Details of a Researcher - Oya, Mototsugu

Papers - Oya, Mototsugu

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Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100)

Choueiri Toni K., Larkin James, Oya Mototsugu, Thistlethwaite Fiona, Martignoni Marcella, Nathan Paul, Powles Thomas, McDermott David, Robbins Paul B., Chism David D., Cho Daniel, Atkins Michael B., Gordon Michael S., Gupta Sumati, Uemura Hirotsugu, Tomita Yoshihiko, Compagnoni Anna, Fowst Camilla, di Pietro Alessandra, Rini Brian I.

The Lancet Oncology 2018.01

Joint Work, ISSN 1470-2045

Background: The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma. Methods: The JAVELIN Renal 100 study is an ongoing open-label, multicentre, dose-finding, and dose-expansion, phase 1b study, done in 14 centres in the USA, UK, and Japan. Eligible patients were aged 18 years or older (≥20 years in Japan) and had histologically or cytologically confirmed advanced renal-cell carcinoma with clear-cell component, life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 1 or less, received no previous systemic treatment for advanced renal cell carcinoma, and had a resected primary tumour. Patients enrolled into the dose-finding phase received 5 mg axitinib orally twice daily for 7 days, followed by combination therapy with 10 mg/kg avelumab intravenously every 2 weeks and 5 mg axitinib orally twice daily. Based on the pharmacokinetic data from the dose-finding phase, ten additional patients were enrolled into the dose-expansion phase and assigned to this regimen. The other patients in the dose-expansion phase started taking combination therapy directly. The primary endpoint was dose-limiting toxicities in the first 4 weeks (two cycles) of treatment with avelumab plus axitinib. Safety and antitumour activity analyses were done in all patients who received at least one dose of avelumab or axitinib. This trial is registered with ClinicalTrials.gov, number NCT02493751. Findings: Between Oct 30, 2015, and Sept 30, 2016, we enrolled six patients into the dose-finding phase and 49 into the dose-expansion phase of the study. One dose-limiting toxicity of grade 3 proteinuria due to axitinib was reported among the six patients treated during the dose-finding phase. At the cutoff date (April 13, 2017), six (100%, 95% CI 54–100) of six patients in the dose-finding phase and 26 (53%, 38–68) of 49 patients in the dose-expansion phase had confirmed objective responses (32 [58%, 44–71] of all 55 patients). 32 (58%) of 55 patients had grade 3 or worse treatment-related adverse events, the most frequent being hypertension in 16 (29%) patients and increased concentrations of alanine aminotransferase, amylase, and lipase, and palmar-plantar erythrodysaesthesia syndrome in four (7%) patients each. Six (11%) of 55 patients died before data cutoff, five (9%) due to disease progression and one (2%) due to treatment-related autoimmune myocarditis. At the end of the dose-finding phase, the maximum tolerated dose established for the combination was avelumab 10 mg/kg every 2 weeks and axitinib 5 mg twice daily. Interpretation: The safety profile of the combination avelumab plus axitinib in treatment-naive patients with advanced renal-cell carcinoma seemed to be manageable and consistent with that of each drug alone, and the preliminary data on antitumour activity are encouraging. A phase 3 trial is assessing avelumab and axitinib compared with sunitinib monotherapy. Funding: Pfizer and Merck.

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Prognostic significance of grade 3/4 neutropenia in Japanese prostate cancer patients treated with cabazitaxel

Kosaka Takeo, Shinojima Toshiaki, Morita Shinya, Oya Mototsugu

Cancer Science (Cancer Science) 109 ( 5 ) 1570 - 1575 2018.01

Research paper (scientific journal), Joint Work, ISSN 1347-9032

The present study aimed to evaluate the efficacy of cabazitaxel in Japanese patients affected by metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel-containing regimen. In this retrospective study, 41 patients with mCRPC treated with cabazitaxel at Keio University Hospital were retrospectively reviewed. Cabazitaxel at a dose of 20-25 mg/m² was administered every 3 or 4 weeks. Clinicopathological factors and laboratory data were collected to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). An upfront dose-reduction was required in 52.5% of patients due to their reduced general condition or advanced age. Prophylactic G-CSF was prescribed to all the patients. Grade ≥3 neutropenia and febrile neutropenia occurred in 21 patients (53.6%) and 3 patients (6.8%), respectively. Treatment was generally well tolerated, with a median of 5 cycles (range 1-17). Median PFS and OS from the start of cabazitaxel treatment were 4.4 and 15.0 months (95% CI 8.9-21.2), respectively. Waterfall plot analysis revealed that a prostate-specific antigen (PSA) decline >50% was noticed in n = 11 patients receiving cabazitaxel (26.8%). Univariate analysis revealed that poor performance status, PSA ≥100 ng/mL prior to cabazitaxel treatment, visceral metastasis, absence of grade 3/4 neutropenia during cabazitaxel therapy and neutrophil-lymphocyte ratio were significantly associated with shorter overall survival. Multivariate analysis revealed that poor performance status, visceral metastasis, and the absence of grade 3/4 neutropenia during cabazitaxel therapy were the independent prognostic indicators for OS. The practical implication of our results might be to tailor cabazitaxel dosing on the basis of its hematological effects.

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Prognostic Value of Baseline Serum C-Reactive Protein Level in Intermediate-Risk Group Patients With Metastatic Renal-Cell Carcinoma Treated by First-Line Vascular Endothelial Growth Factor–Targeted Therapy

Takamatsu Kimiharu, Mizuno Ryuichi, Omura Minami, Morita Shinya, Matsumoto Kazuhiro, Shinoda Kazunobu, Kosaka Takeo, Takeda Toshikazu, Shinojima Toshiaki, Kikuchi Eiji, Asanuma Hiroshi, Oyama Masafumi, Mikami Shuji, Oya Mototsugu

Clinical Genitourinary Cancer (Clinical Genitourinary Cancer) 16 ( 4 ) e927 - e933 2018.01

Research paper (scientific journal), Joint Work, ISSN 1558-7673

Because accumulating evidence underlines the association of systemic inflammation with metastatic renal-cell carcinoma (mRCC) progression, we evaluated baseline C-reactive protein (CRP) levels as a prognostic marker in 107 intermediate-risk mRCC patients treated with first-line targeted therapy. Baseline CRP could be a biomarker correlated with overall survival in the intermediate-risk group. Its cost efficacy and availability make CRP a helpful tool for reclassifying the intermediate-risk group. Background: Almost half of patients with metastatic renal-cell carcinoma (mRCC) are classified as intermediate risk by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. The aim of this study was to evaluate whether baseline C-reactive protein (CRP) levels predict overall survival (OS) in intermediate-risk group mRCC patients. Patients and Methods: Data from 107 intermediate-risk group mRCC patients receiving first-line targeted therapy were retrospectively reviewed. We evaluated the correlation between baseline CRP levels as well as other indices and OS. Results: Of the 107 patients with intermediate-risk disease, 46 patients (43%) were classified as having elevated CRP levels. The elevation of pretreatment serum CRP levels was the independent prognostic factor of OS in patients with intermediate risk (hazard ratio, 4.609; P =.001). The 1- and 3-year survival rates of patients with intermediate–nonelevated CRP were 90.0% and 64.7% compared to the favorable-risk group, at 92.1% and 68.5%, respectively. In contrast, the 1- and 3-year survival rates of patients with intermediate–elevated CRP were 80.5% and 37.4% compared to the poor-risk group, at 65.2% and 24.2%, respectively. Conclusion: Baseline CRP levels could divide mRCC patients in the intermediate-risk group into 2 prognostic subgroups.

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Prostate-specific antigen nadir within 12 months as an early surrogate marker of biochemical failure and distant metastasis after low-dose-rate brachytherapy or external beam radiotherapy for localized prostate cancer

Nishimura Shuichi, Ohashi Toshio, Momma Tetsuo, Sakayori Masanori, Eriguchi Takahisa, Tanaka Tomoki, Yamashita Shoji, Kosaka Takeo, Oya Mototsugu, Shigematsu Naoyuki

Cancer Medicine (Cancer Medicine) 7 ( 5 ) 1794 - 1801 2018.01

Research paper (scientific journal), Joint Work, ISSN 2045-7634

Prostate-specific antigen nadir (nPSA) after radiotherapy for localized prostate cancer has been investigated as a predictor. However, nPSA usually requires several years, limiting its clinical utility. We investigated the significance of nPSA within 12 months (nPSA12) after low-dose-rate prostate brachytherapy (LDR-PB) or external beam radiotherapy (EBRT) on treatment outcomes. Between 2006 and 2014, 663 patients with prostate cancer were treated with LDR-PB or EBRT at two institutions. Four hundred and seventy-four men received LDR-PB and 189 men received EBRT, without androgen deprivation therapy. The Kaplan-Meier method was used for biochemical failure (BF)-free survival (BFFS) and distant metastasis (DM)-free survival (DMFS) analyses, and multivariable Cox regression analysis was performed. The median follow-up was 61.3 months. The median nPSA12 in the LDR-PB and EBRT cohorts was 0.7 and 1.0 ng/mL, respectively. The 7-year BFFS and DMFS rates in LDR-PB patients with nPSA12 ≤ 0.7 ng/mL were 99.1% and 99.5%, respectively; when nPSA12 was >0.7 ng/mL, they were 90.2% and 94.8%, respectively. In EBRT patients with nPSA12 ≤ 1.0 ng/mL, BFFS and DMFS rates were 85.4% and 98.5%, respectively; when nPSA12 was >1.0 ng/mL, they were 67.1% and 87.2%, respectively. nPSA12 was an independent predictor of BF and DM in both cohorts (LDR-PB, P = 0.004 and 0.020, respectively; EBRT, P = 0.005 and 0.041, respectively). The nPSA12 after LDR-PB or EBRT is significantly associated with treatment outcomes of prostate cancer. Higher nPSA12 may identify patients at high risk of relapse who might benefit from salvage treatment.

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Purified Protein Derivative Skin test prior to bacillus Calmette-Guérin Therapy May have Therapeutic Impact in Patients with Nonmuscle Invasive Bladder Cancer

Niwa Naoya, Kikuchi Eiji, Matsumoto Kazuhiro, Kosaka Takeo, Mizuno Ryuichi, Oya Mototsugu

Journal of Urology (Journal of Urology) 199 ( 6 ) 1446 - 1451 2018.01

Research paper (scientific journal), Joint Work, ISSN 0022-5347

Purpose: We investigated the clinical impact of the purified protein derivative skin test prior to bacillus Calmette-Guérin therapy in patients with nonmuscle invasive bladder cancer treated with adjuvant bacillus Calmette-Guérin therapy. Materials and Methods: A total of 498 patients with nonmuscle invasive bladder cancer treated with adjuvant bacillus Calmette-Guérin were included in study, of whom 320 underwent the purified protein derivative skin test 1 to 2 weeks prior to therapy. Oncologic outcomes and the rate of bacillus Calmette-Guérin related side effects were statistically evaluated. Results: The mean ± SD 5-year recurrence-free survival rate in patients who did vs did not undergo the purified protein derivative skin test was 66.6% ± 2.8% and 59.1% ± 4.1%, respectively, which was significantly different (p = 0.048). No significant difference was observed in the progression-free survival rate between patients who did vs did not undergo the test. Multivariate Cox regression analysis revealed that a history of recurrence (HR 1.59, p = 0.02), multiple tumors (HR 1.95, p <0.01), the bacillus Calmette-Guérin Connaught strain (HR 0.71, p = 0.04), 7 or more bacillus Calmette-Guérin instillations (HR 0.70, p = 0.04) and undergoing the purified protein derivative skin test (HR 0.72, p = 0.04) were independently associated with tumor recurrence. Major bacillus Calmette-Guérin related side effects were noted in 77 of the 320 patients (24.1%) who did vs 27 of the 178 (15.2%) who did not undergo the test, which was significantly different (p = 0.02). Conclusions: The purified protein derivative skin test prior to bacillus Calmette-Guérin treatment enhances the therapeutic effects of this treatment and potentially results in a higher incidence of major bacillus Calmette-Guérin related side effects. Combination therapy with bacillus Calmette-Guérin using the purified protein derivative skin test may improve the oncologic outcomes of that therapy.

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Recent progress in prognostic and predictive biomarkers for target therapies in metastatic tenat cell carcinoma

Mizuno Ryuichi, Asanuma Hiroshi, Oya Mototsugu

Japanese Journal of Clinical Urology (Japanese Journal of Clinical Urology) 72 ( 1 ) 64 - 69 2018.01

Research paper (scientific journal), Joint Work, ISSN 0385-2393

The Role of PD-1 Positivity in the Tumour Nest on Clinical Outcome in Upper Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy

Hayakawa N., Kikuchi E., Mikami S., Fukumoto K., Oya M.

Clinical Oncology (Clinical Oncology) 30 ( 1 ) e1 - e8 2018.01

Research paper (scientific journal), Joint Work, ISSN 0936-6555

Aims The role of PD-1 (programmed cell death 1) expression on the clinical outcome of upper tract urothelial carcinoma has not yet been elucidated in detail. Materials and methods PD-1 expression was immunohistochemically examined in 181 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy. A part of PD-1 protein expression in the tumour periphery and tumour nest was evaluated separately. The PD-1-positive cells were counted in the area showing the highest density of PD-1 expression at a magnification of 400×. Results PD-1 staining in the tumour nest was low in 137 (75.7%) and high in 44 (24.3%) patients. PD-1 staining in the tumour periphery was low in 78 (43.1%) and high in 103 (56.9%) patients. The 5 year progression-free survival rates in patients with the high PD-1 expression in the tumour nest and in the tumour periphery were 54.6% and 67.7%, respectively, which were significantly lower than those in their counterparts (79.4%, P < 0.001; 80.0%, P = 0.04). The 5 year cancer-specific survival rates in patients with the high PD-1 expression in the tumour nest and the tumour periphery were 69.1% and 75.7%, respectively, which were significantly lower than those in their counterparts (84.7%, P = 0.007; 87.8%, P = 0.01). A multivariate Cox regression analysis identified the high PD-1 expression in the tumour nest (hazard ratio 3.07, P < 0.001; hazard ratio 2.44, P = 0.011) and positive lymphovascular invasion (hazard ratio 4.86, P < 0.001; hazard ratio 4.03, P < 0.001) as independent predictors of disease progression and of cancer death, respectively. Conclusions PD-1 positivity in the tumour nest could be a strong predictor for a worse clinical outcome and may be a useful indicator for selecting appropriate candidates for adjuvant therapy such as chemotherapy in upper tract urothelial carcinoma patients treated with radical nephroureterectomy.

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Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity (vol 1, pg 796, 2017)

Tanaka, Nobuyuki, Kanatani, Shigeaki, Tomer, Raju, Sahlgren, Cecilia, Kronqvist, Pauliina, Kaczynska, Dagmara, Louhivuori, Lauri, Kis, Lorand, Lindh, Claes, Mitura, Przemyslaw, Stepulak, Andrzej, Corvigno, Sara, Hartman, Johan, Micke, Patrick, Mezheyeuski, Artur, Strell, Carina, Carlson, Joseph W., Moro, Carlos Fernandez, Dahlstrand, Hanna, Ostman, Arne, Matsumoto, Kazuhiro, Wiklund, Peter, Oya, Mototsugu, Miyakawa, Ayako, Deisseroth, Karl, Uhlen, Per

NATURE BIOMEDICAL ENGINEERING 2 ( 1 ) 48 - 48 2018.01

Research paper (scientific journal), Single Work, ISSN 2157-846X

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Overcoming enzalutamide-resistant castration-resistant prostate cancer by targeting transcriptional 71 repressor BCL-6.

Hongo Hiroshi, Kosaka Takeo, Miyazaki Yasumasa, Kikuchi Eiji, Oya Mototsugu

CANCER SCIENCE (WILEY) 109 975 - 975 2018.01

Joint Work, ISSN 1349-7006

The prognostic significance of vasohibin-2 expression in patients with prostate cancer

Miyazaki Yasumasa, Kosaka Takeo, Mikami Shuji, Yasumizu Yota, Tanaka Nobuyuki, Kikuchi Eiji, Sato Yasufumi, Oya Mototsugu

CANCER SCIENCE (WILEY) 109 1070 - 1070 2018.01

Joint Work, ISSN 1349-7006

The effect of sulfasalazine on bladder cancer stem like cells targeting to cystine transporter

Ogihara Koichiro, Kikuchi Eiji, Hagiwara Masayuki, Kosaka Takeo, Saya Hideyuki, Oya Mototsugu

CANCER SCIENCE (WILEY) 109 1049 - 1049 2018.01

Joint Work, ISSN 1349-7006

Laparoscopic vesical diverticulectomy

Shinojima T., Matsumoto K., Oya M.

Japanese Journal of Clinical Urology (Japanese Journal of Clinical Urology) 72 ( 12 ) 1012 - 1017 2018

ISSN 03852393

Investigation of particle balance in fusion experimental devices with QUEST wall model

Hanada K., Miyamoto M., Idei H., Nagashima Y., Onchi T., Hasegawa M., Nakamura K., Zushi H., Kuroda K., Kawasaki S., Higashijima A., Yoshida N., Nagata T., Shimabukuro S., Watanabe O., Takase Y., Murakami S., Takagi I., Hatayama A., Oya Y., Shikama T., Wang Z., Long H., Oya M.

Meeting Abstracts of the Physical Society of Japan (The Physical Society of Japan) 73 ( 0 ) 771 - 771 2018

A novel form of juvenile primary aldosteronism, which defined by immunohistochemistry for aldosterone synthase, super-selective adrenal venous sampling, and next generation sequencer.

Nishimoto Koshiro, Hayashi Yasuki, Nakagawa Ken, Oya Mototsugu

Official Journal of the Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery (Japan Association of Endocrine Surgeons・Japanese Society of Thyroid Surgery) 35 ( 1 ) 13 - 17 2018

ISSN 2186-9545

症例は16歳，女性。８歳時に重度PAを発症し，ミネラルコルチコイド受容体阻害薬を含む薬剤治療を施行したが無効であった。超選択的副腎静脈サンプリングにより，右副腎下部を除く両側副腎から著明な自律的アルドステロン産生が確認された。右副腎下部温存両側副腎摘除術を施行した。術後PAは改善し降圧剤は不要となった。両側副腎皮質は，正常副腎皮質と多発する皮質過形成が混在する所見を認め，過形成はアルドステロン合成酵素強陽性であった。正常・過形成部位からの微量DNAの次世代シーケンサー解析により，すべての過形成部位ではKCNJ5体細胞変異（p.G151R）を認めたが，正常部位では認めなかった。発生学的に中胚葉細胞は左右の副腎原基に分化する。本症例は胎生期早期の中胚葉細胞にKCNJ5変異が発生し，変異のない細胞とモザイクとなって副腎皮質を形成して，左右副腎の多発過形成を発生させたと推定された。

腎癌薬物療法におけるバイオマーカー開発の進歩

Oya Mototsugu

臨床泌尿器科 72巻1号 64 - 69 2018

Accepted

腎細胞がん分子標的治療の国際比較

Oya Mototsugu

腎臓内科・泌尿器科 7巻1号 44 - 49 2018

Accepted

Significance of a frozen section analysis of the ureteral margin in bladder cancer patients treated with radical cystectomy and neoadjuvant chemotherapy

Hakozaki Kyohei, Kikuchi Eiji, Fukumoto Keishiro, Shirotake Suguru, Miyazaki Yasumasa, Maeda Takahiro, Kaneko Gou, Yoshimine Shunsuke, Tanaka Nobuyuki, Kanai Kunimitsu, Oyama Masafumi, Nakajima Yosuke, Momma Tetsuo, Oya Mototsugu

Medical Oncology (HUMANA PRESS INC) 34 ( 12 ) 187 - 187 2017.12

ISSN 1357-0560

Although the clinical utility of a frozen section analysis (FSA) at the time of radical cystectomy (RC) has already been established, its significance and utility in bladder cancer patients receiving neoadjuvant chemotherapy (NAC) have not yet been fully evaluated. We identified 458 patients (937 ureters) who underwent open RC for bladder cancer at our 7 Japanese institutions between 2004 and 2015. Among these patients, 139 (284 ureters) received NAC before RC (NAC group), while 319 (653 ureters) underwent RC alone (non-NAC group). FSA was performed on 356 out of 937 (38.0%) ureters and 179 out of 458 (39.1%) patients. FSA was positive in 30 out of 356 (8.4%) ureters and its sensitivity, specificity, and accuracy were 89.3, 98.5, and 97.8%, respectively. In the NAC group, FSA was performed on 138 out of 284 (48.6%) ureters and 68 out of 139 (48.9%) patients. FSA was positive in 8 out of 138 ureters (5.8%), and its sensitivity, specificity, and accuracy were 77.8, 99.2, and 97.8%, respectively. In the non-NAC group, FSA was performed on 218 out of 653 (33.4%) ureters and 111 out of 319 (34.8%) patients. FSA was positive in 22 out of 218 (10.1%) ureters, and its sensitivity, specificity, and accuracy were 94.7, 98.0, and 97.7%, respectively. No correlation was observed between preoperative clinical factors and FSA positivity in the NAC group; however, in the non-NAC group, the incidence of FSA positivity in the ureters of patients with concomitant CIS in TUR-BT specimens was 8/41 (19.5%), which was significantly higher than that in their counterpart (14/177, 7.9%, p = 0.033). Even in the era of NAC in the management of bladder cancer patients, the performance of FSA does not change and FSA at the time of RC may provide useful diagnostic information.

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Baseline risk stratification or duration of prior therapy predicts prognosis in patients with metastatic renal cell carcinoma treated with axitinib

Mizuno Ryuichi, Mikami Shuji, Takamatsu Kimiharu, Shinojima Toshiaki, Kikuchi Eiji, Oya Mototsugu

Japanese Journal of Clinical Oncology (OXFORD UNIV PRESS) 47 ( 12 ) 1170 - 1174 2017.12

ISSN 0368-2811

Background: To elucidate the clinical prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with axitinib. Methods: A total of 58 patients were retrospectively analyzed. All patients received axitinib treatment for mRCC at Keio University hospital in Japan. Baseline clinical factors and on treatment adverse events were assessed to predict survival. Results: The median progression free survival (PFS) for axitinib treatment was 10.9 months (95% CI 5.8-13.5), and the median overall survival (OS) from the start of axitinib treatment was 39.8 months (95% CI 25.9-NR), respectively. The PFS (P < 0.0001) and OS (P = 0.0022) were significantly correlated with the International mRCC Database Consortium (IMDC) classification, respectively. The PFS and OS were significantly longer in patients who received longer prior treatment (P = 0.0424 and 0.0067, respectively). On-treatment hypertension, hand foot syndrome and hypothyroidism were associated with longer PFS (P = 0.0002, 0.0055 and 0.0290, respectively). Ontreatment hypertension, diarrhea, and hand foot syndrome were associated with longer OS (P = 0.0004, 0.0036 and 0.0115, respectively). Conclusions: Baseline and on treatment factors are identified as prognostic markers in mRCC patients treated with axitinib. Our findings might be helpful for clinicians to select the best treatment to individual patients.

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Can urologists introduce the concept of "oligometastasis" for metastatic bladder cancer after total cystectomy?

Ogihara, Koichiro, Kikuchi, Eiji, Watanabe, Keitaro, Kufukihara, Ryohei, Yanai, Yoshinori, Takamatsu, Kimiharu, Matsumoto, Kazuhiro, Hara, Satoshi, Oyama, Masafumi, Monma, Tetsuo, Masuda, Takeshi, Hasegawa, Shintaro, Oya, Mototsugu

ONCOTARGET (IMPACT JOURNALS LLC) 8 ( 67 ) 111819 - 111835 2017.12

Research paper (scientific journal), ISSN 1949-2553

We investigated whether the concept of oligometastasis may be introduced to the clinical management of metastatic bladder cancer patients. Our study population comprised 128 patients diagnosed with metastatic bladder cancer after total cystectomy at our 6 institutions between 2004 and 2014. We extracted independent predictors for identifying a favorable. Occurrence that fulfilled all 4 criteria which were independently associated with cancer-specific death was defined as oligometastasis: a solitary metastatic organ; number of metastatic lesions of 3 or less; the largest diameter of metastatic foci of 5cm or less; and no liver metastasis. We evaluated differences in clinical outcomes between patients with oligometastasis (oligometastasis group) and those without oligometastasis (non-oligometastasis group). Overall, there were 43 patients in the oligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 53.3%, which was significantly higher than that in the non-oligometastasis group (16.1%, p<0.001). A multivariate analysis revealed that non-oligometastasis (p<0.001), not performing salvage chemotherapy (p<0.001), and not performing metastatectomy (p=0.028) were independent risk factors for cancer-specific death. In the subgroup of 83 patients who received salvage chemotherapy, 30 were in the oligometastasis group. The 2-year cancer-specific survival rate in the oligometastasis group was 55.0%, which was significantly higher than that in the non-oligometastasis group (22.0%, p=0.005). Non-oligometastasis (p=0.009) was the only independent risk factor for cancer-specific death. We presented that urothelial carcinoma with oligometastasis had a favorable prognosis and responded to systemic chemotherapy. Oligometastasis may be treated as a separate entity in the field of metastatic urothelial carcinoma.

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Pre-operative and post-operative estimated glomerular filtration rate in Japanese patients with urological malignancies

Niwa Naoya, Yoshida Tadashi, Mizuno Ryuichi, Kikuchi Eiji, Miyajima Akira, Hayashi Matsuhiko, Oya Mototsugu

Clinical and Experimental Nephrology (SPRINGER) 22 ( 5 ) 1 - 8 2017.11

Research paper (scientific journal), Joint Work, ISSN 1342-1751

Background: The suitable methods evaluating glomerular filtration rate (GFR) have not been established in patients undergoing radical nephrectomy (RN) or radical nephroureterectomy (RNU) due to urological malignancies in Japan as well as worldwide. Methods: We examined the relationship between creatinine clearance-based measured GFR (mGFR) versus estimated GFR (eGFR) calculated by 3 popular equations, 4-variable Modification of Diet in Renal Disease equation adjusted by Japanese correction coefficient (cmMDRD), 3-variable MDRD equation for Japanese population (eGFRcreat), and Chronic Kidney Disease-Epidemiology Collaboration equation adjusted by Japanese correction coefficient (cmCKD-EPI) in Japanese patients who had undergone RN or RNU due to renal cell carcinoma or upper tract urothelial carcinoma before and after surgery. Results: Among the 3 equations examined, eGFRcreat was the closest to mGFR, although each eGFR was significantly higher than mGFR in the pre-operative period. In the post-operative period, cmMDRD and eGFRcreat, but not cmCKD-EPI, were comparable to mGFR. Each of eGFR was significantly correlated with mGFR in both the pre-operative and post-operative periods. Similar results were obtained by the subanalysis of the patients with pre-operative mGFR of < 60 mL/min/1.73 m². Results of κ statistics also showed that eGFRcreat was most appropriate to estimate GFR both before and after heminephrectomy, when cut-off value of GFR of < 60 mL/min/1.73 m² was used. Conclusion: Results of the present study suggest that eGFRcreat is likely to be the most appropriate equation for patients undergoing RN or RNU due to urological malignancies. However, more precise equations will be required for accurately estimating GFR.

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