Search

The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.

Since 2020, the coronavirus disease 2019 pandemic has led to the widespread practice of hand hygiene and wearing face masks, not only among medical personnel, but also among the general population. Thus, the impact of the coronavirus disease 2019 pandemic on the incidence of febrile neutropenia should be verified. This study aimed to examine the incidence of febrile neutropenia in hospitalized patients receiving chemotherapy at Kanazawa University Hospital. Among inpatients at the Department of Urology receiving chemotherapy, we compared the incidence of febrile neutropenia between 317 cases in 2018-2019 and 276 cases in 2020. We retrospectively analyzed the factors of febrile neutropenia via binomial logistic regression analysis based on patient characteristics and the characteristics of primary diseases, with statistical significance set at p 0.05. Febrile neutropenia occurred in 20/317 cases in 2018-2019 and 1/276 cases in 2020, with a significant decrease in the latter (p = 0.005). In a multivariate analysis, we identified the following independent risk factors for febrile neutropenia: non-coronavirus disease 2019 era (p = 0.005), first course of therapy (p = 0.005), malnutrition (p = 0.032), and past history of febrile neutropenia (p = 0.018). Due to the coronavirus disease 2019 pandemic, hygiene policies for medical personnel and quarantine measures for patients were thoroughly implemented. Therefore, the incidence of febrile neutropenia in 2020 decreased to 1/15 of the previous incidence. Thus, the hygiene for medical personnel and patients during the expected period of chemotherapy-induced neutropenia is important for febrile neutropenia prevention.

Ra-223 is a therapeutic agent for bone metastatic castration-resistant prostate cancer (mCRPC). We examined the efficacy of a treatment method using Ra-223 together with ethinylestradiol (EE).Patients who received Ra-223 three or more times were included and two groups (with or without EE) were compared retrospectively.Eighteen patients were treated with Ra-223 and EE concomitantly (EstRadium therapy) and 13 patients were treated with Ra-223 alone or Ra-223 and agents other than EE (non-EstRadium therapy). The number of patients with decreased serum prostate-specific antigen level was significantly higher in the EstRadium therapy group than in the non-EstRadium therapy group (p=0.029).The combination of Ra-223 and EE, compared to Ra-223 alone, is an effective treatment option for bone mCRPC patients, in terms of PSA response.

Advances in imaging technologies have increased the opportunities for treating small-diameter renal cell carcinomas (RCCs) in the elderly. This retrospective study based on real-world clinical practice compared perioperative complications, preoperative and postoperative renal function, recurrence-free survival, and overall survival in elderly patients with RCC who had undergone robot-assisted partial nephrectomy (RAPN) or percutaneous cryoablation (PCA). A total of 99 patients (aged ≥70 years), including 50 and 49 patients in the RAPN and PCA groups, respectively, were analyzed. In the entire cohort, Clavien–Dindo grade ≥3 complications occurred in only one patient who had undergone RAPN. Renal function was significantly lower in the postoperative period than in the preoperative period in both the RAPN and PCA groups. The recurrence-free survival and overall survival rates were worse in the PCA group than in the RAPN group, albeit not significantly. RAPN was considered a safe and effective method for treating RCCs in elderly patients. Moreover, although the recurrence rate was slightly higher in the PCA group than in the RAPN group, PCA was deemed to be a safe alternative, especially for treating patients in whom general anesthesia poses a high risk.

Background: Inchworm sign is considered to be a characteristic finding in non-muscle invasive bladder cancer (NMIBC). Nevertheless, pathologically diagnosed muscle invasive bladder cancers (MIBCs) are occasionally diagnosed from tissue obtained by transurethral resection of bladder tumor (TURBT) in patients with inchworm sign. Methods: We retrospectively investigated the factors related to muscle invasive status in bladder cancer associated with inchworm sign and the role of inchworm sign in tumor outcomes following TURBT. Results: Of the 109 patients with inchworm sign, 94 (86.2%) and 15 (13.8%) were NMIBC and MIBC, respectively. Non-papillary tumors (hazard ratio (HR): 9.55, 95% confidence interval (CI): 2.07–44.10; p < 0.01) and tumors located in the bladder neck (HR: 7.73, 95% CI: 1.83–32.76; p < 0.01) were significant predictors of MIBC in bladder cancer with inchworm sign. Furthermore, recurrence-free survival (RFS) and progression-free survival were compared between patients with NMIBC with and without inchworm sign; however, no significant differences were found. In patients with NMIBC with inchworm sign, positive urine cytology was a prognostic factor for RFS (HR: 1.90, 95% CI: 1.04–3.48; p = 0.04). Conclusions: In bladder cancer with inchworm sign, 86.2% were NMIBC. Even in the case of inchworm sign, the presence of a non-papillary tumor or a bladder neck tumor before TURBT should be noted because of the possibility of MIBC. In this study, the inchworm sign was not a prognostic factor in patients with NMIBC.

Background: Treatment strategies have changed dramatically in recent years with the development of a variety of agents for metastatic hormone-naïve prostate cancer (mHNPC). There is a need to identify prognostic factors for the appropriate choice of treatment for patients with mHNPC, and we retrospectively examined these factors. Methods: Patients with mHNPC treated at our institution from 2000 to 2019 were included in this study. Overall survival (OS) was estimated retrospectively using the Kaplan–Meier method, and factors associated with OS were identified using univariate and multivariate analyses. A prognostic model was then developed based on the factors identified. Follow-up was terminated on 24 October 2021. Results: The median follow-up duration was 44.2 months, whereas the median OS was 85.2 months, with 88 patients succumbing to their disease. Multivariate analysis identified Gleason pattern (GP) 5 content, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) levels ≥ 300 IU/L as prognostic factors associated with OS. We also developed a prognostic model that classified patients with mHNPC as low risk with no factor, intermediate risk with one factor, and high risk with two or three factors. Conclusions: Three prognostic factors for OS were identified in patients with mHNPC, namely GP5 inclusion, BSI ≥ 1.5, and LDH ≥ 300. Using these three factors, we developed a new prognostic model for OS that can more objectively predict patient prognosis.

BackgroundThe detection of microsatellite instability in urologic cancers is rare, especially in metastatic, castration-resistant prostate cancer with neuroendocrine differentiation.Case presentationThis is a case of a 66-year-old Asian male patient with prostate adenocarcinoma who had metastases at initial presentation. Despite combined androgen deprivation therapy, his prostate-specific antigen (PSA) progressively increased, and prostate re-biopsy revealed small cell carcinoma. He was treated with platinum-based systemic chemotherapy, and his tumor markers, including PSA, remained negative; however, his local symptoms worsened. Subsequently, microsatellite instability-high was detected, and pembrolizumab was administered resulting in complete remission with the resolution of symptoms and continued therapeutic effect for more than 14 months.ConclusionMicrosatellite instability testing should be considered, despite its low detection rate, because the response to pembrolizumab in metastatic, castration-resistant prostate cancer with detectable microsatellite instability is associated with a prolonged duration of response.

Objective Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100 ng/mL and chemokine (CC motif) ligand 2 ≥ 320 pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system. Methods Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker. Results Patients with chemokine (CC motif) ligand 2 ≥ 320 pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2 Conclusions This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.

Background/Aim: We evaluated the clinical outcomes of patients with metastatic germ cell tumors (GCT) treated at our hospital, which belongs to a regional cancer center. Patients and Methods: Data pertaining to patients with metastatic GCT were obtained between April 2007-October 2017 and was retrospectively analyzed. Key outcome measures included objective response rates and survival rates.Results: All 42 patients received chemotherapy [complete response: eight (19.0%); partial response: 21 (50.0%); stable disease (SD): nine (21.4%); progressive disease: four patients (9.5%)]. Post-chemotherapeutic surgery was performed for seven out of 21 cases of partial response and two out of nine of stable disease. The 5-year survival rates of patients with good, intermediate and poor prognosis (International Germ Cell Consensus Classification) were 100%, 100%, and 71.4%, respectively. Patients who received induction chemotherapy at other hospitals had significantly poorer prognosis than those at our hospital (p=0.0043). Conclusion: Patients with metastatic GCT should preferably receive chemotherapy at an experienced institution.

BACKGROUND/AIM To investigate the blood markers for predicting pembrolizumab efficacy in advanced urothelial carcinoma (UC). PATIENTS AND METHODS This study included 91 advanced UC patients. The relationship between prognosis and markers from peripheral blood cell counts, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI=monocytes × neutrophils/lymphocytes), was evaluated. RESULTS Multivariate analysis indicated that pretreatment NLR and the 1-month-change NLR were both significantly associated with overall survival (OS) after pembrolizumab initiation. When the patients were divided into four groups according to calculated cutoffs using Cox proportional hazard model, the pretreatment NLR

Background: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. Methods: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. Results: Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7–46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3–26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121–1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418–6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. Conclusions: There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522.

Purpose: Prostate cancer is highly androgen-dependent, and androgen receptor (AR) signaling is suppressed by treatment. However, there are cases in which disease progresses rapidly at the end of treatment even after AR suppression, suggesting that the disease progresses by mechanisms different from AR. The aim of this study is to investigate the KRAS signaling pathway as one of the mechanisms. Methods: We used the hormone-sensitive prostate cancer (HSPC) cell line LNCaP and the castration-resistant prostate cancer (CRPC) cell line DU145. We performed KRAS knockdown by si-RNA and activation of KRAS signaling by EGF stimulation. To examine KRAS signaling, PCR and Western blotting were performed. The changes in proliferation and migration due to inhibition and activation of KRAS signaling were confirmed. Results: RT-PCR showed a fusion gene of ubiquitin-conjugating enzyme UBE2L3 and KRAS (UBE2L3-KRAS) in DU145. Western blotting showed increased phosphorylation of ERK and p38 downstream of KRAS in DU145. KRAS knockdown inhibited proliferation and migration in DU145 but not in LNCaP. In EGF-stimulated activation of KRAS signaling, Western blotting showed activation of downstream KRAS signaling in LNCaP, but no change in proliferation and migration in fetal bovine serum (FBS)-added medium. In contrast, EGF stimulation of DU145 further activated downstream KRAS signaling and promoted proliferation and migration. The AR-dependent LNCaP showed almost no effect of KRAS signaling activation on cancer progression, whereas DU145 showed that KRAS signaling is involved in cancer progression. Conclusion: While HSPC is highly AR-dependent and does not show any effect of KRAS on cancer progression, KRAS may be involved in cancer progression in some CRPCs. Citation Format: Taiki Kamijima, Kouji Izumi, Yoshifumi Kadono, Atsushi Mizokami. KRAS activity-mediated mechanism of castration-resistant prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2625.

Background/Aim: The current standard of care for first-line treatment of locally advanced or metastatic urothelial carcinoma (UC) is platinum-based combination chemotherapy. Recently, immune checkpoint inhibitors have been reported to be effective for UC. Knowing whether immunotherapy or chemotherapy is suitable as first-line treatment is beneficial for patients. A retrospective study was conducted on the clinical outcomes of Japanese patients who received three or more courses of first-line chemotherapy for metastatic UC to assess the outcome of conventional treatments in real clinical situation. Patients and Methods: Patients who received first-line chemotherapy between August 2009 and December 2019 were included. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: The median PFS and OS were 7.1 and 27.1 months, respectively, for patients with no disease progression at the end of three courses. Of 28 patients, 25 (89.3%) received second-line drug therapy and 10 (35.7%) received focal therapy for disease control. Patients with focal therapy had significantly longer OS than those without focal therapy (p=0.019, log-rank test). Conclusion: OS of metastatic UC at our Institution is relatively long, suggesting that aggressive second-line drug therapy and focal therapy may have contributed to such result.

Background Our previous report has shown that the flavonoid 2'-hydroxyflavanone (2'-HF) showed inhibition of androgen receptor (AR) activity against androgen-sensitive prostate cancer (PCa) cells, LNCaP, and exhibited antitumor effects against androgen-insensitive PCa cells, PC-3, and DU145. In the present study, we prepared a derivative of 2'-HF, 16MS7F1924, and confirmed the effects of this derivative on PCa cells. Methods The antiproliferation effects of 16MS7F1924 were investigated in PCa cells using LNCaP, PC-3, DU145 and docetaxel-resistant and cabazitaxel-resistant cell lines of PC-3-TxR/CxR and DU145-TxR/CxR. Prostate-specific antigen (PSA) and AR expression level in whole cells and the nucleus were confirmed in LNCaP by reverse transcriptase polymerase chain reaction and Western blot analysis. AR activity in LNCaP cells was confirmed by luciferase assay using PSA promoter-driven reporter. To analyze the antiproliferative effects, cell-based assays using flow cytometry, immunocytochemistry, and TUNEL assay as well as Western blot analysis were employed. Furthermore, PC-3, DU145 and each chemoresistant strain of human PCa cells were subcutaneously xenografted. The antitumor effects of 16MS7F1924 were evaluated in vivo. Results 16MS7F1924 showed antitumor effect on all PCa cells in a dose-dependent manner. 16MS7F1924 reduced the expression of PSA messenger RNA (mRNA) and protein and inhibited AR activity in a dose-dependent manner, while expression of AR protein and mRNA was reduced by 16MS7F1924. 16MS7F1924 induced mitotic catastrophe and apoptosis. Apoptotic cells were increased in a dose-dependent manner, and the apoptosis was mediated through the Akt pathway. Tumor growth was safely and significantly inhibited by both intraperitoneal and oral administration of 16MS7F1924 in vivo. Conclusion 16MS7F1924 had sufficient antitumor activity against androgen-sensitive and cabazitaxel-resistant PCa cells and may be useful as a novel therapeutic agent overcoming hormone- and chemoresistant PCas.

Background/aim Cabazitaxel is recommended as first-line treatment after docetaxel for metastatic castration-resistant prostate cancer. However, the efficacy, adverse events and prognostic factors associated with cabazitaxel are unclear. Patients and methods This single-centre retrospective study including 30 patients with CRPC treated with cabazitaxel between 2014 and 2020 investigated efficacy, outcomes and prognostic factors. Results Fourteen patients had visceral metastases. The median cabazitaxel dose was 20 mg/m2 The prostate-specific antigen response rate, time to prostate-specific antigen response, and overall survival were 13.3%, 3.48 months, and 7.92 months, respectively. The rates of grade 3 or more neutropenia and febrile neutropenia were 20% and 6.7%, respectively. By multivariate analysis, sarcopenia and visceral metastasis at the time of cabazitaxel initiation were independent and significant factors conferring a poor prognosis. Conclusion The early introduction of cabazitaxel, prior to the development of sarcopenia and visceral metastasis, might contribute to improved prognosis in CRPC.

During radical prostatectomy, the prostate is removed along with the seminal vesicles, and the urinary tract is reconstructed by dropping the bladder onto the pelvic floor and suturing the bladder and urethra together. This process causes damage to the pelvic floor and postoperative complications due to the anatomical changes in the pelvic floor caused by the vesicourethral anastomosis. Urinary incontinence and erectile dysfunction are major complications that impair patients’ quality of life after radical prostatectomy. In addition, the shortening of the penis and the increased prevalence of inguinal hernia have been reported. Since these postoperative complications subsequently affect patients’ quality of life, their reduction is a matter of great interest, and procedural innovations such as nerve-sparing techniques, Retzius space preservation, and inguinal hernia prophylaxis have been developed. It is clear that nerve sparing is useful for preserving the erectile function, and nerve sparing, urethral length preservation, and Retzius sparing are useful for urinary continence. The evaluation of pre- and postoperative imaging to observe changes in pelvic anatomy is also beginning to clarify why these techniques are useful. Changes in pelvic anatomy after radical prostatectomy are inevitable and, therefore, postoperative complications cannot be completely eliminated; however, preserving as much of the tissue and structure around the prostate as possible, to the extent that prostate cancer control is not compromised, may help reduce the prevalence of postoperative complications.

Background Visceral metastasis (VM), an important poor prognostic factor of prostate cancer (PC), is not commonly observed in castration sensitive status but is often observed after castration-resistant progression. However, the site, timing of emergence, and incidence of VM in castration-resistant patients have not yet been fully elucidated. Methods Demographic, surgical, pathological, and follow-up data of PC patients treated at Kanazawa University Hospital between January 2000 and December 2016 were retrospectively analyzed using their medical charts. From this data, risk factors of VM and survival of patients with VM were elucidated. Results Of 1364 patients, 21 (1.5%) had VM at diagnosis. Of 179 (13.1%) castration-resistant patients, 55 experienced emergence of new VM during treatment course. Incidence of new VM, especially nonlung, such as liver and adrenal metastases, increased significantly in proportion with the number of prescribed treatments. Multivariate analysis revealed that T stage, M stage, age, and treatment history with androgen receptor (AR) signaling-targeted agents and/or taxanes significantly increased the risk of VM. Compared with the group with VM at diagnosis, survival after diagnosis of VM following treatment was significantly shorter. Conclusion Although sequential use of new AR signaling-targeted agents and taxanes for castration-resistant PC (CRPC) is a standard treatment strategy, it often results in development of VM. Elucidating the mechanisms of VM are essential to improve survival in patients with CRPC.

A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of ≥ 7 and 273 had a GS of 24, PSA density ≥ 0.24 ng ml−2, positive findings on digital rectal examination, and transrectal with 90.0% sensitivity and 67.4% specificity. In this study, we found that raising the PSA cutoff to 12 ng ml−1 for CSPC in elderly individuals can significantly reduce unnecessary prostate biopsies. Furthermore, CSPC could be efficiently discovered by combining the four supplementary markers in patients with a PSA level of 4–12 ng ml−1. By performing this screening for elderly men over 75 years of age, unnecessary biopsies may be reduced and CSPC may be detected efficiently.

Background/aim This study aimed to assess the efficacy and toxicity of second-line chemotherapy, especially combination chemotherapy, for advanced or metastatic urothelial cancer. Patients and methods This retrospective analysis included patients who received second-line chemotherapy after disease progression during first-line chemotherapy between January 2009 to May 2018. Progression-free survival (PFS), overall survival (OS) and toxicity associated with second-line chemotherapy were assessed. Results In total 25 patients received second-line chemotherapy; 21 patients had combination chemotherapy and 4 had single-agent chemotherapy. Median PFS and OS were 3.6 months (range=0.2-23.5) and 11.9 months (range=0.5-29.0), respectively. Twenty patients (80%) exhibited grade 3 or more severe toxicities. Conclusion PFS and OS benefits of second-line combination chemotherapy corresponded to those of the phase 3 study of pembrolizumab, but adverse events were more severe. Pembrolizumab is potentially a better second-line treatment than combination chemotherapy.

Neuroendocrine prostate cancer (NEPC) is rare and has a poor prognosis; its clinical course and treatment outcomes are also unclear. This study investigated the clinical characteristics, clinical course, and treatment outcomes of patients with NEPC.This retrospective study investigated 14 patients histologically diagnosed with NEPC at Kanazawa University Hospital between 2000 and 2019. Overall survival (OS) and progression-free survival (PFS) were retrospectively analyzed using the Kaplan-Meier method. Additionally, log-rank tests were used to compare survival distributions.We included 14 patients histologically diagnosed with NEPC among 1,845 patients with prostate cancer. Four patients (0.22%) were diagnosed with de novo NEPC, and ten patients were diagnosed with NEPC during treatment. First-line platinum-based therapy's objective response rate (ORR) was 66.7%, and disease control rate was 91.7%; median PFS was 7.5 months. The median OS from NEPC diagnosis was 20.3 months. The median OS of the liver metastasis (-) group was 31.6 months, and that of the (+) group was 9.4 months (p=0.03, hazard ratio=0.24). The median OS of the somatostatin receptor scintigraphy (SRS)-positive group was 31.6 months, and that of the SRS-negative group was 10.6 months (p=0.04, hazard ratio=0.14).Platinum-based chemotherapy is effective to some extent, but the duration of response is not sufficient; therefore, new treatment options are needed. This is the first study to show that SRS findings and the presence of liver metastases might be prognostic predictors of NEPC.

We investigated whether coronavirus disease 2019 (COVID-19) vaccination and its adverse events would cause cancer treatment of patients with urological cancer to be postponed or changed.We collected COVID-19 vaccination information including adverse events from the medical records of 214 patients with urological cancer receiving cancer drug therapy.The cancer types were renal cancer in 40 cases (18.7%), upper urinary tract cancer in 10 cases (4.7%), bladder cancer in 21 cases (9.8%), prostate cancer in 140 cases (65.4%), and others in 3 cases (1.4%). Of the 214 patients, 178 (83.2%) had received the second dose of the vaccine. Out of 180 vaccinated patients, some adverse events were observed in 69 (38.3%). Vaccination rates for males and females were 85.4% (169/198) and 68.8% (11/16), respectively, and were not significantly different (p=0.081). The incidence of adverse events was significantly higher in females [72.7% (8/11)] than in males [36.1% (61/169)]; p=0.015. Treatment was modified in 11 vaccinated patients; postponed or changed at the discretion of the attending physician in 8 cases, skipped at the discretion of the patient in 1 case, and postponed due to side effects of the immune checkpoint inhibitor in 1 case. Treatment for one patient with upper urinary tract cancer on pembrolizumab was postponed for three weeks due to adverse events of the vaccine.Only 0.6% of the adverse events of the vaccine required postponement of treatment, suggesting that vaccination is safe even during cancer drug therapy.

It has been reported that chemotherapy drugs and granulocyte colony-stimulating factor (G-CSF) administered on the same day can aggravate neutropenia. In the present study, we investigated the safety of pegfilgrastim during bleomycin, etoposide, and cisplatin (BEP) therapy. This single-center retrospective study, including 137 cycles of BEP therapy for germ cell tumors between January 2008 and April 2021, investigated safety. Short-acting G-CSF was used for 84 cycles and pegfilgrastim was used for 53 cycles. In the pegfilgrastim group, neutrophil count at nadir was significantly higher than in the G-CSF group (median 1,650/μl and 680/μl, respectively). The incidence of grade 3–4 neutropenia was significantly higher and the duration longer in the G-CSF group. Also, there was no significant difference in the incidence of febrile neutropenia. In conclusion, concomitant use of pegfilgrastim during BEP therapy did not increase neutropenia and was effective in terms of safety.

Background/aim To evaluate the chronological changes in health-related quality of life and treatment satisfaction after robot-assisted radical prostatectomy (RARP). Patients and methods A total of 196 patients were included, and treatment satisfaction was evaluated using the Expanded Prostate Cancer Index Composite (EPIC) score before and at 1, 3, 6, and 12 months after RARP. Results At 12 months after RARP, 64.8% of patients were satisfied. On the contrary, 4.6% of patients were dissatisfied at 12 months after RARP. In a multivariate analysis, only urinary bother of EPIC was significantly associated with satisfaction at 12 months after RARP (p=0.025, odds ratio=1.029). Conclusion Treatment satisfaction with RARP was generally acceptable from 1 to 12 months after surgery and did not change over time. Urinary bother was associated with satisfaction at 12 months after RARP. Compared with the objective 24-hour pad test, questionnaires answered subjectively were more associated with satisfaction.

BACKGROUND Coffee inhibits the progression of prostate cancer; however, the direct mechanism through which coffee acts on prostate cancer cells remains unclear. This study aimed to identify the key compounds of coffee that possess anti-cancer effects and to investigate their mechanisms of action. METHODS The anti-proliferation and anti-migration effects of six potentially active types of coffee compounds, including kahweol acetate, cafestol, caffeine, caffeic acid, chlorogenic acid, and trigonelline hydrochloride, were evaluated using LNCaP, LNCaP-SF, PC-3, and DU145 human prostate cancer cells. The synergistic effects of these compounds were also investigated. Apoptosis-related and epithelial-mesenchymal transition-related proteins, androgen receptor in whole cell and in nucleus, and chemokines were assessed. A xenograft study of SCID mice was performed to examine the in vivo effect of coffee compounds. RESULTS Among the evaluated compounds, only kahweol acetate and cafestol inhibited the proliferation and migration of prostate cancer cells in a dose-dependent manner. The combination treatment involving kahweol acetate and cafestol synergistically inhibited proliferation and migration (combination index

Background: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) has different treatment outcomes across institutions, as seen in conventional TURBT. We retrospectively compared the difference in quality between the two types of endoscopic equipment used for PDD-assisted TURBT in our institution. Methods: This study enrolled 205 consecutive patients who underwent PDD-assisted TURBT. Patients were divided into two groups according to the endoscopic equipment used for PDD-assisted TURBT: Group A using the conventionally used endoscopic system and Aladuck LS-DLED and Group S using the Storz PDD system. Cystoscopy findings of white light (WL), fluorescence light (FL), and combination (positive if either WL or FL was positive) were recorded, and diagnostic quality of PDD was compared between both groups. Results: Group A had 105 cases and 336 specimens, while Group S had 100 cases and 361 specimens, with no significant differences between patient characteristics. The tumor sensitivities of WL, FL, and combination in Group A was 71.9%, 77.1%, 90.5%, respectively, while in Group S, these were 71.5%, 92.2%, 96.1%, respectively. Group S had significantly higher sensitivity of FL and combination than Group A, as well as higher detection of carcinoma in situ lesions. Conclusion: Both endoscopic systems had improved sensitivity with PDD-assistance versus WL only, with Group S having higher sensitivity. Differences in the quality of endoscopic equipment may influence the differences in treatment results with PDD-assisted TURBT across institutions.

Background/aim To investigate whether surgical margin (SM) status would affect the biochemical recurrence (BCR) after robot-associated RP (RARP). Patients and methods We evaluated BCR after RARP and the association between pre- and postoperative predictive factors and BCR. Results Positive SM (PSM) was observed in 97 out of 365 enrolled patients. On multivariate analysis, preoperative prostate specific antigen, biopsy Gleason score (GS), clinical stage, GS ≥7 at the PSM and pathological GS ≥7 were predictive factors for BCR. The 5-year BCR-free survival rate was 84.1% in the negative SM (NSM), 87.4% when GS=6 at the PSM, and 47.6% when GS ≥7 at the PSM. There was no statistically significant difference in BCR-free survival between the NSM group and GS=6 at the PSM group (p=0.966). Conclusion It would be desirable to evaluate GS at PSM when PSM is present in a specimen removed by RP.

Background: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.Methods: The study included 98 patients with advanced UC who were treated with pembrolizumab after platinum-based chemotherapy at eight hospitals. The efficacy, safety, and risk factors for prognosis were evaluated. Results: The median age was 73 years. Nineteen patients (19%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8–4.7) and 11.8 months (95% CI: 6.7–17.0), respectively. Poor PS, liver metastasis, and higher C-reactive protein were poor prognostic factors. Hyperprogression was observed in nine patients (9%), who were mostly of poor PS and had high-volume lesions. Severe adverse events (AEs) were observed in 18 patients (19%), and five patients died because of AEs (5%). Atypical AEs, such as pneumocystis pneumonia and acute myeloid leukemia, were observed in our cohort. Conclusion: The efficacy of pembrolizumab for advanced UC in our cohort was better than a previous phase III trial (KEYNOTE-045), possibly owing to lower cancer volume and fewer visceral metastases in our patients.

Background/aim Hypertension is a risk factor for occurrence of renal cell carcinoma; however, it remains unclear whether hypertension affects development and prognosis of renal cell carcinoma. This study evaluated the impact of hypertension on the progression of renal cell carcinoma. Patients and methods Renal cell carcinoma patients who were treated from October 2007 to December 2018 at our Institution were retrospectively analyzed. Results Of 462 patients, the number of patients with and without hypertension was 234 (including 227 treated with anti-hypertensive agents) and 228, respectively. The tumor size was significantly smaller in the hypertension group than in the non-hypertension group (median 32 and 45 mm, respectively, p=0.010). The 5-year cancer-specific and metastasis-free survival in the hypertension group were significantly better than those in the non-hypertension group (93.6% and 80.4%, and 84.6% and 73.0%, respectively, p=0.021 and p=0.017). Propensity score matching revealed significantly better metastatic-free survival in the hypertension group than the non-hypertension group (p=0.022). Conclusion Renal cell carcinoma patients with hypertension show better prognosis with low metastasis possibility.

Background/aim The best sequential treatment for castration-resistant prostate cancer (CRPC) remains unclear. This study evaluated the therapeutic effects of ethinylestradiol (EE) on CRPC. Patients and methods A total of 80 patients with CRPC, treated with 0.5-1.5 mg/day of EE, were retrospectively assessed. Results The median duration from the initial treatment to the beginning of EE was 48.3 months. A decline in the prostate-specific antigen (PSA) from the baseline was noted in 60 patients (75%) and a >50% PSA decline in 27 patients (34%). The median time of PSA progression, overall survival, and cancer-specific survival after EE were 5.60 months, 24.00 months, and 27.93 months, respectively. Conclusion EE administration for CRPC showed a relatively high PSA response regardless of timing of sequential treatment. The frequency of cardiovascular adverse events was not significantly high. EE administration is a potential treatment option for CRPC.

We appreciate Zins and Abraham [1] commenting on our paper studying the role of the CCL20-CCR6 axis on renal cell carcinoma (RCC) cells [2]. As they pointed out, our study has certain limitations. Although M1- and M2-types cannot be separated clearly and a consecutive change of character might exist between them, it has been reported that plural specific markers express on M1- and M2-types. Unfortunately, a definite difference between M1 and M2 macrophages was not confirmed in our study. For more differentiation, multiple stimulations, such as suggested in the comments of Zins and Abraham, might be needed. Hence, we needed to expediently use “M1-like” and “M2-like” to mention specific status of these macrophage-like cells. Meanwhile, CCL20 expression levels of M2-like-THP-1 cells co-cultured with RCC cells were dramatically increased compared with parental THP-1 cells, indicating that certain stimulations within the tumor microenvironment rather than theoretical stimulations make macrophages differentiated; however, further studies are needed to clarify this mechanism using a more appropriate co-culture system mimicking the tumor microenvironment. Immunohistochemistry of CCL20 and M2 markers will help to better understand the role of tissue infiltrating macrophages, even tissue CD68 staining intensity itself was reported to correlate with prognosis of RCC patients [3]. [...]

122 Background: Enzalutamide and abiraterone plus prednisolone demonstrated improvement of survival for castration-resistant prostate cancer (CRPC). However, it remains quite unclear which agent is better in terms of efficacy and safety for Asian patients. Methods: An investigator-initiated, multicenter, randomized controlled trial was conducted in Japan. CRPC patients before chemotherapy were randomly assigned to the enzalutamide or the abiraterone plus prednisolone arm (1:1). The primary endpoint is time to prostate-specific antigen (PSA) progression and secondary endpoints include PSA response rate (≥50% decline from baseline), overall survival, radiographic progression-free survival, and safety assessment. Results: Between February 20, 2015 and July 30, 2019, 203 patients were enrolled. After randomization, 92 in the enzalutamide and 92 in the abiraterone plus prednisolone arm were treated and analyzed. Time to PSA progression was not significantly different between arms (median 21.2 and 11.9 months in the enzalutamide and the abiraterone plus prednisolone arm, respectively; hazard ration 0.81, 95% CI 0.51-1.27, p = 0.1732). There was a significant difference in PSA response rate between arms (72% and 57% in the enzalutamide and the abiraterone plus prednisolone arm, respectively, p = 0.0425). There were no significant differences in overall and radiographic progression-free survival between arms (median 32.9 and 35.5months in the enzalutamide and the abiraterone plus prednisolone arm, respectively; hazard ration 1.17, 95% CI 0.72-1.88, p = 0.5290 and median 17.6 and 14.0 months in the enzalutamide and the abiraterone plus prednisolone arm, respectively; hazard ration 0.92, 95% CI 0.63-1.34, p = 0.6532). Grade ≥3 of adverse events were observed in 11% and 21% in the enzalutamide and the abiraterone plus prednisolone arm, respectively ( p = 0.1044). Conclusions: Enzalutamide did not show any survival benefits compared with abiraterone plus prednisolone but showed better PSA response rate with no significant differences of severe adverse event rate for Japanese CRPC patients. Our data suggest that antecedent use of enzalutamide to abiraterone plus prednisolone have potentially clinical benefits in Asian CRPC populations. Clinical trial information: UMIN000015529.

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial&ndash, mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial&ndash, mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial&ndash, mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial&ndash, mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.

Once castration-resistant prostate cancer (CRPC) become resistant for cabazitaxel treatment, the patients are obliged to best supportive care. Therefore, the elucidation of the mechanism of the cabazitaxel-resistance and the conquest are important themes to improve the prognosis of the patients. Then we tried to establish cabazitaxel-resistant CRPC cell lines and characterized them. We established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR from PC-3-TxR and DU145-TxR cell lines previously we established. PC-3-TxR/CxR and DU145-TxR/CxR cells became resistant for cabazitaxel by 11.8-fold and 4.4-fold, respectively. The TxR/CxR cells showed cabazitaxel-resistant using SCID mice in vivo. Although expression of multi-drug resistance gene 1 (MDR1) was up-regulated in DU145-TxR compared with DU145 cells, it was not up-regulated in DU145-TxR/CxR cells any more. In contrast, expression of MDR1 gene was up-regulated in PC-3-TxR compared with PC-3 cells and it was further up-regulated in PC-3-TxR/CxR compared with PC-3-TxR cells. Comparison of cDNA microarray between PC-3-TxR and PC-3-TxR/CxR cells or between DU145-TxR and DU145-TxR/CxR cells revealed that many genes were up-regulated or down-regulated. Finally, knockdown of MDR1 recovered the sensitivity to cabazitaxel not only in PC-3-TxR/CxR cells but also DU145-TxR/CxR cells. Together, regulation of MDR1 gene is important for conquest of the cabazitaxel-resistance.

Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling.

When advanced prostate cancer recurred during hormonal therapy and became the castration-resistant prostate cancer, "vintage hormonal therapy," such as antiandrogen alternating therapy or estrogen-related hormonal therapy, was widely carried out in Japan until 2013. This vintage hormonal therapy controlled the progression of castration-resistant prostate cancer. When castration-resistant prostate cancer relapses during these therapies, chemotherapy using docetaxel has been carried out subsequently. Since new hormonal therapies using abiraterone acetate and enzalutamide, which improve the prognosis of castration-resistant prostate cancer, became available in Japan from 2014, therapeutic options for castration-resistant prostate cancer have increased. Furthermore, the improvement of the further prognosis is promising by using cabazitaxel for docetaxel-resistant castration-resistant prostate cancer and radium-223 for castration-resistant prostate cancer with bone metastasis. An increase in therapeutic options gives rise to many questions, including best timing to use them and the indication. Furthermore, physicians have to consider the treatment for the recurrence after having carried out chemotherapy. We want to argue the difference in hormonal therapy between Japan and Western countries, and problems when carrying out new treatments, and the importance of imaging in the present review article. © 2017 The Japanese Urological Association., Embargo Period 12 months

Urachal cancer often presents at an advanced stage with poor prognosis due to the lack of an effective systematic therapeutic strategy. We experienced a case of metastatic urachal cancer treated effectively by combination chemotherapy and radiotherapy. A 55-year-old female presented to our department with right lower abdominal pain. A transurethral biopsy of an urachal tumor suggested urachal adenocarcinoma. The patient underwent chemotherapy with gemcitabine and cisplatin for metastatic urachal cancer. As tumor markers declined and the radiological findings indicated stability of disease, external beam radiotherapy was then administered to the primary site. Chemotherapy was then administered again in response to tumor markers gradually increasing and the progression of multiple peritoneal metastases. However, the patient did not complete chemotherapy due to hematological toxicity. The patient succumbed to primary disease 23 months after initial diagnosis. Previous studies have reported that the median time from the diagnosis of metastatic urachal cancer to mortality is just over 1 year. By contrast, in the present case the patient survived up to 2 years with combination chemotherapy and radiotherapy, a rare incidence worthy of reporting.

Background/aim This study aimed to evaluate the therapeutic effect of enzalutamide (ENZ) or abiraterone acetate (ABI) on bone metastasis in castration-resistant prostate cancer (CRPC), using bone scan index (BSI). Materials and methods Treatment outcomes for 31 patients who had undergone ENZ or ABI treatment were examined for CRPC with bone metastases. Cox proportional-hazards regression models were used to investigate the association between overall survival (OS) and clinical characteristics. Results Median OS after ENZ or ABI treatment was 29 months. Considering the flare phenomenon, BSI in 17 (55%) patients decreased following treatment. In multivariate analysis, low baseline BSI value and a decrease in BSI following treatment were associated with longer OS (hazard ratio [HR]=8.009; p=0.35 and HR=7.025; p=0.045*, respectively). Conclusion Low BSI value before ENZ/ABI treatment and a decrease in BSI following ENZ or ABI treatment are independent predictors of longer OS. BSI could be useful for risk assessment of CRPC patients with bone metastases.

BACKGROUND/AIM To evaluate our initial experience with radium-223 chloride (Ra-223). MATERIALS AND METHODS A total of 26 castration-resistant prostate cancer (CRPC) patients with bone metastases, treated with Ra-223 at our hospital were evaluated. This study aimed to observe adverse events (AEs) and changes in serum markers, and Bone Scan Index (BSI). Additionally, the relationship between these values and OS was investigated. RESULTS The observed AEs mainly included fatigue and nausea. Alkaline phosphatase (ALP) and bone-type alkaline phosphatase (BAP) levels decreased following the treatment; however, those of PSA and 1-CTP tended to increase, regardless of Ra-223 administration. Overall survival (OS) was significantly improved in cases with a baseline BSI value of

43 Background: ARTAs (enzalutamide and abiraterone) have been approved for relapse of prostate cancer in Japan since 2014. However, the efficacy of ARTAs for overall survival (OS) has not yet been proven in Japanese real-world clinical practice. Bone Scan Index (BSI), amount of bone metastasis in a unit of %, has become available for bone scintigraphy using software of BONENAVI (EXINIbone) in Japan. To confirm the benefit of BSI, we conducted a prospective observational study from 2012 to 2017 on mHSPC and mCRPC prior to docetaxel (presented at ASCO-GU 2020). Then we conducted this subanalysis to investigate the real-world benefit of ARTAs on OS before and after docetaxel. Methods: Patients enrolled as the mHSPC (N = 148) and mCRPC (N = 99) groups in the PROSTAT-BSI registry over a 3-year observation period were analyzed with or without ARTAs or flutamide. Patients were evaluated for PSA progression, BSI progression, and OS during hormonal therapy or chemotherapy. Results: In the mHSPC group, 123 patients were treated with combined androgen blockade (androgen deprivation + 80 mg bicalutamide) as an initial hormonal therapy. Thirty-seven patients were treated with flutamide after PSA progression. Thirty-seven patients were also treated with ARTAs as 2nd or later. Docetaxel was used in 25 patients. There was no significant difference in PSA (median: 265.5 and 248.0 ng/mL; P = 0.877) and BSI (median: 1.28% and 1.68%; P = 0.131) between the ARTA (-) and ARTA (+) groups at the start of hormonal therapy, respectively. Despite a median PSA-PFS disadvantage of 16 months in the ARTA (+) group compared to the ARTA (-) group (median: 8.9 and 25.2 months), OS of both groups were comparable (3-year survival rate: 84.0% and 75.7%; HR [95% CI]:0.556 [0.238-1.299], P = 0.232), respectively, indicating favorable effect of ARTA on OS. Furthermore, OS tended to be more extended in patients who received flutamide prior to ARTAs (N = 21) (HR [95% CI]:0.3175 [0.050-2.026], P = 0.225). In the mCRPC group, 8 patients who used ARTA prior to docetaxel were excluded from this analysis. ARTAs were used to treat relapse after docetaxel in 44 patients. Cabazitaxel was used in 14 patients. There was no significant difference in PSA (median: 16.8 and 26.8 ng/mL; P = 0.240) and BSI (median: 2.43% and 1.48%; P = 0.105) between the ARTA (-) and ARTA (+) groups at the start of docetaxel, respectively. There was no significant difference in PSA-PFS between the ARTA (-) and ARTA (+) groups (median PSA-PFS: 4.3 months and 7.0 months; P = 0.999), but OS was significantly better in the ARTA (+) group in the ARTA (-) group (median OS: 28.9 months vs 21.1 months; HR [95% CI]: 0.484 [0.264-0.888]; P = 0.019). Conclusions: This subanalysis demonstrates the benefit of ARTAs for OS before and after docetaxel in clinical practice.

Metastatic urothelial carcinoma is one of the most fatal urological malignancies. Cisplatin-based systemic chemotherapy is the standard treatment for metastatic urothelial carcinoma, and there is little evidence to support metastasectomy. The aims of the study were to evaluate the efficacy of metastasectomy and to investigate the prognoses of the patients. The study included 436 patients with urothelial carcinoma who were treated at our hospital. Of these, we included and retrospectively analyzed 29 patients who received curative treatment for the primary tumor and had been treated for metastases. Seven of these patients underwent metastasectomy. In a multivariate analysis, a serum C-reactive protein level before treatment for metastasis of

Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/androgen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary biomarker to PSA for prostate cancer. Our in vitro approach of enriching for prostate cancer cells with higher migration potential showed that CCL2 activated cellular migration. Importantly, we found that CCL2 levels were significantly different between men (n = 379) with and without prostate cancer. Patients with CCL2 ≥ 320 pg/mL had worse overall survival and prostate cancer -specific survival than those with CCL2 < 320 pg/mL. A novel risk classification was developed according to the risk factors CCL2 ≥ 320 pg/mL and PSA ≥ 100 ng/mL, and scores of 2, 1, and 0 were defined as poor, intermediate, and good risk, respectively, and clearly distinguished patient outcomes. CCL2 may serve as a novel biomarker for prostate cancer. The novel risk classification based on combining CCL2 and PSA is more reliable than using either alone.

Background/aim To evaluate the treatment outcomes, toxicity and health-related quality of life (HRQOL) in prostate cancer (PCa) patients who underwent single-fraction high-dose-rate brachytherapy (single-fraction HDR-BT) with external beam radiotherapy (EBRT). Materials and methods From April 2014 to October 2017, treatment outcomes and toxicity of 85 patients who underwent single-fraction HDR-BT of 13 Gy, followed by 46 Gy EBRT in 23 fractions, were examined. HRQOL of 53 patients was evaluated using the Expanded Prostate Cancer Index Composite (EPIC), International Prostate Symptom Score (IPSS)/QOL index, International Index of Erectile Function 5 (IIEF-5), and 36-Item Short Form Survey (SF-36) scores through one year. Results The median follow-up period was 28.8 months. Only three patients had biochemical recurrence. Toxicities included less than grade 3 lower urinary tract symptoms and grade 1 diarrhea. Urethral stricture, a problem related to late toxicity in conventional HDR-BT, was not observed. The urinary and bowel functions in EPIC scores significantly worsened until three or six months after treatment, respectively. Conclusion Single-fraction HDR-BT with EBRT showed promising biochemical control, tolerant toxicities, and preservation of HRQOL, and can be efficiently performed in a shorter time than conventional HDR-BT.

Background The present study was conducted to investigate whether baseline serum carbohydrate antigen (CA) 19-9 predicts prognosis or treatment effect in patients with advanced urothelial carcinoma (UC). Materials and methods We retrospectively analyzed data of patients diagnosed with locally advanced or metastatic or recurrent UC between April 2008 and November 2014. CA19-9 was determined using enzyme-linked immunosorbent assay (ELISA) and the relationship between CA19-9 and prognosis were analyzed. Results Of 40 patients, seven with CA19-9 ≤2 U/ml who were suspected of having Lewis A-negative blood type and two patients with advanced metastatic liver disease were excluded. UC-specific survival in metastatic disease significantly correlated with prognosis (p=0.018). Overall survival in patients with high serum CA19-9 demonstrated a significantly better prognosis than in those with low concentrations (log-rank test, p=0.032). Conclusion High baseline serum CA19-9 may predict a good prognosis in patients with advanced UC.

Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, developing resistance to cabazitaxel is a major challenge in patients with docetaxel-resistant and castration-resistant prostate cancer (CRPC) because cabazitaxel is often administered as a last resort. However, the mechanism by which cabazitaxel resistance develops is still unclear. C-C motif chemokine ligands (CCL) were shown to contribute to the castration resistance of prostate cancer cells via an autocrine mechanism. Therefore, we focused on CCL as key factors of chemoresistance in prostate cancer cells. We previously established a cabazitaxel-resistant cell line, DU145-TxR/CxR, from a previously established paclitaxel-resistant cell line, DU145-TxR. cDNA microarray analysis revealed that the expression of CCL2 was upregulated in both DU145-TxR and DU145-TxR/CxR cells compared with DU145 cells. The secreted CCL2 protein level in DU145-TxR and DU145-TxR/CxR cells was also higher than in parental DU145 cells. The stimulation of DU145 cells with CCL2 increased the proliferation rate under treatments with cabazitaxel, and a CCR2 (a specific receptor of CCL2) antagonist suppressed the proliferation of DU145-TxR and DU145-TxR/CxR cells under treatments of cabazitaxel. The CCL2-CCR2 axis decreased apoptosis through the inhibition of caspase-3 and poly(ADP-ribose) polymerase (PARP). CCL2 is apparently a key contributor to cabazitaxel resistance in prostate cancer cells. Inhibition of the CCL2-CCR2 axis may be a potential therapeutic strategy against chemoresistant CRPC in combination with cabazitaxel.

Background The effectiveness and safety of pegfilgrastim during bleomycin, etoposide and cisplatin (BEP) chemotherapy have not yet been investigated. Patients and methods Patients with germ cell tumors (GCTs) who received pegfilgrastim during BEP at the Kanazawa University Hospital between January 2014 and December 2016 were retrospectively analyzed. The frequency of adverse events and effectiveness in inhibiting neutropenia were compared between cycles using pegfilgrastim and those using filgrastim. Results Pegfilgrastim and filgrastim were administered in 13 and 22 cycles, respectively. The absolute neutrophil count at the nadir was significantly lower in patients receiving pegfilgrastim than in those receiving filgrastim (p=0.003). The duration of grade 2-4 neutropenia in cycles using filgrastim was significantly longer than that in those pegfilgrastim (p=0.01). No significant differences in the incidence of febrile neutropenia and serious adverse events were observed. Conclusion Pegfilgrastim can be safely and effectively administrated during BEP for patients with GCT.