論文 - 賀本 敏行
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Shirakawa T., Nagano M., Kamoto T., Mukai S., Murashima T., Ueno T., Miyake N., Oshikawa Y.
Nishinihon Journal of Urology 86 ( 1 ) 18 - 22 2023年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Nishinihon Journal of Urology
The patient was an 75‑year‑old man with Lynch syndrome as an underlying disease. He had undergone multiple surgeries for gastric, colorectal, and small intestine cancers. In February 201X, the patient visited our hospital with gross hematuria. Cystoscopy revealed multiple neoplastic lesions in the bladder. Transurethral surgery for malignant bladder tumor was performed, and the patient was diagnosed with urothelial carcinoma. After that, recurrence was observed in the left ureter, and left nephroureterectomy was performed in November 201X. From May 201X+1, pembrolizumab was administered for about 2 years because of the suspicion of recurrence of urothelial carcinoma due to thickening of the left bladder wall and suspicion of urothelial cancer. In May 201X+3, CT examination showed improvement in the wall thickening on the left side wall, and the patient was diagnosed with CR. Accordingly, the administration of pembrolizumab was discontinued. However, thickening of the left wall was confirmed again, and recurrence was suspected again. Six courses of GC therapy were performed, and the thickening improved. Pathological results showed no obvious malignant findings. Six months have passed without recurrence. In this paper, we report a case of urothelial carcinoma in a patient with Lynch syndrome as an underlying disease who achieved a complete response to multidisciplinary therapy.
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Sugimoto M., Kato T., Tohi Y., Shimizu Y., Matsumoto R., Inoue T., Takezawa Y., Masui K., Sasaki H., Hirama H., Saito S., Egawa S., Kamoto T., Teramukai S., Kojima S., Kikuchi T., Kakehi Y.
BMC Urology 22 ( 1 ) 151 2022年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Urology
Background: The effect of enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade, which represents a patient profile similar to real-world clinical practice in Japan, remains unknown. Therefore, we investigate the efficacy and safety of enzalutamide after combined androgen blockade for recurrence following radical treatment in Japanese patients with non-metastatic castration-resistant prostate cancer. Methods: We analyzed 66 patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical prostatectomy or radiation therapy who were prospectively enrolled from October 2015 to March 2018. They received enzalutamide 160 mg orally once daily until the protocol treatment discontinuation criteria were met. The primary endpoint was prostate-specific antigen-progression-free survival, defined as the time from enrollment to prostate-specific antigen-based progression or death from any cause. The secondary endpoints included overall survival, progression-free survival, metastasis-free survival, time to prostate-specific antigen progression, prostate-specific antigen response rate, chemotherapy-free survival, and safety assessment. Results: The median observation period was 27.3 months. The median prostate-specific antigen-progression-free survival was 35.0 months (95% confidence interval, 17.5 to not reached). The median overall survival, median progression-free survival, median metastasis-free survival, and chemotherapy-free survival were not reached, with the corresponding 2-year rates being 91.6%, 67.1%, 72.4%, and 85.8%, respectively. The 50% prostate-specific antigen response rate was 88.9%, with the median time being 2.8 months. In total, 42.2% of the patients experienced adverse events, with malaise being the most common. Conclusions: Enzalutamide effectively manages non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment. Trialregistration: UMIN000018964, CRB6180007.
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Terada N, Sawada A, Kawanishi H, Fujimoto T, Magaribuchi T, Chihara I, Hashimoto K, Sakurai T, Shimizu Y, Uegaki M, Nakashima M, Narita S, Kubota M, Yamada Y, Tohi Y, Okabe K, Yatsuda J, Kamoto T
International journal of urology : official journal of the Japanese Urological Association 30 ( 2 ) 227 - 234 2022年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Urology
Objective: This study investigated the efficacy of docetaxel (DOC) and cabazitaxel (CBZ) and examined the factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment in Japanese real-world data. Methods: We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. Combined progression-free survival (PFS) of DOC-CBZ and overall survival (OS) from the initiation of DOC and the diagnosis of CRPC were evaluated and compared between patients with high and low PSA levels at the start of DOC and CBZ treatment. Results: No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. The patients for whom DOC was started in higher PSA levels had significantly shorter combined PFS (p = 0.003) and OS from the initiation of DOC (p = 0.002). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (p = 0.048). The OS from CRPC of patients who started DOC at low PSA levels was significantly longer than those that started at high PSA levels (p = 0.030). Conclusions: For patients for whom DOC was not effective, sequential CBZ might have change to be effective. The PSA levels at the start of DOC and CBZ might be a potential prognostic biomarker.
DOI： 10.1111/iju.15097
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Uemura H, Oya M, Kamoto T, Sugimoto M, Shinozaki K, Morita K, Koto R, Takahashi M, Nii M, Shin E, Nonomura N
Cancer medicine 12 ( 5 ) 5265 - 5274 2022年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Medicine
Background: Metastatic castration-resistant prostate cancer (mCRPC) is a genetically heterogeneous disease with a poor prognosis. The prevalence of mutations in homologous recombination repair (HRR) pathway genes, including BRCA1/2, as well as treatment patterns and clinical outcomes, are not well characterized among Japanese men with mCRPC. Methods: This multicenter, noninterventional cohort study enrolled Japanese men with mCRPC from 24 institutions between 2014 and 2018. Mutations in the 15 HRR-related genes were assessed using archival primary or metastatic tumor samples. Patterns of sequential therapies for mCRPC were investigated. Patients were followed up for survival evaluation including prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS). Results: Of the 143 patients analyzed, HRR-related mutations were detected in 51 patients (35.7%). The most frequently mutated genes were CDK12 (N = 19, 13.3%), followed by BRCA2 (N = 18, 12.6%), ATM (N = 8, 5.6%), and CHEK2 (N = 3, 2.1%). The most common type of first-line therapy for mCRPC was next-generation hormonal agents (NHA, 44.4%), followed by first-generation antiandrogens (FGA, 30.3%), and taxanes (22.5%). Commonly prescribed first−/second-line sequential regimens included FGA/NHA (17.6%), NHA/NHA (15.5%), and NHA/taxanes (14.1%). The median PSA-PFS and OS for the entire cohort were 5.6 and 26.1 months, respectively. Patients carrying BRCA1/2 mutations had numerically shorter PSA-PFS (median 3.3 vs. 5.9 months) and OS (median 20.7 vs. 27.3 months) than those without mutations. Conclusions: In conclusion, approximately one-third of Japanese patients with mCRPC carried mutations in HRR-related genes in this study. The real-world outcomes of mCRPC are poor with conventional therapy, warranting an expansion of treatment options based on genetic abnormalities of the disease.
DOI： 10.1002/cam4.5333
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Otsuka I, Terada N, Iwamoto H, Kobayashi T, Kamoto T
Urology 172 49 - 54 2022年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Urology
Objective: To examine the safety and efficacy of Endoscopic combined intrarenal surgery (ECIRS) between the lateral decubitus (LD) and Galdakao-modified supine Valdivia (GMSV) position. Methods: We retrospectively reviewed the records of 226 patients with renal stones who underwent ECIRS in the LD and GMSV positions between 2018 and 2022. Surgeries early in the study period were mainly performed in the GMSV position, while later surgeries were mainly performed in the LD position. Results: The number of patients in the LD and GMSV groups was 119 and 107, respectively. The proportion of patients who had no residual stone fragments >2 mm detected on radiography the day after surgery did not significantly differ between the LD group (91.6%) and the GMSV group (97.2%). Operation time was significantly shorter in the LD group (72 vs 81 minutes; P =.02). Total fluoroscopy time was significantly shorter in the LD group (92 vs 189 seconds; P<.001). Complication rates did not significantly differ between the groups. Among the variables analyzed, the patient position was independently impact on the fluoroscopy time (OR 0.309; 95% CI, 0.167-0.571; P<.001). Conclusion: ECIRS in the LD position is safe and effective and associated with shorter fluoroscopy than the GSMV position.
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Nanashima A, Takamori H, Imamura N, Furukawa K, Hiyoshi M, Hamada T, Yano K, Tsuchimochi Y, Kamoto T
The American journal of case reports 23 e938009 2022年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Case Reports
Objective: Background: Case Report: Conclusions: Rare disease Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare malignancy, and complete resection may provide better patient survival. Hepatectomy for intrahepatic tumor recurrence has not been previously reported. A 58-year-old woman underwent resection of an IVC-LMS with en bloc nephrectomy, adrenalectomy, and retroperitoneal soft tissue resection without IVC reconstruction 3 years 8 months ago. Twenty-nine months after the primary operation, a solitary intrahepatic liver tumor was found adjacent to the right and middle hepatic veins during imaging follow-up. The patient was diagnosed with LMS recurrence. As her liver functional parameters permitted major hepatectomy, right hepatectomy combined with resection of the vena cava wall leaving a tumor-free margin and securing the confluence of the middle hepatic vein were successfully accomplished via an anterior approach, without adverse events. Intrahepatic metastasis of LMS invading the vena cava wall has been diagnosed historically. Her postoperative course was uneventful, and at 1-year follow-up after the second surgery, she was observed to have no tumor relapse without any adjuvant treatment. Previous reports have shown that IVC-LMS is often observed, and operative risk or prognosis is based on the extension of the LMS toward the hepatic veins or cardiac atrium. Radical hepatectomy for recurrent IVC-LMS has not been previously reported, and our case experience revealed that a challenging surgical intervention resulting in complete tumor removal can provide good survival outcomes.
DOI： 10.12659/AJCR.938009
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Okabe K., Terada N., Shirakawa T., Onizuka C., Kimura T., Yamashita Y., Otuka I., Ueno T., Nagano M., Takamori H., Mukai S., Kamoto T.
Anticancer Research 42 ( 10 ) 4981 - 4987 2022年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Anticancer Research
Background/Aim: Radium-223 (Ra-223) therapy provides a survival benefit for castration-resistant prostate cancer (CRPC) patients with bone metastasis. The optimal timing of using Ra-223 has not been determined. We evaluated the efficacy and safety of Ra-223 before and after docetaxel (DOC) therapy. Patients and Methods: We retrospectively reviewed 36 CRPC patients with bone metastasis who were treated with Ra-223 in our institution and satellite hospitals. Ra-223 was used before DOC (pre-DOC group) in 17 patients (47%) and after DOC (post-DOC group) in 19 patients (53%). The treatment completion rate of 6 cycles, progression-free survival (PFS), cause-specific survival (CSS) and occurrence rate of adverse events were compared between the groups. Results: The median follow-up duration was 45 months. In the pre-DOC compared with the post-DOC group, treatment completion rate was significantly higher (94% vs. 52%, p<0.01), PFS was significantly longer (median: 8 vs. 5 months, p=0.024) and CSS was significantly longer (median: 32 vs. 15 months, p=0.028). The difference in CSS was significant in multivariate analysis. In the pre-DOC compared with the post-DOC group, the occurrence rate of grade ≥3 adverse events tended to be lower (6% vs. 36%, p=0.322), and the CSS tended to be longer (median: not reached vs. 45 months, p=0.208). Conclusion: Ra-223 could be used more safely and more effectively for CRPC patients with bone metastasis before than after DOC therapy.
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Narita S., Terada N., Nomura K., Sakamoto S., Hatakeyama S., Kato T., Matsui Y., Inokuchi J., Yokomizo A., Tabata K.i., Shiota M., Kimura T., Kojima T., Inoue T., Mizowaki T., Sugimoto M., Kitamura H., Kamoto T., Nishiyama H., Habuchi T., Saito T., Yoshimura K., Takahashi A., Shimazui T., Goto T., Hashimoto Y., Nagumo Y., Yasumoto H., Mitsuzuka K., Ito A., Matsumoto H., Sugiyama T., Miyake H., Kuroiwa K., Tsuchiya N., Fukuta F., Morizane S., Sato H., Saito T., Shinohara N., Enokida H., Yonemori M.
International Journal of Urology 29 ( 10 ) 1147 - 1154 2022年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Urology
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： 10.1111/iju.14938
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Uemura H., Matsumoto R., Mizokami A., Miyake H., Uemura H., Matsuyama H., Nakamura K., Saito K., Kawakita M., Takeshita H., Koroki Y., Ono S., Murota M., Ito M., Kamoto T., Fujimoto K.
International Journal of Urology 29 ( 9 ) 1061 - 1070 2022年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Urology
Objective: The prognosis of high-risk metastatic hormone-naïve prostate cancer is poor, and real-world evidence of therapeutic options and sequences is lacking. The J-ROCK study aimed to evaluate the outcomes in a real-world setting in Japan. Methods: Patients with high-risk metastatic hormone-naïve prostate cancer diagnosed after May 2019 were eligible. Based on their treatment within 3 months after diagnosis, patients were allocated to either cohort 1 (androgen deprivation therapy alone or combined androgen blockade with bicalutamide) or cohort 2 (androgen deprivation therapy with abiraterone acetate+prednisolone, docetaxel, enzalutamide, or apalutamide). Results: In this first interim analysis (cut-off January 2021), 410 patients were enrolled, including 163 patients in cohort 1 and 247 in cohort 2. The median follow-up period was 7.6 (range 0.1–20.5) months. A higher proportion of patients in cohort 2 (42.5%) achieved nadir prostate-specific antigen levels ≤0.2 ng/ml within a year, compared with cohort 1 (22.1%). Prostate-specific antigen-progression-free survival was also more favorable in cohort 2 (adjusted hazard ratio 0.629 [95% confidence interval 0.345–1.147]). Conclusions: The higher proportion of cohort 2 suggest a paradigm shift has occurred in the real-world treatment of high-risk metastatic hormone-naïve prostate cancer in Japan. Some factors including prostate-specific antigen may affect treatment selection but need further observation. Most patients in cohort 2 received abiraterone acetate+prednisolone. The proportion of patients in cohort 1 receiving combined androgen blockade was lower than previously reported in Japan. This analysis suggest that more intensive therapy tends to prolong prostate-specific antigen-progression-free survival in patients with high-risk metastatic hormone-naïve prostate cancer.
DOI： 10.1111/iju.14993
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Identification of the α2 chain of interleukin-13 receptor as a potential biomarker for predicting castration resistance of prostate cancer using patient-derived xenograft models 査読あり
Toshiyuki Kamoto
Cancer reports 2022年8月
掲載種別：学位論文（博士）
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Mukai S., Sakamoto N., Kakinoki H., Shibuya T., Moriya R., Nishihara K., Noguchi M., Shin T., Fujimoto N., Igawa T., Ishii T., Haga N., Enokida H., Eto M., Kamba T., Sakai H., Saito S., Terada N., Kamoto T.
Journal of Clinical Medicine 11 ( 12 ) 2022年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Medicine
Objectives: To evaluate the management and outcome of idiopathic retroperitoneal fibrosis (iRPF) in Japan, and to identify its clinical biomarker. Methods: We retrospectively analyzed 129 patients with iRPF treated between January 2008 and May 2018 at 12 university and related hospitals. Patients treated with glucocorticoid were analyzed to identify a predictive biomarker. These patients were classified into three groups according to overall effectiveness (no change: NC, complete response: CR, and partial response groups: PR), and each parameter was compared statistically. Results: Male–female ratio was 5:1, and median age at diagnosis was 69 (33–86) years. Smoking history was reported in 59.6% of the patients. As treatment, 95 patients received glucocorticoid therapy with an overall response rate of 84%. As a result, serum concentration of IgG4 was significantly decreased in NC group compared with the other two groups (56.6 mg/dL vs. 255 mg/dL, 206 mg/dL, p = 0.0059 and 0.0078). ROC analysis was performed between the nonresponder (NC) and responder groups (CR + PR) to identify the cut-off value of serum IgG4 as a predictive marker. As a result, AUC of 0.793 was confirmed. Conclusions: Pre-treatment serum IgG4 concentration may have potential as a predictive biomarker of steroid treatment.
DOI： 10.3390/jcm11123538
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Serum IgG4 Concentration Is a Potential Predictive Biomarker in Glucocorticoid Treatment for Idiopathic Retroperitoneal Fibrosis. 査読あり
賀本敏行
J Clin Med 2022年6月
掲載種別：研究論文（学術雑誌）
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Fukuokaya W, Kimura T, Komura K, Uchimoto T, Nishimura K, Yanagisawa T, Imai Y, Iwatani K, Ito K, Urabe F, Tsuzuki S, Kimura S, Terada N, Mukai S, Oyama Y, Abe H, Kamoto T, Azuma H, Miki J, Egawa S
Urologic oncology 40 ( 7 ) 346.e1 - 346.e8 2022年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Urologic Oncology: Seminars and Original Investigations
Background: The association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial. Materials and methods: We retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models. Results: Overall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.28–3.18, P = 0.003) and iPFS (HR: 1.70, 95% CI: 1.23–2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR: 0.61, 95% CI: 0.36–1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR: 0.97, 95% CI: 0.93–1.00, P[interaction] = 0.048) and was increased in males (HR: 2.97, 95% CI: 1.10–8.05, P[interaction] = 0.032). Conclusions: PPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.
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Terada N, Aizawa R, Nihei K, Shiota M, Kojima T, Kimura T, Inoue T, Kitamura H, Sugimoto M, Nishiyama H, Mizowaki T, Kamoto T
Japanese journal of clinical oncology 52 ( 6 ) 633 - 641 2022年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Clinical Oncology
The role of local treatment in patients with de novo metastatic prostate cancer is controversial. In population-based retrospective studies, metastatic prostate cancer patients who received local treatment with prostate radiotherapy showed a better prognosis than those who did not. In addition, several prospective randomized studies demonstrated that prostate radiotherapy achieves a survival benefit for patients with oligo-metastasis. Moreover, the efficacy of metastasis-directed radiotherapy was evaluated, revealing a potential benefit for patients with oligo-metastasis. Importantly, these radiotherapies may reduce the occurrence of symptomatic local events. In this review, the rationale, efficacy and future perspectives for local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer were described and summarized.
DOI： 10.1093/jjco/hyac035
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Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy.
Akamatsu S, Terada N, Takata R, Kinoshita H, Shimatani K, Momozawa Y, Yamamoto M, Tada H, Kawamorita N, Narita S, Kato T, Nitta M, Kandori S, Koike Y, Inazawa J, Kimura T, Kimura H, Kojima T, Terachi T, Sugimoto M, Habuchi T, Arai Y, Yamamoto S, Matsuda T, Obara W, Kamoto T, Inoue T, Nakagawa H, Ogawa O
JNCI cancer spectrum 6 ( 1 ) 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：JNCI Cancer Spectrum
Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant–based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer–associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval ¼ 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings.
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Nagumo Y, Onozawa M, Kojima T, Terada N, Shiota M, Mitsuzuka K, Yasumoto H, Matsumoto H, Enokida H, Sugiyama T, Kuroiwa K, Saito T, Yokomizo A, Kohei N, Tabata KI, Takahashi A, Sugimoto M, Kitamura H, Kamoto T, Nishiyama H, Japanese Urological Oncology Group (JUOG).
International journal of urology : official journal of the Japanese Urological Association 29 ( 5 ) 398 - 405 2022年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Urology
Objective: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. Methods: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008–2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. Results: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34–0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60–0.98. Conclusion: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.
DOI： 10.1111/iju.14793
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Akioka T., Terada N., Takamori H., Kamimura T., Mukai S., Kamoto T.
Urology Case Reports 40 101925 2022年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Urology Case Reports
von Hippel–Lindau (VHL) disease is an autosomal dominant hereditary disease with benign and malignant tumors occurring in various organs including the kidneys. In patients with renal cell carcinoma (RCC) lesions in both kidneys, it is difficult to determine the treatment strategy. We report a case of VHL disease with RCC treated via partial nephrectomy after 6 months of axitinib therapy. Then, the patient continued to receive low-dose axitinib therapy without any signs of tumor progression for 3 years after surgery. Axitinib combined with surgery might be a treatment option for patients with VHL disease harboring bilateral RCC.
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Kimura H., Mizuno K., Shiota M., Narita S., Terada N., Fujimoto N., Ogura K., Hatano S., Iwasaki Y., Hakozaki N., Ishitoya S., Sumiyoshi T., Goto T., Kobayashi T., Nakagawa H., Kamoto T., Eto M., Habuchi T., Ogawa O., Momozawa Y., Akamatsu S.
British Journal of Cancer 127 ( 9 ) 1680 - 1690 2022年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：British Journal of Cancer
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.
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Nagai T., Terada N., Fujii M., Nagata Y., Nakahara K., Mukai S., Okasho K., Kamiyama Y., Akamatsu S., Kobayashi T., Iida K., Denawa M., Hagiwara M., Inoue T., Ogawa O., Kamoto T.
Cancer Reports 6 ( 2 ) 2022年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cancer Reports
Background: Several treatment strategies use upfront chemotherapy or androgen receptor axis-targeting therapies for metastatic prostate cancer. However, there are no useful biomarkers for selecting appropriate patients who urgently require these treatments. Methods: Novel patient-derived xenograft (PDX) castration-sensitive and -resistant models were established and gene expression patterns were comprehensively compared. The function of a gene highly expressed in the castration-resistant models was evaluated by its overexpression in LNCaP prostate cancer cells. Protein expression in the tumors and serum of patients was examined by immunohistochemistry and ELISA, and correlations with castration resistance were analyzed. Results: Expression of the α2 chain of interleukin-13 receptor (IL13Rα2) was higher in castration-resistant PDX tumors. LNCaP cells overexpressing IL13Rα2 acquired castration resistance in vitro and in vivo. In tissue samples, IL13Rα2 expression levels were significantly associated with castration-resistant progression (p < 0.05). In serum samples, IL13Rα2 levels could be measured in 5 of 28 (18%) castration-resistant prostate cancer patients. Conclusion: IL13Rα2 was highly expressed in castration-resistant prostate cancer PDX models and was associated with the castration resistance of prostate cancer cells. It might be a potential tissue and serum biomarker for predicting castration resistance in prostate cancer patients.
DOI： 10.1002/cnr2.1701
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SURVEILLANCE OF URACHAL CAECINOMA IN THE KYUSHU-OKINAWA AREA OF JAPAN
Tobu S., Udo K., Noguchi M., Nishihara K., Igawa T., Miyajima S., Tanaka M., Ando T., Shin T., Onizuka C., Kamoto T., Itesako T., Nakagawa M., Ashikari A., Saito S., Hakariya T., Sakai H., Eto M., Kamba T., Fujimoto N.
Nishinihon Journal of Urology 84 ( 5 ) 514 - 519 2022年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Nishinihon Journal of Urology
Objective: To report a multicenter experience with the management of urachal carcinoma treatment in Japan. Methods: This was a retrospective study of 36 cases of urachal carcinoma managed at 12 university hospitals in the Kyushu-Okinawa region over a 10-year period. Age, sex, and clinical features of each patient at diagnosis as well as imaging findings, pathological diagnosis, staging and treatment were collected and analyzed. Results: The study included 36 patients with urachal carcinoma. The average age was 56.5 (range 22-79) years old. Hematuria was the most common cause of discovery, being noted in 47% (17/36). The average tumor diameter was 44.8 mm. The most frequent pathological diagnosis was adenocarcinoma, seen in 86.1% (31/36), followed by urothelial carcinoma in 8.3% (3/36) and squamous cell carcinoma in 5.6% (2/36). Surgical treatment was performed in 77.8% (28/36). The breakdown of surgery was total cystectomy in 25% (7/28) and partial cystectomy in 75% (21/28). Umbilical resection was performed in 50.0% (14/28). Postoperative recurrence cases detected during an average fol low-up period of 30.7 months comprised 57.1% (16/28), with a 5-year progression free survival rate of 39.6% and a 5-year overall survival rate of 59.1%. Cases with a tumor diameter of ≥ 4 cm and Stage IV cases had a significantly poorer prognosis than other cases. Conclusions: There have been no previous studies of a large number of cases related to this disease, which has a relatively low frequency of occurrence, making this the first report of its kind. The extent of resection is decreasing with technical advances. The stage and size of the cancer affect the prognosis, indicating the importance of early detection.