Annual Report 2023

Department of Urology

Yoshiyuki Matsui, Motokiyo Komiyama, Eijiro Nakamura, Yasuo Shinoda, Ayumu Matsuda, Aiko Maejima, Hiroyuki Fujimoto, Tomoya Okuno, Takahiro Kirisawa

Introduction

 In the Department of Urology, all urogenital malignant diseases, including adrenal cancer, kidney cancer, urothelial cancer, prostate cancer, testicular germ cell tumors, and retroperitoneal sarcoma, are the subject of diagnosis and surgical aspects of treatment with comprehensive approaches.

The Team and What We Do

 Our department focuses on surgical treatments against urogenital and retroperitoneal malignancy, while the primary responsibility for pharmacological treatments has been transferred to the Department of Medical Oncology. Among the staff physicians, Dr. Nakamura and Dr. Maejima are actively involved in the Department of Medical Oncology as well. As a major achievement in patient care, we have conducted a total of 341 surgical procedures under general anesthesia (excluding examinations) (Table 1).

 The standard surgical procedures for urological malignancies have shifted towards robotic surgery, leading to an increasing trend in the number of robotic surgeries, while the proportion of laparoscopic surgeries is decreasing. Furthermore, the number of referred cases with refractory/difficult-to-treat conditions requiring multidisciplinary approaches, such as retroperitoneal sarcomas and advanced testicular tumors, remains stable at 15-20% of the annual surgical caseload. To address these challenging conditions, we have established a collaborative system involving multiple departments to provide multidisciplinary treatment.

Research Activities

 We are actively incorporating robot-assisted and laparoscopic surgery, focusing not only on standard procedures but also on minimizing invasiveness in extensive surgeries for refractory conditions.

 On the clinical research front, we are actively engaged in multicenter studies related to JCOG (Japan Clinical Oncology Group) and JUOG (Japan Urological Oncology Group), as well as industry-sponsored trials, and consistently presenting significant results (Matsuda A, et al. BJU Int. 2024 doi: 10.1111/bju.16296.).

 We are also engaged in epidemiological research and the development of new treatment methods for hereditary urological malignancies, such as von Hippel-Lindau disease (VHL) (Takamori H, et al. Cancer Sci. 2023 Apr; 114(4):1208-1217).

Clinical Trials

 We are actively involved in the following ongoing protocol studies:

1) A phase III study: A single early intravesical instillation of pirarubicin in the prevention of bladder recurrence after radical nephroureterectomy for upper tract urothelial carcinoma (JCOG1403)

2) A phase III study: Anti PD-L1 antibody (ATEZOLIZUMAB/ MPDL3280A) for muscle invasive bladder cancer

3) An open -label, randomized phase III study: MK-6482 vs Everolimus in advanced renal cell carcinoma progressing after PD-1/L1 and VEGF-targeted therapies.

4) A randomized controlled phase III trial on continued or paused PD-1 pathway blockade for patients with advanced renal cell carcinoma (JCOG1905)

5) A randomized controlled phase III trial for confirming superiority of local radiotherapy added to anti-androgen therapy for prostate cancer patients with high volume metastasis sensitive to hormone therapy (HimeRT study; JCOG2011)

6) Epidemiological Research and Development of Novel Therapies for von Hippel-Lindau (VHL) Disease (AA Chakraborty and E. Nakamura et al. Sci Transl Med. 2017. SK Flores and E. Nakamura et al. J Clin Endocrinol Metab. 2019.).

7) Epidemiological Research and Development of Novel Therapies for Pheochromocytoma (M Yonamine and E. Nakamura et al. Cancers (Basel). 2021 Aug 9;13(16):4014. doi: 10.3390/cancers13164014.).

Education

 We provide education to urology residents and accept residents from surgical and gynecological departments. We actively instruct residents in laparoscopic or robotic surgeries, and one resident has obtained certification as a urological laparoscopic technique-certified physician. We strongly encourage residents to participate in clinical research and actively support their involvement in presenting at conferences and publishing papers.

Future Prospects

 As our department's goals, we have outlined the following:

1) In standard treatments, we actively incorporate laparoscopic and robotic surgical techniques to advance minimally invasive therapies.

2) We aim to advance the development of treatment options suitable for elderly and vulnerable patients through protocolization of multidisciplinary treatments for refractory conditions and the proactive introduction of robotic and laparoscopic surgeries.

3) We are transferring the complex aspects of drug therapy to the Department of Oncology, focusing on advancing more advanced surgical interventions and localized therapies.

List of papers published in 2023

Journal

1. Yamagata Y, Komiyama M, Iwata S. Clinical characteristics and management of primary retroperitoneal sarcoma: A literature review. Annals of gastroenterological surgery, 8:21-29, 2024

2. Takamizawa S, Koyama T, Sunami K, Sudo K, Hirata M, Kubo T, Tao K, Cho H, Narita Y, Kato K, Yamazaki N, Ohe Y, Okusaka T, Matsui Y, Ogawa C, Yonemori K, Yamamoto N. Identification of barriers to implementation of precision oncology in patients with rare cancers. Cancer science, 115:2023-2035, 2024

3. Matsuoka T, Sugiyama A, Miyawaki Y, Hidaka Y, Okuno Y, Sakai H, Tanaka H, Yoshikawa K, Fukui T, Mizuno K, Sumiyoshi T, Goto T, Inoue T, Akamatsu S, Kobayashi T, Nakamura E. Newly developed preclinical models reveal broad-spectrum CDK inhibitors as potent drugs for CRPC exhibiting primary resistance to enzalutamide. Cancer science, 115:283-297, 2024

4. Kikuchi H, Abe T, Miyake M, Miyata H, Matsumoto R, Osawa T, Nishimura N, Fujimoto K, Inokuchi J, Yoneyama T, Tomida R, Numakura K, Matsushita Y, Matsumoto K, Sato T, Taoka R, Kobayashi T, Kojima T, Matsui Y, Nishiyama N, Kitamura H, Nishiyama H, Shinohara N. The impact of second transurethral resection on survival outcomes in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin therapy. Japanese journal of clinical oncology, 54:192-200, 2024

5. Kita Y, Otsuka H, Ito K, Hara T, Shimura S, Kawahara T, Kato M, Kanamaru S, Inoue K, Ito H, Igarashi A, Sazuka T, Takamatsu D, Hashimoto K, Abe T, Naito S, Matsui Y, Nishiyama H, Kitamura H, Kobayashi T. Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan. International journal of urology, 31:552-559, 2024

6. Matsuda A, Taoka R, Miki J, Saito R, Fukuokaya W, Hatakeyama S, Kawahara T, Fujii Y, Kato M, Sazuka T, Sano T, Urabe F, Kashima S, Naito H, Murakami Y, Miyake M, Daizumoto K, Matsushita Y, Hayashi T, Inokuchi J, Sugino Y, Shiga K, Yamaguchi N, Iio H, Yasue K, Abe T, Nakanishi S, Matsumura M, Fujii M, Nishihara K, Matsumoto H, Tatarano S, Wada K, Sekito S, Maruyama R, Nishiyama N, Nishiyama H, Kitamura H, Matsui Y. Prognostic impact of histological discordance between transurethral resection and radical cystectomy. BJU international, 2024

7. Shiota M, Takamatsu D, Matsui Y, Yokomizo A, Morizane S, Saito R, Miyake M, Tsutsumi M, Yamamoto Y, Tashiro K, Tomida R, Narita S, Edamura K, Yamaguchi T, Hashimoto K, Kato M, Kasahara T, Yoshino T, Akamatsu S, Kaneko T, Matsukawa A, Matsumoto R, Joraku A, Saito T, Kato T, Kato M, Enokida H, Sakamoto S, Terada N, Kanno H, Nishiyama N, Kimura T, Kitamura H, Eto M. Prognostication in Lymph Node-Positive Prostate Cancer with No PSA Persistence After Radical Prostatectomy. Annals of surgical oncology, 31:3872-3879, 2024

8. Miyake M, Kitamura H, Nishimura N, Miyamoto T, Nakahama T, Fujii T, Matsumoto H, Matsuyama H, Yonemori M, Enokida H, Taoka R, Kobayashi T, Kojima T, Matsui Y, Nishiyama N, Nishiyama H, Fujimoto K. Validation of non-muscle-invasive bladder cancer risk stratification updated in the 2021 European Association of Urology guidelines. BJUI compass, 5:269-280, 2024

9. Kato M, Shiota M, Kimura T, Hanazawa R, Hirakawa A, Takamatsu D, Tashiro K, Matsui Y, Hashine K, Saito R, Yokomizo A, Yamamoto Y, Narita S, Hashimoto K, Matsumoto H, Akamatsu S, Nishiyama N, Eto M, Kitamura H, Tsuzuki T. Validation study on the 2 mm diameter cutoff in lymph node-positive cases following radical prostatectomy in accordance with the AJCC/UICC TNM 8th edition: Real-world data analysis from a Japanese cohort. International journal of urology, 31:662-669, 2024

10. Kubota M, Kawakita M, Yoshida S, Kimura H, Sumiyoshi T, Yamasaki T, Okumura K, Yoshimura K, Matsui Y, Sugiyama K, Okuno H, Segawa T, Shimizu Y, Ito N, Onishi H, Ishitoya S, Soda T, Yoshida T, Uemura Y, Iwamura H, Okubo K, Suzuki R, Fukuzawa S, Akao T, Kurahashi R, Shimatani K, Sekine Y, Negoro H, Akamatsu S, Kamoto T, Ogawa O, Kawakami K, Kobayashi T, Goto T. Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy. Scientific reports, 14:5847, 2024

11. Nishimura N, Miyake M, Iida K, Miyamoto T, Tomida R, Numakura K, Inokuchi J, Yoneyama T, Okajima E, Yajima S, Masuda H, Terada N, Taoka R, Kobayashi T, Kojima T, Matsui Y, Nishiyama N, Kitamura H, Nishiyama H, Fujimoto K. Treatment patterns and prognosis in patients with Bacillus Calmette-Guérin-exposed high-risk non-muscle invasive bladder cancer: a real-world data analysis. World journal of urology, 42:185, 2024

12. Kirisawa T, Nakamura E, Okuno T, Hagimoto H, Matsuda A, Shinoda Y, Komiyama M, Fujimoto H, Matsui Y. Significant reduction in burden of metastatic disease by intermittent docetaxel therapy in a patient with castration-resistant prostate cancer. International cancer conference journal, 13:98-102, 2024

13. Takamori H, Yamasaki T, Kitadai R, Minamishima YA, Nakamura E. Development of drugs targeting hypoxia-inducible factor against tumor cells with VHL mutation: Story of 127 years. Cancer science, 114:1208-1217, 2023

14. Takahashi A, Muraoka Y, Koyasu S, Arakawa Y, Nakamura E, Tsujikawa A. Novel Manifestation of Retinal Hemangioblastomas Detected by OCT Angiography in von Hippel-Lindau Disease. Ophthalmology, 130:748-755, 2023

15. Ito K, Yamamoto T, Hayashi Y, Sato S, Nakayama J, Urabe F, Shimasaki T, Nakamura E, Matui Y, Fujimoto H, Kimura T, Egawa S, Ochiya T, Yamamoto Y. Osteoblast-derived extracellular vesicles exert osteoblastic and tumor-suppressive functions via SERPINA3 and LCN2 in prostate cancer. Molecular oncology, 17:2147-2167, 2023

16. Fukagawa A, Hama N, Totoki Y, Nakamura H, Arai Y, Saito-Adachi M, Maeshima A, Matsui Y, Yachida S, Ushiku T, Shibata T. Genomic and epigenomic integrative subtypes of renal cell carcinoma in a Japanese cohort. Nature communications, 14:8383, 2023