Diversity in treatment modalities of Stage II/III urothelial cancer in Japan: sub-analysis of the multi-institutional national database of the Japanese Urological Association.

OBJECTIVE: We aimed to survey treatment modalities for the patients with Stage II/III urothelial cancer in Japan. METHODS: We used the multi-institutional national database of the Japanese Urological Association from 348 Japanese institutions, in which a total of 3707 patients with muscle-invasive bladder cancer and 1538 with upper urinary tract urothelial carcinoma were registered in 2008 and 2011, respectively. Primary treatment was classified as surgery alone, surgery with chemotherapy, surgery with radiation, radiation alone, chemotherapy alone, combination of radiation and chemotherapy and observation. Overall and cancer-specific survivals were examined using the Kaplan-Meier method, and survival in the subgroups was analyzed using the log-rank test. RESULTS: In Stage II/III bladder cancer patients, 49.7% of those were treated with radical operation and 22.3% received observation only. A total 97.2% of Stage II/III upper urinary tract urothelial carcinoma patients treated with radical surgery. A total 30.4% of Stage II/III bladder cancer patients received chemotherapy. Majority of the patients received cisplatin-based regimen, however, regimens of chemotherapy was rich in variety up to 13 regimens. Chemotherapy regimens for the patients with upper urinary tract urothelial carcinoma were also various up to eight regimens. Overall and cancer-specific survivals were statistically significantly stratified according to the clinical stage. The upper urinary tract urothelial carcinoma patients diagnosed with clinical stage T3 had significantly poor prognosis compared with those diagnosed with clinical stage T2. CONCLUSIONS: This study demonstrated the variety of treatments used for Japanese patients with Stage II/III urothelial cancer. Treatment standardization for these entities may be necessary.

Impact of multimodal treatment on prognosis for patients with metastatic upper urinary tract urothelial cancer: Subanalysis of the multi-institutional nationwide case series study of the Japanese Urological Association.

OBJECTIVES: To describe the nature of metastatic upper urinary tract urothelial cancer and determine the prognostic predictors or treatment modality associated with all-cause mortality. METHODS: Within the nationwide case series study of the Japanese Urological Association, consisting of 1509 patients with urinary tract urothelial cancer diagnosed in 2005, we identified 102 patients with metastatic urinary tract urothelial cancer. Univariate and multivariate survival analyses identified prognostic outcome variables. RESULTS: Predominant sites of distant metastasis at diagnosis were the lungs (54.9%), distant lymph nodes (37.3%), bone (32.4%) and liver (19.6%). Of 102 patients, 70 patients (68.6%) died during the median follow-up period of 6 months, and the 2-year overall survival rate was estimated at 22%. The median survival time to all-cause mortality was 8.5 months (95% confidence interval 6.4-10.7 months). On multivariate analysis, independent predictive factors for all-cause mortality were age (hazard ratio 2.36, P = 0.015) and liver metastasis (hazard ratio 2.35, P = 0.037). Patients who received multimodal treatment including chemotherapy and surgery showed significantly better prognosis (median survival time 25.8 months) compared with patients treated with chemotherapy alone (median survival time 7.3 months) or best supportive care (median survival time 4.3 months). CONCLUSIONS: Age at diagnosis and the presence of liver metastasis seem to have an impact on survival of metastatic urinary tract urothelial cancer patients. Multimodal treatment including systemic chemotherapy and surgery might result in better prognosis in some of these patients.

Diagnostic performance and safety of a three-dimensional 14-core systematic biopsy method.

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 <20 ng/mL.

Risk stratification for bladder recurrence of upper urinary tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVES: To identify risk factors and develop a model for predicting recurrence of upper urinary tract urothelial carcinoma (UTUC) in the bladder in patients without a history of bladder cancer after radical nephroureterectomy (RNU). PATIENTS AND METHODS: We retrospectively reviewed 754 patients with UTUC without prior or concurrent bladder cancer or distant metastasis at 13 institutions in Japan. Univariate and multivariate Fine and Gray competing risks proportional hazards models were used to examine the cumulative incidence of bladder recurrence of UTUC. A risk stratification model and a nomogram were constructed. Two prediction models were compared using the concordance index (c-index) focusing on predictive accuracy and decision-curve analysis, which indicate whether a model is appropriate for decision-making and determining subsequent patient prognosis. RESULTS: The cumulative incidence rates of bladder UTUC recurrence at 1 and 5 years were 15 and 29%, respectively; the median time to bladder UTUC recurrence was 10 months. Multivariate analysis showed that papillary tumour architecture, absence of lymphovascular invasion and higher pathological T stage were both predictive factors for bladder cancer recurrence. The predictive accuracy of the risk stratification model and the nomogram for bladder cancer recurrence were not different (c-index: 0.60 and 0.62). According to the decision-curve analysis, the risk stratification was an acceptable model because the net benefit of the risk stratification was equivalent to that of the nomogram. The overall cumulative incidence rates of bladder cancer 5 years after RNU were 10, 26 and 44% in the low-, intermediate- and high-risk groups, respectively. CONCLUSIONS: We identified risk factors and developed a risk stratification model for UTUC recurrence in the bladder after RNU. This model could be used to provide both an individualised strategy to prevent recurrence and a risk-stratified surveillance protocol.

Clinical response to induction chemotherapy predicts improved survival outcome in urothelial carcinoma with clinical lymph nodal metastasis treated by consolidative surgery.

BACKGROUND: To determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Impact of smoking on the age at diagnosis of upper tract urothelial carcinoma: Subanalysis of the Japanese Urological Association multi-institutional national database.

OBJECTIVES: To examine the influence of smoking history on the diagnosis and other tumor characteristics of upper tract urothelial carcinoma in Japan. METHODS: A total of 1509 patients with upper tract urothelial carcinoma who were diagnosed in 2005 from 348 Japanese institutions were registered using the multi-institutional national database of the Japanese Urological Association and included in this analysis. Clinical data of the patients were collected in 2011. The associations between the patients' self-reported smoking history and their age at the diagnosis of upper tract urothelial carcinoma, sex, pathological T stage and tumor grade were analyzed. RESULTS: The mean age at the diagnosis of upper tract urothelial carcinoma was approximately 5 years earlier for the 238 current smokers than for the 618 current non-smokers (P < 0.0001). Similar associations between smoking and the early diagnosis of upper tract urothelial carcinoma were shown in the sex subgroups and in subgroups stratified by pathological T stages. Among the current smokers, the age at diagnosis for the smoking ≥ 20 cigarettes per day group was 6.5 years lower than that of the < 20 cigarettes per day group, which was significantly different (P < 0.0001). CONCLUSION: Current smoking is a significant risk factor for the earlier diagnosis of upper tract urothelial carcinoma. The finding is important from the perspective of both healthcare and medical economies.

Prognostic factors of recurrent disease in upper urinary tract urothelial cancer after radical nephroureterectomy: Subanalysis of the multi-institutional national database of the Japanese Urological Association.

OBJECTIVES: To explore predictive factors of disease recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial cancer. METHODS: A multi-institutional national database promoted by the Japanese Urological Association including 293 institutions and 1172 patients was used for the present study. Patient with non-metastatic upper urinary tract urothelial cancer who underwent primary radical nephroureterectomy with curative intent were analyzed. Univariate analysis using the Kaplan-Meier method and multivariate Cox regression models with stepwise selection was used to evaluate time to recurrence after surgery. RESULTS: The median duration of follow up was 55.8 months, and disease recurred in 325 (27.7%) patients at a median of 11.4 months after radical nephroureterectomy. According to a Cox proportional hazards model, the Union International Contre le Cancer 2002 pathological stage of the primary tumor, lymph node status, presence of lymphatic and/or vascular invasion, infiltrative growth pattern, and age were independent predictors (P < 0.05) of recurrence-free survival. CONCLUSIONS: Despite several limitations, our analysis suggests that pathological tumor stage, lymph node status, lymphovascular invasion, infiltrative growth pattern and age represent important prognostic variables after radical nephroureterectomy in Japanese patients with upper urinary tract urothelial cancer. This information could be potentially used to select patients for adjuvant systemic therapy.

Renal function after radical nephrectomy: development and validation of predictive models in Japanese patients.

OBJECTIVES: To develop and validate predictive models for postoperative estimated glomerular filtration rate and risk of chronic kidney disease after radical nephrectomy in Japanese patients. METHODS: The present retrospective study included a development cohort of 209 patients without preoperative chronic kidney disease who underwent radical nephrectomy between 1994 and 2008, and were followed up for longer than 3 years, and a validation cohort of 144 similar such patients. Univariate and multivariate linear regression or logistic regression analyses were carried out to identify the independent predictors of estimated glomerular filtration rate or chronic kidney disease 3 years after radical nephrectomy. Incorporating all independent predictors, predictive models for postoperative renal function were developed and externally validated. RESULTS: Age, the presence of diabetes mellitus, and preoperative estimated glomerular filtration rate were independent predictors of both postoperative estimated glomerular filtration rate and chronic kidney disease. A formula for predicting the postoperative estimated glomerular filtration rate and a nomogram for predicting the risk of postoperative chronic kidney disease were developed. The adjusted R(2) of the formula and area under the receiver operating characteristic curves of the nomogram were 0.446 and 0.865 in the development cohort, and 0.396 and 0.787 in the validation cohort, respectively. CONCLUSIONS: We developed and validated novel predictive models for the postoperative renal function 3 years after radical nephrectomy in Japanese patients.

First-line combination chemotherapy with cisplatin, etoposide and ifosfamide for the treatment of disseminated germ cell cancer: re-evaluation in the granulocyte colony-stimulating factor era.

BACKGROUND: This study re-evaluated the efficacy and tolerability of cisplatin, etoposide, and ifosfamide (VIP) combination chemotherapy as an alternative first-line regimen for patients with disseminated germ cell cancer (GCC) in this granulocyte colony-stimulating factor (G-CSF) era. METHODS: The medical records of 91 consecutive patients with previously untreated disseminated GCC who received first-line VIP between 1995 and 2011 were retrospectively reviewed. RESULTS: The 5-year overall survival rates for patients with good (n = 49), intermediate (n = 22) and poor (n = 20) prognoses according to the International Germ Cell Cancer Collaborative Group classification were 100, 79 and 83%, respectively. G-CSF was given to all patients, and no treatment-related deaths due to myelosuppression occurred. CONCLUSION: The present study is the first to examine the therapeutic outcomes and safety profile of first-line VIP after routine G-CSF use. VIP might be an alternative first-line regimen for patients with disseminated GCC in this G-CSF era.

Characteristics and clinical significance of prostate cancers missed by initial 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.

Performance of prostate-specific antigen mass in estimation of prostate volume in Japanese men with benign prostate hyperplasia.

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.

Perioperative complications of radical cystectomy after induction chemoradiotherapy in bladder-sparing protocol against muscle-invasive bladder cancer: a single institutional retrospective comparative study with primary radical cystectomy.

OBJECTIVE: To compare rates of early morbidity after radical cystectomy in patients treated with or without induction chemoradiotherapy (CRT) using a standardized reporting methodology. METHODS: All 193 consecutive patients undergoing radical cystectomy for bladder cancer between 1989 and 2010 were retrospectively reviewed. Induction chemoradiotherapy consists of radiation at 40 Gy to the small pelvis and two cycles of concurrent cisplatin at 20 mg/day for 5 days. Deaths within 90 days after radical cystectomy and complications arising within 30 days were recorded and graded according to the Clavien-Dindo classification. Grades 1-2 were considered minor; Grades 3-5 were considered major. RESULTS: Eighty-seven patients underwent radical cystectomy following chemoradiotherapy (chemoradiotherapy group) while the remaining 106 primarily underwent radical cystectomy (no chemoradiotherapy group). No Grade 4-5 complication was observed. Overall, 118 patients (61%) experienced 36 major and 122 minor complications. There was no significant difference in the incidence of overall complications between the chemoradiotherapy and no chemoradiotherapy groups (67 vs. 57%). Overall urinary anastomosis-related complications and major gastrointestinal complications, most of which were Grade 3 ileus, were more frequent in the chemoradiotherapy group than the no chemoradiotherapy group (11 vs. 2%, P = 0.007; and 14 vs. 4%, P = 0.02; respectively). Multivariate analysis identified induction chemoradiotherapy as an independent risk factor for overall urinary anastomosis-related complications (relative risk 6.0, P = 0.01) but not for major gastrointestinal complications. CONCLUSIONS: Induction chemoradiotherapy at 40 Gy in bladder-sparing protocols against MIBC is unlikely to increase the rate of severe complications of radical cystectomy.

Rolipram, a specific type-4 phosphodiesterase inhibitor, inhibits cyclophosphamide-induced haemorrhagic cystitis in rats.

OBJECTIVE: To investigate the protective roles of type 4 phosphodiesterase (PDE4) inhibitor in cyclophosphamide (CYP)-induced haemorrhagic cystitis, as the PDE4 inhibitor has anti-inflammatory effects but its characterization is still unknown in urinary tract diseases. MATERIALS AND METHODS: In female Sprague-Dawley rats, CYP was administered intraperitoneally and bladders were harvested 24 h after CYP injection. In another group, rolipram as a PDE4 inhibitor was administered before CYP treatment. The effects and mechanisms of CYP with/without rolipram pretreatment were evaluated by microscopic features, bladder wet weight, myeloperoxidase (MPO) activity, nitric oxide (NO)-metabolite production and expression levels of inflammation-related genes. RESULTS: CYP injection resulted in severe cystitis. Pretreatment with rolipram significantly reduced the increase in bladder wet weight and MPO activity, and ameliorated histological inflammatory changes caused by CYP. The levels of inflammation-related transcripts including inducible NO synthase (iNOS), interleukin-1beta and tumour necrosis factor-alpha, induced by CYP, were down-regulated significantly by pretreatment with rolipram. Also, rolipram reduced the NO-metabolite production and iNOS protein expression in the immunohistochemical examination. CONCLUSION: These results indicate that rolipram can attenuate the development of CYP-induced cystitis in rats by suppressing cytokine production and iNOS induction. Thus, treatment with PDE4 inhibitor has potential clinical implications of the prevention of bladder inflammatory diseases.

Successful management of life-threatening choriocarcinoma syndrome with rupture of pulmonary metastatic foci causing hemorrhagic shock.

We report a case of a man with testicular cancer metastatic to the lung and retroperitoneal lymph node, with significant elevation of serum levels of human chorionic gonadotropin, 534,000 mIU/mL. Just after the initiation of chemotherapy, life-threatening hemothorax occurred and hemorrhagic shock ensued. The pulmonary tumor had broken off, and lower lobectomy was carried out. Pathologic examination of the specimen revealed choriocarcinoma and yolk sac tumor. Through multimodal treatments he achieved complete remission. To our knowledge, this is the first case report of choriocarcinoma syndrome with life-threatening hemorrhage caused by rupture of pulmonary metastases, resulting in complete remission through multimodal treatments.

Prospective comparative study of single dose versus 3-day administration of antimicrobial prophylaxis in minimum incision endoscopic radical prostatectomy.

OBJECTIVE: From the critical stand point against the overuse of antimicrobial agents, appropriate reduction of antimicrobial prophylaxis (AMP) should be considered. We have prospectively reduced AMP and evaluated the occurrence of surgical site infection (SSI) following radical retropubic prostatectomy (RRP) by minimum incision endoscopic surgery (MIES). METHODS: A total of 101 consecutive patients who underwent MIES-RRP for prostate carcinoma were classified into two groups according to AMP dose. The 3-day group of 52 patients received tazobactam sodium/piperacillin sodium (TAZ/PIPC) 2.5 g intravenously before the operation and continued twice daily until postoperative day 2, and the single dose group of 49 patients received TAZ/PIPC 2.5 g intravenously only once before the operation. Additional antimicrobial agents were given only when SSI occurred. The occurrence of SSI and remote infection (RI) were analyzed. RESULTS: There was no significant difference in the rate of SSI occurrence between the 3-day group (3.8%) and single dose group (6.1%) (P = 0.6). RI did not increase in the single dose group. CONCLUSION: Antimicrobial prophylaxis dose was successfully reduced without increasing SSI or RI. A single dose of AMP is feasible to prevent SSI and RI and would be a standard regimen in MIES-RRP. Active surveillance of postoperative infection is mandatory to promptly administer antimicrobial treatment as the need arises.

Collecting duct carcinoma with acquired cystic disease of the kidney in a long-term hemodialysis patient.

We report a very rare case of collecting or Bellini duct carcinoma (CDC) found in a 60-year-old male who had received hemodialysis therapy for 21 years. Screening with ultrasonography revealed a solid tumor originating from the cyst wall in the right kidney with acquired cystic disease of the kidney. Subsequent computed tomography (CT) and angiography could not detect another renal tumor. Right radical nephrectomy was performed. The tumor detected preoperatively was composed of papillary renal cell tumor (RCC) and multiple clear cell carcinoma, pathologically. In addition to the tumors, CDC was revealed in the central medulla with the involvement of regional lymph nodes. Three months later, left nephrectomy was performed because left RCC was suspected during CT. The histological diagnosis was multiple clear cell carcinomas. Peritonitis carcinomatosa appeared and the patient died 13 months later.

Lymphovascular invasion is independently associated with poor prognosis in patients with localized upper urinary tract urothelial carcinoma treated surgically.

PURPOSE: We explored the prognostic impact of lymphovascular invasion in patients with localized upper urinary tract urothelial carcinoma. MATERIALS AND METHODS: The clinical records of 135 patients treated surgically for localized upper urinary tract urothelial carcinoma (pTa-3N0M0) were reviewed retrospectively. Lymphovascular invasion was defined as cancer cells in an endothelium lined space. Actuarial survival curves were calculated by the Kaplan-Meier method. Differences between survival curves were evaluated by the log rank test. Multivariate analysis was performed using the Cox proportional hazard model. RESULTS: Median followup was 55 months (range 3 to 232). Lymphovascular invasion was present in 57 patients (42.2%) and it was associated with higher pathological T stage and higher tumor grade. Recurrence-free and disease specific survival rates in patients with lymphovascular invasion were significantly worse than those in patients without lymphovascular invasion (p = 0.001 and 0.001, respectively). Multivariate analysis revealed that lymphovascular invasion, patient age and pathological T stage were significant prognostic factors for recurrence-free and disease specific survival. Based on multivariate analysis patients were divided into 4 risk groups, including pT2 or less/negative lymphovascular invasion, pT2 or less/positive lymphovascular invasion, pT3/negative lymphovascular invasion and pT3/positive lymphovascular invasion. Recurrence-free and disease specific survival rates in patients with pT3/positive lymphovascular invasion were significantly worse than rates in the other 3 groups (each p <0.001). CONCLUSIONS: The current study indicates that positive lymphovascular invasion predicts poor survival in patients with pathologically localized upper urinary tract urothelial carcinoma. Risk stratification based on lymphovascular invasion status and pathological T stage would be helpful for selecting patients at high risk who would be appropriate candidates for clinical trials.

Efficacy and Safety Profile of Enzalutamide for Japanese Patients with Castration-resistant Prostate Cancer.

Enzalutamide is a novel, non-steroidal anti-androgen that was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) in 2014 in Japan. To assess the potency of enzalutamide treatment in Japan, we performed a pilot retrospective study. Among 91 patients who received treatment in our Institution between May 2014 and July 2015, 51 patients with docetaxel-naïve CRPC (56.0%) underwent enzalutamide therapy. The median progression-free survival (PFS) and overall survival (OS) were 10.2 months and 27.9 months, respectively. The remaining 40 patients with CRPC (44.0%) underwent enzalutamide therapy after docetaxel. The median PFS and OS were 4.4 months and not reached, respectively. Among patients with docetaxel-naïve CRPC, 12 (24%) experienced adverse events, whereas 16 (40%) experienced adverse events after docetaxel. Fatigue (15%) and appetite loss (13%) were the most common. We partially clarified the characteristics of enzalutamide therapy in Japan. The PFS associated with enzalutamide might be shorter in Japanese patients.

Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association.

OBJECTIVES: Open nephroureterectomy (ONU) is the current standard for muscle-invasive upper tract urothelial carcinoma (UTUC) in the European Association of Urology/Japanese Urological Association (JUA) guidelines. In this study, we compared the postsurgical survival of muscle-invasive UTUC patients treated with ONU or with laparoscopic nephroureterectomy (LNU), using the multi-institutional national database of the JUA. METHODS: The 1509 patients with UTUC who were diagnosed at 348 Japanese institutions in 2005 were registered. We collected the clinical data of the patients in 2011. The muscle-invasive UTUC patients who underwent ONU or LNU were identified, and survival curves were estimated using the Kaplan-Meier method. RESULTS: Overall, 749 pT2≥cNxM0 patients underwent a nephroureterectomy (ONU, n = 527 and LNU, n = 222). The overall survival and cause-specific survival rates were not significantly different between the ONU and LNU groups (p = 0.1263 and p = 0.0893, respectively). In addition, 459 of the 749 (61.3%) patients experienced disease recurrence (bladder recurrence, local recurrence, or distant metastasis), with no significant difference between the ONU and LNU groups. Even when patients were stratified by pT3/pT4 and/or pN+, overall survival was not significantly different between the ONU and LNU groups (p = 0.2876). The results of a univariate analysis showed that lymphovascular invasion was an independent prognostic factor for overall survival, but the surgical approaches were not found to be associated with overall survival. CONCLUSIONS: Our data suggest that there is no evidence that the oncologic outcome of LNU is inferior to that of ONU in muscle-invasive UTUC, when the appropriate patients are selected.

[A case of locally advanced prostate cancer with low serum testosterone associated with intake of an androgenic medicine].

A 74-year-old man was referred to our clinic for the work-up of digitally hard and irregularly surfaced prostate and elevated serum prostate-specific antigen (PSA). His serum PSA was elevated to 41 ng/ml, but testosterone and LH level were decreased to 23.5 ng/dl and 0.5 mIU/ml, respectively. He had a history of taking an androgenic medicine containing methyl-testosterone 2 to 3 times a week for 2 year and 6 months. Transrectal sextant prostatic biopsy revealed moderately differentiated adenocarcinoma (Gleason score: 3 + 4) in 6 of 6 specimens and CT scan of the abdomen showed an enlarged obturator lymph-node (15 mm), resulting in the diagnosis of stage D1 (T3aN1M0) prostate cancer. Since serum testosterone level seemed to recover around the normal level after discontinuation of the exogenous androgen, we treated him with combination androgen blockade with LHRH agonist and bicaltamide, although his testosterone level was very low. Indeed, serum PSA decreased to 0.09 ng/ml and the right obturator node was markedly reduced by the hormone treatment. After the neoadjuvant therapy of 6 months duration, radical prostatectomy and limited pelvic lymph node dissection was carried out. Histologically, viable cancer cells were not found in any of resected lymph nodes, but they remained in bilateral lobes of the prostate (pT2bN0). The histological effect of the neoadjuvant hormone therapy according to General rule for Clinical and Pathological Studies on Prostate Cancer (3rd ed.) was grade 2. The patient has been well with undetectable PSA and no evidence of clinical failure for more than 12 months, though serum testosterone level recovered to near normal (288 ng/dl) 8 months after the cessation of the hormone treatment following the operation. Combination androgen blockade or non-steroidal anti-androgen agent appears to be effective for the treatment of prostatic cancer patients who takes exogenous androgenic medicine, even with a suppressed low serum testosterone level.