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(Objective) We retrospectively analyzed clinical outcome, prognostic factors and adjuvant chemotherapy for bladder cancer patients with open radical cystectomy (ORC) combined with ileal conduit construction (ICC). (Patients and methods) From February 2005 to February 2019, 179 patients underwent ORC and ICC for invasive bladder cancer or BCG unresponsive non-muscle invasive bladder cancer. We investigated intraoperative and early postoperative complications, overall survival (OS), cancer-specific survival (CSS), and poor prognostic factors affecting OS. Furthermore, we evaluated the prognosis of patients with pT3,4 or pN1-3 depending on adjuvant chemotherapy. (Results) Clavien-Dindo Grade 4 or 5 complications were not occurred. The 5-year and 10-year OS probability were 71.1% and 57.4%, respectively, while the 5-year and 10-year CSS probability were 76.5% and 71.5%, respectively. Multivariate analysis revealed that male (HR = 2.70, 95%CI [0.97-7.51]), pT3,4 (HR = 1.83, 95%CI [1.05-3.21]), and pN1-3 (HR = 2.85, 95%CI [1.62-5.03]) were independent poor prognostic factors. Adjuvant chemotherapy significantly improved OS (p = 0.03) and CSS (p = 0.017) in pN1-3 patients. (Conclusion) ORC combined with ICC was an effective operative method, and good results were obtained. Adjuvant chemotherapy may be effective for patients with positive regional lymph nodes.

BACKGROUND Oligometastatic cancer has been suggested as an intermediate state between localized disease and wide-ranging metastases. The clinical significance of local treatment in oligometastatic prostate cancer (PCa) has been a recent topic of interest. However, standard definitions of oligometastasis are lacking. Here we studied risk factors among Japanese de novo oligometastatic patients with PCa. METHODS We retrospectively assessed clinical data from 264 patients, including locally advanced (T3 or T4N0M0) cancer, lymph-node-positive cancer (Tany N1M0), and cancer with ≤10 bone metastases. All patients received androgen deprivation therapy only. The number of bone metastases and clinical factors were evaluated in association with overall survival (OS) and progression-free survival (PFS). The Mann-Whitney U test, Cox proportional hazard models, and Kaplan-Meier methods were used as statistical analyses. RESULTS Median age, PSA at baseline and OS were 74 years, 55.2 ng/mL, and 129.0 months, respectively. The cutoff for the number of bone metastases having the greatest impact on OS was ≥3 (hazard ratio [HR]: 2.67; P = .0001). In multivariate analysis, non-regional lymph node (LN) metastases (HR: 2.15; P = .0222), ISUP grade group (GG) 5 (HR: 2.04; P = .0186) and ≥3 bone metastases (HR: 1.82; P = .0390) were independent predictors of OS. In risk classification based on these factors, OS and PFS were significantly classifiable into poor (2-3 factors), intermediate (1 factor), and good (no factors) risk groups (P

Background The effectiveness of cancer control is unclear after radical prostatectomy for patients with clinical T3 prostate cancer. Methods We retrospectively reviewed 1409 patients who underwent radical prostatectomy between April 2007 and December 2014, including 210 patients with cT3 prostate cancer. Nine patients who received neoadjuvant hormonal therapy and three patients who were lost to follow-up were excluded from the analysis. Clinical staging was performed by an experienced radiologist using preoperative magnetic resonance imaging findings. We analyzed the predictors of biochemical recurrence using Cox proportional hazard analyses. Results A total of 113 patients (57%) underwent radical retropubic prostatectomy and 85 patients (43%) underwent robot-assisted radical prostatectomy. The median follow-up period was 36 months. Downstaging occurred for 60 patients (30%), positive surgical margins were identified in 117 patients (59%), and biochemical recurrence was observed for 89 patients (45%). In the multivariate analyses, the independent preoperative predictors of biochemical recurrence were ≥50% proportion of positive biopsy cores [hazard ratio (HR): 2.858, P < 0.0001] and a biopsy Gleason score of ≥8 (HR: 1.800, P = 0.0093). The independent post-operative predictors of biochemical recurrence were positive surgical margins (HR: 2.490, P = 0.0018) and seminal vesicle invasion (HR: 2.750, P < 0.0001). Conclusions Among patients with cT3 prostate cancer, the percentage of positive biopsy cores and the biopsy Gleason score should be considered to select treatment. Compared with radical retropubic prostatectomy, robot-assisted radical prostatectomy may be a feasible treatment option in this setting.

We conducted a retrospective study to compare the perioperative course and lymph node (LN) counts of patients undergoing limited pelvic lymphadenectomy (lPLND) or extended pelvic lymphadenectomy (ePLND) during robot-assisted radical prostatectomy in an initial Japanese series. The cohort included 1333 patients who underwent either lPLND (n = 902) or ePLND (n = 431) during robot-assisted radical prostatectomy at five institutions in Japan. All complications within 28 days of surgery were recorded, and clinical data were collected retrospectively. The outcomes and complications were compared relative to the extent of lymphadenectomy, and we conducted univariate and multivariate logistic regression analyses to assess the predictors of the major complications. On multivariate analysis for evaluating the associations between major complications and perioperative characteristics, console time (p = 0.001) was significantly associated with major complications, although the extent of lymphadenectomy (p = 0.272) was not significantly associated with major complications. In the distribution of positive LNs removed in the extended pelvic lymphadenectomy cohort, 60.4% of patients had positive LNs only in the obturator/internal iliac region. However, 22.6% of the patients with positive LNs had no positive LNs in the obturator/internal iliac region, but only in the external/common iliac region. ePLND, which significantly increased the console time and blood loss but nearly quadrupled the lymph node yield, is considered a relatively safe and acceptable procedure. Moreover, the results of this study suggest that ePLND improves staging and removes a greater number of metastatic nodes.

The aim of this study was to establish the discriminating accuracy of Kanao’s pre-operative nomogram for renal cell carcinoma in predicting cause-specific survival among representative patients who underwent nephrectomy. Patients originated from two centers: Chiba University Hospital (n ¼ 151) and Chiba Cancer Center (n ¼ 91). We validated the predictive accuracy, which was assessed using Harrell’s concordance-index. The concordance-index values were 0.692 and 0.834 for Chiba University Hospital and Chiba Cancer Center, respectively, although it was 0.822 for the combined data sets. Results of external validation were different at each cohort. We constructed calibration plots of Kanao’s nomogram and confirmed the tendency at each institution. Inconsistency of results among two centers makes it difficult to reach a valid conclusion. Therefore, the predictive accuracy of Kanao’s nomogram was not settled. Clinicians need to confirm the predictive accuracy of Kanao’s nomogram and construct calibration plots when applying this nomogram to different patient populations.

We recently demonstrated efficient antitumor immunity against murine tumors using dendritic cells (DCs) activated by recombinant Sendai viruses (rSeVs), and proposed a new concept, “immunostimulatory virotherapy,” for cancer immunotherapy. However, there has been little information on the efficacy of this method in preventing metastatic diseases. In this study, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV (rSeV/dF) using a murine model of lung metastasis. Bolus and i.v. administration of DCs harboring rSeV/dF-expressing GFP without pulsation of tumor Ag (DC-rSeV/dF-GFP) 2 days before tumor inoculation showed efficient prevention against lung metastasis of c1300 neuroblastoma, but not of RM-9 prostatic cancer. We found that the timing of DC therapy was critical for the inhibition of pulmonary metastasis of RM-9, and that the optimal effect of DCs was seen 28 days before tumor inoculation. Interestingly, the antimetastatic effect was sustained for over 3 mo, even when administered DCs were already cleared from the lung and organs related to the immune system. Although NK cell activity had already declined to baseline at the time of tumor inoculation, Ab-mediated depletion studies revealed that CD4+ cells as well as the presence of, but not the activation of, NK cells were crucial to the prevention of lung metastasis. These results are the first demonstration of efficient inhibition of lung metastasis via bolus administration of virally activated DCs that was sustained and NK/CD4+ cell-dependent, and may suggest a potentially new mechanism of DC-based immunotherapy for advanced malignancies.

We previously reported the development of a prototype 'oncolytic Sendai virus (SeV) vector' formed by introducing two major genomic modifications to the original SeV, namely deletion of the matrix (M) gene to avoid budding of secondary viral particles and manipulation of the trypsin-dependent cleavage site of the fusion (F) gene to generate protease-specific sequences. As a result, the 'oncolytic SeV' that was susceptible to matrix metalloproteinases (MMPs) was shown to selectively kill MMP-expressing tumors through syncytium formation in vitro and in vivo. However, its efficacy has been relatively limited because of the requirement of higher expression of MMPs and smaller populations of MMP-expressing tumors. To overcome these limitations, we have designed an optimized and dramatically powerful oncolytic SeV vector. Truncation of 14-amino acid residues of the cytoplasmic domain of F protein resulted in dramatic enhancement of cell-killing activities of oncolytic SeV, and the combination with replacement of the trypsin cleavage site with the new urokinase type plasminogen activator (uPA)-sensitive sequence (SGRS) led a variety of human tumors, including prostate (PC-3), renal (CAKI-I), pancreatic (BxPC3) and lung (PC14) cancers, to extensive death through massive cell-to-cell spreading without significant dissemination to the surrounding noncancerous tissue in vivo. These results indicate a dramatic improvement of antitumor activity; therefore, extensive utility of the newly designed uPA-targeted oncolytic SeV has significant potential for treating patients bearing urokinase-expressing cancers in clinical settings.

Although transperineal (TP) prostate biopsy is growing in popularity, its safety has not been evaluated based on extensive studies. We prospectively assessed the adverse events associated with transrectal ultrasound (TRUS)-guided TP 16-core prostate biopsy at a single institution. We enrolled 2,086 males who underwent first-time TRUS-guided TP prostate biopsy under lumbar spinal anesthesia at Chiba Cancer Center between 2009 and 2013. Eight adverse events were assessed prospectively using a purpose-designed questionnaire. The prevalence and duration of all adverse events were evaluated. We performed subgroup analyses for hematuria and urinary retention in relation to clinical factors. Questionnaires were collected from 1,663 cases (79.7 %). The cancer detection rate was 53.5 % in all patients. The prevalence and duration of complications were as follows: hematuria, 73.4 % and 4.51 ± 2.88 days; perineal bleeding, 7.1 % and 2.20 ± 2.24 days; hematospermia 14.4 %; dysuria, 15.7 % and 3.12 ± 2.71 days; urinary tract pain, 49.5 % and 2.43 ± 2.08 days; perineal pain, 35.5 % and 3.53 ± 2.59 days; fever ≥37 °C, 1.7 % and 1.79 ± 1.72 days; and headache, 22.1 % and 3.40 ± 2.10 days. Seventeen patients (1.1 %) required indwelling urethral catheterization for grade 2 urinary retention. Pre-biopsy International Prostate Symptom Score (p = 0.014) was an independent related factor for hematuria. Prostate volume (p = 0.001) was an independent related factor for grade 2 urinary retention. TRUS-guided TP prostate biopsy under lumbar spinal anesthesia can be performed safely with only minor adverse events.

To investigate the therapeutic outcomes of neoadjuvant and concurrent androgen-deprivation therapy and intensity-modulated radiation therapy with gold marker implantation for intermediate- and high-risk prostate cancer.This was a retrospective study of 325 patients with intermediate- or high-risk prostate cancer according to the National Comprehensive Cancer Network guidelines who underwent androgen-deprivation therapy and intensity-modulated radiation therapy (76 Gy) after gold marker implantation between 2001 and 2010.The 5-year distant metastasis-free survival rate was significantly lower for very high-risk patients than for intermediate- and high-risk patients (82.6% vs 99.4% and 96.5%, respectively; P 0.01). The 5-year biochemical relapse-free survival rates significantly declined with increasing prostate cancer risk (P 0.01), and were 95.9%, 87.2%, and 73.1% for the intermediate-risk, high-risk and very high-risk patients, respectively. Acute genitourinary and gastrointestinal toxicity grade ≥3 were not observed in any of the patients. Late grade 3 genitourinary toxicity occurred in 0.3% of patients.Combination androgen-deprivation therapy and 76-Gy intensity-modulated radiation therapy with gold marker implantation offers good therapeutic outcomes with few serious complications in patients with intermediate- and high-risk prostate cancer.

We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan-Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20 months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high-grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median progression-free survival times were 4.1 and 11.3 months (P = 0.031), and median overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective.

The incidence of prostate cancer in the Japanese population has increased because of the increase in life expectancy, consumption of westernized diets, and improvements in prostate cancer screening by using the prostate-specific antigen (PSA)test. Further, in the past 10 years, there have been great advancements in the treatment options available for prostate cancer. Radical treatment methods, such as robot-assisted surgery, intensity-modulated radiation therapy, and particle beam radiation therapy, may have anticancer effects and may improve the quality of life by preserving micturition ability and sexual function. Radiotherapy and endocrine therapy have been shown to prevent postoperative recurrence. Endocrine therapy has been demonstrated to be effective in preventing recurrence after radiotherapy. Moreover, endocrine therapy can be administered to patients at all stages of prostate cancer and is often used as the initial treatment for advanced prostate cancer, particularly in patients with metastasis. However, recurrence(relapse)after endocrine therapy is associated with a poor prognosis. In this study, we describe all the available treatment options for prostate cancer and the treatable and untreatable forms of recurrent prostate cancer.

We examined the effect of neoadjuvant hormonal therapy (NHT) on biochemical failure. We retrospectively analyzed 146 high-risk prostate cancer patients (clinically (c), T1c-3N0M0) who underwent radical prostatectomy between June 2002 and March 2008. Thirty-eight patients were treated with NHT for ≥2 months (NHT group), and 108, with surgery alone (SA group). The study population comprised 89 cT1c-2N0M0 patients and 57 cT3N0M0 patients, and pathologically (p), 66 pT0-2N0M0 patients and 76 pT3N0M0 patients. Downstaging was noted in 36.4 and 0% of cT1c-2N0M0 patients and in 74.1 and 20.0% of cT3N0M0 patients in the NHT and SA groups, respectively. For both cT1c-2N0M0 and cT3N0M0 patients, the downstaging rate was significantly higher in the NHT group than in the SA group (p＜0.01). Positive resection margin rates were significantly lower in the NHT group (34.2%) than in the SA group (65.7%) (p＜0.01). The overall prostate-specific antigen (PSA) progression-free rate did not differ significantly between the 2 groups in both pT0-2N0M0 and pT3N0M0 patients. However, in pT0-2N0M0 patients with negative resection margins, the 5-year PSA progression-free rate was significantly lower in the NHT group than in the SA group (p＜0.01), whereas this rate did not differ significantly between the groups in both pT0-2N0M0 and pT3N0M0 patients with positive resection margins. Although NHT seemed to have some effect on downstaging, its pathological effects could be underestimated. Thus, NHT was considered to have no significant effect on biochemical failure.

The aim of the present study was to compare the accuracy of three prognostic models in predicting recurrence-free survival among Japanese patients who underwent nephrectomy for non-metastatic renal cell carcinoma (RCC). Patients originated from two centers: Chiba University Hospital (n = 152) and Chiba Cancer Center (n = 65). The following data were collected: age, sex, clinical presentation, Eastern Cooperative Oncology Group performance status, surgical technique, 1997 tumor-node-metastasis stage, clinical and pathological tumor size, histological subtype, disease recurrence, and progression. Three western models, including Yaycioglu's model, Cindolo's model and Kattan's nomogram, were used to predict recurrence-free survival. Predictive accuracy of these models were validated by using Harrell's concordance-index. Concordance-indexes were 0.795 and 0.745 for Kattan's nomogram, 0.700 and 0.634 for Yaycioglu's model, and 0.700 and 0.634 for Cindolo's model, respectively. Furthermore, the constructed calibration plots of Kattan's nomogram overestimated the predicted probability of recurrence-free survival after 5 years compared with the actual probability. Our findings suggest that despite working better than other predictive tools, Kattan's nomogram needs be used with caution when applied to Japanese patients who have undergone nephrectomy for non-metastatic RCC.

The objective of the present study was to document the treatment efficacy and safety of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). A retrospective analysis of 50 consecutive patients with metastatic RCC between January 2005 and December 2009 was carried out. Patients received sorafenib after failed cytokine therapy or first-line sorafenib treatment. All received 400 mg of sorafenib orally twice daily. Five of 14 patients with bone metastases were also given bisphosphonates. Tumor response was evaluated every 1-2 months according to the Response Evaluation Criteria in Solid Tumors. Adverse events (AE) were evaluated at each visit during and after treatment, and were recorded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. Dose modification of sorafenib was permitted if grade 3 or 4 AE occurred. Treatment continued until disease progression or treatment intolerance occurred. Partial response, and stable disease as best objective responses were observed in 11 (22%) and 23 (46%) patients, respectively. Median progression-free survival was 7.3 months and median overall survival was 11.9 months. All patients experienced AE and one or more grade 3/4 AE occurred in 43 of 50 (86%) patients. Although it requires close monitoring, sorafenib treatment seemed to be effective in the present study population.

Objective: To determine the association between obesity and prostate cancer in Japanese recurrence after primary treatment with radical prostatectomy. Methods: The subjects were 173 Japanese patients with prostate cancer who had been treated with radical prostatectomy at Chiba University Hospital between April 1997 and March 2007. Clinicopathological characteristics and biochemical recurrence outcomes after radical prostatectomy were compared between the three body mass index cohorts. Results: Mean body mass index was 23.4 kg/m 2 with a standard deviation of 2.4, and mean follow-up period was 37.4 months. Operative time was longer and estimated blood loss was much more in obese patients. Patients with pT3� had significantly higher serum prostatespecific antigen, total cholesterol levels, Gleason’s sum and positive of surgical margin than pT2 patients. Recurrence rate was significantly higher in the 26.5 kg/m 2 and hyperlipidemia groups in pT3� patients. Conclusions: Obesity is an independent predictor of disease recurrence in Japanese patients with pT3� prostate cancer who underwent radical prostatectomy. Obese patients who underwent radical prostatectomy require vigilant follow-up care.

Purpose Single-agent interferon (IFN) is no longer regarded as a standard option for first-line systemic treatment of metastatic renal cell carcinoma (RCC) in Western countries. However, some patients with favorable-risk RCC may still achieve complete and long-lasting remission in response to IFN treatment. The present study compared favorable-risk Japanese patients with metastatic RCC Japanese patients who had been treated with IFN or tyrosine kinase inhibitor (TKI) therapy as a first-line systemic therapy. Materials and methods From 1995 to 2014, a total of 48 patients with favorable risk as defined by the Memorial Sloan Kettering Cancer Center criteria who did not receive adjuvant systemic therapy were retrospectively enrolled in this study. We assessed the tumor response rate, progression-free survival (PFS), and overall survival (OS). Results The objective response rate for first-line therapy was 29% in the IFN group and 47% in the TKI group, but this difference did not reach the level of statistical significance. Median OS for IFN and TKI was 71 and 47 months, respectively (p=0.014). Median first-line PFS for IFN and TKI was 20 and 16 months, respectively (no significant difference). First-line IFN therapy did not prove inferior to TKI therapy in terms of OS according to metastatic sites. Conclusions IFN is associated with a survival benefit in Japanese patients with favorable-risk metastatic RCC in the era of targeted therapy. Further prospective study is needed.

Background Limitations of the clinical efficacy of dendritic cell (DC)-based immunotherapy, as well as difficulties in their industrial production, are largely related to the limited number of autologous DCs from each patient. We here established a possible breakthrough, a simple and cytokine-based culture method to realize a log-scale order of functional murine DCs (>1,000-fold), which cells were used as a model before moving to human studies. Methodology/Principal Findings Floating cultivation of lineage-negative hematopoietic progenitors from bone marrow in an optimized cytokine cocktail (FLT3-L, IL-3, IL-6, and SCF) led to a stable log-scale proliferation of these cells, and a subsequent differentiation study using IL-4/GM-CSF revealed that 3-weeks of expansion was optimal to produce CD11b+/CD11c+ DC-like cells. The expanded DCs had typical features of conventional myeloid DCs in vitro and in vivo, including identical efficacy as tumor vaccines. Conclusions/Significance The concept of DC expansion should make a significant contribution to the progress of DC-based immunotherapy.