Faculty Profiles - Katayama Satoshi

Papers - Katayama Satoshi

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A Novel Technique Using Fluorescent Ureteral Catheter and Flexible Ureteroscope for Safe Laparoscopic Fenestration of Lymphocele after Kidney Transplantation. Reviewed International journal

Takanori Sekito, Motoo Araki, Koichiro Wada, Kasumi Yoshinaga, Yuki Maruyama, Takuya Sadahira, Satoshi Katayama, Takehiro Iwata, Shingo Nishimura, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Toyohiko Watanabe

Case reports in transplantation 2022 9948425 - 9948425 2022

Language：English

Laparoscopic fenestration of a postrenal transplant lymphocele is associated with a risk of renal hilar vessel and ureteral injury. Consequently, determination of the incision line is difficult. We describe a case of a 73-year-old man with postrenal transplant lymphocele who underwent a laparoscopic fenestration. We report a surgical video containing a new technique of laparoscopic fenestration using a fluorescent ureteral catheter in combination with a flexible ureteroscope. The combination of a fluorescent ureteral catheter and flexible ureteroscope during surgery enabled us to determine the incision line safely and accurately. Intraoperative real-time visualization of the lymphocele and ureter using a fluorescent ureteral catheter and a flexible ureteroscope is safer than conventional methods for laparoscopic fenestration. To the best of our knowledge, this is the first report of this novel technique.

DOI： 10.1155/2022/9948425

Radiation therapy compared to radical prostatectomy as first-line definitive therapy for patients with high-risk localised prostate cancer: An updated systematic review and meta-analysis. Reviewed International journal

Abdulmajeed Aydh, Reza Sari Motlagh, Mohammad Abufaraj, Keiichiro Mori, Satoshi Katayama, Nico Grossmann, Pawel Rajawa, Hadi Mostafai, Ekaterina Laukhtina, Benjamin Pradere, Fahad Quhal, Victor M Schuettfort, Alberto Briganti, Pierre I Karakiewicz, Haron Fajkovic, Shahrokh F Shariat

Arab journal of urology 20 ( 2 ) 71 - 80 2022

Language：English Publishing type：Research paper (scientific journal)

Objective: To present an update of the available literature on external beam radiation therapy (EBRT) with or without brachytherapy (BT) compared to radical prostatectomy (RP) for patients with high-risk localised prostate cancer (PCa). Methods: We conducted a systematic review and meta-analysis of the literature assessing the survival outcomes in patients with high-risk PCa who received EBRT with or without BT compared to RP as the first-line therapy with curative intent. We queried PubMed and Web of Science database in January 2021. Moreover, we used random or fixed-effects meta-analytical models in the presence or absence of heterogeneity per the I2 statistic, respectively. We performed six meta-analyses for overall survival (OS) and cancer-specific survival (CSS). Results: A total of 27 studies were selected with 23 studies being eligible for both OS and CSS. EBRT alone had a significantly worse OS and CSS compared to RP (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.16-1.65; and HR 1.55, 95% CI 1.25-1.93). However, there was no difference in OS (HR 1.1, 95% CI 0.76-1.34) and CSS (HR 0.69, 95% CI 0.45-1.06) between EBRT plus BT compared to RP. Conclusion: While cancer control affected by EBRT alone seems inferior to RP in patients with high-risk PCa, BT additive to EBRT was not different from RP. These data support the need for BT in addition to EBRT as part of multimodal RT for high-risk PCa.Abbreviations: ADT: androgen-deprivation therapy; BT: brachytherapy; CSS: cancer-specific survival; HR: hazard ratio; MFS, metastatic-free survival; MOOSE: Meta-analyses of Observational Studies in Epidemiology; OR: odds ratio; OS: overall survival; PCa: prostate cancer; RR: relative risk; RP: radical prostatectomy; RCT: randomised controlled trials; (EB)RT: (external beam) radiation therapy.

DOI： 10.1080/2090598X.2022.2026010

Influence of steep Trendelenburg position on postoperative complications: a systematic review and meta-analysis. Reviewed International journal

Satoshi Katayama, Keiichiro Mori, Benjamin Pradere, Takafumi Yanagisawa, Hadi Mostafaei, Fahad Quhal, Reza Sari Motlagh, Ekaterina Laukhtina, Nico C Grossmann, Pawel Rajwa, Abdulmajeed Aydh, Frederik König, Pierre I Karakiewicz, Motoo Araki, Yasutomo Nasu, Shahrokh F Shariat

Journal of robotic surgery 16 ( 6 ) 1233 - 1247 2021.12

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Intraoperative physiologic changes related to the steep Trendelenburg position have been investigated with the widespread adoption of robot-assisted pelvic surgery (RAPS). However, the impact of the steep Trendelenburg position on postoperative complications remains unclear. We conducted a meta-analysis to compare RAPS to laparoscopic/open pelvic surgery with regards to the rates of venous thromboembolism (VTE), cardiac, and cerebrovascular complications. Meta-regression was performed to evaluate the influence of confounding risk factors. Ten randomized controlled trials (RCTs) and 47 non-randomized controlled studies (NRSs), with a total of 380,125 patients, were included. Although RAPS was associated with a decreased risk of VTE and cardiac complications compared to laparoscopic/open pelvic surgery in NRSs [risk ratio (RR), 0.59; 95% CI 0.51-0.72, p < 0.001 and RR 0.93; 95% CI 0.58-1.50, p = 0.78, respectively], these differences were not confirmed in RCTs (RR 0.92; 95% CI 0.52-1.62, p = 0.77 and RR 0.93; 95% CI 0.58-1.50, p = 0.78, respectively). In subgroup analyses of laparoscopic surgery, there was no significant difference in the risk of VTE and cardiac complications in both RCTs and NRSs. In the meta-regression, none of the risk factors were found to be associated with heterogeneity. Furthermore, no significant difference was observed in cerebrovascular complications between RAPS and laparoscopic/open pelvic surgery. Our meta-analysis suggests that the steep Trendelenburg position does not seem to affect postoperative complications and, therefore, can be considered safe with regard to the risk of VTE, cardiac, and cerebrovascular complications. However, proper individualized preventive measures should still be implemented during all surgeries including RAPS to warrant patient safety.

DOI： 10.1007/s11701-021-01361-x

Chemotherapy is superior to checkpoint inhibitors after radical surgery for urothelial carcinoma: a systematic review and network meta-analysis of oncologic and toxicity outcomes. Reviewed International journal

Ekaterina Laukhtina, Reza Sari Motlagh, Keiichiro Mori, Satoshi Katayama, Pawel Rajwa, Takafumi Yanagisawa, Fahad Quhal, Hadi Mostafaei, Nico C Grossmann, Frederik König, Abdulmajeed Aydh, Benjamin Pradere, Irene Resch, Axel S Merseburger, Dmitry Enikeev, Shahrokh F Shariat

Critical reviews in oncology/hematology 169 103570 - 103570 2021.12

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To determine the oncologic and toxicity outcomes of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) compared to adjuvant chemotherapy in patients treated with radical surgery for urothelial carcinoma (UC). METHODS: We used the Bayesian approach in the network meta-analysis of different therapy regimens compared to observation or placebo. RESULTS: Nine studies comprised of 2,444 patients met the eligibility criteria. In bladder UC, chemotherapy, atezolizumab, and nivolumab did not improve disease progression compared to observation/placebo. In upper tract UC (UTUC), chemotherapy was significantly associated with a lower likelihood of disease progression compared to observation/placebo, while atezolizumab and nivolumab were not. Based on the analysis of the treatment ranking, adjuvant chemotherapy appeared as the best treatment approach in both bladder UC and UTUC. The risk of adverse events with ICIs was comparable to that of observation/placebo. CONCLUSION: Our analysis suggests a superior oncologic benefit to adjuvant chemotherapy over ICIs in patients treated with radical surgery for both bladder UC and UTUC.

DOI： 10.1016/j.critrevonc.2021.103570

Prognostic value of the systemic immune-inflammation index in non-muscle invasive bladder cancer. Reviewed International journal

Satoshi Katayama, Keiichiro Mori, Benjamin Pradere, Ekaterina Laukhtina, Victor M Schuettfort, Fahad Quhal, Reza Sari Motlagh, Hadi Mostafaei, Nico C Grossmann, Pawel Rajwa, Marco Moschini, Romain Mathieu, Mohammad Abufaraj, David D'Andrea, Eva Compérat, Martin Haydter, Shin Egawa, Yasutomo Nasu, Shahrokh F Shariat

World journal of urology 39 ( 12 ) 4355 - 4361 2021.12

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: We assessed the prognostic value of systemic immune-inflammation index (SII) to refine risk stratification of the heterogeneous spectrum of patients with non-muscle-invasive bladder cancer (NMIBC) METHODS: In this multi-institutional cohort, preoperative blood-based SII was retrospectively assessed in 1117 patients with NMIBC who underwent transurethral resection of bladder (TURB) between 1996 and 2007. The optimal cut-off value of SII was determined as 580 using the best Youden index. Cox regression analyses were performed. The concordance index (C-index) and decision curve analysis (DCA) were used to assess the discrimination of the predictive models. RESULTS: Overall, 309 (28%) patients had high SII. On multivariable analyses, high SII was significantly associated with worse PFS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.77; P = 0.003) and CSS (HR 2.53; 95% CI 1.42-4.48; P = 0.001). Subgroup analyses, according to the European Association of Urology guidelines, demonstrated the main prognostic impact of high SII, with regards to PFS (HR 3.39; 95%CI 1.57-7.31; P = 0.002) and CSS (HR 4.93; 95% CI 1.70-14.3; P = 0.005), in patients with intermediate-risk group; addition of SII to the standard predictive model improved its discrimination ability both on C-index (6% and 12%, respectively) and DCA. In exploratory intergroup analyses of patients with intermediate-risk, the improved discrimination ability was retained the prediction of PFS and CSS. CONCLUSION: Preoperative SII seems to identify NMIBC patients who have a worse disease and prognosis. Such easily available and cheap standard biomarkers may help refine the decision-making process regarding adjuvant treatment in patients with intermediate-risk NMIBC.

DOI： 10.1007/s00345-021-03740-3

Incidence, risk factors and outcomes of urethral recurrence after radical cystectomy for bladder cancer: A systematic review and meta-analysis. Reviewed International journal

Ekaterina Laukhtina, Keiichiro Mori, David D Andrea, Marco Moschini, Mohammad Abufaraj, Francesco Soria, Andrea Mari, Wojciech Krajewski, Simone Albisinni, Jeremy Yuen-Chun Teoh, Fahad Quhal, Reza Sari Motlagh, Hadi Mostafaei, Satoshi Katayama, Nico С Grossmann, Pawel Rajwa, Dmitry Enikeev, Kristin Zimmermann, Harun Fajkovic, Petr Glybochko, Shahrokh F Shariat, Benjamin Pradere

Urologic oncology 39 ( 12 ) 806 - 815 2021.12

Language：English Publishing type：Research paper (scientific journal)

We aimed to conduct a systematic review and meta-analysis assessing the incidence and risk factors of urethral recurrence (UR) as well as summarizing data on survival outcomes in patients with UR after radical cystectomy (RC) for bladder cancer. The MEDLINE and EMBASE databases were searched in February 2021 for studies of patients with UR after RC. Incidence and risk factors of UR were the primary endpoints. The secondary endpoint was survival outcomes in patients who experienced UR. Twenty-one studies, comprising 9,435 patients, were included in the quantitative synthesis. Orthotopic neobladder (ONB) diversion was associated with a decreased probability of UR compared to non-ONB (pooled OR: 0.44, 95% CI: 0.31-0.61, P < 0.001) and male patients had a significantly higher risk of UR compared to female patients (pooled OR: 3.16, 95% CI: 1.83-5.47, P < 0.001). Among risk factors, prostatic urethral or prostatic stromal involvement (pooled HR: 5.44, 95% CI: 3.58-8.26, P < 0.001; pooled HR: 5.90, 95% CI: 1.82-19.17, P = 0.003, respectively) and tumor multifocality (pooled HR: 2.97, 95% CI: 2.05-4.29, P < 0.001) were associated with worse urethral recurrence-free survival. Neither tumor stage (P = 0.63) nor CIS (P = 0.72) were associated with worse urethral recurrence-free survival. Patients with UR had a 5-year CSS that varied from 47% to 63% and an OS - from 40% to 74%; UR did not appear to be related to worse survival outcomes. Male patients treated with non-ONB diversion as well as patients with prostatic involvement and tumor multifocality seem to be at the highest risk of UR after RC. Risk-adjusted standardized surveillance protocols should be developed into clinical practice after RC.

DOI： 10.1016/j.urolonc.2021.06.009

Testosterone Recovery after Neoadjuvant Gonadotropin-Releasing Hormone Antagonist versus Agonist on Permanent Iodine-125 Seed Brachytherapy in Prostate Cancer Patients: A Propensity Score Analysis. Reviewed

Takehiro Iwata, Yuki Maruyama, Tatsushi Kawada, Takuya Sadahira, Satoshi Katayama, Atsushi Takamoto, Tomoko Sako, Koichiro Wada, Kohei Edamura, Yasuyuki Kobayashi, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Acta medica Okayama 75 ( 6 ) 705 - 711 2021.12

Language：English Publishing type：Research paper (scientific journal)

Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients' prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients.

DOI： 10.18926/AMO/62810

浸潤性膀胱癌に対する開腹膀胱全摘除術(ORC)と比較した腹腔鏡下膀胱全摘除術(LRC)の長期治療成績に関する後方視的検討

和田里章悟, 小林泰之, 河田達志, 定平卓也, 片山聡, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科 84 ( 2 ) 146 - 153 2021.12

Language：Japanese Publisher：(一社)西日本泌尿器科学会

【目的】腹腔鏡下膀胱全摘除術(LRC)と開腹膀胱全摘除術(ORC)の長期制癌性を検討した本邦からの報告は少数である。当院におけるLRCとORCの周術期成績と長期治療成績を後方視的に比較検討した。【対象】2012年5月から2018年6月までに施行した膀胱全摘症例のうち78例(LRC48例,ORC30例)とした。【結果】観察期間中央値はLRC群30ヵ月,ORC群43.5ヵ月であった。LRC群で男性が多く,回腸導管の割合が高かった。手術時間はLRC群で長く(p=0.038),推定出血量と輸血症例が少なかった(ともにp<0.001)。術後病理結果はLRC群でG2症例が少なかった(p=0.008)が,断端陽性率を含む他の結果に差はなかった。リンパ節郭清領域はORCで内外腸骨動脈分岐部以下,LRCで総腸骨動脈分岐部以下を基本としたが,郭清リンパ節の数とリンパ節陽性症例の割合に差はなかった。LRC群とORC群の5年全生存率,癌特異生存率,無再発生存率は72.2%と54.4%(p=0.249),77.7%と63.4%(p=0.376),71.4%と55.0%(p=0.115)であった。【結語】当院におけるLRC群の周術期成績は出血量,輸血頻度においてORC群より優れていた。制癌性についてもORC群に比しLRC群が優れている傾向を認め,リンパ節郭清領域が制癌性に影響する報告を裏付ける結果となった。(著者抄録)

限局性上部尿路上皮癌診断における、tumor grade、tumor stageによる予測モデルの臨床的有用性の検討

片山聡, 荒木元朗, 森啓一郎, 岩田健宏, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 渡部昌実, 渡邉豊彦, Shariat Shahrokh F., 那須保友

日本泌尿器科学会総会 109回 OP19 - 01 2021.12

Impact of preoperative systemic immune-inflammation Index on oncologic outcomes in bladder cancer patients treated with radical cystectomy. Reviewed International journal

Nico C Grossmann, Victor M Schuettfort, Benjamin Pradere, Pawel Rajwa, Fahad Quhal, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Reza S Motlagh, Abdulmajeed Aydh, Satoshi Katayama, Marco Moschini, Christian D Fankhauser, Thomas Hermanns, Mohammad Abufaraj, Dong-Ho Mun, Kristin Zimmermann, Harun Fajkovic, Martin Haydter, Shahrokh F Shariat

Urologic oncology 40 ( 3 ) 106.e11-106.e19 2021.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To investigate the predictive and prognostic value of the preoperative systemic immune-inflammation index (SII) in patients undergoing radical cystectomy (RC) for clinically non-metastatic urothelial cancer of the bladder (UCB). METHODS: Overall, 4,335 patients were included, and the cohort was stratified in two groups according to SII using an optimal cut-off determined by the Youden index. Uni- and multivariable logistic and Cox regression analyses were performed, and the discriminatory ability by adding SII to a reference model based on available clinicopathologic variables was assessed by area under receiver operating characteristics curves (AUC) and concordance-indices. The additional clinical net-benefit was assessed using decision curve analysis (DCA). RESULTS: High SII was observed in 1879 (43%) patients. On multivariable preoperative logistic regression, high SII was associated with lymph node involvement (LNI; P = 0.004), pT3/4 disease (P <0.001), and non-organ confined disease (NOCD; P <0.001) with improvement of AUCs for predicting LNI (P = 0.01) and pT3/4 disease (P = 0.01). On multivariable Cox regression including preoperative available clinicopathologic values, high SII was associated with recurrence-free survival (P = 0.028), cancer-specific survival (P = 0.005), and overall survival (P = 0.006), without improvement of concordance-indices. On DCAs, the inclusion of SII did not meaningfully improve the net-benefit for clinical decision-making in all models. CONCLUSION: High preoperative SII is independently associated with pathologic features of aggressive disease and worse survival outcomes. However, it did not improve the discriminatory margin of a prediction model beyond established clinicopathologic features and failed to add clinical benefit for decision making. The implementation of SII as a part of a panel of biomarkers in future studies might improve decision-making.

DOI： 10.1016/j.urolonc.2021.10.006

Comparison of Clinicopathologic and Oncological Outcomes Between Transurethral En Bloc Resection and Conventional Transurethral Resection of Bladder Tumor: A Systematic Review, Meta-Analysis and Network Meta-Analysis with Focus on Different Energy Sources. Reviewed International journal

Reza Sari Motlagh, Pawel Rajwa, Keiichiro Mori, Ekaterina Laukhtina, Abdulmajeed Aydh, Satoshi Katayama, Takafumi Yanagisawa, Frederik König, Nico C Grossmann, Benjamin Pradere, Hadi Mostafai, Fahad Quhal, Pierre I Karakiewicz, Marek Babjuk, Shahrokh F Shariat

Journal of endourology 36 ( 4 ) 535 - 547 2021.11

Language：English Publishing type：Research paper (scientific journal)

Introduction: It has been hypothesized that transurethral en bloc (TUEB) of bladder tumor offers benefits over conventional transurethral resection of bladder tumor (cTURBT). This study aimed to compare disease outcomes of TUEB and cTURBT with focus on the different energy sources. Methods: A systematic search was performed using PubMed and Web of Science databases in June 2021. Studies that compared the pathological (detrusor muscle presence), oncological (recurrence rates) efficacy, and safety (serious adverse events [SAEs]) of TUEB and cTURBT were included. Random- and fixed-effects meta-analytic models and Bayesian approach in the network meta-analysis was used. Results: Seven randomized clinical trials (RCTs) and seven non-RCTs (NRCT), with a total of 2092 patients. The pooled 3- and 12-month recurrence risk ratios (RR) of five and four NRCTs were 0.46 (95% CI 0.29-0.73) and 0.56 (95% CI 0.33-0.96), respectively. The pooled 3- and 12-month recurrence RRs of four and seven RCTs were 0.57 (95% CI 0.25-1.27) and 0.89 (95% CI 0.69-1.15), respectively. The pooled RR for SAEs such as prolonged hematuria and bladder perforation of seven RCTs was 0.16 (95% CI 0.06-0.41) in benefit of TUEB. Seven RCTs (n = 1077) met our eligibility criteria for network meta-analysis. There was no difference in 12-month recurrence rates between hybridknife, laser, and bipolar TUEB compared with cTURBT. Contrary, laser TUEB was significantly associated with lower SAEs compared with cTURBT. Surface under the cumulative ranking curve ranking analyses showed with high certainty that laser TUEB was the best treatment option to access all endpoints. Conclusion: While NRCTs suggested a recurrence-free benefit to TUEB compared with cTURBT, RCTs failed to confirm this. Conversely, SAEs were consistently and clinically significantly better for TUEB. Network meta-analyses suggested laser TUEB has the best performance compared with other energy sources. These early findings need to be confirmed and expanded upon.

DOI： 10.1089/end.2021.0688

Pretreatment clinical and hematologic prognostic factors of metastatic urothelial carcinoma treated with pembrolizumab: a systematic review and meta-analysis. Reviewed

Takafumi Yanagisawa, Keiichiro Mori, Satoshi Katayama, Hadi Mostafaei, Fahad Quhal, Ekaterina Laukhtina, Pawel Rajwa, Reza Sari Motlagh, Abdulmajeed Aydh, Frederik König, Nico C Grossmann, Benjamin Pradere, Jun Miki, Takahiro Kimura, Shin Egawa, Shahrokh F Shariat

International journal of clinical oncology 27 ( 1 ) 59 - 71 2021.11

Language：English Publishing type：Research paper (scientific journal)

Pembrolizumab is the standard for the first and second lines in treating metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to assess the value of pretreatment clinical characteristics and hematologic biomarkers for prognosticating response to pembrolizumab in patients with metastatic UC. PUBMED®, Web of Science™, and Scopus® databases were searched for articles published before May 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they evaluated overall survival (OS) in patients with metastatic urothelial carcinoma treated with pembrolizumab and pretreatment clinical characteristics or laboratory examination. Overall, 13 studies comprising 1311 patients were eligible for the meta-analysis. Several pretreatment patients' demographics and hematologic biomarkers were significantly associated with worse OS as follows: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 2 (Pooled hazard ratio [HR]: 3.24, 95% confidence interval [CI] 2.57-4.09), presence of visceral metastasis (Pooled HR: 1.84, 95% CI 1.42-2.38), presence of liver metastasis (Pooled HR: 4.23, 95% CI 2.18-8.20), higher neutrophil-lymphocyte ratio (NLR) (Pooled HR: 1.29, 95% CI 1.07-1.55) and, higher c-reactive protein (CRP) (Pooled HR: 2.49, 95% CI 1.52-4.07). Metastatic UC patients with poor PS, liver metastasis, higher pretreatment NLR and/or CRP have a worse survival despite pembrolizumab treatment. These findings might help to guide the prognostic tools for clinical decision-making; however, they should be interpreted carefully, owing to limitations regarding the retrospective nature of primary data.

DOI： 10.1007/s10147-021-02061-0

Impact of systemic Immune-inflammation Index on oncologic outcomes in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer. International journal

Pawel Rajwa, Victor M Schuettfort, David D'Andrea, Fahad Quhal, Keiichiro Mori, Satoshi Katayama, Ekaterina Laukhtina, Benjamin Pradere, Reza Sari Motlagh, Hadi Mostafaei, Nico C Grossmann, Nicolai Huebner, Andreas Aulitzky, Dong-Ho Mun, Alberto Briganti, Pierre I Karakiewicz, Harun Fajkovic, Shahrokh F Shariat

Urologic oncology 39 ( 11 ) 785.e19-785.e27 2021.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To evaluate the predictive and prognostic value of the Systemic Immune-inflammation Index (SII) in a large cohort of patients treated with radical prostatectomy (RP) for clinically non-metastatic prostate cancer (PCa). METHODS: We retrospectively analyzed our multicenter database comprising 6,039 consecutive patients. The optimal preoperative SII cut-off value was assessed with the Youden index calculated on a time-dependent receiver operating characteristic (ROC) curve. Logistic regression and Cox regression analyses were used to investigate the association of SII with pathologic features and biochemical recurrence (BCR), respectively. The discriminatory ability of the models was evaluated by calculating the concordance-indices (C-Index). The clinical benefit of the implementation of SII in clinical decision making was assessed using decision curve analysis (DCA). RESULTS: Patients with high preoperative SII (≥ 620) were more likely to have adverse clinicopathologic features. On multivariable logistic regression analysis, high preoperative SII was independently associated with extracapsular extension (odds ratio [OR] 1.16, P = 0.041), non-organ confined disease (OR 1.18, P = 0.022), and upgrading at RP (OR 1.23, P < 0.001). We built two Cox regression models including preoperative and postoperative variables. In the preoperative multivariable model, high preoperative SII was associated with BCR (hazard ratio [HR] 1.34, 95% CI 1.15-1.55, P < 0.001). In the postoperative multivariable model, SII was not associated with BCR (P = 0.078). The addition of SII to established models did not improve their discriminatory ability nor did it increase the clinical net benefit on DCA. CONCLUSION: In men treated with RP for clinically nonmetastatic PCa, high preoperative SII was statistically associated with an increased risk of adverse pathologic features at RP as well as BCR. However, it did not improve the predictive accuracy and clinical value beyond that obtained by current predictive and prognostic models. SII together with a panel of complementary biomarkers is praised to help guide decision-making in clinically nonmetastatic PCa.

DOI： 10.1016/j.urolonc.2021.05.002

Adjuvant therapy with tyrosine kinase inhibitors for localized and locally advanced renal cell carcinoma: an updated systematic review and meta-analysis. International journal

Ekaterina Laukhtina, Fahad Quhal, Keiichiro Mori, Reza Sari Motlagh, Benjamin Pradere, Victor M Schuettfort, Hadi Mostafaei, Satoshi Katayama, Nico С Grossmann, Pawel Rajwa, Irene Resch, Dmitry Enikeev, Pierre I Karakiewicz, Shahrokh F Shariat, Manuela Schmidinger

Urologic oncology 39 ( 11 ) 764 - 773 2021.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Tyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC. MATERIALS AND METHODS: The MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade. RESULTS: Five trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81-0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83-1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10-6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22-12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity. CONCLUSIONS: The findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.

DOI： 10.1016/j.urolonc.2021.07.022

Prognostic Impact of Preoperative Plasma Levels of Urokinase Plasminogen Activator Proteins on Disease Outcomes after Radical Cystectomy. International journal

Victor M Schuettfort, Benjamin Pradere, David D'Andrea, Nico C Grossmann, Fahad Quhal, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Michael Rink, Pierre I Karakiewicz, Reza Sari Motlagh, Satoshi Katayama, Yair Lotan, Douglas Scherr, Mohammad Abufaraj, Harun Fajkovica, Eva Compérat, Dmitry Enikeev, Shahrokh F Shariat

The Journal of urology 206 ( 5 ) 1122 - 1131 2021.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: We sought to validate the association of plasma levels of urokinase-type plasminogen activator (uPA), its soluble receptor (SuPAR) and its inhibitor (PAI-one) with oncologic outcomes in a large cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: We collected preoperative blood samples from 1,036 consecutive patients treated with RC for UCB. Plasma specimens were assessed for levels of uPA, SuPAR and PAI-one. Retrospective logistic and Cox regression analyses were performed to assess their correlation with clinical outcomes. The additional clinical net benefit provided by the biomarkers was evaluated using decision curve analysis. RESULTS: Preoperative plasma uPA, SuPAR and PAI-one levels were significantly elevated in patients harboring adverse pathological features. Higher levels of all biomarkers were independently associated with an increased risk of lymph node metastasis; uPA levels were also independently associated with ≥pT3 disease. Preoperative uPA and SuPAR were independently associated with recurrence-free and cancer-specific survival. The addition of these biomarkers to standard pre-treatment and post-treatment models improved the discriminatory power for prediction of lymph node metastasis, ≥pT3 disease, and recurrence-free and cancer-specific survival by a prognostically significant margin. CONCLUSIONS: We confirmed that elevated preoperative plasma levels of uPA, SuPAR and PAI-one are associated with features of aggressive disease and worse survival outcomes in patients treated with RC for UCB. These biomarkers hold potential in identifying patients who are likely to benefit from intensified/multimodal therapy. They also demonstrated the ability to improve the discriminatory power of predictive/prognostic models, thus refining personalized clinical decision-making.

DOI： 10.1097/JU.0000000000001936

Oncologic impact of delaying radical prostatectomy in men with intermediate- and high-risk prostate cancer: a systematic review. Reviewed International journal

Ekaterina Laukhtina, Reza Sari Motlagh, Keiichiro Mori, Fahad Quhal, Victor M Schuettfort, Hadi Mostafaei, Satoshi Katayama, Nico C Grossmann, Guillaume Ploussard, Pierre I Karakiewicz, Alberto Briganti, Mohammad Abufaraj, Dmitry Enikeev, Benjamin Pradere, Shahrokh F Shariat

World journal of urology 39 ( 11 ) 4085 - 4099 2021.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To summarize the available evidence on the survival and pathologic outcomes after deferred radical prostatectomy (RP) in men with intermediate- and high-risk prostate cancer (PCa). METHODS: The PubMed database and Web of Science were searched in November 2020 according to the PRISMA statement. Studies were deemed eligible if they reported the survival and pathologic outcomes of patients treated with deferred RP for intermediate- and high-risk PCa compared to the control group including those patients treated with RP without delay. RESULTS: Overall, nineteen studies met our eligibility criteria. We found a significant heterogeneity across the studies in terms of definitions for delay and outcomes, as well as in patients' baseline clinicopathologic features. According to the currently available literature, deferred RP does not seem to affect oncological survival outcomes, such as prostate cancer-specific mortality and metastasis-free survival, in patients with intermediate- or high-risk PCa. However, the impact of deferred RP on biochemical recurrence rates remains controversial. There is no clear association of deferring RP with any of the features of aggressive disease such as pathologic upgrading, upstaging, positive surgical margins, extracapsular extension, seminal vesicle invasion, and lymph node invasion. Deferred RP was not associated with the need for secondary treatments. CONCLUSIONS: Owing to the different definitions of a delayed RP, it is hard to make a consensus regarding the safe delay time. However, the current data suggest that deferring RP in patients with intermediate- and high-risk PCa for at least around 3 months is generally safe, as it does not lead to adverse pathologic outcomes, biochemical recurrence, the need for secondary therapy, or worse oncological survival outcomes.

DOI： 10.1007/s00345-021-03703-8

Tumor suppressor REIC/Dkk-3 and its co-chaperone SGTA: Two aspects of a GR inhibitor and AR activator as a modifier of the steroid signaling(和訳中)

岩田健宏, 定平卓也, 片山聡, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科学会総会抄録集 73回 175 - 175 2021.11

癌抑制因子REIC/Dkk-3とそのコシャペロンSGTA ステロイドシグナル伝達の調節因子としてのGR阻害剤とAR活性化剤の二つの側面(Tumor suppressor REIC/Dkk-3 and its co-chaperone SGTA: Two aspects of a GR inhibitor and AR activator as a modifier of the steroid signaling)

岩田健宏, 定平卓也, 片山聡, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科学会総会抄録集 73回 175 - 175 2021.11

腎盂尿管鏡検査における生検組織診断率向上のためのPilot study

岩田健宏, 和田耕一郎, 長尾賢太郎, 富永悠介, 片山聡, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 P - 9 2021.11

Selection and evaluation of preoperative systemic inflammatory response biomarkers model prior to cytoreductive nephrectomy using a machine-learning approach. International journal

Ekaterina Laukhtina, Victor M Schuettfort, David D'Andrea, Benjamin Pradere, Fahad Quhal, Keiichiro Mori, Reza Sari Motlagh, Hadi Mostafaei, Satoshi Katayama, Nico C Grossmann, Pawel Rajwa, Pierre I Karakiewicz, Manuela Schmidinger, Harun Fajkovic, Dmitry Enikeev, Shahrokh F Shariat

World journal of urology 40 ( 3 ) 747 - 754 2021.10

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: This study aimed to determine the prognostic value of a panel of SIR-biomarkers, relative to standard clinicopathological variables, to improve mRCC patient selection for cytoreductive nephrectomy (CN). MATERIAL AND METHODS: A panel of preoperative SIR-biomarkers, including the albumin-globulin ratio (AGR), De Ritis ratio (DRR), and systemic immune-inflammation index (SII), was assessed in 613 patients treated with CN for mRCC. Patients were randomly divided into training and testing cohorts (65/35%). A machine learning-based variable selection approach (LASSO regression) was used for the fitting of the most informative, yet parsimonious multivariable models with respect to prognosis of cancer-specific survival (CSS). The discriminatory ability of the model was quantified using the C-index. After validation and calibration of the model, a nomogram was created, and decision curve analysis (DCA) was used to evaluate the clinical net benefit. RESULTS: SIR-biomarkers were selected by the machine-learning process to be of high discriminatory power during the fitting of the model. Low AGR remained significantly associated with CSS in both training (HR 1.40, 95% CI 1.07-1.82, p = 0.01) and testing (HR 1.78, 95% CI 1.26-2.51, p = 0.01) cohorts. High levels of SII (HR 1.51, 95% CI 1.10-2.08, p = 0.01) and DRR (HR 1.41, 95% CI 1.01-1.96, p = 0.04) were associated with CSS only in the testing cohort. The exclusion of the SIR-biomarkers for the prognosis of CSS did not result in a significant decrease in C-index (- 0.9%) for the training cohort, while the exclusion of SIR-biomarkers led to a reduction in C-index in the testing cohort (- 5.8%). However, SIR-biomarkers only marginally increased the discriminatory ability of the respective model in comparison to the standard model. CONCLUSION: Despite the high discriminatory ability during the fitting of the model with machine-learning approach, the panel of readily available blood-based SIR-biomarkers failed to add a clinical benefit beyond the standard model.

DOI： 10.1007/s00345-021-03844-w

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