Absorption of the orally active multikinase inhibitor axitinib as a therapeutic index to guide dose titration in metastatic renal cell carcinoma.

Purpose Axitinib is an orally active multikinase inhibitor currently used to treat patients with metastatic renal cell carcinoma (RCC). This study examined the pharmacokinetics of axitinib and the relationship between peak drug concentration (Cmax) and clinical outcomes in real-world practice. Methods Twenty patients with metastatic RCC treated with axitinib monotherapy were enrolled. Post-dose (1-4 h) blood samples were obtained, and axitinib Cmax in plasma was measured by liquid chromatography-tandem mass spectrometry. Efficacy endpoints were best overall response (per RECIST 1.1) and progression-free survival (PFS). The safety endpoint was the cumulative incidence of dose-limiting toxicities (DLTs). Results Large inter- and intra-individual variability in dose-adjusted Cmax was observed (0.02-11.2 ng/mL/mg). Axitinib absorption was significantly influenced by glucuronidation activity (P = 0.040). Cmax at steady state was significantly higher in responders than in non-responders (P = 0.013). The optimal Cmax cutoff to predict a clinical response was 12.4 ng/mL. The median PFS was significantly longer in patients who achieved an average steady state Cmax above the threshold than in those who did not (799 vs. 336 days; P = 0.047). The cumulative incidence of DLTs was significantly higher in patients with Cmax ≥ 40.2 ng/mL than in other patients (sub-hazard ratio, 4.13; 95% confidence interval, 1.27-13.5; P = 0.019). Conclusions The potential therapeutic window of axitinib Cmax in metastatic RCC was estimated at 12.4-40.2 ng/mL. Pharmacokinetically guided dose titration using therapeutic drug monitoring may improve the efficacy and safety of axitinib, warranting further investigation in a larger patient population.

Pharmacokinetically guided dosing has the potential to improve real-world outcomes of pazopanib.

It remains unclear whether therapeutic drug monitoring (TDM) of pazopanib improves treatment outcomes in routine clinical practice. We did a prospective cohort study to evaluate the benefits of TDM for pazopanib therapy in real-world practice. Among 25 patients with pharmacokinetically guided dosing, only 5 (20%, 95% confidence interval 6.8-40.7%) discontinued treatment because of adverse events. However, 5 (41.7%, 95% confidence interval 15.2-72.3%) of historical controls including 12 patients not receiving such a strategy experienced adverse events leading to early termination. PK-guided dosing significantly increased median time-to-treatment discontinuation (252 vs 74 days, P = .012) with reduced toxicity and improved overall survival (not reached vs 313 days, P = .002) relative to conventional dosing in the control group. In conclusion, PK-guided dose adaptation through the use of TDM has the potential to improve treatment outcomes of pazopanib in routine clinical practice, warranting larger, randomized studies.

Long-term persistence with mirabegron in a real-world clinical setting.

OBJECTIVES: To examine the long-term persistence rate with mirabegron in a real-world clinical setting. METHODS: We retrospectively collected the data of patients who were prescribed mirabegron. We investigated the persistence rate and the reason for the discontinuation. The analysis included patient's age, diagnosis, Overactive Bladder Symptom Score, prostatic volume, the prescription by specialists for lower urinary tract dysfunction, drug-naïve patients, replacement of antimuscarinics or add-on therapy to antimuscarinics. RESULTS: A total of 556 patients were included. Among them, 401 patients (72%) had overactive bladder and the other 155 (28%) were categorized as having other storage symptoms. During the observation period, 170 patients (42%) with overactive bladder discontinued mirabegron. The reasons for discontinuation in patients with overactive bladder included unmet expectation of treatment (45 patients, 26%), any adverse events (38 patients, 22%) or symptom improvement (37 patients, 22%). The persistence or discontinuation was not related with age, Overactive Bladder Symptom Score, prostatic volume or the prescription by specialists, while older male patients tended to continue mirabegron. The 3-year persistence rates in female and male overactive bladder patients were 46% and 51%, respectively, and these were better than those in patients with storage symptoms without urgency. In female overactive bladder patients, the persistence rate with mirabegron used as add-on therapy to antimuscarinics was higher than that in the drug-naïve patients on the Kaplan-Meier curve. CONCLUSIONS: The present study shows a relatively good long-term persistence rate with mirabegron in overactive bladder patients, notwithstanding the retrospective study in an academic hospital. The combined treatment with antimuscarinics could result in a good persistence rate with mirabegron.

Diagnostic Efficacy of Percutaneous Renal Tumor Biopsy - Concomitant Use of Frozen Section to Accurately Diagnose Renal Tumor with Necrosis.

OBJECTIVES: To evaluate the diagnostic efficacy of percutaneous renal tumor biopsy. METHODS: We retrospectively investigated 23 patients who underwent percutaneous renal tumor biopsy since 2008 at Department of Renal and Urologic Surgery, Asahikawa Medical University Hospital. We examined indications of biopsy, diagnostic concordance rate between urologists, radiologists and biopsy findings, pathological findings and biopsy-related complications. RESULTS: Renal tumor biopsy was performed under ultrasonography guidance in 21 patients and computed tomography guidance in 2. The most frequent indication to perform biopsy was to determine histological subtype of renal cell carcinoma(RCC)before treatment. The second indication was to clarify the nature of renal tumor. Biopsy findings revealed RCC in 17 patients and urothelial carcino- ma(UC)in 6. Diagnostic concordance rate between urologist's diagnosis and biopsy findings was 91%(21/23), which showed the same result between radiologists and biopsy findings. Biopsy-related adverse event included needle tract implantation in 1 patient with UC. Another patient who had central necrosis in the tumor showed insufficient material causing repeat biopsy with frozen section. Except this patient, initial renal tumor biopsy was successful in all patients by concomitant use of frozen section for tumor with central necrosis. The overall diagnostic rate of initial biopsy was 95.7%(22/23). CONCLUSIONS: Despite a small number of patients and a retrospective nature, the present study shows that renal tumor biopsy plays an important role in diagnosis of renal tumor. Concomitant use of frozen section might be considered at the time of renal tumor biopsy in patients with necrotic renal tumor to avoid repeat biopsy. However, we should take into consideration that there are some possible risks of needle tract implantation in cases with UC when we perform percutaneous renal tumor biopsy.

[Clinical Significance of Primary Tumor Resection in Patients with Metastatic Urothelial Carcinoma at Initial Presentation].

We retrospectively reviewed 67 patients who presented with metastatic urothelial carcinoma to the Department of Urology, Asahikawa Medical University Hospital between 2000 and 2013. Furthermore, 13 patients with comparatively longer survival (2 years or longer after diagnosis) were analyzed to find any clinical characteristics among these patients. The primary site was the upper tract in 41 patients and bladder in 26. The most frequent metastatic site was regional lymph nodes (49 patients), followed by viscera (36 patients) and distant lymph nodes (17 patients). Primary tumor resections were performed on 83% of the patients with only regional lymph node metastasis, but on only 35% of the patients with distant metastasis. Median overall survival (OS) of patients was 8.5 months in this series. Median OS of patients with only regional lymph node metastasis was 15 months, which was significantly longer than that (8 months) of patients with distant metastasis. Multivariate analysis revealed only regional lymph node metastasis and the number of metastatic sites were significant prognostic factors for OS. We further investigated the clinical characteristics of 13 patients with comparatively longer survival. Other than a small number of metastatic sites (1 or 2) and no distant lymph node metastasis, we could not find any significant characteristics to predict longer prognosis. The present study showed that primary tumor resection did not have a significant benefit on survival in patients with metastatic urothelial carcinoma at initial presentation. However, primary tumor resection should be considered when there is only regional lymph node metastasis and few metastatic sites.

[Successful Management by Immunoglobulin for Sunitinib-Induced Thrombocytopenia in a Patient with Advanced Metastatic Renal Cell Carcinoma].

An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-week-on, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×10(9)/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.

[A Case Report of Suspected Tuberculous Granuloma in the Kidney after BCG Perfusion Therapy for Urothelial Carcinoma of the Renal Pelvis].

A 66-year-old male patient was referred to our hospital for bilateral renal pelvic tumors. Ureteroscopic biopsy revealed urothelial carcinoma (UC) of low grade (G1) of the renal pelvis. Renal sparing treatment with systemic chemotherapy and percutaneous tumor resection was performed. However, during subsequent follow up, a recurrent tumor was found on the left ureter. After ureteroscopic laser ablation of the tumor, Bacillus Calmette-Guerin (BCG) perfusion therapy (once a week, total 6 weeks) was performed via a single J ureteral catheter with no adverse events. Later, another recurrent recurrence was found on the right ureter, and was managed by ureteroscopic laser ablation followed by BCG perfusion therapy via a single J ureteral catheter. However, the patient developed high fever with chill from the day after initial BCG perfusion therapy on the right side. Although we started antibiotics, high fever continued. Then antituberculous drugs were administered and his condition was improved. Computed tomographic scan revealed a right renal mass 57 mm in diameter, which was consistent with tuberculous granuloma. The tuberculous granuloma persisted despite the continuation of anti-tuberculous drugs. In exceptional cases of upper tract UC such as single kidney and bilateral tumor, BCG perfusion therapy has been used as adjunctive treatment to cure or prevent UC. However, dosages and administration methods of BCG perfusion therapy for upper tract UC still remain to be standardized. Serious adverse events after BCG perfusion therapy require prompt and proper management including the use of anti-tuberculous drugs.

Combination of GnRH Antagonist Degarelix and Antiandrogen Is Effective in PSA Reduction and Bone Management in Patients with Prostate Cancer.

OBJECTIVES: To investigate the efficacy of combination treatment of degarelix and antiandrogen in patients with prostate cancer. METHODS: We prospectively investigated the efficacy of combination treatment of degarelix and antiandrogen in 12 patients with treatment-naive prostate cancer. We surveyed PSA, LH, FSH and testosterone at day 3, 7, 14 and 28 during the initial month and thereafter once a month for 1 year. In cases with bone metastasis, we analyzed serum bone markers such as alkaline phosphatase(ALP), bone-type ALP and carboxyterminal telopeptide of type- I collagen once a month. Skeletal related events (SREs) were also monitored. RESULTS: PSA progression free survival was 65%. PSA was reduced from baseline by 80% at day 14 and by 93% at day 28. In all patients serum testosterone immediately reached castrate level at day 3 and was maintained for 1 year without breakthrough escape. Both LH and FSH were reduced to within normal range at day 3. In contrast, all bone markers temporarily increased at day 28, and thereafter decreased. Although 2 patients had suffered from SREs before treatment, there were no SREs after combination treatment. CONCLUSIONS: The present study showed that combination of degarelix and antiandrogen could lead to favorable PSA reduction and immediate castrate level at an earlier phase. However, further study is needed to compare the difference between degarelix monotherapy and these combinations.

[Perioperative complications of transurethral resection of bladder tumor in patients receiving antithrombotic therapy].

We examined perioperative complications of transurethral resection of bladder tumor (TURBT) in patients receiving antithrombotic therapy. We retrospectively studied 276 patients who underwent TURBT in our institute from January 2007 to March 2013. The study group consisted of 105 patients (38%) who were receiving antithrombotic agents, and the other 171 patients (62%) without antithrombotic agents were assigned to the control group. The period of discontinuation of antithrombotic agents complied with our institutional rule. The most frequently used agent was aspirin (69 patients : 66%), followed by warfarin (25 patients : 24%). Fourteen patients receiving warfarin (56%) needed heparin bridging therapy. There was no significant difference in average operative time (51 minutes versus 54 minutes), or average days to removal of urethral catheter (3.7 days versus 3.3 days) between the study and control groups. Hemorrhagic and ischemic complications were noted in 11 (10.5%) and 2 (1.9%) patients in the study group and 11 (6.4%) and none (0%) of the patients in the control group, respectively, with no significant difference between the 2 groups. However, prevalence of hemorrhagic complications in patients receiving heparin bridging therapy (21.4%) was significantly higher than that in the control group. Ischemic complications in the study group included chest pain suggestive of angina in one patient and acute myocardial infarction leading to death in another patient. We should pay attention to hemorrhagic complications in patients receiving heparin bridging therapy and keep in mind the possibility of lethal ischemic complications after discontinuation of antithrombotic agents.

Characterization of human CD4 helper T cell responses against Aurora kinase A.

Aurora kinase A (Aurora-A) is a cell cycle-associated serine-threonine kinase that is overexpressed by various types of cancer and is highly associated with poor prognosis. Since the expression of Aurora-A in normal tissues has been shown to be significantly lower as compared to tumor cells, this protein is being considered as a potential tumor-associated antigen for developing immunotherapies. The goal in the present study was to identify CD4 helper T lymphocyte (HTL) epitopes for Aurora-A for the design of T cell-based immunotherapies against Aurora-A-expressing tumors. Synthetic peptides corresponding to potential HTL epitopes were identified from Aurora-A and used to stimulate CD4 T lymphocytes in vitro to generate antigen-specific HTL clones that were evaluated for antigen specificity, MHC restriction and for their ability to interact with Aurora-A-expressing tumor cells. The results show that two peptides (Aurora-A(161-175) and Aurora-A(233-247)) were effective in generating HTL responses that were restricted by more than one MHC class II allele (i.e., promiscuous responses). The CD4 HTL clones were able to directly recognize Aurora-A-expressing tumor cells in an antigen-specific and MHC class II-restricted manner and some of the clones displayed cytolytic activity toward Aurora-A + tumor cells. Both of these peptides were capable of stimulating in vitro T cell responses in patients with bladder cancer.

Six-transmembrane epithelial antigen of the prostate as an immunotherapeutic target for renal cell and bladder cancer.

PURPOSE: T-cell based immunotherapy for renal cell and bladder cancer is one of the most promising therapeutic approaches. STEAP is a novel cell surface protein that is over expressed in various cancers, including renal cell and bladder cancer. Recently we induced STEAP specific helper T lymphocytes that recognize the naturally processed STEAP peptide epitopes STEAP(102-116) and STEAP(192-206) arising from STEAP expressing tumor cells. Thus, STEAP may be a useful tumor associated antigen for designing T-cell based immunotherapy. We determined whether STEAP could induce anti-cellular immune responses to urological cancer. MATERIALS AND METHODS: We selected 2 previously described STEAP derived epitope peptides, STEAP(102-116) and STEAP(192-206), and examined their ability to elicit helper T-lymphocyte responses by in vitro vaccination of CD4 T lymphocytes from healthy individuals and patients with cancer. RESULTS: STEAP peptides induced helper T-lymphocyte responses using lymphocytes from healthy individuals that directly recognized STEAP expressing, DR positive renal cell and bladder cancer cells, and autologous dendritic cells pulsed with STEAP expressing tumor cell lysates in a major histocompatibility complex class II restricted manner. These peptides also stimulated T-cell responses in patients with renal cell or bladder cancer. Each STEAP peptides behaved as a promiscuous T-cell epitope, in that they stimulated T cells in the context of multiple major histocompatibility complex class II alleles. CONCLUSIONS: Results show that STEAP helper T-lymphocyte epitopes could be used to optimize T-cell based immunotherapy against STEAP expressing renal cell and bladder cancer.

Focal adhesion kinase as an immunotherapeutic target.

BACKGROUND: Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine kinase involved in cancer progression and metastasis that is found overexpressed in a large number of tumors such as breast, colon, prostate, melanoma, head and neck, lung and ovary. Thus, FAK could be an attractive tumor associated antigen (TAA) for developing immunotherapy against a broad type of malignancies. In this study, we determined whether predicted T cell epitopes from FAK would be able to induce anti-tumor immune cellular responses. METHODS: To validate FAK as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and melanoma patients. RESULTS: Two synthetic peptides, FAK(143-157) and FAK(1,000-1,014), induced HTL responses that directly recognized FAK-expressing tumor cells and autologous dendritic cells pulsed with FAK-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK peptides were recognized by melanoma patient's CD4 T cells, this is indicative that T cell precursors reactive with FAK already exist in peripheral blood of these patients. CONCLUSIONS: Our results provide evidence that FAK functions as a TAA and describe peptide epitopes that may be used for designing T cell-based immunotherapy for FAK-expressing cancers, which could be used in combination with newly developed FAK inhibitors.

Recognition of prostate and melanoma tumor cells by six-transmembrane epithelial antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen class II-restricted manner.

The six-transmembrane epithelial antigen of prostate (STEAP) protein is an attractive candidate for T cell-based immunotherapy because it is overexpressed in prostate cancer and various other tumor types. Several peptide epitopes capable of stimulating CTLs that killed STEAP-expressing tumor cells have been described. Our goal was the identification of helper T lymphocyte (HTL) epitopes of STEAP for the optimization of T cell-based immunotherapies against STEAP-expressing malignancies. Candidate HTL epitopes for STEAP were predicted using in silico algorithms for HLA class II-binding peptides and were tested for their ability to elicit HTL responses by in vitro peptide vaccination of CD4 T lymphocytes from healthy individuals and prostate cancer patients. Two peptides (STEAP(102-116) and STEAP(192-206)) were effective in stimulating in vitro antitumor HTL responses in both normal individuals and prostate cancer patients. Notably, both STEAP HTL peptides behaved as promiscuous T-cell epitopes because they stimulated T cells in the context of more than one MHC class II allele. These newly described STEAP HTL epitopes could be of value for the design and optimization of T cell-based immunotherapy against STEAP-expressing tumors.

[A case of infected renal cyst suspected of originating from retrograde infection].

A 63-year-old man who had undergone Miles' operation for rectal cancer in another hospital was referred due to a high fever and renal failure. Abdominal computed tomographic (CT) scan revealed metastatic liver tumor, paraaortic lymph node swelling, bilateral hydronephrosis and a left simple renal cyst located at the lower pole. Bilateral ureteral stenting was undertaken for relieving ureteral obstruction. Serum creatinine and high fever improved immediately. However, at 11 days after the ureteral stenting the high fever recurred. CT scan and ultrasonography revealed persistent left hydronephrosis and a change of left simple renal cyst into infected cyst. After an exchange of left ureteral stent and percutaneous pus drainage from the left infected renal cyst, high fever declined immediately. A review of the literature suggests that this is the 100th case report of infected renal cyst in Japan. We discuss the clinical features, etiology, imaging study and treatment of infected renal cyst.

[Multiple paraganglioma of the urinary bladder].

A 77-year-old woman who was treated for malignant melanoma was incidentally found to have a bladder tumor on a screening computed tomography (CT). On CT and magnetic resonance imaging (MRI), the tumor was detected as a well-enhanced tumor (4 x 5 cm at horizontal plane) on the left side of the bladder wall. Cystoscopy revealed a small non-papillary pedunculated tumor on the posterior wall and a submucosal tumor on the left side of the wall. We performed transurethral resection of the tumor on the posterior wall and biopsy of the tumor on the left side wall. The pathological diagnosis was paraganglioma of the urinary bladder. Serum and urine levels of noradrenaline and dopamine were elevated. 123I-metaiodobenzylguanidine (MIBG) scintigraphy showed a significant uptake on the left side of the bladder. Blood pressure was normal at rest but elevated after micturition. No pelvic lymph node swelling or distant metastasis was detected. We performed partial cystectomy for the tumor on the left side wall. After operation, serum catecholamine level was normalized and post-voiding fatigue that was present before operation disappeared. Six months after operation, a followup CT revealed a small well-enhanced tumor on the anterior wall of the bladder. Her serum noradrenaline level was slightly elevated. However, she was normotensive and had no symptoms. Therefore, a careful follow-up continued for 2 years there after has revealed no increase in tumor size and no symptoms.

Case report of renal pelvic adenocarcinoma associated with a renal stone that produced carbohydrate antigen 125 and carbohydrate antigen 19-9.

A 68-year-old man underwent left side simple nephrectomy for symptomatic severe hydronephrosis with decreased function due to a renal stone. Because of severe adhesion around the kidney, the renal pelvic wall was torn during the operation. Pathological diagnosis was papillary adenocarcinoma of the renal pelvis with positive staining for carbohydrate antigen 125 (CA125) and carbohydrate antigen 19 9 (CA19-9). Retrospective analysis of preoperative blood sample showed a high level of CA125 and CA19-9. Four-cycle adjuvant chemotherapy with paclitaxel/carboplatin (TJ regimen) was performed. However, local recurrence developed 1 month after the termination of chemotherapy. Although papillary adenocarcinoma of the renal pelvis is extremely rare, the possibility of renal pelvic tumor should be kept in mind for patients who have a long-standing renal stone and hydronephrosis with irregularity at the renal pelvic wall. CA125 and CA19-9 can be useful markers for upper urinary tract tumor.

[Histological investigation of prostate cancer treated with hormonal agents].

The histological diagnosis of prostate cancer treated with hormonal agents is often difficult because of various morphological changes induced by androgen ablation. Immunostaining of cytokeratins may be useful to prevent the underdetection of cancer cells. We examined prostatic specimens with histological diagnosis of 11 pTO patients who had undergone neoadjuvant endocrine therapy followed by radical prostatectomy. Anti-cytokeratin antibody, AE1/AE3 was used to detect the prostatic epithelial cells. Anti-cytokeratin antibody, 34/3 E12 was used to detect the prostatic basal cells. The loss of basal cells indicates the acini to be cancer. The immunostaining with these antibodies revealed that 2 out of 11 cases had residual cancer and were not pTO. The immunostaining of cytokeratins was useful to detect the residual prostatic cancer after endocrine therapy.

[Indication of repeat prostate biopsy for the diagnosis of prostate cancer].

There is no standard criterion for repeat prostate biopsy in cases with a negative initial biopsy. We retrospectively analyzed our experience of repeat prostate biopsy to establish its indication for the diagnosis of prostate cancer. From April 1997 to March 2005, 35 consecutive patients underwent repeat prostate biopsy at the department of Urology, Asahikawa Medical College Hospital because of clinically suspicious prostate cancer despite a negative initial biopsy. We compared patients' age, number of cores obtained during repeat biopsy, digital rectal examination findings, total prostate volume, the time from the first to the last biopsy, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity between cancer-positive and cancer-negative groups. Prostate cancer was detected in 17 of 35 patients (49%). Fifteen patients with prostate cancer were diagnosed by the first repeat biopsy and other 2 patients were diagnosed by the second repeat biopsy. A statistically significant difference was only noted in age and PSA density. Persistently elevated total PSA and a higher PSA density in cases with a negative initial biopsy might be a good indication of repeat prostate biopsy for the diagnosis of prostate cancer.

[Clinical significance of cystoscopy in transrectal prostate biopsy].

The clinical significance of cystoscopy in patients with benign prostatic hyperplasia or prostate cancer remains open to discussion. We have always performed cystoscopy with prostate biopsy and have discovered bladder cancer in some patients. The present study investigated the clinical significance of performing cystoscopy with prostate biopsy. Subjects were 458 patients who underwent cystoscopy and ultrasound-guided transrectal prostate biopsy from January 1998 to December 2004. Mean age of subjects was 71.3 years (range, 52-93 years). Prostate biopsy was performed modified Eskews systematic 5-region prostate biopsy (12 core). Some abnormalities were found in 43 of the 458 patients (9.3%). Among these 43 patients, bladder cancer was found in 11 patients (2.4%), and transurethral resection bladder tumor (TUR-Bt) was performed on all 11 patients. Pathological staging of bladder cancer was pT1 and G2 in all cases. Bladder stones were seen in 13 patients (2.8%), benign bladder tumor in 5 patients (1.1%), urethral polyp in 7 patients (1.5%), urethral stenosis in 6 patients (1.3%) and ureteral stones associated with ureterocele in 1 patient (0.2%). Appropriate examinations and treatments were performed for all cases. Cystoscopy may be needed at the time of prostate biopsy because: the above-mentioned abnormalities were first discovered on cystoscopy; and the frequency of bladder cancer was 2.4% for the total patient population, and endoscopic surgery was performed.