Outcomes in patients with high- and very high-risk localized prostate cancer treated with definitive IMRT and long-term hormone therapy.

BACKGROUND: The aim of this study was to evaluate the effectiveness of intensity-modulated radiation therapy in combination with long-term androgen deprivation therapy for high-risk and very high-risk localized prostate cancer while also investigating factors associated with the therapeutic effect. METHODS: Men who fulfilled criteria for the National Comprehensive Cancer Network high-risk or very high-risk localized prostate cancer and were treated with definitive intensity-modulated radiation therapy (74-78 Gy) of the prostate and the seminal vesicle combined with androgen deprivation therapy in our institution from 2007 to 2016 were identified (n = 197). In principle, patients received androgen deprivation therapy for 3-6 months before radiation, concurrently, and for 2 years after completion of intensity-modulated radiation therapy. RESULTS: The median follow-up period was 96 months. The 5-year and 10-year overall survival rates in the overall population were 96.9% and 89.3%, respectively. The 5-year and 10-year cumulative incidence rates of biochemical failure were 2.5% and 16.3% in the high-risk group, and 8.6% and 32.0% in the very high-risk group, respectively, indicating a significant difference between the two groups (P = 0.023). Grade Group 5 and younger age (cutoff: 70 years old) were independent predictors of recurrence (P = 0.016 and 0.017, respectively). Patients exhibiting biochemical failure within <18 months after completion of androgen deprivation therapy displayed an increased risk of cancer-specific mortality (P = 0.039) when contrasted with those who had a longer interval to biochemical failure. CONCLUSIONS: Patients with the National Comprehensive Cancer Network very high-risk prostate cancer, particularly those with Grade Group 5 and younger age, showed worse outcomes following intensity-modulated radiation therapy and long-term androgen deprivation therapy.

Efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer: A single-center study in Japan.

OBJECTIVES: Cabazitaxel is a next-generation taxane that can prolong overall survival after docetaxel treatment in patients with metastatic castration-resistant prostate cancer. However, the efficacy of cabazitaxel varies among these patients. The clinical indicators of the prognosis after cabazitaxel treatment were analyzed. METHODS: A retrospective review of patients who received cabazitaxel between February 2015 and June 2021 was performed. All patients had metastatic castration-resistant prostate cancer. Prognostic factors for prostate-specific antigen progression-free and overall survival were analyzed by Cox proportional-hazards analysis and the log-rank test. RESULTS: The study comprised 57 patients who received cabazitaxel (median 4 cycles, range 1-27) at a starting dose of 15-25 mg/m2 . The median age and follow-up duration were 70 years and 9.2 months. The median prostate-specific antigen progression-free survival and overall survival were 2.6 and 10.5 months, respectively. Univariate analysis showed that previous androgen receptor-axis-targeted therapy before cabazitaxel treatment was the only significant risk factor (hazard ratio 2.784, p = 0.022) for prostate-specific antigen progression-free survival. Multivariate analysis for overall survival revealed that poor performance status (≥1) (hazard ratio 2.107, p = 0.039), low hemoglobin (hazard ratio 0.142, p = 0.010), and high neutrophil-lymphocyte ratio (hazard ratio 9.150, p = 0.032) at baseline were significantly associated with a poor prognosis. CONCLUSIONS: Previous androgen receptor-axis-targeted therapy was the only risk factor for biochemical progression. Poor performance status, anemia, and high neutrophil-lymphocyte ratio were risk factors for poor prognosis in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel. These risk factors seem useful for identifying patients with survival benefit from cabazitaxel treatment.

A comparative study on nivolumab and axitinib as secondary treatment in patients with metastatic renal cell carcinoma: A multi-institutional retrospective study in Japan.

OBJECTIVES: When primary treatment has been inadequate, nivolumab and axitinib are often used as a secondary treatments for patients with metastatic renal cell carcinoma (mRCC). However, there have been few reports comparing the efficacy and safety of these drugs. METHODS: We retrospectively investigated 58 patients treated with nivolumab and 57 patients treated with axitinib as secondary treatment between April 2013 and December 2019. We then assessed the clinical efficacy and safety of the treatments in both groups. RESULTS: The most common primary therapy was sunitinib (61.7%). Both nivolumab and axitinib groups showed no significant differences in terms of the objective response rate and disease control rate (p = 0.280 and p = 0.518, respectively). Importantly, progression-free survival (PFS) and overall survival (OS) seemed to be similar in patients treated with nivolumab and axitinib (p = 0.527 and p = 0.266, respectively), irrespective of the objective response to primary therapy. Furthermore, a Cox proportional hazards model showed that pretreatment Karnofsky Performance Status was significantly associated with PFS and OS. Although the incidence of adverse events was significantly higher in the patients treated with axitinib, there was no significant difference in time to treatment failure between the two groups. CONCLUSIONS: Nivolumab and axitinib showed similar clinical benefits as secondary treatment in patients with mRCC; thus, they should be an option in sequential therapy following treatment with tyrosine kinase inhibitors (TKIs). Future studies and feasible therapeutic biomarkers would help predict the clinical response to TKIs or immune checkpoint inhibitors in patients with mRCC.

Real-world effectiveness of nivolumab and subsequent therapy in Japanese patients with metastatic renal cell carcinoma (POST-NIVO study): 36-month follow-up results of a clinical chart review.

OBJECTIVES: To examine the long-term effectiveness of nivolumab monotherapy and following subsequent therapies for metastatic renal cell carcinoma (mRCC) in Japanese real-world settings. METHODS: This was a multicenter, retrospective, observational study, with a 36-month follow-up, and conducted in Japanese patients with mRCC who initiated nivolumab monotherapy between 1 Feb 2017 and 31 Oct 2017. Endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: Of the 208 patients, 36.5% received nivolumab monotherapy as second-line, 30.8% as third-line, and 31.7% as fourth- or later-line therapy. By 36 months, 12.0% of patients continued nivolumab monotherapy; 88.0% discontinued, mainly because of disease progression (66.7%). The median (m) OS was not reached irrespective of treatment line, with a 36-month OS rate of 54.3% (second-line, 57.4%; third-line, 52.6%; fourth- or later-line, 52.9%). The ORR was 24.2% and five patients achieved complete response. The OS from first-line therapy was 8.9 years. In the 95 patients receiving therapy after nivolumab, 87.4% received vascular endothelial growth factor receptor-tyrosine kinase inhibitors, with mOS and mPFS of 27.4 and 8.1 months, respectively. Irrespective of treatment line, the mOS was not reached in patients with International Metastatic RCC Database Consortium (IMDC) favorable or intermediate risk at mRCC diagnosis. CONCLUSIONS: This 36-month real-world follow-up analysis showed a survival benefit of nivolumab monotherapy for patients with mRCC. The long-term effectiveness of sequential therapy from first-line therapy to therapy after nivolumab was also demonstrated. Additionally, nivolumab monotherapy was beneficial for patients with favorable IMDC risk at the time of mRCC diagnosis.

[A Case of Primary Signet Ring Cell Carcinoma of the Urinary Bladder Showing Effectiveness of Chemotherapy with Gemcitabine and Cisplatin].

A 55-year-old female presented to the hospital with a complaint of gross hematuria. Transurethral resection of bladder tumor was performed. The specimens pathologically showed signet ring cells and no urothelial carcinoma components. Magnetic resonance imaging and computed tomographic (CT) scan revealed bladder tumor, cervical metastasis, bilateral ovarian metastasis, and multiple lymph node metastasis. She was diagnosed with a primary signet ring cell carcinoma of the urinary bladder with cT3bN2M1, and was treated with chemotherapy of gemcitabine and cisplatin combination (GC). After 2 cycles of GC, the value of CEA which was elevated to 106 ng/ml before treatment, became negative. CT scan showed that her disease had successfully responded to the chemotherapy, and remained efficacious till the end of 6 cycles. The patient subsequently received 1 cycle of gemcitabine and nedaplatin and 3 cycles of avelumab due to renal insufficiency. Yet, 14 months after diagnosis, cerebellar metastases appeared and the patient died of meningeal carcinomatosis.

Overview of clinical management for older patients with renal cell carcinoma.

The rapidly increasing pool of older patients being diagnosed with and surviving their cancer is creating many challenges. Regarding localized renal cell carcinoma, surgery is considered as gold standard treatment options even in older men, whereas active surveillance and ablation therapy are alternative options for a proportion of these patients. With regard to advanced disease, anti-vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKI) and immune check point inhibitor are standard treatment modalities, although treatment choice from multiple regimens and prevention of adverse events need to be considered. Better assessment techniques, such as comprehensive geriatric assessment to meet the unique needs of older patients, are a central focus in the delivery of high-quality geriatric oncology care. Through this process, shared decision-making should be adopted in clinical care to achieve optimal goals of care that reflect patient and caregiver hopes, needs and preferences. It is necessary to continue investigating oncological outcomes and complications associated with treatment in this population to ensure appropriate cancer care. In this narrative review, we completed a literature review of the various treatments for renal cell carcinoma in older patients that aimed to identify the current evidence related to the full range of the treatments including active surveillance, surgery, ablation therapy and systemic therapy. Prospectively designed studies and studies regarding geriatric assessment were preferentially added as references. Our goals were to summarize the real-world evidence and provide a decision framework that guides better cancer practices for older patients with renal cell carcinoma.

Real-world efficacy and safety of nivolumab plus ipilimumab in untreated metastatic renal cell carcinoma, and the impact of previous nephrectomy on clinical outcome: Japanese multi-institutional retrospective study.

BACKGROUND: In metastatic renal-cell carcinoma (mRCC), recent clinical trials have shown efficacy of first-line combination therapy, as evidenced by better clinical outcome over target therapy. However, there are insufficient real-world evidences in mRCC patients in Japan. METHODS: We performed a multicenter retrospective study of 72 mRCC patients who received nivolumab plus ipilimumab as first-line treatment between September 2018 and July 2021. Patient's characteristics, clinical outcomes and safety were retrospectively reviewed. We analyzed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in patients treated with combination therapy. RESULTS: Of all patients, the median age was 70 years (range, 36-86) and the major type of histology was clear cell RCC (n = 55; 76.4%). Progressive disease (n = 25; 34.8%) and irAEs (n = 22; 30.6%) were the most common causes for discontinuing treatment. Median PFS and OS seemed similar between patients who discontinued treatment because of irAEs and for patients who did not (p = 0.360 and p = 0.069, respectively). Importantly, for patients with synchronous metastatic disease at diagnosis (n = 56), nephrectomy before initiating nivolumab plus ipilimumab had a significantly positive impact on better OS when compared to that in patients without nephrectomy (p = 0.028). CONCLUSION: This study confirms efficacy and safety of nivolumab plus ipilimumab for mRCC patients in real-world settings. Furthermore, nivolumab plus ipilimumab was associated with a better outcome in patients who had undergone nephrectomy at diagnosis for synchronous mRCC.

[A Case of Pleural Empyema with Fistula Caused by Endobronchial Metastasis of Renal Cell Carcinoma].

A 52-year-old man complained of asymptomatic gross hematuria and cough. Chest and abdominal computed tomography (CT) revealed a right renal tumor, mediastinal lymph node metastasis, and right endobronchial metastasis. The right endobronchial metastasis was causing obstructive atelectasis in the lower lobe of the right lung. After tumor biopsy, the pathological diagnosis was clear cell renal cell carcinoma. Combination immunotherapy with ipilimumab and nivolumab was initiated, but CT showed enlargement of the metastatic lesion and lung abscess after two courses of treatment. The therapy was then switched to axitinib. Six days after initiation of axitinib, the lung abscess perforated into the pleural cavity, which resulted in the formation of pleural empyema with fistula. Ten days after initiation of axitinib, obstruction of the bronchus was relieved due to shrinkage of the right endobronchial metastasis, which resulted in development of a pneumothorax. Placement of a thoracic drainage tube and administration of an antimicrobial agent improved the pneumothorax and inflammatory response, but the drainage tube could not be removed. Long-term insertion of the thoracic drainage tube considerably diminished the patient's quality of life, and after 4 months, he was transferred to another hospital to receive the best supportive care.

Antiresorptive agent-related osteonecrosis of the jaw in prostate cancer patients with bone metastasis treated with bone-modifying agents.

INTRODUCTION: The incidence rate and risk factors of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate cancer patients with bone metastasis are not clear. MATERIALS AND METHODS: We retrospectively reviewed patients' records of prostate cancer patients with bone metastasis who were treated with zoledronic acid or denosumab between 1/Dec/2008 and 31/Mar/2019. ARONJ-free survival rate was analyzed with Kaplan-Meier analysis, and risk factors for ARONJ were analyzed with Cox proportional hazard model. RESULTS: We identified 124 and 67 patients treated with zoledronic acid and denosumab, respectively. Seventy-six patients were hormone sensitive, and 115 patients were castration resistant when they started bone-modifying agents (BMA). Twenty-eight patients developed ARONJ during the observation period (median: 23 months, range 1-130 months). Their number of doses of BMA ranged 3-69 (median: 21.5). The 2-year ARONJ-free survival rate was 91.1%, and the 5-year ARONJ-free survival rate was 72.5%. There was no significant difference in the incidence rate of ARONJ between zoledronic acid and denosumab. However, multivariate analysis revealed that use of denosumab (hazard ratio [HR] 3.67, 95% confidence interval [CI] 1.01-13.31; p = 0.0484), serum calcium < 9.2 mg/dL (HR 3.16, 95% CI 1.10-9.13; p = 0.033)), and concomitant or prior use of chemotherapeutic agents (HR 4.71, 95% CI 1.51-14.71; p = 0.0076) were independent risk factors for the development of ARONJ. CONCLUSION: Almost one-quarter of patients had a risk of developing ARONJ within 5 years after starting BMA. Low serum calcium, use of chemotherapeutic agents, and use of denosumab might contribute to the development of ARONJ.

External validation of the albumin, C-reactive protein and lactate dehydrogenase model in patients with metastatic renal cell carcinoma receiving second-line axitinib therapy in a Japanese multi-center cohort.

PURPOSE: To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients. PATIENTS AND METHODS: The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group. RESULTS: The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, <1 year from diagnosis to targeted therapy, a high neutrophil count, and low albumin, elevated C-reactive protein, and elevated lactate dehydrogenase, and the Japan Urologic Oncology Group model was newly developed based on the presence/absence of these independent factors. In this cohort, 151 (35.9%), 125 (27.7%) and 145 (34.4%) patients were classified into the favorable, intermediate and poor risk groups, respectively, according to the albumin, C-reactive protein and lactate dehydrogenase model; however, the proportions of patients in the intermediate risk group stratified by the Japan Urologic Oncology Group, Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models were >50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses. CONCLUSIONS: The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib.

Clinical indicators for predicting prognosis after radium-223 administration in castration-resistant prostate cancer with bone metastases.

BACKGROUND: Radium-223 (Ra-223) is a targeted alpha therapy that has been shown to prolong overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. However, prognosis after Ra-223 administration varies among patients. The aim of the present study was to assess risk factors associated with the poor prognosis of patients treated with Ra-223. METHODS: We retrospectively reviewed patients' records of treatment with Ra-223 between October 2016 and December 2019. All patients had mCRPC, bone metastasis, and no known visceral metastases, and received up to six cycles of Ra-223 (55 kBq/kg). Prognostic factors for OS were analyzed by Cox proportional hazards model and log-rank test. RESULTS: We identified 42 patients who received at least one cycle of Ra-223 (median six cycles, range 1-6). Approximately two-thirds of patients had received at least two lines of therapy for mCRPC. The median age was 74 years, and the median follow-up duration was 13.6 months. The median OS time was 16.6 months. On multivariate analysis, PSA doubling time (PSADT) (0-3 months) at baseline, number of bone metastases (≥ 20), and treatment line of Ra-223 (4th-5th line) remained significantly correlated with the poor OS (HR 4.354, P = 0.003; HR 2.855, P = 0.020; and HR 4.871, P = 0.001, respectively). CONCLUSIONS: Our study demonstrated that a shorter PSADT, a heavier volume of bone metastases, and a later treatment line before Ra-223 are poor prognostic factors for mCRPC patients. These newly discovered risk factors may help select patients who potentially have long-term OS after Ra-223 treatment.

Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma.

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

Utility of index lesion volume assessed by multiparametric MRI combined with Gleason grade for assessment of lymph node involvement in patients with high-risk prostate cancer.

PURPOSE: We examined the potential predictors of lymph node involvement and evaluated whether index lesion volume assessed using multiparametric magnetic resonance imaging is associated with lymph node involvement among patients with high-risk prostate cancer. METHODS: Extended pelvic lymph node dissection was used to evaluate patients with lymph node involvement. We retrospectively analyzed consecutive 102 patients with high-risk prostate cancer who underwent extended pelvic lymph node dissection at our institution between 2011 and 2017. To evaluate the index lesion volume at multiparametric magnetic resonance imaging (mrV), lesions were manually contoured on each T2-weighted axial slice in combination with diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging and integrated using image analysis software. Logistic regression analysis was performed to identify predictors of lymph node involvement. RESULTS: The median mrV was 1.4 ml (range 0-30.1 ml), and the median number of resected lymph nodes was 14 (range 7-38). Among 102 patients, 28 (28%) had lymph node involvement. Multivariate analysis identified significant predictors of lymph node involvement as follows: biopsy Gleason-grade group 5 (odds ratio = 17.2; 95% confidence interval, 2.1-299.0; P = 0.005), preoperative mrV (odds ratio = 1.14; 95% confidence interval, 1.02-1.30; P = 0.025) and percentage of positive cores with highest Gleason-grade group (odds ratio = 1.05; 95% confidence interval, 1.01-1.10; P = 0.005). Lymph node involvement was prevalent (69%) among tumors with Gleason-grade group 5 and mrV ≥3.4 ml, but was infrequently (10%) present among tumors with Gleason-grade group ≤4 and mrV <3.4 ml. CONCLUSIONS: The combination of biopsy Gleason-grade and mrV may serve as a useful tool to stratify patients according to their risk of nodal metastases.

A multicenter retrospective study of nivolumab monotherapy in previously treated metastatic renal cell carcinoma patients: interim analysis of Japanese real-world data.

BACKGROUND: In a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients. METHODS: This is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events). RESULTS: Of 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression (n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade ≥ 3, 10.1%). CONCLUSION: Nivolumab was effective and well-tolerated in real-world Japanese mRCC patients. TRIAL REGISTRATION: UMIN000033312.

[A Case of Myocardial Metastasis of Renal Cell Cancer Treated with Nivolumab].

The patient a 48-year-old male, underwent nephrectomy for clear cell renal cell carcinoma. After surgery, the patient was treated sequentially with sunitinib, axitinib, and everolimus for multiple pulmonary metastases and iliopsoas muscle metastasis. After 16 months, subcutaneous metastasis and left ventricular myocardial metastasis developed without any symptoms. He was treated with pazopanib for these metastases. However, no shrinkage was seen and bone metastasis in right acetabulum appeared. After radiation therapy (20 Gy/5 Fr) for right acetabulum, nivolumab was administered for myocardial metastasis and subcutaneous metastasis. Significant shrinkage of metastases was seen after 3 courses of nivolumab and the patient's condition remained stable after 31 courses of nivolumab.

[A Case of Primary Central Nervous System Lymphoma that Developed during the Treatment of Castration-Resistant Prostate Cancer].

A 64-year-old man was diagnosed with metastatic prostate cancer (cT3bN0M1b) and treated with combined androgen blockade. After two years and three months, he developed castration-resistant prostate cancer. Multiple lung metastases appeared after the administration of five courses of docetaxel and four courses of cabazitaxel therapy. Pulmonary metastases disappeared following rechallenge with docetaxel. Enzalutamide administration was initiated because docetaxel had to be discontinued due to adverse events. Although enzalutamide lowered the prostate specific antigen value, the patient staggered while walking and developed homonymous hemianopsia. Magnetic resonance imaging revealed a brain tumor. Although the brain tumor was considered to have metastasized from the prostate cancer, it was diagnosed as a primary central nervous system lymphoma using open-ended tumor biopsy. The brain tumor was eliminated with whole-brain irradiation. Thereafter, he has been treated with enzalutamide for 3 years without clinical progression of either disease.

Impact of sex difference on survival of bladder cancer: A population-based registry data in Japan.

OBJECTIVE: To investigate the impact of sex on the prognosis of bladder cancer in Japan. METHODS: In total, 18 728 patients diagnosed as having bladder cancer from 1993 to 2006 were registered in population-based cancer registries of six prefectures in Japan. We estimated relative survival by sex, age, clinical stage at initial diagnosis and pathology. RESULTS: Patients included 14 203 men (75.8%) and 4525 women (24.2%). The stage at initial diagnosis in women was significantly higher than in men (P < 0.0001). Pathologically, women were more likely to have non-urothelial cancer than men (women 18.0%, men 9.5%, P < 0.0001). The 5-year relative survival was 80.3% for men and 67.7% for women. The 5-year relative survival was 93.0% for men and 87.7% for women in the localized cancer group, 34.8% for men and 23.9% for women in the locally advanced cancer group, and 7.1% for men and 8.3% for women in the metastatic cancer group. The relative survival of women was worse than that of men in the localized cancer group (hazard ratio 1.29, 95% confidence interval 1.05-1.57; P = 0.0145) and locally advanced cancer group (hazard ratio 1.32, 95% confidence interval 1.15-1.52; P = 0.0001), but not different in the metastatic cancer group (hazard ratio 1.04, 95% confidence interval 0.87-1.25; P = 0.6555). CONCLUSIONS: Population-based registry data in Japan show that the cancer stage at initial diagnosis is higher in women than in men, and women with localized or locally advanced bladder cancer have a worse prognosis compared with men.

Aortic Dissection and Cardiac Dysfunction Emerged Coincidentally During the Long-Term Treatment with Angiogenesis Inhibitors for Metastatic Renal Cell Carcinoma.

Angiogenesis inhibitors, such as sorafenib and axitinib, which target vascular endothelial growth factor (VEGF) signaling, are widely used for renal cell carcinoma, including metastasis. In this study, we report a case of cardiovascular adverse events of aortic dissection and cardiac dysfunction during treatment with sorafenib and axitinib for metastatic renal cell carcinoma. A 66-year-old man had been administered sorafenib for 2 years after nephrectomy due to renal cell carcinoma. To control the progression of metastatic lung tumor, axitinib was started after sorafenib for four years. During the treatment, angiotensin II type 1 receptor blockers and Ca antagonists were used to strictly control the axitinib-induced hypertension and proteinuria. Aortic dissection and cardiac dysfunction occurred coincidentally. Considering the critical role of VEGF signaling in the homeostasis of the cardiovascular system, we speculated that the long-term use of axitinib and sorafenib directly influenced the initiation of aortic dissection and cardiac dysfunction. Although the precise mechanisms underlying the aortic dissection and cardiac dysfunction induced by angiogenesis inhibition are still elusive, onco-cardiologists and oncologists should pay careful attention to cardiovascular toxicity and complications in patients with cancer, particularly patients undergoing long-term cancer treatment.

[A Case of Retroperitoneal Liposarcoma in which Magnetic Resonance Imaging was Useful in the Decision of Resection of Primary and RecurrentTumors].

A 47-year-old female was referred to our hospital because of retroperitoneal tumor which was detected by computer tomography (CT). Since the tumor was considered to be benign by magnetic resonance imaging (MRI), she was followed by MRI every 3 months. The site of the tumor was gradually increased, and 15 months after presentation, a lesion with high signal intensity on diffusion weighted image (DWI) appeared in the tumor. At that time, we performed tumor resection considering the tumor to be malignant. Pathological diagnosis was dedifferentiated liposarcoma. Three years and two months after the operation, liposarcoma recurred in the left retroperitoneal space. Because it showed low signal intensity on DWI, which was compatible with well-differentiated liposarcoma, further follow-up was carried out. Eleven months after the recurrence, a lesion with high signal intensity on DWI appeared in the tumor. We performed tumor resection again, leading to pathological diagnosis of recurrence of dedifferentiated liposarcoma. She remained free of disease at 4 months after surgery.

Postoperative early ultrasensitive prostate-specific antigen identifies patients at risk for biochemical recurrence in margin positive prostate cancers: a single-center study.

OBJECTIVE: To identify predictors for biochemical recurrence among patients with positive surgical margins (RM1) after radical prostatectomy and to examine the effect of ultrasensitive prostate-specific antigen measured early after prostatectomy on biochemical recurrence. METHODS: We identified 705 patients with prostate cancer who were treated with radical prostatectomy without preoperative hormonal therapy at our institution between 2000 and 2014. The patients with RM1 who had a postoperative prostate-specific antigen <0.2 ng/ml without lymph node metastasis were evaluated for biochemical recurrence-free survival. Survival rates were calculated using the Kaplan-Meier method. The Cox regression model was used for multivariate analysis. The prediction of biochemical recurrence was assessed using area under the curve of the receiver operating characteristic. RESULTS: Among the 705 patients, 190 (27%) had RM1. Biochemical recurrence was evaluated in 164 patients, excluding 26 patients who underwent adjuvant therapy with or without lymph node metastasis. With a median follow-up of 55 months, the biochemical recurrence-free survival rate of the entire RM1 cohort was 78% at 2 years and 64% at 4 years. The multivariate analysis revealed that postoperative early ultrasensitive prostate-specific antigen >0.02 ng/ml was the significant risk factor for biochemical recurrence (hazard ratio 13.10). Meanwhile, the patients with postoperative early ultrasensitive prostate-specific antigen <0.01 ng/ml had a significantly lower risk for biochemical recurrence (hazard ratio 0.12). Area under the curve for the postoperative early ultrasensitive prostate-specific antigen value to predict biochemical recurrence was 0.789. CONCLUSIONS: The ultrasensitive prostate-specific antigen value measured early after prostatectomy was the potent predictor of biochemical recurrence among the patients with RM1.