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To clarify the diagnostic performance of the three-dimensional reconstructed virtual image (3D-RVI) in evaluating RENAL nephrometry score (RENAL-NS).This study included 130 patients who underwent preoperative contrast-enhanced computed tomography followed by partial nephrectomy for renal tumors suggestive of renal cell carcinoma. RENAL-NS was calculated prior to the surgery, and tumor resection was performed referring to the score. We retrospectively reviewed preoperative contrast-enhanced computed tomography images. We calculated the inter-observer variability of RENAL-NS using 3D-RVI vs two-dimensional (2D) imaging and compared the ability of RENAL-NS using 3D-RVI vs 2D imaging to predict the risk of opening of the urinary collecting system. We also compared the two modalities for the time required to evaluate RENAL-NS.RENAL-NS evaluated using 3D-RVI showed a higher inter-observer agreement compared to 2D-imaging (rUsing 3D-RVI improves the accuracy, reliability and efficiency of RENAL-NS evaluation in preoperative assessment and can play an important role in preoperative assessment and intraoperative navigation.

ObjectiveTo compare renal function (RF) outcomes after bladder-preserving tetramodal therapy against muscle-invasive bladder cancer (MIBC) to those after radical cystectomy (RC).MethodsThis study included 95 patients treated with tetramodal therapy consisting of transurethral bladder tumour resection, chemoradiotherapy and partial cystectomy (PC) and 300 patients treated with RC. The annual change in the estimated glomerular filtration rate (eGFR) was compared using the linear mixed model. Renal impairment was defined as a >25% decrease from the pretreatment eGFR, and renal impairment-free survival (RIFS) was calculated. The association between treatment type and renal impairment was assessed.ResultsThe number of patients who received neoadjuvant chemotherapy was 8 (8.4%) in the tetramodal therapy group and 75 (25.0%) in the RC group. After the inverse probability of treatment weighting adjustments, the baseline characteristics were balanced between the treatment groups. The mean eGFR before treatment in tetramodal therapy and RC groups was 69.4 and 69.6 mL/min/1.73 m2 and declined with a slope of −0.7 and −1.5 mL/min/1.73 m2/year, respectively. The annual deterioration rate of post-treatment eGFR in the tetramodal therapy group was milder than in the RC group. The 5-year RIFS rate in the tetramodal therapy and the RC groups was 91.2 and 85.2%, respectively. Tetramodal therapy was an independent factor of better RIFS compared with RC.ConclusionsRF was better preserved after tetramodal therapy than after radical therapy; however, even after tetramodal therapy, the eGFR decreased, and a non-negligible proportion of patients developed renal impairment.

Enzalutamide is a novel, non-steroidal anti-androgen that has demonstrated excellent anti-tumor activity for both non-metastatic and metastatic castration-resistant prostate cancer (nmCRPC and mCRPC) patients, and that is being rapidly introduced into clinical practice in Japan.We retrospectively investigated the treatment efficacy, safety profile, and prognostic factors of enzalutamide over a relatively long observation period in Japanese patients with nmCRPC and mCRPC.The medical records of 184 consecutive Japanese patients with nmCRPC and mCRPC who started enzalutamide treatment in our institution between January 2012 and April 2018 were reviewed. Efficacy and safety profiles were assessed and statistically analyzed.Among these 184 patients, 44 (23.9%) nmCRPC patients, 89 (48.4%) docetaxel-naïve mCRPC patients, and 51 docetaxel-pretreated (27.7%) mCRPC patients underwent enzalutamide therapy. The median prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS) periods for nmCRPC patients were 39.2 months and not reached; those for docetaxel-naïve mCRPC patients were 16.5 months and 59.8 months; and those for docetaxel-pretreated mCRPC patients were 7.0 months and 30.4 months, respectively. Multivariate analysis identified performance status ≥ 2, PSA 8.89 ng/mL (median value), hemoglobin lower limit of normal range, neutrophil to lymphocyte ratio 3.0, and 4-week PSA decline 50% as the predictive factors for shorter OS. Our respective prognostic models using these factors successfully demonstrated distinctly separated survival curves (p 0.001). In addition, among these patients, 30 (16.3%) experienced adverse events and 16 (8.7%) experienced adverse events resulting in the discontinuation of therapy. Fatigue (14%) and appetite loss (7%) were the most common such events.Both the survival period and risk factors were extracted from a relatively long-term observation period. Since enzalutamide was approved for administration to patients with castration-sensitive prostate cancer earlier this year (2020), we believe that the data presented here will be useful for both physicians and patients in clinical practice.

Background/aim To evaluate the efficacy and toxicity of paclitaxel, gemcitabine, and cisplatin (TGP) as second-line treatment for advanced urothelial carcinoma (UC). Patients and methods This study comprised advanced UC progressed after first-line cisplatin-based chemotherapy. Advanced UC was defined as a non-resectable (T4b, any N or any T, or N2-3) or metastatic disease. Twenty-one patients were included in this study. TGP was administered every 3 weeks. The primary endpoint was objective response rate (ORR); the secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. Results The ORR with TGP was 23.8%; the median PFS and OS were 4 and 8.4 months, respectively. The primary side effect was myelosuppression. Grade 3-4 neutropenia and thrombocytopenia were observed in 71.4% and 42.9%, respectively. There were no toxic deaths. Conclusion TGP is moderately effective and tolerable as second-line chemotherapy for patients with UC.

Introduction: In spite of the high incidence of infectious complications (ICs), appropriate duration of antimicrobial prophylaxis (AMP) for radical cystectomy (RC) with intestinal urinary diversion (IUD) has not been established. We compared the incidence of ICs after RC with IUD in patients using only intraoperative AMP or extended duration AMP. Risk factors for ICs were also investigated. Patients and Methods: One hundred twenty-three consecutive patients who underwent RC with IUD were divided into 2 groups based on the AMP duration (intraoperative only vs. extended duration for a median of 3 days). Between the groups, the incidence of ICs was compared. Risk factors for ICs were investigated in multivariate analysis. Results: The IC rate was 44%. No significant difference was found in the rate of ICs between the groups. The IC rate was significantly higher in patients with lower estimated glomerular filtration rate (eGFR). Rates of ICs were 60 and 38% in patients with eGFR of less than 60 and equal or more than 60 mL/min/1.73 m2, respectively. Conclusions: Our result indicates that AMP that is administered more than intraoperatively may be excessive in RC with IUD. Patients with a lower eGFR should be particularly cared for postoperative ICs.

Background We aimed to establish an external validation of the Briganti 2019 nomogram in a Japanese cohort to preoperatively evaluate the probability of lymph node invasion in patients with high-risk, clinically localized prostate cancer. Methods The cohort consisted of 278 patients with prostate cancer diagnosed using magnetic resonance imaging-targeted biopsy who underwent radical prostatectomy and extended pelvic lymph node dissection from 2012 to 2020. Patients were rated using the Briganti 2019 nomogram, which evaluates the probability of lymph node invasion. We used the area under curve of the receiver operating characteristic analysis to quantify the accuracy of the nomogram. Results Nineteen (6.8%) patients had lymph node invasion. The median number of lymph nodes removed was 18. The area under the curve for the Briganti 2019 was 0.71. When the cutoff was set at 7%, 84 (30.2%) patients with extended pelvic lymph node dissection could be omitted, and only 1 (1.2%) patient with lymph node invasion would be missed. Sensitivity, specificity, and negative predictive values at the 7% cutoff were 94.7, 32.0, and 98.8%, respectively. Conclusion This external validation showed that the Briganti 2019 nomogram was accurate, although there may still be scope for individual adjustments.

OBJECTIVES To evaluate the efficacy and safety profiles of first-line etoposide, ifosfamide and cisplatin and primary prophylaxis with pegfilgrastim as first-line chemotherapy for disseminated germ cell cancer. METHODS This study reviewed 154 consecutive patients with previously untreated disseminated germ cell cancer who received first-line etoposide, ifosfamide and cisplatin between 1995 and 2020. Of these, 54 patients were managed with primary prophylaxis using pegfilgrastim (primary prophylaxis group), and 100 were managed with the therapeutic use of short-acting granulocyte colony-stimulating factor (non-primary prophylaxis group). RESULTS The International Germ Cell Cancer Collaborative Group classification identified 90 (58%)/40 (26%)/24 (16%) patients with good/intermediate/poor prognosis, respectively. Overall, 139 patients (90%) were disease free after etoposide, ifosfamide and cisplatin with/without post-chemotherapy surgery. The median relative dose intensity of etoposide, ifosfamide and cisplatin was 96%, and there was a significant difference between the primary prophylaxis and non-primary prophylaxis groups (100% vs 90%, P

Background To assess the prophylactic efficacy of postoperative single intravesical instillation with pirarubicin (THP) and mitomycin C (MMC) for low-risk non-muscle-invasive bladder cancer (NMBC). Patients and methods A total of 103 clinically low-risk NMBC patients were preoperatively randomized into either THP (n=49) or MMC (n=54) groups. The primary endpoint was recurrence-free survival. Results The median follow-up periods of the THP and MMC groups were 955 and 1008 days, respectively (p=0.76). Twelve patients (24.5%) in the THP group and 7 (13%) in the MMC group had bladder cancer recurrences. The two-year recurrence-free survival of the THP group and the MMC group was 77.8% and 86.4%, respectively (p=0.20). Neither groups had severe toxicity. Conclusion In low-risk NMBC, the prophylactic effect against postoperative single intravesical instillation with THP was not superior to that with MMC.

Background Second-line salvage therapy for patients with metastatic germ-cell cancer (GCC) after the first-line combination of VIP (etoposide, ifosfamide, cisplatin) therapy has not been established. This study evaluated the efficacy and tolerability of the TGP (paclitaxel, gemcitabine, cisplatin) combination chemotherapy as a second-line salvage therapy. Patients and Methods The medical records of 16 consecutive patients with metastatic GCC who had been treated with first-line VIP therapy followed by second-line TGP therapy between 2005 and 2019 were reviewed and statistically analyzed. Ten patients, excluding the 6 patients treated with TGP without unequivocal progression, were included in the efficacy analysis. All 16 patients were included in the safety analysis. Results The median follow-up period from initial TGP administration was 78 months (interquartile range, 46-120 months). The estimated 5-year progression-free and overall survival rates for the 10 patients in the efficacy analysis were 70% and 100%, respectively. Grade 3/4 hematologic toxicity occurred in all 16 patients, but none developed uncontrollable infections or life-threatening bleeding. One patient died of treatment-related secondary leukemia, however. Conclusion The present study is to our knowledge the first to examine the therapeutic outcomes and safety profile of second-line TGP chemotherapy. VIP followed by TGP might be an alternative first- and second-line conventional regimen for patients with metastatic GCC in this granulocyte colony-stimulating factor era, especially for patients at a high risk of bleomycin-induced pulmonary toxicity.

Historically, gastric metastasis from renal cell cancer (RCC) has been extremely rare. As RCC is now being treated with various agents of targeted therapy, however, the rate of unusual visceral metastases might increase as outcomes improve and follow-up periods grow longer. Here we present a valuable case of gastric metastasis from RCC detected in a routine CT scan during sequential targeted therapy. A 73-year-old man was referred to our hospital, presenting with left renal cell cancer with multiple lung metastases at stage cT1bN0M1. He received first-line targeted therapy consisting of sunitinib and subsequently underwent left radical nephrectomy. He then underwent sequential therapy consisting of interferon-alpha, sunitinib, everolimus, and axitinib for multiple lung metastases. Five years after nephrectomy, a follow-up computed tomography scan revealed a 2.2 × 1.6 cm mass in the stomach without any symptoms. Gastrointestinal endoscopy disclosed a polypoid lesion at the gastric fundus. Endoscopic submucosal resection was performed. Microscopic diagnosis revealed gastric metastasis from RCC. As various new therapeutic agents increase survival periods for metastatic RCC patients in this era of targeted therapy, clinicians must watch for metastasis in the stomach, though this was formerly a rare event.

Background To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). Methods A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. Results The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). Conclusions Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Objectives: To analyze the incidence and predictors of deep vein thrombosis (DVT) in patients with elevated D-dimer prior to surgery for urologic malignancy. Methods: Between January 2015 and September 2017, 987 consecutive patients underwent surgery for urologic malignancy under general anesthesia in our institution. Of these, 191 patients underwent preoperative venous ultrasonography of the lower extremities for DVT due to elevated D-dimer. We analyzed the incidence and predictors of DVT in these patients. Results: The median age was 69 years. DVT was detected in 18% of patients (35/191). Multivariate analysis showed that the primary site of urologic malignancy (p < 0.01) and older age (p Conclusions: DVT was found in 18% of patients with elevated D-dimer prior to surgery for urologic malignancy. Bladder cancer patients and older patients in whom D-dimer has been elevated should undergo careful early examination for DVT.

Background In order to help in selecting the optimum bone-modifying agent (BMA; zoledronic acid or denosumab), we investigated the impact of the BMA on the renal function of patients with bone metastases. Materials and methods The present study consisted of 118 patients who were treated with denosumab for bone metastases secondary to prostate cancer, renal cell cancer, and urothelial cancer at our hospital between 2012 and 2015. The clinical course of the renal function of these patients, treated with zoledronic acid or denosumab, was retrospectively evaluated. Results Of the 118 patients who were treated with denosumab during the study period, 57 (48 %) had previously been administered zoledronic acid and 61 (52 %) had received denosumab as the first-line BMA. The reasons for changing from zoledronic acid to denosumab were increased creatinine serum level (26 patients, 46 %), patient preference (16 patients, 28 %), difficulty with venous infusion (10 patients, 17 %), and other reasons (5 patients, 9 %). The median level of creatinine clearance in the patients who changed from zoledronic acid to denosumab due to increased serum creatinine level was 59.9 ml/min before administration of zoledronic acid, 40.9 ml/min at the beginning of denosumab treatment, 47.5 ml/min at 3 months after administration of denosumab, and 52.0 ml/min at the last follow-up. There were significant differences. Conclusions For the first time, we demonstrated that the renal function of some patients, which had deteriorated following zoledronic acid administration, successfully improved after changing to denosumab.

The outcome of treatment of Japanese patients with urachal cancer is not well known. The purpose of this study is to clarify the characteristics and outcomes of Japanese patients with urachal cancer. The medical records of patients with urachal cancer who were treated in our hospital between 1994 and 2014 were retrospectively reviewed and statistically analyzed. We found 28 patients who had been diagnosed with urachal cancer and treated in our hospital during the study period. The median age of these patients was 52.3 years [interquartile range (IQR), 46.0–56.8 years]. Seventeen patients underwent surgery in our department. The median observation period of these patients was 42.6 months (IQR, 21.1–49.7 months). Among patients who had undergone surgery, cancer recurred in 7 (41 %). The estimated median time from surgery to recurrence and overall survival (OS) period were 35.8 months [95 % confidence interval (CI), 7.7 months–not determined] and not reached, respectively. Seventeen patients received chemotherapy for metastatic disease. The estimated median OS time from initial metastasis was 23.5 months (95 % CI, 11.8–33.3 months). Urachal cancer is usually locally advanced at presentation and it has a high risk of distant metastases. However, long-term survival following surgical treatment occurs in a significant fraction of patients. This study indicates the current treatment results for patients with urachal cancer in Japanese clinical practice. To establish a standard operation method and chemotherapy, a multicenter, prospective study is needed in a larger population in the future.

Objective: To determine the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting metastasis and its impact on patient management with upper tract urothelial carcinoma (UTUC). Patients and Methods: Consecutive patients with UTUC underwent 18F-FDG PET/CT after CT for initial staging (n = 47) and for restaging at recurrence (n = 9). Diagnostic accuracy for detecting metastases with PET/CT and CT was compared statistically. The impact of PET/CT on patient management was assessed by comparing questionnaires that were completed by the attending physicians before and after PET/CT. Results: In the lesion-based analysis, 142 lesions were diagnosed as metastases. The sensitivity of PET/CT was significantly better than that of CT (85 vs. 50%, p = 0.0001). In the patient-based analysis, 22 patients were diagnosed as having metastases. The sensitivity/specificity/accuracy of PET/CT tended to be superior to those of CT, but these values were not significantly different (95, 91, and 93% vs. 82, 85, and 84%; p = 0.25, 0.50, and 0.063, respectively). The clinicians changed their assessments of disease extent and management plans in 18 (32%) and 11 (20%) patients, respectively, based on the PET/CT results. Conclusions: The diagnostic accuracy of PET/CT for detecting metastasis was superior to that of CT. PET/CT provided additional information to the CT-based staging, which had an impact on patient management.

To determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC). Sixty UC patients with measurable cN+ but without detectable systemic visceral/bone dissemination received induction platinum-based chemotherapy. Consolidative surgery was offered to all patients except for those with progressive disease. We retrospectively analyzed the clinicopathological response to induction chemotherapy and identified prognostic factors for overall survival (OS). The primary cancer site was the urinary bladder in 31 patients (52 %) and upper urinary tract in 29 (48 %). The median number of chemotherapy courses was 4. Forty-five patients (75 %) showed a clinically objective response to the induction chemotherapy. Fifty-one patients (85 %) underwent subsequent consolidative surgery. Histopathological analysis indicated pT0 status in 10 (20 %) and pN0 in 17 (33 %). When all 60 patients were considered, clinical tumor response was found to be significantly correlated with achievement of pathological complete response. At the median follow-up of 22 months, the median progression-free survival and OS periods were excellent: 18.6 and 31.6 months, respectively. In the multivariate analysis, clinical tumor response was found to be an independent pre-surgical prognostic factor for OS, and pathologically negative lymph node, negative resection margin, more LNs removed, and negative lymphovascular invasion were found to be independent post-surgical prognostic parameters for OS. The median OS in induction chemotherapy followed by consolidative surgery was very encouraging. Our results suggest that achieving a good clinical response to pre-surgical induction chemotherapy is a good indication for subsequent consolidative surgery in UC patients with cN+ to improve OS through a good pathological response.

Objective To assess the change in disease-specific health-related quality of life and to evaluate patient-perceived satisfaction after radical prostatectomy (RP) or intensity-modulated radiotherapy (IMRT) with androgen deprivation therapy (ADT) for patients with high-risk prostate cancer (PCA) that has been defined by the European Association of Urology guideline. Methods Between 2006 and 2010, 150 patients with high-risk PCA who underwent either RP (n = 97) or IMRT with ADT (n = 53) were enrolled in this prospective health-related quality of life study. Disease-specific health-related quality of life at baseline, 3, 6, 12, and 24 months and patient-perceived satisfaction at 12 and 24 months after these treatments were estimated using the Expanded Prostate Cancer Index Composite. Results Urinary bother and irritation and obstruction scores did not change significantly between both treatment groups throughout the 2-year follow-up. ADT greatly influenced sexual and hormonal functions and bothers in patients who received IMRT with ADT. The patient-perceived satisfaction at 12 months after the treatments was approximately 80% in both treatment groups, and there was no significant difference between the 2 groups. At 12 months after the treatments, urinary function ( P = .001) was identified as the most significant predictor of patient-perceived satisfaction, although it was not associated with the treatment type. Conclusion The majority of patients with high-risk PCA who received RP or IMRT with ADT reported high patient-perceived satisfaction after the treatments. This study showed that improvement in urinary function might contribute to patient-perceived satisfaction after the treatments.

Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer treated with combined androgen blockade (CAB). AWS is generally defined as subjective and/or objective improvement following discontinuation of an antiandrogen. However, the duration of the AWS response is usually limited. In addition, a complete response is quite rare. We herein present the case of a patient who achieved complete response from AWS, with the duration of this response lasting for >6 years. A 72-year-old man with metastatic prostate cancer received CAB with a luteinizing hormone-releasing hormone analog and bicalutamide. In addition, for local cancer control, external beam radiation therapy (70 Gy) to the prostate was performed. Subsequently, the serum prostate-specific antigen (PSA) level reached a nadir (undetectable level). Four years later, the patient's serum PSA level started to rise, and bicalutamide was discontinued to confirm AWS at a serum PSA level of 0.34 ng/ml. The PSA level immediately decreased again to an undetectable level (0.00 ng/ml), where it has been remained for 6 years. Bone scintigraphy and computed tomography scans have shown no evidence of bone or other metastases since the introduction of AWS. To the best of our knowledge, there have been no reports of such a long duration of complete response from AWS. Therefore, this phenomenon should always be considered, even in patients with advanced disease.

Persistent androgen synthesis under castration status in adrenal gland, testes and tumor cells is thought to be one of the major causes of development and progression of castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA), the prodrug of abiraterone, which is an inhibitor of androgen synthesis enzymes, was evaluated for pharmacokinetics, pharmacodynamics, preliminary efficacy and safety in Japanese patients with CRPC in a phase-1, open-label and dose-escalation study. Chemotherapy-naïve Japanese CRPC patients (N = 27) received one of four AA daily doses (250 mg [n = 9], 500 mg [n = 6], 1000 [1 h premeal] mg [n = 6] and 1000 [2 h postmeal] mg [n = 6]) continuously through 28-day treatment cycles. In the first cycle, AA monotherapy was given on days 1–7 for pharmacokinetics, and AA plus prednisone (5 mg twice daily) from days 8 to 28. Of 27 patients, 9 continued treatment with AA until the data cut-off date (18 July 2013). Over the evaluated dose range, plasma abiraterone concentrations increased with dose, with median tmax 2–3 h. At each dose level, mean serum corticosterone concentrations increased, while testosterone and dehydroepiandrosterone sulfate concentrations rapidly decreased following a single AA dose and were further reduced to near the quantification limit on day 8 regardless of the dose. At least 3 patients from each dose-group experienced ≥50% prostate-specific antigen reduction, suggesting clinical benefit from AA in Japanese CRPC patients. AA was generally well-tolerated, and, therefore, the recommended AA dosage regimen in Japanese CRPC patients is 1000 mg oral dose under modified fasting conditions (at least 1 h premeal or 2 h postmeal). This study is registered at ClinicalTrials.gov: NCT01186484.

Objective To investigate the diagnostic performance and safety of a three-dimensional 14-core biopsy (3D14PBx) method, which is a combination of the transrectal six-core and transperineal eight-core biopsy methods. Patients and Methods Between December 2005 and August 2010, 1103 men underwent 3D14PBx at our institutions and were analysed prospectively. Biopsy criteria included a PSA level of 2.5–20 ng/mL or abnormal digital rectal examination (DRE) findings, or both. The primary endpoint of the study was diagnostic performance and the secondary endpoint was safety. We applied recursive partitioning to the entire study cohort to delineate the unique contribution of each sampling site to overall and clinically significant cancer detection. Results Prostate cancer was detected in 503 of the 1103 patients (45.6%). Age, family history of prostate cancer, DRE, PSA, percentage of free PSA and prostate volume were associated with the positive biopsy results significantly and independently. Of the 503 cancers detected, 39 (7.8%) were clinically locally advanced (≥cT3a), 348 (69%) had a biopsy Gleason score (GS) of ≥7, and 463 (92%) met the definition of biopsy-based significant cancer. Recursive partitioning analysis showed that each sampling site contributed uniquely to both the overall and the biopsy-based significant cancer detection rate of the 3D14PBx method. The overall cancer-positive rate of each sampling site ranged from 14.5% in the transrectal far lateral base to 22.8% in the transrectal far lateral apex. As of August 2010, 210 patients (42%) had undergone radical prostatectomy, of whom 55 (26%) were found to have pathologically non-organ-confined disease, 174 (83%) had prostatectomy GS ≥7 and 185 (88%) met the definition of prostatectomy-based significant cancer. Conclusions This is the first prospective analysis of the diagnostic performance of an extended biopsy method, which is a simplified version of the somewhat redundant super-extended three-dimensional 26-core biopsy. As expected, each sampling site uniquely contributed not only to overall cancer detection, but also to significant cancer detection. 3D14PBx is a feasible systematic biopsy method in men with PSA

Objective To evaluate the long-term effect of the processus vaginalis transection method, which we previously developed to prevent postradical prostatectomy inguinal hernia. Methods Our hernia prevention procedure is designed to prevent postoperative indirect hernias. The procedure is performed in the following order: (1) the spermatic cord is isolated and mobilized in the pelvis, (2) the vas deferens is isolated from the spermatic cord and ligated, and (3) the processus vaginalis is dissected free of the other spermatic cord elements, mainly spermatic vessels, ligated near the peritoneum, and transected. Between February 2006 and August 2008, 435 consecutive patients underwent the inguinal hernia prevention procedure concurrently with open radical retropubic prostatectomy. The control group comprised 433 patients who had undergone radical retropubic prostatectomy without hernia prevention immediately before the introduction of this hernia prevention procedure was introduced (between January 2001 and January 2006). Results No significant complications associated with the hernia prevention procedure were observed, except for a few minor peritoneal injuries that were easily repaired during surgery. An inguinal hernia developed postoperatively in 109 of the 433 control patients (25.2%) during the median follow-up of 68 months. In contrast, 4 of the 435 patients (0.9%) who underwent the hernia prevention procedure developed an inguinal hernia during the median follow-up of 42 months. Conclusion The processus vaginalis transection method is safe and effective in the long-term prevention of postradical prostatectomy inguinal hernia.

Objective To investigate the association between lower urinary tract symptoms status and prostate cancer risk at initial extended biopsy. Methods Between 2005 and 2011, the International Prostate Symptom Score was completed on 1467 consecutive men with prostate-specific antigen 50 cc) was also carried out. Results Of 1159 patients, 421 (36.3%) had a positive biopsy and 590 (51.0%) had moderate or severe lower urinary tract symptoms. On multivariate analysis, absent or mild lower urinary tract symptoms had a significant and positive impact on the risk of prostate cancer and high-grade disease (odds ratio 1.64 and 1.70, P = 0.0007 and 0.0121, respectively). Furthermore, the aforementioned findings for prostate cancer detection did not change throughout every prostate volume subgroup. In contrast, in men with prostate volume ≤50 cc, but not in those with prostate volume >50 cc, prostate-specific antigen or %free prostate-specific antigen remained as a significant predictor of prostate cancer. Conclusion In men with elevated prostate-specific antigen, absent or mild lower urinary tract symptoms are positively associated with prostate cancer and high-grade disease regardless of the prostate volume. This finding is especially useful in men with enlarged prostates.

Objectives To determine the relationship between body mass index and prostate cancer risk at biopsy in Japanese men, and to compared the risk with that of Caucasian men. Methods We retrospectively evaluated 3966 men with prostate-specific antigen levels from 2.5 to 19.9 ng/mL who underwent an initial extended prostate biopsy. Using logistic regression, odds ratios of each body mass index category for risk of prostate cancer and high-grade disease (Gleason score ≥4 + 3) were estimated after controlling for age, prostate-specific antigen, %free prostate-specific antigen, prostate volume, digital rectal examination findings, family history of prostate cancer and the number of biopsy cores. Patients were divided into six categories according to their body mass index (kg/m2) as follows

Objective: The RENAL nephrometry scoring system characterizes tumors according to their size, growth pattern, location and nearness to the renal sinus or collecting system. The current study aims to evaluate the RENAL nephrometry scoring system in adopting nephron-sparing surgery (NSS) for cT1 renal cancer. Methods: Clinicopathological data of 200 consecutive patients who had undergone radical nephrectomy (RN) or NSS for clinical stage T1 renal cell cancer at our single institution during 2005-2009 were investigated retrospectively. Results: Of 200 patients, 103 were scheduled for RN, whereas 97 were planned to undergo NSS, 9 of whom actually underwent RN. Those who were planned to undergo NSS were younger and had smaller tumors (p < 0.001). The median RENAL score was significantly lower among those who were originally assigned to NSS (5, range 4-10) versus RN (8, range 4-11) (p < 0.001). Three months after surgery, the renal function of patients who had been scheduled for NSS was significantly better than in those treated by RN (p < 0.001). Conclusions: This study suggests that the RENAL nephrometry scoring system is a useful tool in adopting NSS for cT1 renal cancer and that objective decision-making for NSS was possible.

C-reactive protein (CRP) was an independent prognostic factor for metastatic renal cell carcinoma in the cytokine era. However, the impact of CRP on the survival of metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors has not yet been investigated. Therefore, we further evaluated the prognostic impact of CRP for patients with metastatic renal cell carcinoma treated with molecular-targeted agents of tyrosine kinase inhibitors.Fifty-two patients were treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma at our institution. Overall, 31 and 21 patients were administered sunitinib and sorafenib, respectively. The prognostic value of all variables, including CRP, for overall survival was assessed using the Cox proportional hazards model.The median baseline CRP level was 4.9 mg/l. In multivariate analysis, CRP was an independent predictor for overall survival as both continuous and categorical variable. The median overall survival times of patients with non-elevated CRP concentration (8 mg/l) were not reached, compared with those of patients with elevated CRP concentration (8 mg/l or greater) of 15.9 months. There was a significant difference in overall survival rates between the two groups, with 1- and 3-year overall survival rates of 92.8 and 69.3% versus 50.2 and 22.9% for the non-elevated CRP group and the elevated CRP group (p = 0.003), respectively.CRP has a significant impact on overall survival of patients with metastatic renal cell carcinoma carcinoma treated with tyrosine kinase inhibitors.

Study Type – Prognosis (inception cohort) Level of Evidence 2 What's known on the subject? and What does the study add? The criteria used for selecting patients with prostate cancer for active surveillance (AS) are still not satisfactory due to the difficulty in predicting the significance of the prostate cancer. Urologists could predict insignificant prostate cancer by incorporating cumulative cancer length and biopsy Gleason score, derived from extended biopsy. The present study has added new criteria for predicting insignificant prostate cancer, which would lead to a better selection of candidates for AS. OBJECTIVE • To develop extended biopsy based criteria for predicting insignificant cancer (IC) using extended biopsy findings. PATIENTS AND METHODS • From 2000 to 2009, 1575 patients with prostate cancer were primarily treated by radical prostatectomy in two referral hospitals. • Of these, the study cohort comprised 499 patients with extended biopsy confirmed, clinically organ-confined (cT1–2N0M0) prostate cancer with PSA levels of

Objectives: Obese men with benign prostate hyperplasia might have lower serum prostate-specific antigen because of hemodilution, resulting in underestimation of total prostate volume by serum prostate-specific antigen. The aim of this study was to compare the performance of prostate-specific antigen mass as the absolute amount of prostate-specific antigen protein secreted into circulation with that of serum prostate-specific antigen in the prediction of total prostate volume. Methods: A total of 1517 men with serum prostate-specific antigen up to 10 ng/mL, including 1425 with biopsy-proven benign prostate hyperplasia, were enrolled in this study. Height and weight were used to estimate body mass index, body surface area and plasma volume. Prostate-specific antigen mass was calculated as serum prostate-specific antigen multiplied by plasma volume. The association between serum prostate-specific antigen or prostate-specific antigen mass and transrectal ultrasound-measured total prostate volume were evaluated by Pearson's correlation coefficient (Υ), linear regression analyses and receiver operating characteristic curves. Results: Serum prostate-specific antigen had an inverse relationship with plasma volume, decreasing as plasma volume increased, after adjustment of total prostate volume. Larger total prostate volume per serum prostate-specific antigen was found in men with higher body mass index or plasma volume. Among all participants, the correlation (Υ = 0.456) between prostate-specific antigen mass and total prostate volume was apparently stronger than that (Υ = 0.442) between serum prostate-specific antigen and total prostate volume. Prostate-specific antigen mass outperformed serum prostate-specific antigen at estimating total prostate volume cut-off values of 30 and 40 mL. These findings were more significant in men aged ≥60 years. Conclusions: Prostate-specific antigen mass performs better than serum prostate-specific antigen in estimating TPV, especially in men aged ≥60 years.

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? C-reactive protein (CRP) level has been shown to be a significant prognostic factor for various malignancies, including urothelial carcinoma treated surgically. Apart from CRP level, several prognostic factors have been identified for advanced urothelial carcinoma patients receiving a second-line chemotherapy. CRP could also be a significant prognostic factor for advanced urothelial carcinoma patients receiving a second-line chemotherapy. CRP kinetics, the dynamic change of CRP concentration, has a strong impact on survival. Adding to the baseline CRP status at the start of treatment, the normalization of CRP during treatment is significantly associated with prognosis. The period with normalized CRP level was strongly correlated with survival period. Therefore, CRP could be a potential biomarker for advanced urothelial carcinoma patients. OBJECTIVE • To assess the impact of C-reactive protein (CRP) kinetics, the effect of dynamic changes of CRP concentration on the survival of patients with locally advanced or metastatic urothelial carcinoma (UC) treated by single chemotherapeutic regimen including cisplatin was examined. PATIENTS AND METHODS • Eighty patients with advanced UC, who failed treatment of advanced UC with the first-line chemotherapy or who received perioperative treatment of neoadjuvant or adjuvant settings, were treated with gemcitabine, etoposide and cisplatin (GEP) as second-line chemotherapy. • Patients were divided into three groups according to CRP kinetics based on baseline and nadir CRP concentrations. Patients whose baseline CRP levels were

Renal cell carcinoma (RCC) with t(6;11) translocation, involving the transcription factor EB (TFEB) and Alpha, also known as MALATI, (TFEB RCC), is extremely rare, with only 20 cases reported to date. It may be frequently misdiagnosed because of a lack of established characteristics. TFEB RCCs are predominantly seen in younger patients and are generally indolent, with only 2 cases of metastasis. Genetic analysis has been limited, showing break points upstream of TFEB exon 3, yielding only a single transcript. We examined 3 new adult Japanese TFEB RCC cases by means of precise clinicopathologic, immunohistochemical, cytogenetic, and molecular analyses and compared them with 200 ordinary RCCs. A 57-year-old man was the oldest patient with TFEB RCC at the time of this study. Although the tumor had histology typical of translocation RCC, its fusion points were different between the genomic and transcript coordinates. A 37-year-old man had an aggressive course resulting in death. The tumor had 2 variants of messenger ribonucleic acid. A 47-year-old man showed borderline histologic and immunohistochemical features between TFEB RCC and chromophobe-type RCC. The tumor had a fusion point in TFEB exon 4, downstream of the wild-type ATG in exon 3. Nuclear expression of the TFEB protein was detected, and a Western blotting analysis identified a protein similar in size to the wild-type TFEB protein. Immunohistochemistry is useful for the diagnosis of these tumors, and TFEB RCCs have heterogeneous clinicopathologic features and more diverse fusion patterns than previously thought, requiring attention to polymerase chain reaction experiments for diagnosis. Our study will contribute to the correct diagnosis of TFEB RCC.

Study Type – Diagnostic (exploratory cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Initial transrectal 12-core biopsy has a small but definite risk of missing anterior significant prostate cancers irrespective of age, PSA, prostate volume and DRE findings. Our study yields valuable information for diagnosis and treatment decision of prostate cancer based on transrectal 12-core biopsy. OBJECTIVE • To characterize prostate cancers missed by initial transrectal 12-core biopsy. PATIENTS AND METHODS • Between 2002 and 2008, 715 men with prostate-specific antigen levels in the range 2.5–20 ng/mL or abnormal digital rectal examination underwent three-dimensional 26-core prostate biopsy (i.e. a combination of transrectal 12-core biopsy and transperineal 14-core biopsy) on initial examination. • Of the 257 patients diagnosed with cancer, 120 patients subsequently underwent radical prostatectomy. • Cancers were grouped into TR12-negative cancers (i.e. not detected through transrectal 12-core biopsy but detected through transperineal 14-core biopsy) and TR12-positive (i.e. detected through transrectal 12-core biopsy) cancers. • Clinicopathological characteristics of the TR12-negative and TR12-positive cancers were evaluated. RESULTS • TR12-negative cancers comprised 21% of the three-dimensional 26-core biopsy-detected cancers. • The frequency of cancers with a biopsy Gleason score ≤6 and that of cancers with a biopsy primary Gleason grade ≤3 was higher in TR12-negative cancers, at 58% and 83%, respectively, than in TR12-positive cancers, at 25% (P < 0.001) and 53% (P < 0.001), respectively. • The median number of positive cores in TR12-negative cancers was two out of 26. • TR12-negative cancers were more frequently located anteriorly than posteriorly. • The incidence of the TR12-negative cancers was not associated significantly with any clinical variable. CONCLUSION • Many of the cancers missed by initial transrectal 12-core biopsy are probably low-grade and low-volume diseases, although initial transrectal 12-core biopsy has a small but definite risk of missing anterior significant cancers.

Sunitinib is an orally-administered, multitargeted tyrosine kinase inhibitor. The main targets are vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α, and PDGFR-β. Among therapeutic targeting agents, it is the best available in the USA for patients with metastatic renal cell cancer (RCC). Well-constructed clinical trials have led to the worldwide approval of various agents for RCC. However, in clinical practice, it remains difficult to determine the best treatment strategy with these agents. Therefore, the identification of biomarkers to predict response and side-effects and to select optimal dosages is urgently needed. Potential mechanisms of action and resistance need to be understood in order to make accurate predictions. This article briefly reviews candidate biomarkers of sunitinib therapy in terms of clinical variables, genetic factors, and circulating proteins and endothelial cells. Although further validation and implementation is necessary, if validated, biomarkers will help measure the therapeutic response in individual patients and establish treatment strategies for metastatic RCC.

Study Type--Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? A randomized prospective phase III clinical trial for systemic treatment-naive metastatic renal cell cancer (RCC) patients demonstrated the superiority of sunitinib over interferon with an acceptable safety profile. However, a commonly asked question is whether patients with RCC in clinical trials are representative of those with this disease being seen in ordinary clinical practice. To our knowledge, this is the first report of sunitinib for the Japanese patients with metastatic RCC in ordinary clinical practice. The estimated median PFS and OS in this study were 9.3 and 32.2 months, respectively. The application of the MSKCC model distinctly separated OS curves (P Objectives • To report the treatment efficacy and safety profile of sunitinib for patients with metastatic renal cell carcinoma (RCC) in ordinary clinical practice. • In addition, to investigate the prognostic clinicopathological factors in these patients. Patients and methods • The present study consisted of native Japanese patients with metastatic RCC, comprising 29 pretreated and 34 systemic treatment-naive patients. • Univariate and multivariate analyses were performed by the log-rank test and the Cox proportional hazards model, respectively. Results • Estimated median progression-free survival and overall survival (OS) were 9.3 months (95% confidence interval, CI, 5.0-13.7) and 32.2 months (95% CI, 24.4-40.0), respectively. • Among the patients pretreated before sunitinib, two patients were treated with initialized systemic therapy with sorafenib and the remaining 27 were initialized with interferon-α. • The OS from the initial systemic therapy of the patients in pretreated groups was 79.6 months (95% CI, 14.6-144.5). • The application of the Memorial Sloan-Kettering Cancer Center model distinctly separated the OS curves (P Conclusions • Sunitinib has a favourable efficacy/safety profile for Japanese metastatic RCC patients in clinical practice. • The estimated median OS was >2 years with acceptable tolerability. • The median OS from the initial systemic therapy of the pretreated patients was >6 years. • Memorial Sloan-Kettering Cancer Center prognostic factors still appear to be valid for predicting survival in metastatic RCC in the era of molecular targeted therapy.

Interaural time differences (ITDs) are the primary cue animals, including humans, use to localize low-frequency sounds. In vertebrate auditory systems, dedicated ITD processing neural circuitry performs an exacting task, the discrimination of microsecond differences in stimulus arrival time at the two ears by coincidence-detecting neurons. These neurons modulate responses over their entire dynamic range to sounds differing in ITD by mere hundreds of microseconds. The well-understood function of this circuitry in birds has provided a fruitful system to investigate how inhibition contributes to neural computation at the synaptic, cellular, and systems level. Our recent studies in the chicken have made significant progress in bringing together many of these findings to provide a cohesive picture of inhibitory function.

We investigated the inhibitory effect of sunitinib, a newly approved multitargeted tyrosine kinase inhibitor, against the progression of renal cell cancer (RCC) bone metastases in vivo. In vitro cell proliferation was determined using the MTS assay. To investigate the inhibitory effects of sunitinib in vivo, we established luciferase-labeled ACHN(Luc) cells derived from papillary RCC. Mice in which ACHN(Luc) cells had been transplanted into the left ventricle to establish bone metastases were treated orally with 40 mg/kg/day sunitinib or vehicle control for 3 weeks. Growth of the cancer cells was monitored using an in vivo imaging system. In addition, 16 patients with metastatic RCC were treated with sunitinib, and serum and urine levels of amino-terminal telopeptide (NTx) were measured as markers of bone resorption. Sunitinib did not inhibit the growth of RCC cells in vitro at clinically or experimentally achievable serum levels (100 nM-1 μM). To investigate the inhibitory effect of sunitinib in vivo, we established luciferase-labeled human RCC cells (ACHN(Luc) ). Sunitinib prevented the growth of ACHN(Luc) RCC cells in the bone metastatic mouse model. The number of osteoclasts in sunitinib-treated mice was significantly less than that in control mice. Serum and urine levels of NTx in patients with metastatic RCC declined significantly during the first 4 weeks of sunitinib treatment (p = 0.027). Sunitinib is a potent anticancer agent for RCC bone metastases, at least for papillary RCC.

Objectives To evaluate the prognostic effect of age in patients with localized renal cell carcinoma (RCC) and investigate the incidence of Xp11 translocation RCC in young patients who developed recurrence. Methods From 1990 to 2007, 2403 Japanese patients underwent nephrectomy for presumed RCC at 9 institutions. Of those, 1143 patients had localized RCC (Stage pT1-2N0M0). Their clinical data were retrospectively reviewed. In the present study, 131 patients (11%) were considered young (≤45 years at diagnosis). In the young patients with recurrence, the nephrectomy specimens were immunostained with TFE3 to determine the incidence of Xp11 translocation RCC. Results During the median follow-up of 47 months, 3 cancer deaths (2.2%) occurred among young patients and 51 (5.0%) among older patients. The 5-year cancer-specific survival (CSS) rate was significantly better for the younger patients than for the older patients ( P = .049). Multivariate analysis showed that age was significantly associated with CSS, as were the pathologic T stage, tumor grade, and symptoms at diagnosis. The hazard ratio of young age was 0.31 (95% confidence interval 0.077-0.87). The recurrence-free survival curves revealed no difference between these 2 groups. Of the 74 patients with recurrence, the CSS after recurrence was significantly better in the younger patients than in the older patients ( P = .0010). Of the 8 young patients with recurrence, 4 had Xp11 translocation RCC, and 3 survived for >5 years after recurrence. Conclusions Compared with the older patients, the young patients with RCC had similar recurrence-free survival rates but better CSS rates. This might have been because significant numbers of the young patients had Xp11 translocation RCC.

Objective: It was the aim of this study to assess the outcome of prostate cancer patients with preoperative prostate-specific antigen (PSA) levels ≧100 ng/ml who were treated with antegrade radical prostatectomy with intended wide resection (aRP). Patients and Methods: Eighteen patients who underwent aRP had an initial PSA level ≧100 ng/ml. Overall survival, disease-specific survival and biochemical progression-free survival (bPFS) rates were determined, and predictors of treatment outcome were examined. Results: The median serum PSA level was 159.5 ng/ml. All patients but one had received neoadjuvant androgen deprivation therapy (ADT), while only 2 patients received adjuvant ADT. Five patients were classified as stage pT2, 6 as pT3a, 6 as pT3b and 1 as pT4. Four patients had locoregional lymph node metastases. Twelve patients developed PSA failure. Eight of them received salvage ADT. The estimated 10-year bPFS rate was 25.0% and the overall survival and disease-specific survival rates were 92.9 and 100%, respectively, at a median follow-up of 6 years. Multivariate analysis revealed only the clinical stage to be predictive of bPFS based on preoperative variables. On the other hand, surgical margin status, extracapsular extension and organ-confined disease were identified as being significant postoperative predictors. Conclusions: This study showed a comparatively satisfactory outcome for clinically non-metastatic prostate cancer with PSA levels ≧100 ng/ml treated by aRP.

Objectives: To investigate intraoperative and early postoperative complications of antegrade radical prostatectomy with intended wide resection (aRP) for clinically locally advanced prostate cancer (cLAD) and to compare with those of aRP for clinically localized prostate cancer (cLD). Methods: Between March 1994 and June 2007, 800 consecutive Japanese patients including 625 with cLD and 175 with cLAD underwent aRP and bilateral limited lymphadenectomy. Clinicopathological data including intraoperative and early postoperative complications (within 30 days after operation) were compared between cLD and cLAD groups. Results: No deaths occurred. Operative time and blood loss did not differ significantly between the groups. Intraoperative and early postoperative complications were observed in 11 (1.4%) and 123 (15.4%) of the entire cohort, respectively. Prevalent early postoperative complications were pelvic hematoma, wound infection, urinary retention and lymphocele or prolonged lymph drainage. There were no significant differences in the entire intraoperative and early postoperative complications between the groups. The majority of the early postoperative complications were minor. Conclusions: aRP for cLAD is technically feasible and a safe surgical procedure. If radical prostatectomy could be established as a standard treatment for cLAD in the future, aRP might be valuable as the first step of multimodal treatments.

PURPOSE The aim of this study is to analyze the incidence of involvement of ipsilateral adrenal gland from renal cell carcinoma and assess the actual significance of ipsilateral adrenalectomy at nephrectomy. PATIENTS AND METHODS From 1981 to 2007, 588 patients were diagnosed as having renal cell carcinoma pathologically at our institution. Of those patients, we retrospectively reviewed the clinicopathologic data in the 426 renal cell carcinoma patients who were eligible for evaluation. Of the 426 patients, 193 (AD group) and the remaining 233 (AS group) underwent radical or partial nephrectomy with or without adrenalectomy, respectively. RESULTS Five patients (2.6%) of AD group had adrenal involvement and all of them presented T4 and/or M1 disease. The three patients presented direct involvement of adrenal gland, while metastasis in the remaining 2. All the 5 patients had disease progression after surgery and 4 of them died of disease. The remaining one patient, in whom interferon showed a remarkable response, has been alive with disease for 31 months. The ipsilateral adrenal gland was abnormal on preoperative computed tomography (CT) in 8 patients (1.8%), of whom, 4 had adrenal involvement. One of the five adrenal involvements was overlooked by CT. Thus, in this study, CT showed 80% sensitivity, 98% specificity, 99% negative predictive value and 50% positive predictive value. The 18 patients (7.7%) in AS group later developed nodal and/or visceral metastasis, while no solitary ipsilateral adrenal recurrence was observed in this group. CONCLUSIONS Ipsilateral adrenal involvement from renal cell carcinoma is rare, especially after the adrenal-sparing surgery. It is concluded that concomitant adrenalectomy appears to give a very limited therapeutic benefit in this

Objective: The aim of this study was to assess the surgical outcome of high-grade prostate cancer (PCA) treated with antegrade radical prostatectomy with intended wide resection (aRP) and to establish the risk stratification. Methods: A consecutive 77 Japanese patients with Gleason score 8‐10 PCA were treated with aRP alone and excluding patients with persistently elevated prostate-specific antigen (PSA), prospectively observed without any treatment until PSA failure was confirmed. PSA failure-free, cancer-specific and overall survival curves were generated with Kaplan‐Meier method and the difference between groups was assessed with log-rank test. Cox’s proportional hazards model was used to elucidate predictors of PSA failure. Results: During a median follow-up of 6 years, PSA failure was observed in 41 (53%) of the 77 patients. Five- and 10-year PSA failure-free survival rates of the entire cohort were 44.6% and 40.1%, respectively. Both overall and cancer-specific survival rates of the entire cohort at 5 and 10 years were 96.8% and 87.9%, respectively. In a multivariate analysis, PSA (P ¼ 0.008), specimen confinement (SC) (P ¼ 0.006) and persistently elevated PSA after aRP were identified as significant and independent predictors of PSA failure. When stratifying patients into three risk groups according to PSA level and SC status, PSA failure-free survival rate in patients with PSA , 10 ng/ml and specimen-confined disease (SCD) was significantly better than that in those of any other groups. Conclusions: Good prognosis can be expected in patients with high-grade PCA treated with aRP alone when PSA , 10 ng/ml and the tumor was removed as an SCD.

Purpose: To determine the incidence of Xp11 translocation renal cell carcinoma (RCC) in adult patients using cytogenetics and immunohistochemstry. Experimental Design: Cytogenetic studies were prospectively done using tumor samples from 443 consecutive adult Japanese patients (ages 15-89 years) who underwent nephrectomy for RCC. TFE3 immunohistochemistry was done for cases in which cytogenetic results were not obtained. Clinicopathologic characteristics of Xp11 translocation RCC were examined. Results: Mitotic cells suitable for cytogenetic analysis were obtained in 244 tumor samples (55%); among these, we identified 4 cases (1.6%) of Xp11 translocation RCC. TFE3 immunohistochemistry identified 3 positive cases (1.5%) among the remaining 199 cases. The median age of the 7 patients was 41 years (range, 15-59 years), and 15% of RCC patients (4 of 26) who were younger than ages 45 years had this type of RCC. Of the four Xp11 translocation RCC patients whose karyotypes were determined, two had an ASPL-TFE3 gene fusion. Of these 2, 1 had pulmonary metastasis at presentation, and the other developed liver metastasis 12 months after nephrectomy and died of the disease. The remaining two patients had PRCC-TFE3 and PSF-TFE3 gene fusions, respectively. Both had nodal involvement but remained disease free for 3 and 5 years, respectively, after surgical resection of lymph node metastases. Of the 3 immunohistochemically diagnosed patients, 1 had nodal metastases at presentation and died 9 months after surgery. Conclusions: This is the first report to determine the incidence of Xp11 translocation RCC in adult patients. We found that this disease is relatively common in young adults.

Objectives: To examine whether history of malignancy adds any significant information to the prediction of positive prostate biopsy in referred men with moderately elevated prostate-specific antigen (PSA) and to develop a predicting nomogram that does not require extra examinations other than PSA. Methods: A total of 1767 consecutive Japanese men with PSA less than 10 ng/mL who underwent prostate biopsy were included in the study cohort. Age, digital rectal examination (DRE), PSA, body mass index, family history of prostate cancer and number of previous malignancies other than the prostate were evaluated in regard to their association with prostate cancer. A logistic regression-based nomogram for predicting prostate cancer was developed and externally validated. Results: Of the 1767 men, 269 had a history of malignancy with a total of 312 primary sites. Univariate and multivariate analyses revealed that DRE, PSA, age, family history and number of previous malignancies are independent and significant predictors of positive biopsy result. External validation revealed that the predicting accuracy of a nomogram incorporating these five variables is significantly higher than those of PSA or PSA and DRE. Using the nomogram, 8% of unnecessary biopsies would be saved at 95% sensitivity. Conclusions: We demonstrated for the first time that history of malignancy is a potent predictor of prostate cancer in men with moderately elevated PSA even if the established risk factors are adjusted. The nomogram can be a useful tool in decision-making of prostate biopsy. In daily practice, history of malignancy should be rigorously taken from these men before a decision is made regarding prostate biopsy.

Objectives: Most of the previously reported patient selection criteria for nerve-sparing radical prostatectomy were based on conventional sextant biopsy, and those based on extended biopsy have been scarcely investigated. In the current study, we developed patient selection criteria for nerve-sparing RP based on the three-dimensional 26-core (3D26) biopsy-derived variables. Methods: We evaluated 202 non-nerve-spared sides in 109 consecutive patients in whom prostate cancer was diagnosed by the 3D26 biopsy and who underwent RP without neoadjuvant treatment. Associations of clinical and pathological variables with side-specific posterolateral extraprostatic extension (SS-PL-EPE) were analyzed. Subgroup analysis using transperineal 14-core (TP14) and transrectal 12-core (TR12) biopsies as representative subsets of the 3D26 biopsy was also performed. Results: Maximum cancer length in positive cores ≥5 mm and biopsy Gleason score ≥4 + 3 were independent and were significant risk factors of SS-PL-EPE in the 3D26 cohort at multivariate analysis. In the prostatic side with none, one, and two risk factors, the incidences of SS-PL-EPE were 0, 14 and 52% in the 3D26 cohort, 3.4,15 and 57% in the TP14 cohort and 2.6, 20 and 61% in the TR12 cohort, respectively. Conclusions: We developed simple patient selection criteria for nerve-sparing RP. According to our criteria, the nerve-sparing side can be selected in the majority of patients who undergo the 3D26, TP14 or TR12 biopsy with a less-than-4% risk of SS-PL-EPE.