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The aims of this study were to investigate prognosis and validate prognostic models [Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Data Consortium (IMDC), and Japanese metastatic renal cancer (JMRC) models] in the targeted therapy era in Japanese patients with metastatic renal cell carcinoma. We retrospectively analyzed 692 patients who were diagnosed with mRCC from January 2008 to August 2018 in the Michinoku Japan Urological Cancer Study Group database. Nivolumab as sequential therapy was widely used. Other immune checkpoint inhibitors were excluded from this study. The median overall survival (95% confident interval) in all, MSKCC favorable, intermediate, and poor risk patients was 41.0 months (33.9–46.8), not reached (63.5 to not estimable), 46.8 months (37.1–52.9), and 10.4 months (8.9–14.4), respectively. The median overall survival (95% confident interval) in IMDC favorable, intermediate, and poor risk patients was not reached (61.6 to not estimable), 47.4 months (41.4–56.5), and 11.5 (9.9–16.3), respectively. The c-index of the MSKCC, IMDC, and JMRC models calculated at mRCC diagnosis was 0.680, 0.689, and 0.700, respectively. No statistical differences were found in the c-index among the models. While the real-world overall survival in Japanese patients with mRCC in the targeted therapy era improved compared to that previously reported in the cytokine era, there was no clear difference in the survival of poor risk patients between these eras. There were no differences in the superiority among the models.

Objectives To evaluate the histologic findings and clinical outcomes of post-chemotherapy retroperitoneal lymph node dissection for advanced germ cell tumor. Methods We analyzed the medical records of 66 patients who underwent post-chemotherapy retroperitoneal lymph node dissection between 2005 and 2019 at Tsukuba University Hospital. Results The proportions of necrosis, teratoma, and viable germ cell tumor in the specimens were 62.1%, 36.4%, and 1.5%, respectively. The 5-year progression-free and overall survival rates were 82.3% and 91.3%, respectively. The 5-year overall survival rate of patients with residual teratoma was significantly worse than that of patients with necrosis only (74.1% vs 100%). Overall, three patients died: one from cancer and two from teratoma with somatic-type malignancy. Of these, two patients relapsed after incomplete resection of residual teratoma. When limited to patients with completely resected teratoma, the 5-year overall survival rate was 91.7%, which did not differ from that for patients with necrosis only. Multivariate analysis showed that presence of teratoma in the primary site and decrease in retroperitoneal lymph node mass to less than 50% of the initial tumor size were independent factors for residual teratoma. However, the absence of these factors could not reliably predict necrosis only in retroperitoneal lymph node dissection specimens. Conclusions In our series, 98% of post-chemotherapy retroperitoneal lymph node dissection pathology was either necrosis or teratoma, with viable germ cell tumor only found in 2% of patients. Residual teratoma was associated with poorer prognosis, especially in cases of incomplete resection.

OBJECTIVE To examine the discrepancy between clinical and pathological T stages in patients with urothelial carcinoma of the upper urinary tract treated with radical surgery, and to compare them with the corresponding discrepancy in urothelial carcinoma of the bladder. METHODS We used the Hospital-Based Cancer Registry data in Japan to extract urothelial carcinoma of the bladder cases (n = 3747) and urothelial carcinoma of the upper urinary tract cases (n = 6831), including urothelial carcinoma of the renal pelvis (n = 3295) and urothelial carcinoma of the ureter (n = 3536) with cT1-4N0M0 diagnosed in 2012-2015, histologically confirmed, and treated with radical surgery without chemotherapy or radiotherapy. We compared the T-stage discrepancy among different tumor locations. RESULTS The proportions of overall T-stage discrepancy in the urothelial carcinoma of the renal pelvis (40.8%) and urothelial carcinoma of the ureter (42.9%) groups tended to be higher compared with that in the urothelial carcinoma of the bladder (38.8%) group. The upstaging rate from clinical non-muscle-invasive cancer (≤cT1) to pathological muscle-invasive cancer (≥pT2) was significantly higher in the urothelial carcinoma of the renal pelvis and urothelial carcinoma of the ureter groups compared with the urothelial carcinoma of the bladder group (P = 0.002, P

Introduction Granulocyte colony‐stimulating factor‐associated arteritis is a rare adverse event of granulocyte colony‐stimulating factor, with an incidence of 0.47% among all patients who receive granulocyte colony‐stimulating factor. We herein present a case of granulocyte colony‐stimulating factor‐associated arteritis. Case presentation A 72‐year‐old man with castration‐resistant prostate cancer and multiple bone metastases was treated with docetaxel and pegfilgrastim. He developed a high fever on day 12 without other symptoms. His white blood cell count and C‐reactive protein levels were high. Antibiotic therapy was ineffective, and contrast‐enhanced computed tomography showed thickened subclavian and brachiocephalic artery walls. He was diagnosed with granulocyte colony‐stimulating factor‐associated arteritis. Conclusion When patients receiving chemotherapy with granulocyte colony‐stimulating factor develop an unexplained fever, granulocyte colony‐stimulating factor associated arteritis should be considered.

Intravesical Bovis bacillus Calmette-Guerin (BCG) therapy is the most effective immunotherapy for bladder cancer, but it sometime causes serious side effects because of its inclusion of live bacteria. It is necessary to develop a more active but less toxic immunotherapeutic agent. Trehalose 6,6'-dimycolate (TDM), the most abundant hydrophobic glycolipid of the BCG cell wall, has been reported to show various immunostimulatory activities such as granulomagenesis and adjuvant activity. Here, we developed cationic liposomes incorporating TDM purified from Mycobacterium bovis BCG Connaught, and we investigated the antitumor effect of the cationic liposome TDM (Lip-TDM). Lip-TDM exerted an antitumor effect in bladder cancer, colon cancer, and melanoma-bearing mouse models that was comparable or even superior to that of BCG, with no body weight loss or granuloma formation. The antitumor effect of Lip-TDM disappeared in two types of mice: those with depletion of CD8+ T cells, and those with knockout of macrophage-inducible C-type lectin (Mincle) which recognize TDM. Lip-TDM treatment enhanced the maturation and migration of dendritic cells in the tumor microenvironment in a Mincle-dependent manner. Our results elucidate mechanisms that underlie Lip-TDM treatment and suggest that Lip-TDM has potential as a safe and effective treatment for various cancers.

Objectives To compare overall survival between patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy and those not treated by cytoreductive nephrectomy. Methods We retrospectively evaluated 278 patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors between January 2008 and November 2019. Patients were divided into two groups: a cytoreductive nephrectomy group (immediate or deferred cytoreductive nephrectomy) and a group who received systemic tyrosine kinase inhibitor therapies alone without cytoreductive nephrectomy (control group). Overall survival comparisons were made in all patients in the control versus the cytoreductive nephrectomy group, the control versus the immediate cytoreductive nephrectomy group, the control versus the deferred cytoreductive nephrectomy group, and the deferred cytoreductive nephrectomy versus the immediate cytoreductive nephrectomy group. Analyses were weighted using the propensity score-based inverse probability of treatment weighting method to adjust for group imbalances. Results The median (range) age of the patients was 65 (59-73) years. Of the 278 patients, 132 and 146 were in the control group and the cytoreductive nephrectomy (immediate, n = 107 and deferred, n = 39) group, respectively. A significant difference was noted between the control and cytoreductive nephrectomy groups in age, clinical stage, International Metastatic Renal Cell Carcinoma Database Consortium risk factors, and the number of metastatic sites. Inverse probability of treatment weighting-adjusted Cox regression analysis showed a significant difference in overall survival between the control and the cytoreductive nephrectomy groups and between the control and the immediate or deferred cytoreductive nephrectomy groups. However, there was no significant difference in overall survival between the immediate and the deferred cytoreductive nephrectomy groups. Conclusions Our findings suggest that metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy are more likely to have longer overall survival than those who receive tyrosine kinase inhibitor therapy only.

OBJECTIVES To identify the prognosis of patients with non-urothelial carcinoma of the upper urinary tract and compare it with that of patients with urothelial carcinoma. METHODS We used hospital-based cancer registry data in Japan to extract histologically confirmed non-urothelial carcinoma and urothelial carcinoma cases of the upper urinary tract diagnosed in 2008-2009. We estimated the 5-year overall survival by a Kaplan-Meier analysis. The Cox proportional hazards regression analysis was used to evaluate prognostic factors. RESULTS A total of 2567 upper urinary tract cancer patients with confirmed histological subtypes were identified. The most common histology of non-urothelial carcinoma was squamous cell carcinoma (n = 88, 3.4%) followed by adenocarcinoma (n = 33, 1.3%) and small cell carcinoma (n = 10, 0.4%). The proportion of advanced stage in the squamous cell carcinoma patients was significantly higher than that in the urothelial carcinoma patients (P = 0.003). In stage IV, the proportion of patients who received a combination of surgery + chemotherapy in the urothelial carcinoma group was higher than that in the non-urothelial carcinoma group (34% vs 16%, respectively). The 5-year overall survival rates of the non-urothelial carcinoma patients at stages I-III and stage IV were significantly worse than those of the urothelial carcinoma patients (P = 0.003, P

OBJECTIVES To investigate the clinical characteristics of patients with penile cancer in Japan using the nationwide hospital-based cancer registry database. METHODS Using hospital-based cancer registry data, we described the distribution of age, pathology, tumor-node-metastases classification, and first-course treatment in patients treated between 2012 and 2015. We compared the patterns of first-line treatment between elderly and non-elderly patients. RESULTS A total of 1012 patients were diagnosed with squamous cell carcinoma among 1773 patients with penile tumors who registered under topography code C60. The median age at diagnosis was 74 years, and 85.9% of patients were aged >60 years. The most common pathology was usual-type squamous cell carcinoma (91.9%), followed by verrucous carcinoma (5.0%), sarcomatoid carcinoma (1.1%), papillary carcinoma (0.7%), basaloid carcinoma (0.6%), adenosquamous carcinoma (0.4%), warty carcinoma (0.2%) and mixed carcinoma (0.1%). A total of 61.3% of patients were diagnosed with localized disease. In contrast, the proportions of patients with lymph node and distant metastases were 27.5% and 2.1% at diagnosis, respectively. The proportion of patients who were treated with chemotherapy as the first-course treatment was significantly lower among elderly patients (≥80 years) with clinical stage III (27.6% vs 7.1%, P = 0.0312) and clinical stage IV (53.2% vs 14.3%, P = 0.0086). CONCLUSIONS Most penile cancer patients in Japan are diagnosed with usual-type squamous cell carcinoma, and those with human papilloma virus-related squamous cell carcinomas are

Introduction A double inferior vena cava is a rare anomaly with an incidence ranging from 0.3% to 3.0%. In patients with a double inferior vena cava, it is important to understand the precise anatomy and possible irregular lymph node flow when performing surgery for malignancies. Case presentation A 60-year-old man with a non-seminoma was referred to our hospital after left high orchiectomy. Computed tomography revealed a double inferior vena cava and swollen masses in the para-aortic region. After four cycles of chemotherapy with etoposide and cisplatin, retroperitoneal lymph node dissection was safely performed with a modified template extended to the right side of the paracaval region by referring to three-dimensional images created by SYNAPSE VINCENT® software. Conclusion Preoperative three-dimensional images were useful to understand this patient's unusual and complicated anatomical positions.

Renal cell carcinoma (RCC) is an aggressive genitourinary malignancy which has been associated with a poor prognosis, particularly in patients with metastasis, its major subtypes being clear cell RCC (ccRCC), papillary PCC (pRCC) and chromophobe RCC (chRCC). The presence of intracellular lipid droplets (LDs) is considered to be a hallmark of ccRCC. The importance of an altered lipid metabolism in ccRCC has been widely recognized. The elongation of very-long-chain fatty acid (ELOVL) catalyzes the elongation of fatty acids (FAs), modulating lipid composition, and is required for normal bodily functions. However, the involvement of elongases in RCC remains unclear. In the present study, the expression of ELOVL2 in ccRCC was examined; in particular, high levels of seven ELOVL isozymes were observed in primary tumors. Of note, elevated ELOVL2 expression levels were observed in ccRCC, as well as in pRCC and chRCC. Furthermore, a higher level of ELOVL2 was significantly associated with the increased incidence of a poor prognosis of patients with ccRCC and pRCC. The CRISPR/Cas9-mediated knockdown of ELOVL2 resulted in the suppression of the elongation of long-chain polyunsaturated FAs and increased LD production in renal cancer cells. Moreover, ELOVL2 ablation resulted in the suppression of cellular proliferation via the induction of apoptosis in vitro and the attenuation of tumor growth in vivo. On the whole, the present study provides new insight into the tumor proliferation mechanisms involving lipid metabolism, and suggests that ELOVL2 may be an attractive novel target for RCC therapy.

ObjectiveWe retrospectively analyzed the incidence and localization of venous thromboembolism in patients undergoing chemotherapy for advanced germ cell tumor and separately evaluated the risk factors for venous thromboembolism development before and during chemotherapy.MethodsWe included 121 patients treated with cisplatin-based chemotherapy between 2005 and 2018. Venous thromboembolism was defined as venous thrombosis diagnosed using radiological imaging with or without thromboembolic symptoms. We analyzed the clinical parameters for identifying the possible venous thromboembolism risk factors. Khorana score was used to calculate the venous thromboembolism risk.ResultsThirteen patients showed prechemotherapy venous thromboembolism and 13 developed venous thromboembolism during chemotherapy. The most common venous thromboembolism was deep vein thrombosis (10 patients), followed by inferior vena cava thrombus (eight patients) and pulmonary thrombus (six patients). Compared to the group without venous thromboembolism, the group with prechemotherapy venous thromboembolism showed higher proportion of patients with tumors originating in the right testis (10 out of 13), significantly higher lactate dehydrogenase levels (828 IU/L versus 436 IU/L, P = 0.013), significantly higher proportion of patients with retroperitoneal lymph node (RPLN) metastases >5 cm in diameter (76.9% versus 33.7%, P = 0.003) and slightly higher proportion of patients with high-risk Khorana score (≥ 3; 30.8% versus 11.6%). No significant differences were observed between the clinical characteristics of patients with venous thromboembolism developed during chemotherapy and patients without venous thromboembolism.ConclusionsWe show that both RPLN mass > 5 cm and high lactate dehydrogenase levels are significant risk factors for prechemotherapy venous thromboembolism but not for venous thromboembolism development during chemotherapy.

We retrospectively evaluated the clinical outcomes of patients with histologic variants of muscle invasive bladder cancer (MIBC) treated with trimodal bladder-preserving therapy (TMT). Among 148 patients with clinical T2-3N0M0 MIBC treated with TMT at Tsukuba University Hospital from 1990 to 2015, 11 patients (7.4%) had pathological components of variant urothelial carcinoma (UC). The complete response (CR), overall survival (OS), cause-specific survival (CSS) and progression-free survival (PFS) rates were analyzed in these 11 patients. Among the 11 patients with variant UC, 7 (64%) had UC with squamous and/or glandular differentiation and 4 (36%) had sarcomatoid (n = 1), plasmacytoid (n = 1), signet ring cell (n = 1), or clear cell variant (n = 1). Median follow-up was 49.0 months. Nine (82%) out of 11 patients achieved CR and 2 (22%) out of the 9 developed recurrence. Among seven patients who had UC with squamous and/or glandular differentiation, two developed recurrence and one died of disease. In contrast, 2 (50%) out of four patients with other variants, which were sarcomatoid variant or signet ring cell, developed recurrence and died of disease. Overall, the 5-year OS, CSS, and PFS rates of variant UC were 75%, 75%, and 58%, respectively. TMT might provide acceptable clinical outcomes for well-selected MIBC patients with histologic variants, especially for those with squamous and/or glandular differentiation. However, we need to pay special attention to other variants such as sarcomatoid variant or signet ring cell. TMT might be an alternative treatment option for patients with histologic variants, although further experiments will be needed to confirm this.

The Tumor-Node-Metastasis (TNM) staging system, jointly developed by the American Joint Commission on Cancer (AJCC) and the Union for International Cancer Control (UICC), is widely employed in clinical practice and research on patients with cancer. The definitions of TNM classification have recently been changed, improving patient stratification for management and prognosis. As the feature of new editions, biomarkers which are necessary for the stratification of patients are included to adapt for personalized medicine. Although it would be ideal for the AJCC and UICC have identical TNM staging systems, there are some differences between these two publications. In this review, we introduce the significant changes and differences in the eighth edition of the AJCC and UICC TNM staging systems for urologic cancers and summarize the evidence supporting these changes.

Objectives This study aims to evaluate the utility of the scoring system of the Registry for Metastatic Renal Cell Carcinoma (REMARCC) model on the overall survival (OS) of patients undergoing cytoreductive nephrectomy (CN). Methods A total of 278 patients with primary metastatic renal cell carcinoma (mRCC) treated with first-line tyrosine kinase inhibitors (TKIs) between January 2008 and November 2019 were identified. The c-index and net benefit between the REMARCC score were compared with the International mRCC Database Consortium (IMDC) score in patients with CN (CN group, n = 146). The effect of the REMARCC score on OS was compared between the CN group and patients without CN (non-CN group, n = 132) using Cox regression analysis under the propensity score-based inverse probability of treatment weighting (IPTW) method to adjust for group imbalances. Results Of the 146 patients with CN, the c-index of the REMARCC model (0.60) was higher than the IMDC model (0.54). The decision curve analysis showed the advantage of REMARCC model predicting OS compared with the IMDC model. OS was significantly longer in the REMARCC low-score (0–2) than that in the high-score (3–6) among the patients with CN. IPTW-adjusted Cox regression analyses showed that OS was significantly longer in the CN group than that in the non-CN group among the patients with REMARCC low-score but was not significantly different between the groups among the patients with REMARCC high-score. Conclusions The REMARCC score may be active for selecting the CN candidate in patients treated with TKIs.

Invasion of bladder cancer (BC) cells from the mucosa into the muscle layer is canonical for BC progression while phospholipase D isoform 1 (PLD1) is known to mediate development of cancer through phosphatidic acid (PA) production. We therefore used in silico, in vitro and in vivo approaches to detail the effect of PLD1 on BC invasion. In BC patients, higher levels of PLD1 expression were associated with poor prognoses. PLD1 knockdown significantly suppressed cellular invasion by human BC cells and matrix metalloproteinase-13 (MMP-13) was observed to mediate this effect. In our mouse bladder carcinogenesis model, the development of invasive BCs was suppressed by PLD1 knockout and a global transcriptomic analysis in this model indicated MMP-13 as a potential tumor invasion gene with NF-κB (nuclear factor-kB) as its transcriptional regulator. Furthermore, PA administration increased MMP-13 expression in line with NF-κB p65 phosphorylation levels. Collectively, we demonstrate that PLD1 promotes tumor invasion of BC by regulation of MMP-13 expression through the NF-κB signaling pathway and that PLD1 might be a potential therapeutic target to prevent clinical progression in BC patients.

Radical cystectomy is the gold standard treatment for muscle invasive bladder cancer, but some patients have medically inoperable disease or refuse cystectomy to preserve their bladder function. Bladder preservation therapy with transurethral resection of the bladder tumor and concurrent chemoradiotherapy, known as trimodal treatment, is regarded to be a curative-intent alternative to radical cystectomy for patients with muscle invasive bladder cancer during the past decade. After the development of immune checkpoint inhibitors, a world-changing breakthrough occurred in the field of metastatic urothelial carcinoma and many clinical trials have been conducted against non-muscle invasive bladder cancer. Interestingly, preclinical and clinical studies against other malignancies have shown that immune checkpoint inhibitors interact with the radiation-induced immune reaction. As half of the patients with muscle invasive bladder cancer are elderly, and some have renal dysfunction, not only as comorbidity but also because of hydronephrosis caused by their tumors, immune checkpoint inhibitors are expected to become part of a new therapeutic approach for combination treatment with radiotherapy. Accordingly, clinical trials testing immune checkpoint inhibitors have been initiated to preserve bladder for muscle invasive bladder cancer patients using radiation and immune checkpoint inhibitors with/without chemotherapy. The objective of this review is to summarize the evidence of trimodal therapy for muscle invasive bladder cancer during the past decade and to discuss the future directions of bladder preservation therapy in immuno-oncology era.

Objective Japan’s national database of hospital-based cancer registries is estimated to cover ~67% of all new cancer cases. Using this database, we analyzed the characteristics of the recently diagnosed testicular malignancy. Methods We obtained data for 6510 adult testicular malignancy patients diagnosed in 2012–2015. The distributions of patient ages, histological diagnoses and testicular germ cell tumor hospital care volumes were determined. Results The most common histology was seminoma (60.3% of all testicular malignancies), followed by non-seminoma (24.1%) and diffuse large B-cell lymphoma (13.1%). The median and mean ages of the testicular germ cell tumor patients were high at 38 and 39.8 years, respectively. The age distribution peaked at 30–40 years, followed by 40–50 years. Approximately 18% of testicular germ cell tumor patients were ≥50 years. The ages of the diffuse large B-cell lymphoma patients peaked at 70–80 years (mean 67.7 years). When the analysis was limited to the testicular germ cell tumor patients who received first-course cancer treatment at the participating hospitals, the number of high-volume hospitals with ≥20 testicular germ cell tumor care volume was limited to 61 (10.0% of the 605 hospitals that treated ≥1 testicular germ cell tumor patient). However, when the patients who changed hospitals during treatment or relapsed after treatment completion were analyzed together, the number of high-volume hospitals increased to 104 (17.0% of 612 hospitals). Conclusion The testicular germ cell tumor patients’ mean age was nearly 40 years. The proportions of older testicular germ cell tumor patients and diffuse large B-cell lymphoma patients were higher than previously thought. The reasons for this trend are unknown, but it is important to address the trend identified herein in a country with a super-aging population.

Background: Urological education is as important as surgical training for undergraduates. However, those in undergraduate medical schools have less exposure to surgery and urology as their curriculum focuses more on clinical skills, particularly community-based healthcare for a super-aging society. This study aimed to evaluate whether urologic hands-on training could encourage surgical and urological interest in medical undergraduate students. Methods: A one-day elective program in urologic surgery at the University of Tsukuba, particularly in robotic, laparoscopic, and endoscopic surgeries, was offered to 58 fourth-year medical students in 2018 and 2019, prior to their clinical clerkship. The average age of participants was 22 (range: 21–25) years. We assessed scores (1–5 Likert-type items) in training activity, interest in surgery, and interest in urology before and after the course. Results: Before attending the program, average scores in interest in urology were 3.53 in 2018 and 3.15 in 2019. After training, the total likely scores of this program in 2018 and 2019 were 4.59 and 4.76, respectively. The likely scores in surgery increased after the program; however, this was not significantly different to that prior to the program. However, the average interest scores in urology were significantly increased to 3.91±0.63 (p

We conducted the present phase I/IIa positron emission tomography (PET) imaging study with 89Zr conjugated with desferroxamine-IAB2M (89Zr-Df-IAB2M), an anti-prostate-specific membrane-antigen minibody, to assess its safety and feasibility in patients with urological cancer. 89Zr-Df-IAB2M was synthetized by IBA Molecular (Somerset, NJ, USA) and transported by air to Tsukuba Molecular Imaging Center (Tsukuba, Ibaraki, Japan).17 patients received 74 MBq (2 mCi) of 89Zr-Df-IAB2M at total mass doses of 10 mg. Whole-body and plasma clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated. We also preliminarily tested the performance of 89Zr-immuno-PET imaging for 13 patients with prostate cancer and 4 patients with other urological cancer. The administration of 89Zr-Df-IAB2M was well-tolerated, and no infusion-related reactions were observed in any patient. No adverse events were noted in the laboratory parameters, vital signs, or other parameters. The plasma clearance was biphasic, with an initial rapid phase (t 1/2 fast: 10.1 ± 3.4 h) followed by a slow phase (t 1/2 slow: 49.0 ± 22.7 h). The half-life of radioactivity in the whole body (WB t1/2) was 237 ± 9 h. The highest absorbed radiation dose was 1.67 mGy/MBq, observed in the liver and kidney. The effective dose was 0.68 ± 0.08 mSv/MBq. The radiation dose rate at 0.5 m distance from the patient was 8.67 µSv/h on day 1, and decreased to 2.26 µSv/h at 5 days after injection. Both bone and lymph node metastases were detected with 89Zr-Df-IAB2M by 24 or 48 h imaging. Administration of 89Zr-Df-IAB2M was well-tolerated and safe in terms of adverse events and radiation exposure and protection. 89Zr-Df-IAB2M is feasible for usage by long-distance transportation. Further studies are warranted for analysis of its use for tumor lesion detection (UMIN000015356).

To elucidate the clinicopathological features, hospital-based care volume and prognoses associated with primary retroperitoneal sarcoma (PRS). Clinical data on PRS cases, diagnosed from 2008 to 2009 (cohort A) and from 2012 to 2015 (cohort B), were obtained from the national hospital-based cancer registry in Japan. Since data on survival, 5 years after PRS diagnosis, were available only for cohort A, patient prognoses were analyzed in this group alone. The numbers of participating hospitals were 154 in cohort A and 537 in cohort B. In total, 380 and 2011 patients with PRS were identified in cohorts A and B, respectively. The incidence of PRS among all the registered urogenital malignancies was 0.52% (2391/462,866). Liposarcoma was the most commonly observed PRS subtype (55.8%), followed by leiomyosarcoma (19.0%). In cohort A, the 5-year overall survival (OS) was 40.4%. The 5-year OS associated with stage I (n = 107), stages II and III (n = 61), and stage IV (n = 59) disease were 59%, 39%, and 6%, respectively. Only two institutions treated over ten patients per year in each cohort. When institutions were divided by hospital care volume (8 hospitals with ≥ = 3 cases and 149 with

Objectives To identify the prognosis of pure non-urothelial carcinoma (non-UC) of bladder and to compare them with those of pure urothelial carcinoma (UC). Methods We used Japan’s nationwide hospital-based cancer registry data to extract histologically confirmed pure non-UC and UC cases of bladder diagnosed in 2008–2009. We estimated the 5-year overall survival (OS) by a Kaplan–Meier analysis. Results A total of 8094 patients with confirmed histological subtypes of bladder cancer were identified. The most common pure non-UC was squamous cell carcinoma (SQ, n = 192, 2.4%) followed by adenocarcinoma (AC, n = 138, 1.7%) and small cell neuroendocrine carcinoma (SmC, n = 54, 0.7%). The proportion of female patients (48%) was significantly higher in the SQ group compared with the pure UC group (P Conclusion The prognosis of pure non-UC was worse than that of pure UC, especially in the stage I and III non-UC patients. To improve these patients’ oncologic outcomes, a more aggressive surgical approach may be necessary in stage I patients with non-UC, especially in pure SQ.

Objectives To identify the clinicopathological features of malignant urachal tumor in Japan, and analyze the 5-year overall survival of malignant urachal tumor patients. Methods We used the hospital-based cancer registry data to extract malignant urachal tumor cases that were diagnosed in 2008-2009 and 2012-2015, histologically confirmed, and received the first course of treatment. We analyzed the 5-year overall survival using the 2008-2009 cohort's data. Results We identified 456 patients, and malignant urachal tumor accounted for 0.4% of all malignant bladder cancers. The median age was 61 years (range 2-97), and 66% were men. The most common histology was adenocarcinoma (80%), followed by urothelial carcinoma (11%) and squamous cell carcinoma (3%). The proportions of patients were: 19% Ta/Tis/T1N0M0, 55% T2-3N0M0, 13% T4/N+ and 13% M+. Regarding the initial treatment, the proportions of surgery alone were 79% and 33% in cases of T3 or less N0M0 and T4/N+, respectively. The proportion of combination therapy including surgery and chemotherapy were 13% and 44% in T2-3N0M0 and T4/N+, respectively. Radiation therapy was not common at any stage. In the 2008-2009 cohort, the 5-year overall survival rate in Ta/Tis/T1N0M0, T2-3N0M0, T4/N+ and M+ were 60%, 64%, 63% and 12%, respectively. Conclusions Malignant urachal tumors are quite rare in Japan, and most of those without metastasis are likely to be treated by surgery alone, even at advanced stages. A standard of care must be established for malignant urachal tumor patients at advanced stages or with metastasis, as the prognosis of these patients can be poor.

OBJECTIVES We aimed to compare the diffusion capacity of carbon monoxide (DLCO), which was adjusted using the two equations the Cotes method and the Dinakara method, to assess bleomycin-induced lung injury in testicular cancer patients preparing for post-chemotherapy surgery. METHODS Between November 1990 and October 2018, 89 patients with advanced testicular cancer were recruited into the study. All patients received chemotherapy and underwent DLCO measurements using the single-breath technique prior to surgery for residual tumor removal. RESULTS The mean DLCO adjusted for hemoglobin using the Cotes and Dinakara methods was 69.5% and 86.0%, respectively (P < 0.001). According to the Cotes method, adjusted DLCO was severely diminished to below 65% in 40 patients (45%), whereas this proportion was only 16% according to the Dinakara method. We observed a significant correlation between hemoglobin levels and DLCO adjusted using the Cotes method (P < 0.001), but not using the Dinakara method. Four patients received a clinical diagnosis of bleomycin-induced pneumonitis (BIP), and all patients recovered after oral steroid therapy or observation. The DLCO adjusted by either methods was not well correlated with the development of BIP. No patients had major postoperative respiratory complications. CONCLUSIONS We found that Cotes-adjusted DLCO may be influenced by anemia. We recommend the addition of Dinakara-adjusted DLCO, along with chest computed tomography, for preoperative risk assessment.

Background We retrospectively analyzed castration-resistant prostate cancer (CRPC) patients treated with secondary hormonal therapies (SHTs) prior to docetaxel therapy. Methods The cases of 73 CRPC patients who underwent docetaxel therapy in 2005–2011 at four hospitals in Ibaraki, Japan were analyzed. We determined the cause-specific survival (CSS) from the start of docetaxel therapy and the time point of CRPC diagnosis, and we compared the CSS achieved with/without prior classical SHTs, which were defined as low-dose steroid and estramustine phosphate. Results Of the 73 enrolled patients, 26 underwent docetaxel therapy (DOC group), and 47 underwent SHTs (SHTs-DOC group) as the initial treatment for CRPC. In the docetaxel therapy, the rate of prostate-specific antigen responses were higher in the DOC group compared with the SHTs-DOC group (76.9% vs. 44.7%, P = 0.0066). The median CSS from the docetaxel therapy initiation was not significant but longer in the DOC group than in the SHTs-DOC group (23.4 months vs. 16.6 months, P = 0.0969). However, the median CSS from the time of CRPC diagnosis did not significantly differ between the DOC and SHTs-DOC groups (23.4 months vs. 24.7 months, P = 0.9233). In a univariate analysis, pain and visceral metastasis appeared to be risk factors for the CSS in the SHTs-DOC group. The patients with pain and/or visceral metastasis had significantly poorer survival than those without these factors in the SHTs-DOC group (31.5 months vs. 16.8 months, P = 0.0053). Conclusion The induction of SHTs prior to docetaxel therapy is an acceptable treatment option with some survival benefits for CRPC patients without pain and visceral metastases.

Objective We conducted the present study to elucidate the clinical presentation, treatment outcomes and risk factors for the development of metachronous brain metastasis at a single progressive disease site, the so-called isolated brain metastasis, in patients with testicular germ cell tumors. Methods To identify metachronous brain metastasis in a timely manner, brain imaging was performed when the re-elevation of tumor markers was observed during chemotherapy, even in patients who were free from central nervous system symptoms. The medical records of 147 patients with metastatic germ cell tumors who were treated between 1991 and 2015 were retrospectively reviewed. Results Eight (5.4%) of the 147 patients presented synchronous brain metastasis. Of these, five patients suffered from metachronous brain metastasis relapse. An additional nine patients developed metachronous brain metastasis during or after chemotherapy. Ten of the 14 patients with metachronous brain metastasis did not have central nervous system symptoms. Eight (57%) patients had isolated brain metastasis. Ten patients underwent multimodal treatments, predominantly chemotherapy and radiotherapy. The 3-year overall survival of all 14 patients was 34.6%, but that of the patients with isolated brain metastasis was high as 66.7%. The development of metachronous brain metastasis was associated with a choriocarcinoma element at the primary site and an human chorionic gonadotropin level of >50 000 IU/L and brain metastasis at the initial diagnosis. Conclusions In our series, we identified isolated brain metastasis in 57% of the metachronous brain metastasis patients. The monitoring of tumor markers and appropriate brain imaging are mandatory for the diagnosis of isolated brain relapse, which is associated with a higher rate of long-term survival.

Objective DNA methyltransferase 3-like plays an important role in germ cell development. The aim of this study was to analyse the DNA methyltransferase 3-like protein expression in testicular germ cell tumors. Methods The immunohistochemical expression of DNA methyltransferase 3-like was examined in 86 testicular germ cell tumor specimens in various clinical settings. The association between DNA methyltransferase 3-like expression and disease stage was analyzed. Results DNA methyltransferase 3-like was strongly expressed in seven of the eight pure embryonal carcinomas (87.5%). Partial DNA methyltransferase 3-like expression was observed in 6 of 23 (26.1%) pure seminomas. Various degrees of DNA methyltransferase 3-like expression was observed in all four pure yolk sac tumors, of which three were prepubertal yolk sac tumors. In mixed germ cell tumors, DNA methyltransferase 3-like protein was expressed in various degrees in elements of the embryonal carcinoma (14/18, 77.8%), seminoma (4/11, 36.4%), teratoma (4/7, 57.1%) and choriocarcinoma (3/3, 100%) but not in the yolk sac tumors (0/4). When DNA methyltransferase 3-like expression was analyzed according to disease stages, it was significantly correlated with advanced seminoma rather than Stage I seminoma (46.2 vs. 0%, P = 0.019), whereas there was no significant difference in the DNA methyltransferase 3-like-positive proportion between Stage I and advanced disease in the mixed germ cell tumors. Conclusions Our findings suggest that DNA methyltransferase 3-like protein may play roles not only in the development of embryonal carcinoma but also in the development of advanced pure seminoma and pure yolk sac tumor.

Background: Urological education is as important as surgical training for undergraduates. However, students in undergraduate medical schools have less exposure to urology as their curriculum focuses more on clinical skills, particularly community-based healthcare for a super-aging society. This study aimed to evaluate whether urology-related hands-on training could increase the interest of undergraduate medical students in urology. Methods: A 1-day elective program in urological surgery at the University of Tsukuba, particularly in robotic, laparoscopic, and endoscopic surgeries, was offered to 85 fourth-year medical students from 2018 to 2020, prior to their clinical clerkship. The average age of the participants was 22 (range: 21-25) years. We used a scoring system that comprised 1-5 Likert-type items to assess training activity, interest in surgery, and interest in urology before and after the course. Results: Before attending the program, the average scores of interest in urology were 3.53 in 2018, 3.15 in 2019, and 3.00 in 2020. The scores in surgery increased after the program; however, this was not significantly different from scores prior to the program. However, the average interest scores in urology were significantly increased to 3.91 ± 0.63 ( P Conclusions: Urological hands-on training facilitated interest in urology in medical students prior to their clinical clerkship.

Background We analyzed the efficacy and toxicity of cabazitaxel (CBZ) at high and low initial doses in Japanese patients with docetaxel-resistant castration-resistant prostate cancer (CRPC). Methods We retrospectively evaluated 118 patients who received CBZ for docetaxel-resistant CRPC in 10 university hospitals in Japan between 2014 and 2016. The rate of decrease of prostate-specific antigen (PSA), adverse events, progression-free survival (PFS), and overall survival (OS) were compared between patients receiving initially high (≥22.5 mg/m2, n = 36) and low (≤20 mg/m2, n = 80) CBZ doses. Factors associated with survival and grade 4 neutropenia were evaluated. Results PSA values decreased by > 50% in 22 patients (19%), with a higher frequency in the high-dose group than in the low-dose group (29 and 14%, P = 0.073). The median PFS time for the all-patient, high- and low-dose groups was 2.8 months (95% confidence interval [CI] 1.9–4.4), 2.1 months (1.2–5.5), and 3.0 months (2.0–4.4), respectively (P = 0.904). The median OS times were 16.3 months (95% CI 9.7–30.9), 30.9 months (11.8–47.4), and 10.2 months (8.6–20), respectively (P = 0.020). In multivariate analyses, PFS was significantly associated with existing bone metastasis at diagnosis (P = 0.005) and OS with PSA > 100 ng/ml (P = 0.007), hemoglobin

Intravesical therapy using Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most established cancer immunotherapy for bladder cancer. However, its underlying mechanisms are unknown. Mycolic acid (MA), the most abundant lipid of the BCG cell wall, is suspected to be one of the essential active components of this immunogenicity. Here, we developed cationic liposomes incorporating three subclasses (α, keto, and methoxy) of MA purified separately from BCG, using the dendron-bearing lipid D22. The cationic liposomes using D22 were efficiently taken up by the murine bladder cancer cell line MB49 in vitro, but the non-cationic liposomes were not. Lip-kMA, a cationic liposome containing keto-MA, presented strong antitumor activity in two murine syngeneic graft models using the murine bladder cancer cell lines MB49 and MBT-2 in comparison to both Lip-aMA and Lip-mMA, which contained α-MA and methoxy-MA, respectively. Interestingly, Lip-kMA(D12), which was made of D12 instead of D22, did not exhibit antitumor activity in the murine syngeneic graft model using MB49 cells, although it was successfully taken up by MB49 cells in vitro. Histologically, compared to the number of infiltrating CD4 lymphocytes, the number of CD8 lymphocytes was higher in the tumors treated with Lip-kMA. Antitumor effects of Lip-kMA were not observed in nude mice, whereas weak but significant effects were observed in beige mice with natural killer activity deficiency. Thus, a cationized liposome containing keto-MA derived from BCG induced in vivo antitumor immunity. These findings will provide new insights into lipid immunogenicity and the underlying mechanisms of BCG immunotherapy.

p16INK4a (p16) is a key molecule in bladder tumor (BT) development. We previously reported that a p16 antitumor peptide inhibited the growth of subcutaneous BT grafts in mice through restoration of p16 function using a Wr-T peptide transporter system. In the present study, the efficacy of mouse p16 peptide administration in a mouse lung metastasis model for BT and also the toxicity of peptides by cardiac peptide injection were evaluated. Mouse lung metastases were developed by tail vein injection of a p16-deficient MBT-2 cell line. Six-week-old C3H/He female mice were divided into three groups: A control group (n=12) receiving no treatment; a group treated once on the 3rd experimental day (n=12); and a group treated three times on the 3rd, 5th and 7th experimental days (n=10) with an injection of a mixture of 80 nmol mouse p16 peptide and 50 nmol Wr-T into the tail vein. At the 14th experimental day, the lung metastases were histologically evaluated. Lung metastases were observed in 100% (12/12), 41.7% (5/12) and 30% (3/10) of the aforementioned three groups, respectively. The number and area of metastatic lung tumors were significantly different between control and treatment groups (control vs. triple treatment group for the number and area, P=0.0029 and P=0.0296, respectively). Immunohistochemistry demonstrated that phosphorylated retinoblastoma (Rb) protein was decreased in lung tumors of the treatment groups, compared with the control group. The toxicity of p16 peptide transduction was evaluated by using low-dose treatment (three dosages) and high-dose treatment (two dosages) on three male and three female C3H/He mice in early and late experimental phases. In low and high dose groups, no notable change was determined in body weight or blood analyses in early or late phases following mouse p16 peptide administration. In addition, no notable change was observed histologically in bone marrow of treatment groups. To conclude, systemic p16 peptide administration decreased lung tumor development in a mouse metastatic BT model without severe adverse events, as assessed by blood analyses and histological evaluation.

432 Background: Activation of FGFR signals in bladder cancer is frequently observed. Previous study reported that infiltration of tumor immune cells is suppressed in FGFR3 mutated bladder cancer. In this study, we elucidate the relationship between molecular mechanism of FGFR activation and tumor immune environment in bladder cancer. Methods: We analyzed 103 tissues of bladder cancer patients. Detection of somatic mutations were performed by target sequencing and gene expressions were analyzed by RNA-seq. Immunohistochemical staining of CD8 was performed for evaluating tumor-infiltrating lymphocytes. We compared the relationship between molecular mechanism of FGFR activation and tumor immune environment. Results: FGFR3 activated mutation or fusion was found in 37 cases (36%). FGFR1 overexpression was found in 10 cases (10%). FGFR3 activated mutation or fusion and FGFR1 overexpression were mutually exclusive. Tumors harboring FGFR3 mutation showed less infiltration of CD8 positive cells ( p = 0.01) and low PD-L1 expression ( p = 0.08) compared to those without. On the other hand, tumors with FGFR1 overexpression showed more infiltration of CD8 positive cells ( p = 0.06) and high PD-L1 expression ( p = 0.02). Conclusions: Clinicopathological features and intratumor immune environment of bladder cancer is different depending on the molecular mechanism of FGFR activation. These results suggest a possible association between molecular mechanism of FGFR activation and sensitivity of immunotherapy.

579 Background: Accurate staging in patients with urothelial carcinoma (UC) of the bladder (UCB) or the upper urinary tract (UTUC) is essential for planning the appropriate treatment strategy. Although an underestimation of the pathological stage may result in missing the opportunity to perform preoperative treatment, the actual rate of the discrepancy between the clinical and pathological stages in UC is not known. Methods: We used Hospital-Based Cancer Registry (HBCR) data in Japan to extract 3,747 cases of UCB and 6,831 cases of UTUC with cT1-4N0M0 that were diagnosed in 2012–2015, histologically confirmed, and treated with radical surgery. We excluded patients who received chemotherapy or radiotherapy and those with an unknown clinical or pathological stage. Results: The proportion of UCB patients whose pathological stage was up-staged was 25%, and that of the UTUC patients was 30%. Among the patients with cT1 at each tumor location, up-staging to muscle-invasive cancer occurred in 30.9% (UCB, n=1132: pT2, 21.6%; pT3, 7.9%; pT4, 1.5%) and 37.5% (UTUC, n=2526: pT2, 16.9%; pT3, 20.2%; pT4, 0.4%), respectively. In particular, in the group of UTUC patients with cT1, the proportion of up-staging for pT3 was higher than that in the group of UCB patients with cT1. In the cases with cTis, up-staging to muscle-invasive cancer occurred in 10.5% (UCB, n=391: pT2, 6.9%; pT3, 1.8%; pT4, 1.8%) and 18.5% (UTUC, n=872: pT2, 9.7%; pT3, 8.7%). In contrast, the proportion of down-staging to non-muscle-invasive cancer in cases with cT2 or higher was 12% in the UCB group (n=2291) and 15% in the UTUC group (n=504). Conclusions: Among UC patients, up-staging from non-muscle-invasive cancer to muscle-invasive cancer is relatively common, and the frequency of this discrepancy in clinical and pathological stages tends to be especially higher in UTUC patients. More accurate diagnostic imaging techniques and biomarkers are urgently needed for the identification of the appropriate UC candidates for preoperative treatment.

ObjectiveTP53, a well-known tumor-suppressor gene in bladder carcinogenesis, has a functional single-nucleotide polymorphism on codon 72. The aim of this study was to elucidate the association between TP53 codon 72 polymorphism and somatic mutations in bladder cancer.Material and methodsGermline TP53 codon 72 polymorphism and somatic mutations of 50 cancer-associated genes were analyzed in 103 bladder cancer patients (59 non-muscle-invasive and 44 muscle-invasive), using Taqman genotyping assay and target sequencing, respectively. The expression of FGF-FGFR signaling pathway genes was analyzed by RNA sequencing of frozen tissue.ResultsThe allele frequency of TP53 codon 72 in our cohort was 37, 42, and 21% for Arg/Arg, Arg/Pro, and Pro/Pro, respectively. Interestingly, the prevalence of FGFR3 mutation was higher in patients with the Arg allele, whereas that of the RAS mutation was higher in patients without the Arg allele. The same association was seen in non-muscle-invasive bladder cancer (NMIBC) patients and no differences were observed in muscle-invasive bladder cancer patients. In NMIBC, FGFR1 expression was higher in patients without the Arg allele and FGFR3 expression was higher in patients with the Arg allele.ConclusionThe germline TP53 codon 72 polymorphism was associated with mutations of FGFR3 or RAS and expression of FGFR1 and FGFR3 in NMIBC. These findings provide new insight into the molecular mechanisms underlying the influence of the genetic background on carcinogenesis in bladder cancer.

421 Background: The current guidelines for muscle-invasive bladder cancer recommend the use of neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. However, a trimodal approach involving the combination of maximal transurethral resection (TUR) and combined chemoradiotherapy is an alternative in selected patients. Clinical outcomes of patients with histologic variants have not well been known. Methods: From 1990 to 2015, 148 patients with cT2-3N0M0 muscle-invasive bladder cancer underwent trimodal bladder-preserving therapy consisting of maximal TUR of the bladder tumor, intra-arterial chemotherapy and radiotherapy at our institution. We compared complete response rate (CRR) of bladder preservation, 5-yr cause-specific survival (CSS), and 5-yr overall survival (OS) for the patients with pure urothelial carcinoma (UC) or variant UC. OS and CSS were analyzed by using the Kaplan-Meier method and log-rank test. Results: The median follow-up was 38.3 months. All patients were T2-T3N0M0 (T2, n = 90; T3, n = 58). There were no significant differences in clinical characteristics between pure and variant UC groups. Eleven (7%) of the 148 patients had variant UC; 7 (64%) had UC with squamous and/or glandular differentiation, and 4 (36%) had other forms, including sarcomatoid (n = 1), plasmacytoid (n = 1), signet ring cell (n = 1), and clear cell variants (n = 1). There was no significant difference between pure UC and variant UC for CRR of bladder preservation (85% vs 82%, p = 0.66), the 5-yr CSS (88% vs 75%, p = 0.86) and the 5-yr OS (81% vs 75%, p = 0.66). Conclusions: Our findings indicate that trimodal bladder-preserving therapy can be an effective treatment option for selected muscle-invasive bladder cancer patients with variant UC.

Chronic kidney disease (CKD) is a major long-term morbidity of testicular cancer (TC) survivors cured by cisplatin-based chemotherapy. We conducted the present study to elucidate the usefulness of cystatin-based estimated glomerular filtration rates (eGFRcys) for diagnosis of CKD compared to creatinine-based eGFR (eGFRcreat) in those patients. eGFRcys and eGFRcreat were measured in 53 TC survivors. The 24-h creatinine clearance (CrCl) was measured in 12 TC survivors and 17 CKD patients with medical disease; all of them had eGFRcreat

461 Background: Intravesical instillation of live bacillus Calmette-Guérin (BCG) is an established immunotherapy for non-muscle invasive bladder cancer. However, development of non-infectious agents has been expected, because there are several problems due to instillation of live bacteria. BCG cell wall skeleton is known to stimulate host immune system, but the mechanism is still unknown. Mycolic acid (MA), which consist of three subclasses (α, keto, methoxy), is the most abundant lipid component of BCG cell wall and is expected to be one of essential active components. Objective: In order to identify active component from BCG cell wall and develop non-infectious BCG-derived immunotherapy, anti-tumor activities of cationic liposomes incorporating each subclass of MA were assessed using mouse syngeneic graft model. Methods: Heat killed packed cells of M. bovis BCG Tokyo 172 were fully hydrolyzed and MA was obtained. MA was separated to three subclasses by thin layer chromatography. Cationic and hydrophilic liposomes incorporating each subclass of MA were prepared. C57BL/6 mice were subcutaneously inoculated with a mixture of MB49 cells and PBS or liposome with/without MA followed by additional injection of PBS or liposome. Tumor growth was monitored. Infiltration of CD4/8 lymphocytes was examined by immunostaining. Results: Cationic liposomes were internalized into cytoplasm of MB49 cells, a mouse bladder cancer cell line. Cell proliferation was not affected by liposome incorporating MA. Tumor growth was significantly suppressed in mice treated with keto MA-liposome (vs PBS, p = 0.007), but not in mice treated withα-or methoxy-MA liposomes. Number of infiltrating CD8 lymphocytes was higher in tumor treated with keto MA-liposome than control. Antitumor effect of keto MA-liposome disappeared in nude mouse, while the effect existed in beige mouse with NK activity deficiency (vs PBS, p = 0.045). Conclusions: Keto MA-liposome showed the strongest antitumor effects in mouse model among three subclasses. T cell immunity may contribute to those effects.

A 40-year-old man was referred to our hospital for treatment of metastatic testicular cancer. Computerized tomography revealed multiple lung, liver, and retroperitoneal lymph node metastases. In addition, magnetic resonance imaging revealed multiple brain metastases. Induction chemotherapy with bleomycin, etoposide, and cisplatin was started the day after a high orchiectomy. The pathological diagnosis of the surgical specimen was yolk sac carcinoma. The serum human chorionic gonadotropin (hCG) was markedly increased to 630,000 mIU/ml, which suggested the presence of a choriocarcinoma element at metastatic sites. The patient subsequently suffered respiratory failure due to pulmonary hemorrhage. Intensive supportive care prevented a fatal outcome. Physicians who treat advanced testicular tumors should be aware of the potential complication of acute pulmonary hemorrhage, called choriocarcinoma syndrome, in cases with a high hCG level, which indicates a rapidly progressive and high-volume choriocarcinoma.

555 Background: Urothelial carcinoma (UC) is the most common histology of genitourinary (GU) tract cancer. Non-UC tumors in the GU tract appear to be more aggressive than UC at that location, but the clinicopathological features and their impacts on the prognoses of the non-UC patients are not known due to the low numbers of these patients. Methods: We used Hospital-Based Cancer Registry (HBCR) data in Japan to extract non-UC cases, i.e., patients with adenocarcinoma (AC), squamous cell carcinoma (SCC), or small cell carcinoma (SmCC) of the GU tract who were diagnosed in 2008–2009 with histological confirmation and had received first course of treatment. We retrospectively analyzed the clinicopathological features of these patients, stratified by the bladder and the upper urinary tract (UUT) as tumor locations. We used a Cox proportional hazards regression to identify prognostic factors associated with the overall survival (OS). Results: Of the 8,095 cases at the bladder and 2,580 cases at the UUT, 384 (4.7%) and 131 (5.1%) non-UC cases were identified, respectively. The proportions of histologic subtypes in the bladder were 1.7% AC, 2.4% SCC, and 0.7% SmCC. In the UUT group, these proportions were 1.3%, 3.4%, and 0.4%, respectively. At both tumor locations, the distribution of ages was similar across all subtypes, with the age peak in the 70s. More patients with non-UC were diagnosed at an advanced clinical stage compared to the patients with UC at either location. The 5-yr OS rates of the non-UC patients with a tumor in the bladder and at the UUT were 40% and 26%, whereas the corresponding 5-yr OS rates among the UC patients were 61% and 52%, respectively. A multivariate analysis revealed that the presence of non-UC was significantly associated with increased mortality (hazard ratio 1.66, 95% confidence interval 1.48–1.87) regardless of the tumor location. Conclusions: The clinicopathological features of the non-UC patients were similar between both tumor locations. The presence of non-UC was associated with poor prognosis regardless of the tumor location. A standard of care must be established for non-UC patients, since the prognoses of these patients are not satisfactory.