Kazuro Kikkawa

Squamous Cell Carcinoma of the Urachus Producing Granulocyte Colony-Stimulating Factor

Urachal carcinoma is a rare cancer. This is the first report of a case of squamous cell carcinoma of the urachus producing granulocyte colony-stimulating factor. The patient underwent partial cystectomy with urachal remnant resection and pelvic lymphadenectomy. No evidence of tumor recurrence or metastasis was found at 17 months after surgery.

Dendritic cells with transduced survivin gene induce specific cytotoxic T lymphocytes in human urologic cancer cell lines.

OBJECTIVES To investigate whether survivin-specific cytotoxic T lymphocytes (CTLs) could be induced by dendritic cells (DCs) transduced with survivin gene by adenoviral vector, and whether these CTLs would display cytotoxic activities against human urologic cancer cell lines. Survivin, a member of the inhibitor of apoptosis protein family, is expressed in most malignancies, but not in normal tissue. METHODS Adenoviral vector encoding the human survivin gene was generated. Human DCs from healthy donors were transduced with human survivin gene by infection with adenoviral vector encoding the human survivin gene using the centrifugal method. Survivin-specific CTLs were induced from autologous peripheral blood mononuclear cells by DCs transduced with the survivin gene. The ability of CTLs to lyse cancer cell lines was assessed using the (51)Cr-release assay. RESULTS DCs transduced with survivin gene could induce survivin-specific CTLs against various urologic malignancies such as bladder, kidney, and prostate cancer cells. This cytotoxic activity could be blocked by anti-CD8 and anti-major histocompatibility complex class I antibodies. We also found that this cytotoxic activity was specific for the survivin protein and human leukocyte antigen haplotype. CONCLUSIONS DCs transduced with the survivin gene induced potent survivin-specific CTL responses in vitro. This suggests that cancer immunotherapy targets for survivin might offer a novel approach to treating various urologic cancers.

Prognostic factors and risk stratification in patients with castration-resistant prostate cancer receiving docetaxel-based chemotherapy

BackgroundWhile novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy.MethodsThis study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis.ResultsPSA response ≥50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS.ConclusionsAge, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival.

External validation of European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment scoring models to predict recurrence and progression in Japanese patients with non‐muscle invasive bladder cancer treated with bacillus Calmette–Guérin

To validate two prediction models (European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment) for recurrence and progression of non‐muscle invasive bladder cancer in Japanese patients who underwent bacillus Calmette–Guérin instillation therapy.

Bacillus Calmette‐Guérin cell‐wall skeleton enhances the killing activity of cytotoxic lymphocyte‐activated human dendritic cells transduced with the prostate‐specific antigen gene

To determine whether dendritic cells (DC) transduced with the prostate‐specific antigen (PSA) gene can induce PSA‐specific cytotoxic lymphocytes (CTL) against prostate cancer cells, and whether bacillus Calmette‐Guérin (BCG) cell‐wall skeleton (CWS) can enhance the maturation of DC‐PSA and the killing activity of subsequently induced PSA‐specific CTL.

Impact of age on quality of life in patients with localized prostate cancer treated with high‐dose rate brachytherapy combined with external beam radiotherapy

To evaluate age‐related quality of life changes in patients with localized prostate cancer treated by high‐dose rate brachytherapy combined with external beam radiation therapy.

Zoledronic acid prevents decreases in bone mineral density in patients with prostate cancer undergoing combined androgen blockade

The aim of this study was to evaluate the effect of zoledronic acid (ZA) on bone mineral density (BMD) in patients with prostate cancer receiving combined androgen blockade (CAB) as a first-line androgen deprivation therapy. Patients receiving CAB for prostate cancer without bone metastasis were candidates for this study. Forty-two patients were randomly assigned to receive either ZA or no treatment. BMD were measured at baseline and at 12 months. Bone-turnover markers, including cross-linked N-telopeptide of type I collagen (NTX), C-telopeptide of type I collagen (ICTP), and bone-specific alkaline phosphatase (BAP), were assessed during study periods. Patients on ZA maintained BMD after a year of treatment. Change in T-score from baseline differed significantly between the two groups (P=0.009). An inverse correlation was demonstrated between baseline and change in T-score in the ZA group. While ZA prevented an increase in ICTP and BAP, the increase in NTX was suppressed only in patients with low baseline T-score. ZA prevented a decrease in BMD in patients undergoing CAB, especially those with lower baseline BMD.

Overexpression of ribonucleotide reductase subunit M1 protein predicts shorter survival in metastatic bladder cancer patients treated with gemcitabine‐containing combination chemotherapy

To identify biomarkers predicting prognosis in bladder cancer patients undergoing the gemcitabine and cisplatin regimen.

Enzalutamide Versus Abiraterone as a First-Line Endocrine Therapy for Castration-Resistant Prostate Cancer: Protocol for a Multicenter Randomized Phase 3 Trial

Background Recent large-scale randomized studies have demonstrated that 2 new hormone preparations (abiraterone and enzalutamide) prolong survival in docetaxel-treated or -naïve castration-resistant prostate cancer patients. However, no studies have directly compared antitumor effects between these 2 agents, and no clear guidelines are available for choosing between them. Objective The objective of this clinical study is to compare antitumor effects and adverse events between abiraterone and enzalutamide by allocating castration-resistant prostate cancer patients deemed not indicated for docetaxel treatment to receive either of the 2 agents. Methods This study is an open-label, comparative study allocating castration-resistant prostate cancer patients to abiraterone or enzalutamide treatment arms (allocation factors: age <70 vs ≥70 years, and presence vs absence of metastases) and assessing the treatment results. Each arm will contain 25 patients. On confirmation of prostate-specific antigen failure or progression on imaging, patients undergo crossover to receive the alternative study drug. The primary end point is prostate-specific antigen response rate (percentage of patients with a decrease in prostate-specific antigen level by ≥50%) in the abiraterone and enzalutamide treatment arms. Results Recruitment started in May 2016, and 13 patients have been recruited so far. We expect to complete enrollment by December 2020. Conclusions Recently, cross-resistance between abiraterone and enzalutamide has been an issue of focus. Urologists thus tend to prefer docetaxel rather than sequential therapies using 2 hormonal preparations after the progression of a first hormonal preparation. From that perspective, our clinical trial is rather out of fashion. Nevertheless, we assume that many patients receive hormonal sequential therapy in the actual clinical setting, since most such patients cannot receive chemotherapeutic agents due to old age or poor performance status. This is why we are attempting this randomized clinical trial comparing abiraterone versus enzalutamide. We will try to identify which drug is suitable for initial hormonal therapy among castration-resistant prostate cancer patients who do not meet the indications for docetaxel therapy in terms of not only antitumor effect, but also adverse events and quality of life. Trial Registration University Hospital Medical Information Network UMIN000022102; https://upload.umin.ac.jp /cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025463 (Archived by WebCite at http://www.webcitation.org/70xaQfGlJ)

MP64-14 SIMPLE PROGNOSTIC MODEL FOR HIGH-RISK PROSTATE CANCER AFTER RADICAL PROSTATECTOMY

Patients were categorized into three risk groups: 1) men with N1 disease (N1), 2) men without N0, but who had either pT3 stage, RP Gleason score 8, lymphovascular invasion or tertiary Gleason 5 pattern (N0 high-risk [HR]) and 3) men with no high-risk features at RP (N0IR). Decipher scores were obtained from 263 RP specimens and 25 matching biopsy specimens. Fisher’s exact test was used to compare the difference in patient risk groups. Logistic regression analysis was used to evaluate performance of Decipher for prediction of LNI. Discrimination of the Partin tables ( 2%) and combined model of Partin tables ( 2%) and Decipher (>0.6) was assessed using c-index. Concordance of biopsy and RP Decipher (lowand intermediatevs high-risk) was also assessed. RESULTS: Of the 263 men, 42 (16.0%), 98 (37.2%) and 123 (46.8%) men were categorized as N1, N0HR and N0IR risk groups, respectively. Partin tables classified 34/42 (81%) N1, 70/98 (71%) N0HR and 66/123 (54%) N0IR men as high clinical risk ( 2%) for LNI (p1⁄40.0012). Decipher classified 23/42 (55%) N1, 34/98 (35%) N0HR and 35/123 (29%) N0IR as high genomic risk (>0.6) for metastasis (p1⁄40.013). After adjusting for Partin Tables, Decipher high genomic risk had an odds ratio of 2.3 (95% CI 1.2-4.5) as a predictor of LNI (p1⁄40.02). Addition of Decipher to Partin Tables improved the c-index from 0.60 (95%CI 0.530.67) to 0.66 (95%CI 0.57-0.75). The concordance of Decipher risk groups between matched Biopsy and RP specimens was 84%. CONCLUSIONS: Decipher may be an important adjunct tool to improve preoperative staging that may be useful for prioritizing intermediate risk patients to ePLND. Further investigation of Decipher biopsy specimens is required to validate these findings.