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Objectives: Clinical guidelines recommend that patients with non‐muscle‐invasive bladder cancer (NMIBC) should be treated with appropriate adjuvant therapy. However, compliance with guideline recommendations is insufficient, and this may lead to unfavorable outcomes. We aimed to investigate the level of adherence to guideline recommendations in patients with NMIBC and evaluate the outcomes of those who did and did not receive guideline‐recommended therapies. Methods: We performed a retrospective analysis of patients with histologically diagnosed NMIBC. The percentage of patients with intermediate‐ and high‐risk tumors who received adjuvant intravesical therapy or second transurethral resection (TUR) was calculated. Recurrence‐free survival was assessed in patients who did and did not receive the therapies. We conducted a propensity score‐matched analysis to compare outcomes between patients with intermediate‐risk and T1 NMIBC who did and did not undergo guideline‐recommended therapies. Results: Overall, 1204 patients from the Tohoku Urological Evidence‐Based Medicine Study Group and Kyoto University Hospital were included. Of patients with intermediate‐ and high‐risk tumors, 91.0% and 74.0% did not receive maintenance bacillus Calmette–Guérin (BCG), respectively. In both groups, significantly better recurrence‐free survival was found for patients treated with maintenance BCG. Among patients with T1 NMIBC, only 16.7% underwent guideline‐recommended therapies, that is, a second TUR and maintenance BCG. Significantly greater recurrence‐free survival was observed in patients who received guideline‐recommended therapies compared with propensity‐matched patients who did not. Conclusions: Guideline‐recommended therapies may contribute to improvements in outcomes for patients with NMIBC, suggesting that improvements in adherence to clinical guidelines may lead to favorable outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluated the trends of local intervention and their impact on oncological outcomes in metastatic hormone‐naïve prostate cancer (mHNPC) in real‐world practice. Methods: This retrospective multicenter study included 760 patients treated with either androgen deprivation therapy (ADT) without local treatment (no castration‐resistant prostate cancer [CRPC] progression within 12 months, control group) or ADT plus local intervention (intervention group) between January 2005 and March 2022. We evaluated the trends in the use of local intervention in patients with mHNPC and factors associated with CRPC‐free survival in the intervention group. Results: The use of local intervention gradually increased in combination with upfront combination treatment (docetaxel or androgen receptor axis‐targeted agents) for the duration of our study. The number of patients with local intervention combined with upfront treatment was significantly higher in patients with high tumor burden disease than in those with low tumor burden disease. Of the 108 patients who received local intervention, a duration of ≤7 months of initial therapy before local intervention and a level of prostate‐specific antigen ≥0.20 ng/mL at the time of local intervention were significantly associated with poor CRPC‐free survival. Conclusions: The use of local intervention in combination with upfront therapy to treat mHNPC increased for the duration of our study regardless of the tumor burden. Local intervention in addition to the standard of care for mHNPC may be a feasible treatment option for selected patients, taking into consideration the duration of and response to initial treatment. [ABSTRACT FROM AUTHOR]

Objectives: To investigate how much minimal residual membranous urethral length (mRUL) and maximal urethral length (MUL) measured on MRI preoperatively affect postoperative urinary incontinence (PUI) and recovery in robot‐assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP). Methods: The subjects were 190 and 110 patients undergoing RARP and ORP, respectively, in our institution. Patients underwent preoperative MRI for prostate cancer evaluation and completed the quality of life questionnaire of the Expanded Prostate Cancer Index Composite instrument before and 1, 3, 6, and 12 months after surgery. The parameters of mRUL and MUL were measured on MRI and analyzed along with other parameters including age, body mass index, and nerve sparing. Results: The median mRUL and MUL were 7.81 and 14.27 mm in the RARP group and 7.15 and 13.57 mm in the ORP group, respectively. Recovery rates from PUI were similar in the two groups. Multivariate analyses showed that mRUL was a predictor of baseline continence, whereas shorter MUL was a predictor of poor recovery from PUI. Patients with both shorter mRUL and MUL had significantly worse recoveries from PUI after RARP and ORP than patients with longer mRUL and MUL. Conclusions: Minimal residual membranous urethral length contributes to urethral function as basal urinary continence, whereas MUL represents the potential of recovery from PUI in RARP and ORP. The MUL measured by preoperative MRI can predict poor recovery from PUI after radical prostatectomy and combined evaluation of MUL and mRUL support to anticipate poor recovery of PUI. [ABSTRACT FROM AUTHOR]

Objectives: To compare the medical costs of active surveillance with those of robot‐assisted laparoscopic prostatectomy, brachytherapy, intensity‐modulated radiation therapy, and hormone therapy for low‐risk prostate cancer. Methods: The costs of protocol biopsies performed in the first year of surveillance (between January 2010 and June 2020) and those of brachytherapy and radiation therapy performed between May 2019 and June 2020 at the Kagawa University Hospital were analyzed. Hormone therapy costs were assumed to be the costs of luteinizing hormone‐releasing hormone analogs for over 5 years. Active surveillance‐eligible patients were defined based on the following: age <74 years, ≤T2, Gleason score ≤6, prostate‐specific antigen level ≤10 ng/ml, and 1–2 positive cores. We estimated the total number of active surveillance‐eligible patients in Japan based on the Japan Study Group of Prostate Cancer (J‐CAP) study and the 2017 cancer statistical data. We then calculated the 5‐year treatment costs of active surveillance‐eligible patients using the J‐CAP and PRIAS‐JAPAN study data. Results: In 2017, number of active surveillance‐eligible patients in Japan was estimated to be 2808. The 5‐year total costs of surveillance, prostatectomy, brachytherapy, radiation therapy, and hormone therapy were 1.65, 14.0, 4.61, 4.04, and 5.87 million United States dollar (USD), respectively. If 50% and 100% of the patients in each treatment group had opted for active surveillance as the initial treatment, the total treatment cost would have been reduced by USD 6.89 million (JPY 889 million) and USD 13.8 million (JPY 1.78 billion), respectively. Conclusion: Expanding active surveillance to eligible patients with prostate cancer helps save medical costs. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of combined androgen blockade with a first‐generation anti‐androgen on the prognoses of metastatic hormone‐sensitive prostate cancer patients stratified by tumor burden. Methods: We retrospectively analyzed the cases of metastatic hormone‐sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008–2017 at 30 institutions in Japan. To compare the overall survival and progression‐free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High‐burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. Results: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low‐ and high‐burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between‐group difference in the overall survival according to the androgen deprivation therapy method, in the high‐burden group the progression‐free survival of the combined androgen blockade‐treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34–0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60–0.98. Conclusion: In the high‐burden group, combined androgen blockade with a first‐generation anti‐androgen resulted in superior progression‐free survival compared with castration monotherapy. For well‐selected metastatic hormone‐sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the impact of Gleason pattern 5 presence on prognosis among de novo metastatic hormone‐sensitive prostate cancer patients with a Gleason score ≥8. Methods: The data of 559 patients diagnosed as metastatic hormone‐sensitive prostate cancer with a Gleason score ≥8, who were initially treated with androgen deprivation therapy from 2008 to 2016, were retrospectively collected. Patients were divided into two groups as high and low volume based on the CHAARTED trial criteria. Results: The median overall survival of the 559 metastatic hormone‐sensitive prostate cancer patients with Gleason score ≥8 was 70 months, with a median follow‐up period of 36 months. Gleason pattern 5 was confirmed in 341 patients (61.0%), in which primary Gleason pattern 5 was confirmed in 164 patients (29.3%). The number of patients with high metastatic volume group was 363 (64.9%). In total and high metastatic volume groups, hemoglobin and lactate dehydrogenase were significant factors for predicting overall survival, but both Gleason pattern 5 and primary Gleason pattern 5 did not show a statistically significant difference. In the low‐volume metastatic group, the median overall survival in patients with or without primary Gleason pattern 5 was 40 and 78 months, respectively. In multivariate analysis, only primary Gleason pattern 5 was an independent predictive factor for overall survival in the low‐volume metastatic group (hazard ratio 2.76, 95% confidence interval 1.88–8.67; P = 0.0026). Conclusion: The presence of Gleason pattern 5 was not associated with overall survival in metastatic hormone‐sensitive prostate cancer with a Gleason score ≥8. In low‐metastatic volume metastatic hormone‐sensitive prostate cancer, primary Gleason pattern 5 was a poor prognostic factor, which might show a separate treatment option for this group. [ABSTRACT FROM AUTHOR]

To improve treatment outcomes in real practice, useful biomarkers are desired when predicting postoperative recurrence for renal cell carcinoma (RCC). We collected data from patients who underwent definitive surgery for RCC and for benign urological tumor at our department between November 2016 and December 2019. We evaluated the differences in pre‐ and postoperative urinary metabolites with our precise quantitative method and identified predictive factors for RCC recurrence. Additionally, to clarify the significance of metabolites, we measured the intracellular metabolite concentration of three RCC cell lines. Among the 56 patients with RCC, nine had a recurrence (16.0%). When comparing 27 patients with T1a RCC and 10 with benign tumor, a significant difference was observed between pre‐ and postoperative concentrations among 10 urinary metabolites. In these 10 metabolites, multiple logistic regression analysis identified five metabolites (lactic acid, glycine, 2‐hydroxyglutarate, succinic acid, and kynurenic acid) as factors to build our recurrence prediction model. The values of area under the receiver operating characteristic curve, sensitivity, and specificity in this predictive model were 0.894%, 88.9%, and 88.0%, respectively. When stratified into low and high risk groups of recurrence based on this model, we found a significant drop of recurrence‐free survival rates among the high risk group. In in vitro studies, intracellular metabolite concentrations of metastatic tumor cell lines were much higher than those of primary tumor cell lines. By using our quantitative evaluation of urinary metabolites, we could predict postoperative recurrence with high sensitivity and specificity. Urinary metabolites could be noninvasive biomarkers to improve patient outcome. [ABSTRACT FROM AUTHOR]

Metastatic burden is a critical factor for therapy decision‐making in metastatic hormone‐sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high‐ or low‐metastatic burden treated with primary androgen‐deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen‐deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression‐free survival (PFS) and overall survival (OS) in patients stratified by low‐ or high‐metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low‐ and high‐metastatic burden, respectively. Median PFS of the low‐ and high‐burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy‐positive core, biopsy Gleason grade group, T‐stage, and N‐stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low‐burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high‐burden group. Differential prognostic factors were identified for patients with low‐ and high‐burden metastatic prostate cancer. These results may assist in decision‐making to select the optimal therapeutic strategies for patients with different metastatic burdens. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of cancer therapy on post‐treatment ejaculation in patients with testicular cancer. Methods: A total of 74 testicular cancer survivors provided completed International Index of Erectile Function‐15 questionnaires before and after treatment between 2010 and 2017. Sexual function, particularly ejaculatory function, was evaluated before and after treatment. In this study, patients who answered "1 = almost never/never" or "2 = a few times" for questionnaire number 9 (ejaculation frequency) were defined as having "ejaculation disorder." Results: Of 74 testicular cancer survivors, 50 (68%) had no ejaculation disorders before treatment. Four (44%) of nine survivors, who received chemotherapy and retroperitoneal lymph node dissection, developed ejaculation disorders after treatment. On multivariate analysis, retroperitoneal lymph node dissection was a significant predictor of post‐treatment ejaculation disorder (P = 0.042). Of 60 survivors with evaluable ejaculation function after treatment, 24 (40%) did not attempt sexual intercourse, and multivariate analysis showed ejaculation disorder had a significant negative impact on having sexual intercourse (P = 0.035). Furthermore, the mean International Index of Erectile Function‐15 scores in the groups with and without ejaculation disorders after treatment were 24.0 and 51.9, respectively (P < 0.001). Conclusion: Ejaculation disorders occur at high rate after retroperitoneal lymph node dissection. Many testicular cancer survivors reporting no sexual intercourse have ejaculation disorders, suggesting an adverse impact on sexual life. Urologists should provide proper counselling regarding the risk of ejaculation disorder and its possible impact on sexual life. [ABSTRACT FROM AUTHOR]

Using surgically resected tissue, we identified characteristic metabolites related to the diagnosis and malignant status of clear cell renal cell carcinoma (ccRCC). Specifically, we quantified these metabolites in urine samples to evaluate their potential as clinically useful noninvasive biomarkers of ccRCC. Between January 2016 and August 2018, we collected urine samples from 87 patients who had pathologically diagnosed ccRCC and from 60 controls who were patients with benign urological conditions. Metabolite concentrations in urine samples were investigated using liquid chromatography‐mass spectrometry with an internal standard and adjustment based on urinary creatinine levels. We analyzed the association between metabolite concentration and predictability of diagnosis and of malignant status by multiple logistic regression and receiver operating characteristic (ROC) curves to establish ccRCC predictive models. Of the 47 metabolites identified in our previous study, we quantified 33 metabolites in the urine samples. Multiple logistic regression analysis revealed 5 metabolites (l‐glutamic acid, lactate, d‐sedoheptulose 7‐phosphate, 2‐hydroxyglutarate, and myoinositol) for a diagnostic predictive model and 4 metabolites (l‐kynurenine, l‐glutamine, fructose 6‐phosphate, and butyrylcarnitine) for a predictive model for clinical stage III/IV. The sensitivity and specificity of the diagnostic predictive model were 93.1% and 95.0%, respectively, yielding an area under the ROC curve (AUC) of 0.966. The sensitivity and specificity of the predictive model for clinical stage were 88.5% and 75.4%, respectively, with an AUC of 0.837. In conclusion, quantitative analysis of urinary metabolites yielded predictive models for diagnosis and malignant status of ccRCC. Urinary metabolites have the potential to be clinically useful noninvasive biomarkers of ccRCC to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association of tumor burden with the prognosis in real‐world patients with metastatic castration‐sensitive prostate cancer and to investigate the eligibility for upfront intensification therapy. Methods: We retrospectively evaluated 679 patients with metastatic castration‐sensitive prostate cancer who were initially treated with conventional androgen deprivation therapy between August 2001 and November 2018. The primary purpose was to investigate the eligibility for upfront intensification therapy based on the progression of metastatic castration‐resistant prostate cancer. The secondary purpose included the comparison of the metastatic castration‐resistant prostate cancer progression rate, metastatic castration‐resistant prostate cancer‐free survival and overall survival after castration‐resistance in CHAARTED low‐ or high‐volume disease patients. Results: The number of patients with metastatic castration‐resistant prostate cancer progression was 119 (52%) and 319 (71%) in the low‐ and high‐volume disease groups, respectively. The metastatic castration‐resistant prostate cancer progression rate (P < 0.001) and castration‐resistant prostate cancer‐free survival (P < 0.001) were significantly different between the low‐ and high‐volume disease groups, but no difference was found for overall survival after castration resistance (P = 0.363). Multivariate Cox regression analysis showed no significant association between tumor burden and overall survival after castration resistance (P = 0.522; hazard ratio 1.14). Conclusions: The progression rate in metastatic castration‐resistant prostate cancer patients with the low‐volume disease under conventional androgen deprivation therapy is approximately 50%. Upfront intensification therapy might be beneficial for approximately half of patients with low‐volume disease. A novel maker to predict the castration‐resistant status is required to select optimal patients for upfront intensification therapy. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone‐naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). Methods: At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer‐specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results: During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5‐year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5‐year net CSS and OS survival gradually increased for all the patients. In patients given a 5‐year survivorship, the conditional 5‐year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) ≥2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions: The conditional 5‐year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient's risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5‐year follow‐up. Conditional net survival can play a role in clinical decision‐making, providing intriguing information for cancer survivors. [ABSTRACT FROM AUTHOR]

To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc‐glycosylated prostate‐specific antigen (LDN‐PSA) and LDN‐PSA normalized by prostate volume (LDN‐PSAD). We retrospectively measured LDN‐PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop‐PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN‐PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN‐PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN‐PSA and LDN‐PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop‐PSA cohort, LDN‐PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc‐glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution ("The Study about Carbohydrate Structure Change in Urological Disease"; approval no. 2014‐195). [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is a malignant tumor that currently lacks clinically useful biomarkers indicative of early diagnosis or disease status. RCC has commonly been diagnosed based on imaging results. Metabolomics offers a potential technology for discovering biomarkers and therapeutic targets by comprehensive screening of metabolites from patients with various cancers. We aimed to identify metabolites associated with early diagnosis and clinicopathological factors in RCC using global metabolomics (G‐Met). Tumor and nontumor tissues were sampled from 20 cases of surgically resected clear cell RCC. G‐Met was performed by liquid chromatography mass spectrometry and important metabolites specific to RCC were analyzed by multivariate statistical analysis for cancer diagnostic ability based on area under the curve (AUC) and clinicopathological factors (tumor volume, pathological T stage, Fuhrman grade, presence of coagulation necrosis and distant metastasis). We identified 58 metabolites showing significantly increased levels in tumor tissues, 34 of which showed potential early diagnostic ability (AUC >0.8), but 24 did not discriminate between tumor and nontumor tissues (AUC ≤0.8). We recognized 6 pathways from 9 metabolites with AUC >0.8 and 7 pathways from 10 metabolites with AUC ≤0.8 about malignant status. Clinicopathological factors involving malignant status correlated significantly with metabolites showing AUC ≤0.8 (p = 0.0279). The tricarboxylic acid cycle (TCA) cycle, TCA cycle intermediates, nucleotide sugar pathway and inositol pathway were characteristic pathways for the malignant status of RCC. In conclusion, our study found that metabolites and their pathways allowed discrimination between early diagnosis and malignant status in RCC according to our G‐Met protocol. What's new? Clinically relevant biomarkers are needed to advance renal cell carcinoma (RCC) diagnosis and assessments of therapeutic response. Here, using a liquid chromatograph‐mass spectrometer‐based global metabolomics protocol, RCC tissues were examined for metabolites relevant to RCC early diagnosis and malignant status. In total, 58 metabolites were found to be elevated in surgically resected RCC tissues. Of these, 34 metabolites, primarily from the glutathione, glycoglycerolipid, carnitine, tocopherol, and glycolysis pathways, were associated with early diagnosis of RCC. Most other metabolites identified in RCC tissues were from the tricarboxylic acid cycle, nucleotide sugar, and inositol pathways and were characteristic of malignant status. [ABSTRACT FROM AUTHOR]

Abstract: Androgen deprivation therapy continues to be widely used for the treatment of prostate cancer despite the appearance of new‐generation androgen‐receptor targeting drugs after 2000. Androgen deprivation therapy can alleviate symptoms in patients with metastatic prostate cancer and might have a survival benefit in some patients, but it causes undesirable changes in lipid, glucose, muscle or bone metabolism. These metabolic changes could lead to new onset or worsening of diseases, such as obesity, metabolic syndrome, diabetes mellitus, cardiovascular disease, sarcopenia or fracture. Several studies examining the influence of androgen deprivation therapy in Japanese patients with prostate cancer also showed that metabolic changes, such as weight gain, dyslipidemia or fat accumulation, can occur as in patients in Western countries. Efforts to decrease these unfavorable changes and events are important. First, overuse of androgen deprivation therapy for localized or elderly prostate cancer patients should be reconsidered. Second, intermittent androgen deprivation therapy might be beneficial for selected patients who suffer from impaired quality of life as a result of continuous androgen deprivation therapy. Third, education and instruction, such as diet or exercise, to decrease metabolic changes before initiating androgen deprivation therapy is important, because metabolic changes are likely to occur in the early androgen deprivation therapy period. Fourth, routine monitoring of weight, laboratory data or bone mineral density during androgen deprivation therapy are required to avoid unfavorable events. [ABSTRACT FROM AUTHOR]

Serum biomarker monitoring is essential for management of germ-cell tumors (GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N-glycan-based biomarkers can be applied for detection and prognosis in patients with GCT. We performed a comprehensive N-glycan structural analysis of sera from 54 untreated GCT patients and 103 age-adjusted healthy volunteers using glycoblotting methods and mass spectrometry. Candidate N-glycans were selected from those with the highest association; cutoff concentration values were established, and an N-glycan score was created based on the number of positive N-glycans present. The validity of this score for diagnosis and prognosis was analyzed using a receiver operating characteristic (ROC) curve. We identified five candidate N-glycans significantly associated with GCT patients. The accuracy of the N-glycan score for GCT was significant with an area-under-the-curve (AUC) value of 0.87. Diagnostically, the N-glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers. Prognostically, the N-glycan score comprised four candidate N-glycans. The predictive value of the prognostic N-glycan score was significant, with an AUC value of 0.89. A high value prognostic N-glycan score was significantly associated with poor prognosis. Finally, to identify a potential carrier protein, immunoglobulin (Ig) fractions of sera were subjected to N-glycan analysis and compared to whole sera. Candidate N-glycans in Ig-fractions were significantly decreased; therefore, the carrier protein for candidate N-glycans is likely not an immunoglobulin. In summary, our newly developed N-glycan score seems to be a practical diagnostic and prognostic method for GCT. [ABSTRACT FROM AUTHOR]

Objectives To verify whether abdominal pressure during urination represents an important factor in the postoperative development of inguinal hernia after radical retropubic prostatectomy. Methods Participants comprised 228 patients who underwent radical retropubic prostatectomy without prophylaxis for inguinal herniation between 2002 and 2007. Development of inguinal hernia was assessed from clinical records. Straining was rated on a six-point scale (straining score) according to frequency of straining using answers to question 6 of the International Prostate Symptom Score questionnaire preoperatively, and at 1, 3, 6, 12, 18, 24 and 36 months after prostatectomy. Straining scores were compared between patients with and without postoperative inguinal hernia. Multivariate analysis was carried out to identify parameters associated with inguinal hernia development after prostatectomy. Associations between inguinal hernia development and frequency of postoperative urinary straining were also estimated. Results Straining score in both groups was significantly increased at 1 month after radical retropubic prostatectomy. This increase was significantly greater in the postoperative inguinal hernia group ( P < 0.05). Throughout the observation period, postoperative straining scores were higher in the group with postoperative inguinal hernia than in the group without. On multivariate analysis, postoperative urinary straining and previous hernia repair represented significant risk factors for postoperative inguinal hernia. The proportion of patients without inguinal hernia decreased significantly with increasing frequency of postoperative urinary straining. Conclusion Urinary straining is associated with inguinal hernia development after radical retropubic prostatectomy. [ABSTRACT FROM AUTHOR]

Objectives To characterize the site and clinical implications of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. Methods Patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma between 2000 and 2011 at 12 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were included in the present study. Those who underwent prior or simultaneous radical cystectomy were excluded. The site of intravesical recurrence was investigated, and the survival curves after radical nephroureterectomy were analyzed retrospectively using the Kaplan-Meier method. Multivariate analyses of factors predicting survival were carried out. Results A total of 534 patients were eligible for the present study. With a median follow up of 47 months, 205 patients (38.4%) had intravesical recurrence. The intravesical recurrence-free survival rates at 1, 2, and 5 years were 74.6%, 62.5% and 56.3%, respectively. In a subset of 137 patients with intravesical recurrence who did not have bladder cancer before or at the diagnosis of upper urinary tract urothelial carcinoma, the most frequent site of intravesical recurrence was around the cystotomy (52.6%), followed by at the posterior wall (39.4%) and at the bladder neck (35.8%). A total of 36 patients (17.6%) developed muscle-invasive bladder cancer after radical nephroureterectomy. On multivariate analyses for the subset of patients with non-muscle invasive (≤pT1) upper urinary tract urothelial carcinoma, intravesical recurrence was an independent predictor of cancer-specific survival (HR 4.27, P = 0.016) and overall survival (HR 3.00, P = 0.018). Conclusions Most intravesical recurrences occur around the site of bladder mucosal injury within 1 year after radical nephroureterectomy, providing important insight into the mechanism of intravesical recurrence. Intravesical recurrence after radical nephroureterectomy had an impact on oncological outcomes of patients with non-muscle invasive upper urinary tract urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Objective To perform a longitudinal investigation of the correlation between functional recovery and sex hormone concentrations after radical prostatectomy ( RP). Patients and Methods A total of 72 consecutive patients undergoing RP between January 2012 and June 2013 were prospectively included and serially followed after surgery for comparative analysis. Their luteinizing hormone ( LH) and total testosterone ( TT) concentrations were measured before surgery and 3 and 12 months after surgery. They also filled out a health-related quality of life questionnaire before and at 1, 3, 6 and 12 months after surgery. Results The mean LH concentration increased from 4.28 U/L at baseline to 5.53 U/L at 3 months and remained high at 12 months after RP (both P < 0.001). There were no significant changes in the TT concentration after RP. LH at baseline was negatively correlated with the urinary function ( UF) score at 3 and 12 months after RP ( P = 0.030 and 0.032, respectively). After RP, subjects with high baseline LH ( n = 37) were more likely than those with low LH concentrations to report lower UF scores ( P = 0.014). Multivariate analysis of variance in an interaction of time × LH concentration for UF scores indicated a significant relationship between changes in UF score and LH concentration ( P = 0.004). Conclusions Radical prostatectomy affects sex hormones by increasing LH concentrations, while TT concentrations remain stable after surgery. Baseline LH concentrations are significantly associated with the recovery of urinary outcomes after RP. [ABSTRACT FROM AUTHOR]

Objectives To assess the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. Methods We retrospectively reviewed the medical records of 1268 men with prostate cancer treated using radical prostatectomy without neoadjuvant therapy. The association between various risk factors and biochemical recurrence was then statistically evaluated. The Kaplan-Meier method, log-rank tests and Cox proportional hazards models were used for statistical analysis. Results In the intermediate-risk group, 96 patients (14.5%) experienced biochemical recurrence during a median follow up of 41 months. In the intermediate-risk group, preoperative prostate-specific antigen level, prostate volume and prostate-specific antigen density were significant preoperative risk factors for biochemical recurrence, whereas other factors including age, primary Gleason 4, clinical stage >T2 and percentage of positive biopsies were not. In multivariate analysis, higher preoperative prostate-specific antigen level and density, and a smaller prostate volume were independent risk factors for biochemical recurrence in the intermediate-risk group. Biochemical recurrence-free survival of patients in the intermediate-risk group with a higher prostate-specific antigen level and density (≥15 ng/mL, ≥0.6 ng/mL/cm3, respectively), and lower prostate volume (≤10 mL) was comparable with that of high-risk group individuals ( P = 0.632, 0.494 and 0.961, respectively). Conclusions Preoperative prostate-specific antigen, prostate volume and prostate-specific antigen density are significant risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. Using these variables, a subset of the intermediate-risk patients can be identified as having equivalent outcomes to high-risk patients. [ABSTRACT FROM AUTHOR]

Objective To determine whether the currently available pretreatment risk classification systems are applicable in Japanese prostate cancer patients. Methods Using data obtained from 1264 consecutive patients with prostate cancer treated with radical prostatectomy at four hospitals in Japan, biochemical recurrence-free survival rates were estimated and compared between the D' Amico, the National Institute for Health and Clinical Excellence, the Cancer of the Prostate Strategic Urological Research Endeavor, the National Comprehensive Cancer Network, and the European Society of Medical Oncology risk groups by using the Kaplan- Meier method and log-rank test. Results The 5-year biochemical recurrence-free survival rates in the D' Amico low-, intermediate-, and high-risk groups were 88.3%, 84.7% and 66.9%, respectively (low and intermediate risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in the National Institute for Health and Clinical Excellence, National Comprehensive Cancer Network, and European Society of Medical Oncology low-, intermediate- and high-risk groups were 88.3%, 84.3%, and 60.3%, respectively (low and intermediate risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in the Cancer of the Prostate Strategic Urological Research Endeavor low-, intermediate-, and high-risk groups were 90%, 83.5% and 60.3%, respectively (low and intermediate risk vs high risk, P < 0.001). Low- and intermediate-risk groups according to any of the risk stratification systems did not show significant differences in biochemical recurrence-free survival. Conclusion Current risk stratification systems do not discriminate between low- and intermediate-risk groups in the Japanese population. A novel, pretreatment risk stratification system including other prognostic factors is necessary for an adequate prostate cancer risk assessment in the Japanese population. [ABSTRACT FROM AUTHOR]

Objectives To assess long-term health-related quality of life in patients undergoing radical prostatectomy. Methods A total of 120 patients with at least 5 years of follow up after radical prostatectomy were included in the present study. Health-related quality of life outcomes were assessed using three questionnaires, the Short Form 36- Item Health Survey, the University of California, Los Angeles Prostate Cancer Index and the International Prostate Symptom Score. Results A total of 91 patients (73%) responded at a median follow-up time of 102 months (range 85-123 months). Among general health-related quality of life domains, mental and role composite summary score remained stable throughout the follow-up period. At the final survey, no significant differences were observed in any of the domains compared with the age-matched average score of the Japanese population. Although the slight decrease in urinary function scores and International Prostate Symptom Score beyond 5 years postoperatively compared with 5 years, the differences were not significant. The sexual function summary score showed a substantially lower score just after radical prostatectomy and remained at a deteriorated level ( P < 0.001). Responders at the final survey were more likely to report favorable general, urinary and sexual outcomes at 60 months compared with non-responders. Conclusions When taking age-related changes into account, general health-related quality of life seems to remain stable in the long term after radical prostatectomy: patients with favorable health-related quality of life outcomes during the first 5 years after radical prostatectomy maintain favorable outcomes thereafter. [ABSTRACT FROM AUTHOR]

Objectives To examine whether low-dose maintenance gemcitabine-carboplatin chemotherapy is beneficial for patients with metastatic urothelial carcinoma. Methods We retrospectively reviewed the records of 36 patients with metastatic urothelial carcinoma who received first-line chemotherapy (gemcitabine/cisplatin, gemcitabine/carboplatin, or methotrexate/vinblastine/adriamycin/cisplatin) between 2006 and 2012. Those who had responded, but were unable to tolerate ongoing first-line chemotherapy, had been switched to low-dose maintenance chemotherapy consisting of 1 g/m2 of gemcitabine and area under the curve 2-4 of carboplatin given on day 1 of a 6-week cycle, and were continued unless disease progression was seen. Results After a median of three cycles of first-line chemotherapy, 17 patients had been switched to low-dose maintenance chemotherapy. The median age was 70 years (range 56-79 years), and 12 patients (70.6%) had renal dysfunction (creatinine clearance <60 mL/min). The median number of cycles of low-dose maintenance chemotherapy was six (range 2-22), and the median survival time from initiation of first-line chemotherapy was 12 months (range 4-32 months). Adverse events requiring hospitalization were seen in three patients, but all of them recovered within a few days with conservative treatment. Seven patients discontinued within 9 months, whereas 10 patients continued on low-dose maintenance chemotherapy for ≥9 months. Patients with only lymph node metastases or who had a good response to previous first-line chemotherapy were likely to be able to continue low-dose maintenance chemotherapy. Conclusions Low-dose maintenance gemcitabine-carboplatin chemotherapy might represent an alternative for patients with metastatic urothelial carcinoma not tolerating continuous first-line standard chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Objectives To determine the necessity of pelvic lymph node dissection for low-risk prostate cancer, we analyzed the incidence of lymph node invasion and the therapeutic value of pelvic lymph node dissection in low-risk prostate cancer patients. Methods Medical records for 1268 patients undergoing open radical prostatectomy between January 2000 and December 2009 who had not undergone neoadjuvant therapy were retrospectively reviewed. Patients with low-risk disease ( n = 222; prostate-specific antigen <10 ng/mL, biopsy Gleason score ≤6, clinical T1c or T2a) were classified according to whether they underwent pelvic lymph node dissection (pelvic lymph node dissection group, n = 147) or did not (no pelvic lymph node dissection group, n = 75). Pelvic lymph node dissection was carried out in a limited style, which included the external iliac vein and the obturator fossa. The incidence of lymph node invasion was determined and referred to the preoperative nomogram developed for Japanese patients ( Japanese nomogram), Partin and Kattan nomograms. The 5-year biochemical recurrence-free survivals in both groups were analyzed. Results Lymph node invasion in low-, intermediate- and high-risk disease was 0.7% (1/147), 1.2% (7/595) and 6.1% (23/374). The 5-year biochemical recurrence-free survival rates for patients with low-risk disease were 87.6% in the pelvic lymph node dissection group and 87.1% in the no pelvic lymph node dissection group ( P = 0.65, log-rank). No patients in the pelvic lymph node dissection group exceeded 2% of lymph node invasion risk with Japanese and Partin nomograms. With the Kattan nomogram, 22.4% (33/147) of the pelvic lymph node dissection group exceeded 2% of lymph node invasion risk, and one patient had documented lymph node invasion, but none exceeded 2.5%. Conclusions Pelvic lymph node dissection can be spared at radical prostatectomy for low-risk disease, as its diagnostic and therapeutic value is poor. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Active surveillance has been widely accepted as a treatment tool for low-risk prostate cancer, and use of the Prostate Cancer Research International: Active Surveillance ( PRIAS) criteria can select smaller and less aggressive tumours in low-risk disease., The study shows the pathological outcomes of radical prostatectomy for patients with low-risk disease who met the PRIAS criteria. It found that ∼20% had unfavourable pathological features and only 30% satisfied insignificant cancer criteria with p T2 stage, a Gleason score ≤6 and tumour volume <2.5 mL. It concludes that close follow-up including repeat biopsy or MRI is necessary to minimize unexpected progression of disease., Objective To assess the effectiveness of the Prostate Cancer Research International Active Surveillance ( PRIAS) criteria in identifying indolent cancer., Patients and Methods Data from 1268 patients undergoing radical prostatectomy without neoadjuvant therapy were retrospectively reviewed., Within this cohort, patients with low-risk disease ( n = 211) were classified according to whether they met (Group A, n = 87) or did not meet (Group B, n = 124) the PRIAS criteria., Pathological upstaging, upgrading, tumour volume and 5-year prostate-specific antigen ( PSA) recurrence-free survival were compared between the two groups, and factors that predicted upstaging, upgrading and PSA recurrence were analysed by univariate and multivariate methods., Results Pathological T3 stage was present in 10.3% of patients in Group A and in 18.5% of patients in Group B ( P = 0.08). Gleason score upgrading to 4+3 or greater was seen in 19.5% of Group A and in 29.9% of Group B ( P = 0.01)., The mean (range) tumour volume was 0.81 (0.03-5.09) mL in Group A and 1.40 (0.04-8.21) mL in Group B ( P < 0.01). The rates of insignificant cancer with total tumour volume <2.5 mL, Gleason score ≤6 and stage p T2 were 30.6% in Group A and 15.4% in Group B ( P = 0.07)., With a median follow-up of 44 months, the 5-year PSA recurrence-free survival rates were 91.2% in Group A and 86.4% in Group B ( P = 0.47)., In multivariate analysis, PSA density and the PRIAS criteria were independent factors that predicted upstaging., Conclusions Although use of the PRIAS criteria could select more favourable tumours even in low-risk prostate cancer, about one in five men had unfavourable pathological outcomes and only three in ten had insignificant cancer., Close and careful follow-up is necessary to avoid misclassification or progression of disease, especially during the first few years of active surveillance. [ABSTRACT FROM AUTHOR]

Human renal cell carcinoma (RCC) has been characterized by remarkable changes in ganglioside composition. TOS1 cells, typical of metastatic RCC, are characterized by predominance of GM2 as monosialoganglioside, and β1,4GalNAc disialyl-Lc4 (RM2 antigen) as disialoganglioside [J. Biol. Chem. 276 (2001) 16695]. In order to observe the functional role of gangliosides in RCC malignancy, TOS1 cells were transfected with short interfering RNA (siRNA) based on open reading frame sequence of β1,4GalNAc transferase (β1,4GalNAc-T), and its disordered sequence of siRNA (dsiRNA) as control. In siRNA transfectant, β1,4GalNAc-T mRNA level and GM2 expression were greatly reduced, whereby GM3 expression appeared. In contrast, RM2 antigen level was unchanged, even though it has the same β1,4GalNAc epitope at the terminus. dsiRNA transfectant showed no change of β1,4GalNAc-T mRNA and did not express GM3. Concomitant with reduction of GM2 and appearance of GM3, siRNA transfectant showed greatly reduced motility and invasiveness, although growth rate was unaltered. Both transfectants with siRNA and dsiRNA expressed the same level of tetraspanin CD9. Since CD9/GM3 complex is known to reduce integrin-dependent motility and invasiveness [Biochemistry 40 (2001) 6414], it is plausible that motility and invasiveness of siRNA transfectant of TOS1 cells may be reduced by enhanced formation of such complex. [Copyright &y& Elsevier]

The present case report describes two cases of unresectable advanced primary urethral carcinoma. Case 1 was a 61-year-old man with squamous cell carcinoma of the urethra that directly invaded into the perineal skin. Case 2 was a 64-year-old woman with adenocarcinoma, and solitary lung and lymph node metastases. Both patients received docetaxel/cisplatin/5-fluorouracil chemotherapy with concurrent radiation. The docetaxel/cisplatin/5-fluorouracil chemotherapy regimen consisted of docetaxel (75 mg/m2) on day 2, cisplatin (100 mg/m2) on day 2 and 5-fluorouracil (1000 mg/m2) on days 1 to 5 and was repeated every 4 weeks. Complete response was achieved after two cycles of chemotherapy combined with radiation in case 1. In case 2, complete response was achieved locally after six cycles of chemotherapy combined with radiation, but the solitary lung lesion remained viable. We experienced two cases with advanced urethral carcinoma for whom docetaxel/cisplatin/5-fluorouracil chemotherapy chemotherapy with radiation was effective. [ABSTRACT FROM AUTHOR]

The author discusses the effectiveness of prostate-specific antigen (PSA) kinetics as marker for predicting disease progression during active surveillance (AS). It offers details of the study that shows how pre- and post-diagnostic PSA kinetics do not have predictive value of disease progression during AS. However, the author also recognizes that such methods were insufficient for AS follow and requires magnetic resonance imaging (MRI) to improve the reliability of AS.

An editorial discussing the optimal sequence of abiraterone and enzalutamide in patients with chemotherapy-naïve castration-resistant prostate cancer is presented.

A letter to the editor is presented which discusses the case report of a 64-year-old man diagnosed with squamous cell carcinoma at bulbar urethra and was completely reacted to chemotherapy and radiation therapy.

Objective To understand the current practice pattern of active surveillance using a nationwide survey among Japanese urologists. Methods A new questionnaire about active surveillance was developed and mailed to 863 training institutes in January 2014. The questionnaire included indications for active surveillance, percentage of active surveillance for localized prostate cancer, problems with active surveillance, which protocol was used, timing of first repeat biopsy, use of prostate-specific antigen or doubling time and use of magnetic resonance imaging. Results A total of 2133 Japanese urologists in the 632 training institutes answered the questionnaire. The median age was 42 years (26-84 years). Of the responders, 26.9% had no use of active surveillance for localized prostate cancer. The Prostate Cancer Research International: Active Surveillance criteria were most frequently used (29.7%), followed by a low-risk group without a definitive follow-up protocol (29.4%). Regarding repeat biopsy, 40.6% carried it out at 1 year after active surveillance initiation, but 24.1% did not usually carry it out and 31.8% carried it out only when they considered it necessary. Magnetic resonance imaging was used routinely in 22.2% and as required in 67.6%. Re-biopsy or magnetic resonance imaging was less carried out in general hospitals than in universities. The percentage of no usual repeat biopsy was significantly higher in urologists who had more than 10 years of experience. Repeat biopsies (60.3%), inadequate inclusion criteria (49.9%), psychological burden for patients (43.7%), unexpected progression (41.1%) and unknown long-term outcomes (40.6%) were considered the major problems of active surveillance in the responders. Conclusions The practice pattern of active surveillance varies widely among Japanese urologists. It is necessary to gain a correct understanding of active surveillance. [ABSTRACT FROM AUTHOR]

Treatment for ruptured renal angiomyolipoma in pregnancy requires immediate and appropriate decision-making based on the condition of the mother and fetus, and gestational age. A 37-year-old woman at 25 weeks of pregnancy presented with severe right flank pain. Computed tomography showed a ruptured right renal angiomyolipoma (8 cm in diameter). The maternal and fetal conditions were stable. Transcatheter arterial embolization was carried out electively 4 days after the rupture. Minimization of radiation exposure to the fetus was achieved by X-ray shielding for the fetus, low-dose-rate fluoroscopy, minimal angiography imaging and a color Doppler ultrasonography-guided procedure. Although threatened premature labor occurred because of post-embolization syndrome, the pregnancy was continued until cesarean section at 37 weeks of pregnancy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Transperineal template-guided mapping biopsy of the prostate" by A. Sivaraman and colleagues that was published in the previous issue.