Annual Report 2018

Department of Urology

Hiroyuki Fujimoto, Motokiyo Komiyama, Yoshiyuki Matsui, Tomohiko Hara, Yasuo Shinoda, Aiko Maejima

Introduction

 In the Department of Urology Division, all urogenital malignant diseases, including kidney cancer, urothelial cancer, prostate cancer, testicular germ cell tumors and retroperitoneal sarcomas, are the subject of diagnosis and treatment with comprehensive approaches, including radical surgery, irradiation, and chemotherapy.

The Team and What We Do

 The urology team consists of six staff physicians and three residents. In addition, with the participation of a radiation oncologist, multi-disciplinary treatments for advanced disease including renal cancer, urothelial cancer, hormone-refractory prostate cancer and metastatic germ cell tumors, are performed. Every morning clinical rounds start at 7:30 a.m., and a weekly conference to discuss inpatient management is held on Monday evenings. Patient statistics by major treatment were summarized in Table 1.

 Major urological malignant diseases are treated according to the following strategies:

1) Renal cell carcinoma: M0, partial or radical nephrectomy; M1: chemotherapy with target drugs with TKI or IO with or without palliative nephrectomy. A selected small size (less than 3cm) tumor: cryotherapy.

2) Bladder cancer. Carcinoma in situ: BCG instillation therapy. Ta, T1, transurethral resection of bladder cancer (TURBT), often combined with preoperative or postoperative BCG instillation. T2-T4, radical cystectomy with neoadjuvant chemotherapy by an M-VAC/GC regimen. N+, systemic chemotherapy, radiation; sometimes urinary diversion alone. M+, chemotherapy with an M-VAC /GC or IO regimen.

3) Prostate cancer. Organ-confined disease, active surveillance, robotic-assisted radical prostatectomy, irradiation, or endocrine therapy. Specimen-confined disease, extended radical prostatectomy without neoadjuvant endocrine therapy, radiation therapy with endocrine therapy, or endocrine therapy alone. For high risk prostate cancer, extended pelvic lymph node dissection by robotics was performed. M1 disease, endocrine therapy and palliative radiation if necessary. For castration refractory disease, docetaxel or cabazitaxel chemotherapy is indicated.

4) Testicular germ cell tumor (GCT): Stage I, careful observation regardless of a pathological element. Stage II or higher, EP or BEP chemotherapy as the first line. In nonseminomatous cases, a salvage operation is performed after induction chemotherapy. In seminoma cases, careful observation rather than surgery is selected.

Table 1. Patients statistics: Major treatment

Research activities

 We are constantly seeking ways to improve the treatment for malignant urological tumors.

1) Urothelial cancer: The effectiveness of a phase III study to confirm the efficacy of pirarubicin in the prevention of bladder recurrence after radical nephroureterectomy for upper tract urothelial carcinoma (JCOG1403) is ongoing. For metastatic disease, a weekly CBDCA + PTX regimen has been indicated.

2) Prostate cancer: A phase II study to evaluate the efficacy of robotic assisted laparoscopic radical prostatectomy for T1cT3a prostate cancer is no longer recruiting. A new robotic operative method to achieve a complete surgical margin (extended radical prostatectomy) has been developed, and its efficacy in patients with specimenconfined disease has been evaluated without neoadjuvant endocrine therapy. This method was introduced in robotic assisted laparoscopic radical prostatectomy with extended lymph node dissection.

3) Testicular germ cell tumors (GCTs): Advanced and/or refractory cases: A so-called "desperate operation", which was designed for patients whose tumor markers do not normalize after induction chemotherapy, has been shown to be both efficacious and clinically significant. For CDDP-refractory germ cell tumors, a second line TIP/TIN regimen has completed enrollment.

Clinical trials

 We are actively involved in the following mainly 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) A phase II study: Robotic assisted laparoscopic prostatectomy for intermediate or high risk prostate cancer

4) A phase II study: ICG navigated pelvic LN dissection for robotic assisted laparoscopic prostatectomy

List of papers published in 2018

Journal

1. Usuba W, Urabe F, Yamamoto Y, Matsuzaki J, Sasaki H, Ichikawa M, Takizawa S, Aoki Y, Niida S, Kato K, Egawa S, Chikaraishi T, Fujimoto H, Ochiya T. Circulating miRNA panels for specific and early detection in bladder cancer. Cancer Sci, 110:408-419, 2019

2. Nakamura Y, Shida D, Shibayama T, Yoshida A, Matsui Y, Shinoda Y, Iwata S, Kanemitsu Y. Giant multilocular prostatic cystadenoma. World J Surg Oncol, 17:42, 2019

3. Nagumo Y, Maejima A, Toyoshima Y, Komiyama M, Yonemori K, Yoshida A, Fujimoto H. Neoadjuvant crizotinib in ALK-rearranged inflammatory myofibroblastic tumor of the urinary bladder: A case report. Int J Surg Case Rep, 48:1-4, 2018

4. Kashihara T, Nakamura S, Wakita A, Okamoto H, Inaba K, Umezawa R, Shima S, Tsuchida K, Kobayashi K, Takahashi K, Murakami N, Ito Y, Igaki H, Fujimoto H, Uno T, Itami J. Importance of the site of positive surgical margin in salvage external beam radiation therapy for biochemical recurrence of prostate cancer after radical prostatectomy. Cancer Med, 7:1723-1730, 2018

5. Makise N, Sekimizu M, Kubo T, Wakai S, Hiraoka N, Komiyama M, Fukayama M, Kawai A, Ichikawa H, Yoshida A. Clarifying the Distinction Between Malignant Peripheral Nerve Sheath Tumor and Dedifferentiated Liposarcoma: A Critical Reappraisal of the Diagnostic Utility of MDM2 and H3K27me3 Status. Am J Surg Pathol, 42:656-664, 2018

6. Yotani T, Yamada Y, Arai E, Tian Y, Gotoh M, Komiyama M, Fujimoto H, Sakamoto M, Kanai Y. Novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application. Cancer Sci, 109:1690-1700, 2018

7. Shinoda Y, Matsui Y, Fujimoto H. Outcomes of active surveillance of clinical stage I non-seminomatous germ cell tumors: sub-analysis of the multi-institutional nationwide case series of the Japanese Urological Association. Jpn J Clin Oncol, 48:565-569, 2018

8. Arai S, Hara T, Matsui Y, Koido K, Hashimoto H, Shinoda Y, Komiyama M, Fujimoto H, Terakado H. Tolerability and Efficacy of Neoadjuvant Chemotherapy with a Tri-Weekly Interval Methotrexate, Doxorubicin, Vinblastine, and Cisplatin Regimen for Patients with Locally Advanced Bladder Cancer. Case Rep Oncol, 11:450- 460, 2018

9. Shiraishi T, Nakamura T, Ukimura O. Chemotherapy for metastatic testicular cancer: The first nationwide multi-institutional study by the Cancer Registration Committee of the Japanese Urological Association. Int J Urol, 25:730-736, 2018

10. Toyoshima Y, Hara T, Matsui Y, Nagumo Y, Maejima A, Shinoda Y, Komiyama M, Watanabe SI, Fujimoto H. Nodule Size After Chemotherapy and Primary-Tumor Teratoma Components Predict Malignancy of Residual Pulmonary Nodules in Metastatic Nonseminomatous Germ Cell Tumor. Ann Surg Oncol, 25:3668- 3675, 2018

11. Ohara K, Arai E, Takahashi Y, Fukamachi Y, Ito N, Maeshima AM, Fujimoto H, Yoshida T, Kanai Y. Feasibility of methylome analysis using small amounts of genomic DNA from formalin-fixed paraffin-embedded tissue. Pathol Int, 68:633-635, 2018