in EuroQol Visual Analog Scale score 4.60 (95% confidence interval 2.17-7.02, P = 0.0003). Overall and recurrence-free survival 5 years after robot-assisted partial nephrectomy were 97.9% and 92.8%, respectively. After an early postoperative decrease, the estimated glomerular filtration rate remained stable over time. CONCLUSIONS: Robot-assisted partial nephrectomy in patients with a T1 renal tumor is safe, feasible, and effective from the perspective of quality of life and survival, even after 5 years. When making treatment decisions, perioperative and quality of life outcomes should be considered together with long-term oncological outcomes.
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【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)
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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
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ラード食による前立腺癌発症・増殖における腸内細菌環境の解析(Specific Gut Microbial Environment in Lard Diet-Induced Prostate Cancer Development and Progression)
佐藤 博美, 成田 伸太郎, 石田 雅宣, 高橋 佳子, 黄 明国, 嘉島 相輝, 山本 竜平, 小泉 淳, 奈良 健平, 沼倉 一幸, 齋藤 満, 吉岡 年明, 羽渕 友則
日本癌学会総会記事 ( (一社)日本癌学会 ) 81回 J - 3038 2022年09月
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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
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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
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A CASE OF RENAL ANASTOMOSING HEMANGIOMA
Sasaki Y.
Acta Urologica Japonica ( Acta Urologica Japonica ) 68 ( 8 ) 265 - 269 2022年08月
A 65-year-old man was found to have a 1.7 cm right renal mass by follow-up abdominal computed tomography for left total nephrectomy after a traffic accident. The renal mass progressed slowly to 2.2 cm in three years and enhanced magnetic resonance imaging revealed marked T2 weighting hyperintensity of the lesion. Although a radiologist (TK) suggested the diagnosis renal anastomosing hemangioma preoperatively, we could not deny the possibility of renal cell carcinoma completely. Therefore, the patient underwent robot-assisted laparoscopic partial nephrectomy. The tumor was successfully removed without any renal arterial clamping or parenchymal excision. Histopathologically, the lesion was composed of capillary-size blood vessels lined by a single layer of endothelial cells, and was diagnosed as a renal anastomosing hemangioma. There were no signs of postoperative recurrence during the 3 month follow-up.
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Kobayashi M.
BJU International ( BJU International ) 130 ( 2 ) 226 - 234 2022年08月
OBJECTIVES: To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo-resistant urothelial carcinoma (UC). PATIENTS AND METHODS: The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). RESULTS: Overall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68-1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15-0.90; P = 0.023) compared to patients with PUC. CONCLUSIONS: The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo-resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC.
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【泌尿器科領域の遺伝性疾患とゲノム医療の最前線】腎がんの組織型に応じた生殖細胞系列病的バリアントの特徴
関根 悠哉, 沼倉 一幸, 羽渕 友則, 桃沢 幸秀
泌尿器科 ( (有)科学評論社 ) 16 ( 2 ) 117 - 121 2022年08月
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佐々木 禎, 嘉島 相輝, 小山 貴, 廣嶋 優子, 天野 賢士, 高橋 修平, 奈良 健平, 小泉 淳, 山本 竜平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 南條 博, 佐藤 滋, 羽渕 友則
泌尿器科紀要 ( 泌尿器科紀要刊行会 ) 68 ( 8 ) 265 - 269 2022年08月
65歳男。35年前に外傷性左腎静脈損傷で左腎摘除術を施行され、そのときの輸血によってC型肝炎を発症し、治療と経過観察を行っていた。3年前に腹部CTで右腎外側に造影効果を伴う17×9mm大の腫瘤を認めた。今回、腹部CTで22×13mmと増大を認め、放射線科医にCTの読影を依頼し、腎anastomosing hemangiomaと診断された。しかし、腫瘤は増大傾向を示しているため悪性を完全には否定できないことと、患者が外科的摘除と病理学的診断を希望したことから手術の方針となった。MRIで腫瘤はT1強調像で低信号、T2強調像で高信号を示し、造影ダイナミックCTで腫瘤辺縁から経時的・求心性に造影される特徴的な所見を呈したことからanastomosing hemangiomaと術前診断した。ロボット支援腹腔鏡下腫瘤摘除術を施行し、摘出標本の病理組織所見からanastomosing hemangiomaと確定診断した。術後経過は良好で2日目に退院し、術後3ヵ月時の胸腹部CTで再発・転移は認めなかった。
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転移性去勢感受性・抵抗性前立腺癌におけるアビラテロンおよびD4A血中濃度と臨床因子の関連検討
高橋 佳子, 成田 伸太郎, 塩田 真己, 三浦 昌朋, 江藤 正俊, 羽渕 友則
泌尿器外科 ( 医学図書出版(株) ) 35 ( 8 ) 905 - 908 2022年08月
アビラテロン酢酸エステルおよび代謝産物であるΔ4a-abiraterone(D4A)の血中濃度と治療効果の関連が報告されるが本邦の検討は少ない。今回われわれはアビラテロン酢酸エステルを投与したmetastatic castration-sensitive prostate cancer(mCSPC)およびmetastatic castration-resistant prostate cancer(mCRPC)症例における血中濃度とアウトカムの関連を検討した。2016年3月から2021年5月までに国内2施設でアビラテロン酢酸エステルを投与したmCSPC、mCRPC症例のうち、血中濃度測定が可能な68例を対象とした。患者血漿を用い高速液体クロマトグラフィー法で血中濃度を測定し、ABI濃度中央値18.1ng/mL、D4A濃度中央値0.97ng/mL、D4A/ABI中央値0.047であった。治療効果と血中濃度に有意な関連を認めなかった。Grade 1以上の有害事象発症率は51.5%であり、有害事象ありは有意にABI濃度が高値であった。有害事象発症を予測するABI濃度最適カットオフ値は20.6ng/mLであり、ABI高値(≧20.6ng/mL)はABI低値(<20.6ng/mL)に比較しアビラテロン酢酸エステル継続期間が有意に短かった。ABI濃度はmCSPC、mCRPC症例の患者モニタリングに有用な可能性がある。(著者抄録)
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Iwamura H.
Cancer Science ( Cancer Science ) 113 ( 7 ) 2434 - 2445 2022年07月
Early diagnosis of urological diseases is often difficult due to the lack of specific biomarkers. More powerful and less invasive biomarkers that can be used simultaneously to identify urological diseases could improve patient outcomes. The aim of this study was to evaluate a urological disease-specific scoring system established with a machine learning (ML) approach using Ig N-glycan signatures. Immunoglobulin N-glycan signatures were analyzed by capillary electrophoresis from 1312 serum subjects with hormone-sensitive prostate cancer (n = 234), castration-resistant prostate cancer (n = 94), renal cell carcinoma (n = 100), upper urinary tract urothelial cancer (n = 105), bladder cancer (n = 176), germ cell tumors (n = 73), benign prostatic hyperplasia (n = 95), urosepsis (n = 145), and urinary tract infection (n = 21) as well as healthy volunteers (n = 269). Immunoglobulin N-glycan signature data were used in a supervised-ML model to establish a scoring system that gave the probability of the presence of a urological disease. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). The supervised-ML urologic disease-specific scores clearly discriminated the urological diseases (AUC 0.78-1.00) and found a distinct N-glycan pattern that contributed to detect each disease. Limitations included the retrospective and limited pathological information regarding urological diseases. The supervised-ML urological disease-specific scoring system based on Ig N-glycan signatures showed excellent diagnostic ability for nine urological diseases using a one-time serum collection and could be a promising approach for the diagnosis of urological diseases.
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Kobayashi M.
Genes ( Genes ) 13 ( 7 ) 2022年07月
Single nucleotide polymorphisms (SNPs) reportedly influence the effect of nivolumab in metastatic renal cell carcinoma (mRCC). This study aimed to evaluate the relationship between the clinical outcomes of patients with mRCC and SNPs in programmed cell death protein 1 (PD-1) protein-coding gene (PDCD1) and explore any potential correlation with patient prognosis and incidence of immune-related adverse events (irAEs). In total, 106 patients with mRCC, who were treated with nivolumab alone (n = 59) or nivolumab and ipilimumab (n = 47), were enrolled in the study. Three SNPs in the PDCD1 gene, namely PD-1.3, PD-1.5, and PD-1.6, were assessed. Patients harboring the PD-1.6 G allele experienced more severe (odds ratio, 3.390; 95% confidence interval 1.517-7.756; p = 0.003) and multiple (OR, 2.778; 95% CI, 1.020-6.993 p = 0.031) irAEs than those harboring the AA genotype. Thus, the existence of the PDCD1 PD-1.6 polymorphism (G allele) was associated with the occurrence of severe and multiple irAEs in patients with mRCC. Further evaluation of PDCD1 polymorphisms might help identify patients experiencing irAE by nivolumab treatment.