Improving compliance with guidelines may lead to favorable clinical outcomes for patients with non-muscle-invasive bladder cancer: A retrospective multicenter study.

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.

Sexual function using the EORTC QLQ-TC26 in testicular cancer survivors: A multi-institutional, cross-sectional study.

OBJECTIVE: To evaluate sexual function after treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 (EORTC QLQ-TC26) questionnaire in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study. METHODS: This study enrolled TC survivors who visited any of eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants completed the EORTC QLQ-TC26 questionnaires. We evaluated sexual function after treatment for TC using the EORTC QLQ-TC26 and analyzed the impact of treatment on sexual function in TC survivors. RESULTS: A total of 567 TC survivors responded to the EORTC QLQ-TC26. Median age at the time of response was 43 years (interquartile range [IQR] 35-51 years), and median follow-up period after treatment was 5.2 years (IQR 2.2-10.0 years). Sexual function, particularly ejaculatory function, was significantly lower after post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) than after Surveillance or Chemotherapy groups (p < 0.05). In the PC-RPLND group, nerve-sparing procedure preserved postoperative ejaculatory function after RPLND compared with the non-nerve-sparing and offered improved ejaculatory function with time. On multivariate analysis, RPLND was a significant predictor of post-treatment ejaculatory dysfunction, particularly without nerve-sparing (odds ratio 3.0, 95% CI 1.2-7.7, p < 0.05). In addition, TC survivors with nerve-sparing RPLND had higher sexual activity than those without. CONCLUSION: This survey of the EORTC QLQ-TC26 showed that sexual function and activity in TC survivors after RPLND was reduced in the absence of nerve-sparing techniques.

Significance of upfront cytoreductive nephrectomy stratified by IMDC risk for metastatic renal cell carcinoma in targeted therapy era - a multi-institutional retrospective study.

BACKGROUND: This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria. METHODS: We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method. RESULTS: Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months, p < 0.01) and in patients with IMDC poor risk (27.2 versus 11.4 months, p < 0.01). In IPTW-adjusted Cox regression analysis of time-varying covariates, upfront CN was independently associated with OS benefit in patients with IMDC intermediate risk (hazard ratio 0.52, 95% confidence interval 0.29-0.93, p = 0.03) and in patients with IMDC poor risk (0.26, 0.11-0.59, p < 0.01). CONCLUSIONS: Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.

Minimal residual membranous urethral length and membranous urethral length predict poor recovery from incontinence after robot-assisted radical prostatectomy and after open radical prostatectomy.

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.

Outcomes of artificial urinary sphincter implantation in patients with diabetes mellitus: A subgroup analysis.

OBJECTIVES: To estimate the surgical and quality-of-life outcomes of artificial urinary sphincter implantation in patients with diabetes mellitus (DM). Subanalyses were performed using the same population as that in our previous multicenter, prospective, observational study. METHODS: A total of 135 male patients who underwent primary artificial urinary sphincter implantation were divided into two groups: those with and without DM. The revision-free rates, that is, the percentage of patients who did not require revision surgery, were compared between patients with and without DM. The number of urinary pads required per day, International Consultation on Incontinence Questionnaire-Short Form, and King's Health Questionnaire were used to compare the continence status and quality of life (QOL) between the two groups preoperatively and at 1, 3, and 12 months after surgery. RESULTS: Revision-free rates were significantly lower in the DM group (83.9%, 77.4%, and 67.8% at 1, 2, and 3 years after implantation, respectively) than in the non-DM group (95.5%, 92.5%, and 85.5% at 1, 2, and 3 years after implantation, respectively). Both continence status and QOL, assessed by questionnaires, markedly improved after surgery in patients with and without DM. CONCLUSIONS: Despite differences in the durability of the artificial urinary sphincters, patients with DM can obtain as much benefit from artificial urinary sphincter implantation regarding continence and quality-of-life improvement as patients without DM. Therefore, DM was not considered a comorbidity that contraindicated artificial urinary sphincter implantation. Additional large-scale studies are required to verify our findings.

Impact of Gleason pattern 5 on prognosis for newly diagnosed metastatic hormone-sensitive prostate cancer with Gleason score ≥8.

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.

Association of financial toxicity with quality of life in testicular cancer survivors.

OBJECTIVES: Most testicular cancer (TC) survivors have long-term survival. However, the association between financial toxicity (FT), which is an economic side effect of cancer treatment, and the quality of life (QOL) of TC survivors is still unclear. Thus, the impact of FT on the QOL of TC survivors was examined in a multi-institutional cross-sectional study. METHODS: We recruited TC survivors from eight high-volume institutions in Japan between January 2018 and March 2019. A total of 562 participants completed the EORTC QLQ-C30, EORTC QLQ-TC26 and the questionnaires on demographics, including annual income. Financial difficulty in the EORTC QLQ-C30 and low income were used to assess financial distress (FD) and financial burden (FB), respectively. FT was defined as FD and FB. The QOL scores were compared, and a multivariate logistic regression analysis for FT was performed. RESULTS: With severe FD, TC survivors had more treatment side effects, physical limitations, and anxiety concerning employment and future. The TC survivors who reported low income were worried about their jobs and the future. The QOL of the survivors with FT exhibited high impairment, except for sexual activity. In particular, the TC survivors with FT were physically limited and anxious concerning the future. The multivariate logistic regression analysis revealed that four or more chemotherapy cycles were substantial risk factors for FT (4 cycles, odds ratio (OR) = 4.17; ≥5 cycles, OR = 6.96). CONCLUSIONS: TC survivors who received multi-cycle chemotherapy were prone to experience FT, resulting in a decline in their health-related QOL.

Impact of Nerve-Sparing Status on Positive Surgical Margin Location and Biochemical Recurrence in Patients with Prostate Cancer Post Radical Prostatectomy.

PURPOSE: This study was designed to assess the relationship between nerve-sparing (NS) status, positive surgical margin (PSM) location, and biochemical recurrence (BCR) based on a multicenter, radical prostatectomy (RP) database. METHODS: We retrospectively reviewed data from 726 patients who underwent RP without any neoadjuvant or adjuvant treatment between 2010 and 2014. We statistically assessed the impact of NS sides on PSM location and BCR. RESULTS: PSM rates were 21.9% in the 726 patients studied, 13.2% in patients with ≤pT2, and 46.8% in patients with ≥pT3. Regarding PSM locations, the anterior-apex (AA) was the most common site for PSM (43.3%). After adjusting for confounding factors, bilateral nerve sparing (BNS) had a significantly higher odds ratio of PSM than the absence of NS did (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.85-4.99). In the UNS RP in patients with ≤pT2, non-AA PSM on the non-NS side was significantly higher than that on the NS side (92.9% vs. 45.5%, p = 0.009). In all patients, 5.8% experienced BCR during a median follow-up of 43.5 months. PSM was significantly associated with BCR-free survival in patients with ≤pT2 (p = 0.013), but not in patients with ≥pT3 (p = 0.185). Non-AA PSM at the non-NS side was an independent risk factor for BCR (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.12-5.85), whereas AA PSMs, including NS/non-NS sides and non-AA PSM at the NS side, were not associated with BCR-free survival. CONCLUSIONS: Avoidance of non-AA PSM on the non-NS side may be rather important for maintaining BCR-free survival after RP.

Impact of cancer therapy on post-treatment ejaculation disorder and sexual life in testicular cancer survivors.

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.

Fertility and reproductive technology use in testicular cancer survivors in Japan: A multi-institutional, cross-sectional study.

OBJECTIVE: To evaluate fertility and use of reproductive technology of testicular cancer survivors in a multi-institutional, cross-sectional study. METHODS: This study recruited testicular cancer survivors who were followed after treatment for testicular cancer at eight high-volume institutions between 2018 and 2019. The participants completed the questionnaires on marital status, fertility and use of reproductive technology. RESULTS: A total of 567 testicular cancer survivors, with a median age of 43 years, responded to the questionnaire. Chemotherapy was given to 398 survivors, including three cycles of cisplatin-based chemotherapy in 106 patients and four cycles in 147 patients. Among 153 survivors who attempted sperm cryopreservation, 133 (87%) could preserve sperm. Of the 28 survivors whose cryopreserved sperm was used, 17 (61%) fathered children. Of the 72 survivors who fathered children without the use of cryopreserved sperm, 59 (82%) fathered naturally. Whereas 33 (20%) of 169 survivors treated without chemotherapy fathered children without using cryopreserved sperm, 39 (10%) of 398 treated with chemotherapy fathered children (P < 0.05). Furthermore, the paternity rate was 12% and 5% in testicular cancer survivors with three and four cycles of cisplatin-based chemotherapy, respectively (P < 0.05). However, of 121 survivors who wanted to have children, 14 (12%) received counseling about infertility treatment. CONCLUSIONS: Testicular cancer survivors preserving their sperm have a higher paternity rate after chemotherapy, especially after four cycles, than those not using cryopreserved sperm. Physicians who give chemotherapy for testicular cancer need to take particular care not only with respect to recurrence of testicular cancer, but also to post-treatment fertility.

Validation study of the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 for patients with testicular cancer.

OBJECTIVE: To validate the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 in Japanese-speaking testicular cancer survivors. METHODS: A total of 200 testicular cancer survivors were recruited at eight high-volume institutions in Japan. The participants completed the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the International Index of Erectile Function 15 questionnaires. A total of 40 participants completed a retest of the questionnaires 2 weeks after the first response. The psychometric properties of the Japanese version including test-retest reliability, internal consistency and concurrent validity were evaluated. RESULTS: The mean age at response was 43 years (range 22-74 years), and the mean period after treatment was 77 months (range 0-416 months). The response rate for each item, except sexual function, was high, and the percentage of missing values was less than 3.5%. For test-retest reliability, seven of 12 scales met the criteria (intraclass correlation 0.70-0.86). For internal consistency, four of seven scales met the criteria (Cronbach's alpha 0.62-0.91). For concurrent validity, treatment side effects of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were related to some domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The sex-related subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were moderately correlated with some International Index of Erectile Function 15 domains. CONCLUSIONS: The psychometric properties of the Japanese version are equivalent to the properties of the original European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26. The Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 questionnaire is a useful tool to assess the health-related quality of life of testicular cancer patients.

Clinical outcomes and prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy: a retrospective multicenter study in Japan.

PURPOSE: Clinical outcomes of patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC) and initially treated with androgen deprivation therapy (ADT) were evaluated. METHODS: The medical records of 605 consecutive mHNPC patients with initial ADT or combined androgen blockade (CAB) at nine study centers between 2008 and 2016 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free and overall survival (OS) were estimated by the Kaplan-Meier method. The association of pretreatment risk factors with CRPC-free survival and OS was evaluated by Cox proportional hazard models and differences in survival were classified by the number of risk factors. RESULTS: Median follow-up was 2.95 years, median CRPC-free survival was 21.9 months and median OS was 5.37 years. Multivariable analysis found that four risk factors, a Gleason score ≥ 9, lymph node metastasis, an extent of disease score ≥ 2, and serum LDH of > 220 IU were independently associated with both CRPC-free survival and OS. Median CRPC-free survival of low-risk patients with no or one factor was 86.5 months, 17.9 months in intermediate-risk patients with two or three factors, and 11.0 months in high-risk patients with four factors. Median OS was 4.72 years in intermediate- and 2.44 years in high-risk patients. It was not reached in low-risk patients. CONCLUSION: In this series, CRPC-free and OS of a subset of mHNPC patients in Japan who were treated with ADT or CAB had better CRPC-free and overall survivals in Japan. Risk-adapted treatment based on the presence of novel prognostic factors may be beneficial for selected mHNPC patients.

Trends in Age and Histology of Testicular Cancer from 1980-2019: A Single-Center Study.

Testicular cancer occurs in the testes of the male reproductive system and is the most common cancer in adolescent and young adult (AYA) men. However, recently, there have been more cases of testicular cancer in men older than 40 years. Therefore, trends of testicular cancer during the past 40 years were retrospectively examined, focusing on age and histology. Patients who were diagnosed with testicular cancer at our institution between 1980 and 2019 were enrolled in this study. The patients were divided into groups by the year of diagnosis (1980s, 1990s, 2000s, and 2010s), age at diagnosis (14, 15 to 39, and older than 40 years), and histological type (seminoma and non-seminoma). A total of 563 patients were diagnosed with testicular cancer over the 40-year period. The median age at diagnosis increased continuously, from 28 years to 31 years, 34 years, and 38 years in each period, respectively (p < 0.001). Moreover, most testicular cancer patients were of the AYA generation, whereas the ratio of patients older than 40 years increased significantly since 2000 (p < 0.001). The relative proportion of seminoma also increased more than 50% since 2000. In the seminoma group, median age increased from 31 years to 41 years during the 40-year period (p < 0.001). In conclusion, the age at diagnosis is rising for testicular cancer patients. Clinicians should recognize that testicular cancer affects not only the AYA generation, but there has been a shift to older than 40 years, especially in seminoma.

Association of tumor burden with the eligibility of upfront intensification therapy in metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

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.

Value of global metabolomics in association with diagnosis and clinicopathological factors of renal cell carcinoma.

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.

Phosphodiesterase type 5 inhibitor attenuates chronic ischemia-induced prostatic hyperplasia in a rat model.

BACKGROUND: Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated. RESULTS: In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group. CONCLUSIONS: Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.

The efficacy and toxicity of cabazitaxel for treatment of docetaxel-resistant prostate cancer correlating with the initial doses in Japanese patients.

BACKGROUND: We analyzed the efficacy and toxicity of cabazitaxel (CBZ) at high and low initial doses in Japanese patients with docetaxel-resistant castration-resistant prostate cancer (CRPC). METHODS: We retrospectively evaluated 118 patients who received CBZ for docetaxel-resistant CRPC in 10 university hospitals in Japan between 2014 and 2016. The rate of decrease of prostate-specific antigen (PSA), adverse events, progression-free survival (PFS), and overall survival (OS) were compared between patients receiving initially high (≥22.5 mg/m2, n = 36) and low (≤20 mg/m2, n = 80) CBZ doses. Factors associated with survival and grade 4 neutropenia were evaluated. RESULTS: PSA values decreased by > 50% in 22 patients (19%), with a higher frequency in the high-dose group than in the low-dose group (29 and 14%, P = 0.073). The median PFS time for the all-patient, high- and low-dose groups was 2.8 months (95% confidence interval [CI] 1.9-4.4), 2.1 months (1.2-5.5), and 3.0 months (2.0-4.4), respectively (P = 0.904). The median OS times were 16.3 months (95% CI 9.7-30.9), 30.9 months (11.8-47.4), and 10.2 months (8.6-20), respectively (P = 0.020). In multivariate analyses, PFS was significantly associated with existing bone metastasis at diagnosis (P = 0.005) and OS with PSA > 100 ng/ml (P = 0.007), hemoglobin < 12 g/dl (P = 0.030), and low initial CBZ dose (P = 0.030). Grade 4 neutropenia occurred in 53 patients (45%) and was associated with a low CBZ dose (hazard ratio 0.21, 95% CI 0.08-0.59, P = 0.002). CONCLUSIONS: CBZ at a higher initial dose may have similar response rate and response duration, but longer survival duration after treatment with higher toxicity than a lower initial dose for docetaxel-resistant CRPC in Japanese patients.

Penile blood pressure is useful to identify candidates for tadalafil treatment in patients with lower urinary tract symptoms.

OBJECTIVES: To determine whether penile blood pressure (PBP) can be used to identify patients who can benefit from tadalafil treatment, the correlation between PBP at baseline and changes in lower urinary tract symptoms (LUTS) induced by tadalafil treatment was studied prospectively. PATIENTS AND METHODS: Patients with BPH who were poor responders to α1 -blockers and took tadalafil instead of an α1 -blocker were registered between 2014 and 2016. The patients were divided into two groups (low- and high-PBP groups) using the median baseline PBP of 110 mmHg as the threshold. The changes in the International Prostate Symptom Score (IPSS) between before and at 4 and 12 weeks after tadalafil treatment were compared between the low- and high-PBP groups. Multivariate analysis was performed to identify parameters associated with IPSS improvement with tadalafil treatment. RESULTS: In all, 51 patients were investigated. The IPSS in the low-PBP group decreased immediately after the start of treatment, and there was significant improvement in the IPSS from baseline at 4 and 12 weeks after the start of treatment, whilst the IPSS in the high-PBP group did not show significant changes. On multivariate analysis, PBP at baseline, anticholinergic drug use, and IPSS at baseline were significant predictors of a good IPSS response to tadalafil treatment. CONCLUSIONS: This study demonstrated that PBP could reliably identify patients with BPH who could benefit from tadalafil treatment. Patients with low PBP could be better responders to tadalafil.

Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer.

PURPOSE: We determine whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: We reviewed the Michinoku Japan Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW)-adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis. RESULTS: Median age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir > 0.64 ng/mL and TTN < 7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC. The IPTW-adjusted multivariate model revealed that the unfavorable group had a negative impact on OS in mCRPC patients [hazards ratio (HR) 2.98, P < 0.001]. CONCLUSIONS: Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.

Impact of nutritional status on the prognosis of patients with metastatic hormone-naïve prostate cancer: a multicenter retrospective cohort study in Japan.

PURPOSE: To investigate the association between the Geriatric Nutritional Risk Index (GNRI) and prognosis of patients with metastatic hormone-naïve prostate cancer (mHNPC) and to design the optimal risk score predicting for prognosis. METHODS: We retrospectively reviewed data from the Michinoku Japan Urological Cancer Study Group database, containing information about 656 patients with mHNPC who initially received androgen-deprivation therapy between 2005 and 2017. The baseline GNRI was calculated using serum albumin level and body mass index. Poor nutrition was defined as GNRI < 92.0. The impact of GNRI, CHAARTED criteria, and laboratory parameters on oncological outcomes was investigated using the multivariable Cox regression models. We developed the risk comprising GNRI and laboratory parameters and compared its prognostic performance with the CHAARTED criteria using the receiver operating characteristic curve with the DeLong method. RESULTS: Of 339 patients with sufficient data, 66 (19%) were diagnosed with poor nutrition. Multivariate analyses showed that GNRI < 92.0 was an independent prognostic factor of cancer-specific survival [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.04-2.98, P = 0.035] and overall survival (HR 1.80; 95% CI 1.13-2.89, P = 0.013), in addition to hemoglobin (Hb) and lactic dehydrogenase (LDH) levels. We designed the risk score comprising GNRI < 92.0, Hb < 13.0 g/dL, and LDH > 222 IU/L. The predictive value of the risk score was significantly superior to that of the CHAARTED criteria. CONCLUSIONS: Poor nutrition may predict mortality in patients with mHNPC. Risk factors, such as nutritional status and laboratory parameters, may be useful in decision-making regarding aggressive treatments for patients with mHNPC.