Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

Prevention of local symptoms in muscle invasive bladder cancer patients: clinical significance of local radiation therapy.

PURPOSE: To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain. RESULTS: One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades. CONCLUSIONS: We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in urological malignancies: a multi-center retrospective study.

INTRODUCTION: We evaluated the incidence and risk factors for antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate and kidney cancer patients. MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 547 patients from 13 hospitals. Prostate and kidney cancer patients with bone metastases who were treated with a bone-modifying agent (BMA) between January 2012 and February 2019 were enrolled. Exclusion criteria were BMA use for hypercalcemia, a lack of clinical data, a follow-up period of less than 28 days and a lack of evaluation by dentists before BMA administration. The diagnosis and staging of ARONJ were done by dentists. RESULTS: Two-hundred eighteen patients were finally enrolled in the study, including 168 prostate cancer patients and 50 kidney cancer patients. Of them, 49 (29%) prostate cancer patients and 18 (36%) kidney cancer patients needed tooth extraction prior to BMA initiation. The mean follow-up period after BMA initiation was 552.9 ± 424.7 days (mean ± SD). In the cohort, 23% of the patients were diagnosed with ARONJ in the follow-up period. The 1-year cumulative incidences of ARONJ were 9.4% and 15.4% in prostate and kidney cancer patients, respectively. Multivariate analysis indicated that kidney cancer, tooth extraction before BMA and a body mass index (BMI) ≥ 25 kg/m2 were significant predictors for ARONJ. CONCLUSION: ARONJ is not a rare adverse event in urological malignancies. Especially, kidney cancer, high BMI patients and who needed tooth extraction before BMA were high risk for developing ARONJ.

[A Case of Diagnosed Lynch Syndrome in a Patient with Ureteral Cancer].

Lynch syndrome (LS) is an autosomal dominant genetic disorder in which tumors are known to develop at an early age. Upper tract urothelial carcinoma is one of the tumors related to Lynch syndrome. A 49-year-old woman visited a urologic clinic due to left abdominal pain. She had a history of ovarian cancer. Her mother had a history of colorectal cancer and renal pelvic cancer, and her grandmother had had colorectal cancer. After detailed examination, she received laparoscopic left nephroureterectomy and she was pathologically diagnosed with left ureteral cancer. LS was suspected based on her past history, family history, and age. A microsatellite instability (MSI) test gave a positive result, and genetic analysis confirmed a mutation in the MSH2 gene, leading to the diagnosis of Lynch syndrome. Although LS has a high frequency of carcinogenesis, it is thought that an improved prognosis can be achieved by early discovery and treatment of cancer in LS patients. From our case report, we recommend screening of LS in patients with a past/family history, who have had an upper tract urothelial carcinoma. Once LS is diagnosed, the patient should be followed by a planned surveillance of cancer development.

[Predictive Factor of Urinary Continence after Robot-Assisted Laparoscopic Radical Prostatectomy].

We examined the postoperative urinary continence rate, and preoperative and postoperative factors predicting postoperative urinary continence for patients who underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our hospital. In all, 122 patients who received RARP were retrospectively analyzed. All patients answered a questionnaire to evaluate the urinary condition and also had a follow-up period of 6 months or longer after surgery. We defined urinary continence to be the use of 1 pad per day or less, including a safety pad. Membranous urethral length (MUL) was measured using sagittal sections of T1-weighted MRI. Postoperative urinary incontinence rates were 48.7, 72.4, 82.6 and 86.8% at 3, 6, 12 and 24 months after surgery, respectively. MUL was a significant predictive factor of urinary continence at 6 months after surgery (p<0.01). We examined the factors predicting the urinary continence recovery at 6 months after surgery, including only patients who did not obtain urinary continence at 1 month after surgery. Two factors, MUL of 11 mm or longer and two pads per day at 1 month after surgery, were significant predictive factors of urinary continence recovery at 6 months after surgery (P=0.02, P=0.04). Patients who had a long MUL could easily obtain urinary continence after RARP compared to those with a short MUL. Most patients with a long MUL and with use of 2 pads per day at 1 month after surgery could obtain urinary continence at 6 months after surgery, even if they had urinary incontinence at 1 month after surgery.

[A Case of Refractory Hemorrhagic Cystitis in which Bleeding Control was Finally Achieved by Cystectomy].

A 60-year-old man presented at our hospital with gross hematuria. He had been treated for nephrotic syndrome with cyclophosphamide and steroids since he was in his 20s. We detected diffuse hemorrhagic cystitis on cystoscopy and diagnosed him with cyclophosphamide-induced hemorrhagic cystitis. He was hospitalized due to clot retention. We treated him with blood transfusion for severe anemia and conducted continuous bladder irrigation. We performed hyperbaric oxygen therapy and transurethral electric coagulation, and increased the steroid dose. However, we could not control the hematuria. Finally, we performed cystectomy, and he is now well without hematuria. Although cystectomy is the final option, it is important to decide it in a timely manner because a delay decreases the quality of life.

Natural history of hematospermia in 189 Japanese men.

OBJECTIVES: To prospectively investigate the natural history of hematospermia. METHODS: This study included 189 patients with hematospermia. All the patients underwent watchful waiting without any empirical treatment. RESULTS: The median observation period was 52 months. Hematospermia resolved spontaneously in 168 (88.9%) of the 189 patients, and the median disease duration was 1.5 months. Kaplan-Meier analysis showed that the persistence rates of hematospermia were 57.7% at 1 month, 34.2% at 3 months, 23.3% at 6 months, 12.5% at 1 year and 7.6% at 2 years. Hematospermia reoccurred in 20 (13.5%) of the 148 patients who had adequate follow up. The recurrence-free rates were 96.6% at 3 months, 89.0% at 1 year, 84.8% at 5 years and 78.2% at 10 years. Multivariate analysis showed that seminal vesicle hemorrhage and a midline cyst of the prostate were significant factors to predict the duration of hematospermia until spontaneous resolution. The nine patients with persisting hematospermia for more than 1 year were treated with transurethral endoscopic surgery (unroofing of the midline cyst in six, and transurethral resection of the ejaculatory duct in three), and hematospermia resolved postoperatively in all these patients. CONCLUSIONS: In patients with hematospermia without inflammation, infection or malignancy, it is important to provide information on the possibility that symptoms will resolve spontaneously and to implement measures to relieve their anxiety. Detection of seminal vesicle hemorrhage and a midline cyst of the prostate is important for prediction of the duration of hematospermia.

Changes of sexual function and perception in Japanese men: A 15-year cross-sectional community-based study.

OBJECTIVES: To investigate the longitudinal changes of sexual function of Japanese men. METHODS: From 1992 to 1993, we carried out a cross-sectional community-based study on sexual function in Japanese men aged 40-79 years. After 15 years, a follow-up study was carried out to determine longitudinal changes of their sexual function. Of the 319 participants in the initial study, 135 participated again in the follow-up study. Sexual function was assessed using the same validated questionnaire in the two studies. RESULTS: Erectile rigidity declined in men of each age decade at baseline (40s, 50s, 60s and 70s) of the initial study (P < 0.01, <0.01, <0.01 and <0.05). The frequency of sexual drive was significantly decreased in men aged in their 40s, 50s and 60s (P < 0.05, <0.01 and <0.01). Men aged in their 40s were dissatisfied with their decreased sexual function (P < 0.05). In contrast, men aged in their 70s were satisfied with their sexual life (P < 0.01). CONCLUSIONS: Over a 15-year period, the sexual function of Japanese men declined in each age decade. However, the perception of this decline differed among different age group. Most elderly Japanese men did not worry about their impaired sexual function.

Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous Nerve Injury.

INTRODUCTION: We evaluated the potential preventive effects and mechanisms of intravenously preloaded mesenchymal stem cells (MSCs) for erectile dysfunction (ED) in a cavernous nerve (CN) injury model. METHODS: Male Sprague-Dawley (SD) rats were used for this study. Rats were randomized into two groups. One group was intravenously preloaded with MSCs (1.0 × 10(6) cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL Dulbecco's modified Eagle's medium [DMEM]) for sham control, respectively. Crushed CN injury was induced immediately after infusion. The surgeon was blind to the experimental conditions (MSC or medium). MAIN OUTCOME MEASURES: To assess erectile function, we measured the intracavernous pressure (ICP) and arterial pressure (AP) at 1 hour and 2 weeks after CN injury. After measuring the initial ICP/AP of pre-injury (normal) male SD rats, they were randomized into the two groups and infused with MSCs or medium. PKH26-labelled MSCs were used for tracking. To investigate the mRNA expression levels of neurotrophins in the major pelvic ganglia (MPG), we performed real-time quantitative real-time polymerase chain reaction. RESULTS: The reduction of ICP/AP and area under the curve of ICP (ICP-AUC) in the MSC group was significantly lower than in the DMEM group (P < 0.05; P < 0.05) at 1 hour. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group was significantly higher than in the DMEM group (P < 0.01; P < 0.05). The preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal microscopy indicating homing of the cells to the injured nerve and ganglia. Glia cell-derived neurotrophic factor (GDNF) and neurturin, which are important neurotrophic factors for erection, had expression levels in MPG significantly higher in the MSC group than in the DMEM group (P < 0.01, 0.05). CONCLUSION: Intravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.

Comparison of Oncological Outcomes of Pembrolizumab as Second-line Therapy and Maintenance Avelumab Therapy in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy.

BACKGROUND/AIM: Sequential therapy using chemotherapy and subsequent immune checkpoint inhibitor (ICI) treatment prolongs the survival of patients with advanced urothelial carcinoma (UC). However, no comparison data for oncological outcome between pembrolizumab and avelumab has been reported. Thus, we compared oncological outcomes between pembrolizumab as second-line therapy and maintenance avelumab therapy in patients with advanced UC. PATIENTS AND METHODS: We retrospectively evaluated patients with advanced UC treated with pembrolizumab or avelumab between January 2018 and February 2023. We compared oncological outcomes after adjusting for patient characteristics. Immune-related adverse events (AEs) in each group were evaluated using the Common Terminology Criteria for Adverse Events. RESULTS: There were 186 and 44 patients in the pembrolizumab- and avelumab-treated cohorts, respectively. After propensity score matching, 43 patients from each group were selected and analyzed. Median progression-free survival from the initiation of pembrolizumab and avelumab treatments was 126 and 139 days, respectively (log-rank test, p=0.625). Median overall survival in the pembrolizumab and avelumab cohorts were 658 days and not reached, respectively (log-rank test, p=0.249). Thirty-eight (20.4%) and 14 (31.8%) all-grade immune-related AEs were observed in 186 pembrolizumab- and 44 avelumab-treated patients, respectively (chi-squared test, p=0.112). Regarding endocrine-related AEs, 12 (6.5%) and none (0%) were observed in pembrolizumab- and avelumab-treated patients, respectively (Fisher's exact probability test, p=0.129). CONCLUSION: Pembrolizumab and maintenance avelumab therapy provide equivalent oncological outcomes in patients with advanced UC. Although no significant difference was observed, there might be a potential risk of higher endocrine-related AEs due to pembrolizumab compared to avelumab maintenance therapy.

[Pathological complete response to gemcitabine and cisplatin chemotherapy for advanced upper tract urothelial carcinoma: a case report].

A 61-year-old man was referred to our hospital with the chief complaint of right leg weakness. Abdominal magnetic resonance imaging (MRI) and computed tomography (CT) demonstrated a ureteral tumor and a neighboring massive retroperitoneal tumor in addition to retroperitoneal lymph node and right renal metastases. The tumor was diagnosed as upper tract urothelial carcinoma (cT4N1M1) by percutaneous tumor biopsy. As the patient achieved a partial response after three courses of combination chemotherapy with gemcitabine and cisplatin, he received total nephroureterectomy and lymph node dissection. The pathology showed no viable cancer cells, demonstrating a pathological complete response. He remains alive after 26 months with no evidence of disease.

Upper urinary tract recurrence after radical cystectomy for bladder cancer: incidence and risk factors.

OBJECTIVES: To examine the incidence of and the risk factors for upper urinary tract recurrence in patients undergoing a radical cystectomy for bladder cancer, and to examine the clinical course of patients harboring upper urinary tract recurrence. METHODS: This retrospective study included 362 patients who underwent radical cystectomy for bladder cancer. Patients with a history of upper urinary tract recurrence and concomitant upper urinary tract recurrence at cystectomy were excluded. RESULTS: After a median follow up of 48 months (range 0-214) after radical cystectomy, 11 patients (3.0%) developed upper urinary tract recurrence. The median time to upper urinary tract recurrence was 48.4 months (range 11.6-78.6). The overall probability of upper urinary tract recurrence was 3.3% at 5 years. The median overall survival period after upper urinary tract recurrence was 23.5 months (range 4.3-53.9), with a better overall survival for patients who received a radical operation than for those who did not (38.6 months vs 11.9 months, respectively; P=0.03). At multivariable analysis, the presence of carcinoma in situ (P < 0.01) and invasion of the urethra (P = 0.02) were independent risk factors for upper urinary tract recurrence. The 5-year upper urinary tract recurrence was significantly higher for patients positive for either of these risk factors than for those without risk factors (12.0% vs 0.9%, respectively; P < 0.001). CONCLUSIONS: This study shows that the presence of carcinoma in situ and cancer invading the urethra are risk factors for upper urinary tract recurrence. Close follow up is needed for early detection of upper urinary tract recurrence in patients at higher risk.

[THE USEFULNESS OF POSITRON EMISSION TOMOGRAPHY / COMPUTED TOMOGRAPHY IN THE DIAGNOSIS OF METASTASIS IN PATIENTS WITH UROTHELIAL CARCINOMA].

(Purpose) This study examined the usefulness of positron emission tomography (PET) / computed tomography (CT) in the diagnosis of metastasis in patients with urothelial carcinoma. (Materials and methods) The subjects were patients who were newly diagnosed with urothelial carcinoma in our department on whom we performed CT and PET/CT to search for metastasis. (Results) The median age of the 92 subjects was 71 years, and bladder and upper tract urotherial cancer were underlying diseases in 41 (46%) and 51 (54%) patients, respectively. In 66 (72%) of the 92 cases, no metastasis was observed by CT, while PET/CT revealed metastasis in 9 (14%). The 57 (86%) patients in whom both CT and PET/CT showed no metastasis underwent radical surgery, while 2 patients (4%) exhibited pathological lymph node metastasis.Of the 26 patients in whom CT revealed metastasis, PET/CT showed no metastasis in 3 (12%), and the absence of pathological metastasis was confirmed in all patients. Of the 23 patients found to have metastasis in both CT and PET/CT, metastasis that could not be identified by CT was discovered by performing PET/CT in 10 (43%) patients.PET/CT showed significantly higher diagnostic accuracy than CT alone (p< 0.01), with sensitivities of 94.1% and 67.6%, specificities of 100% and 94.8%, and positive diagnosis rates of 97.8% and 84.7%, respectively. (Conclusions) PET/CT in patients with urothelial cancer revealed that metastases that cannot be diagnosed by CT alone are found at a significant frequency. Since these metastases can affect treatment choices in patients with urothelial cancer, PET/CT is considered to be useful in diagnosing patients with urothelial cancer.

Serum testosterone level to predict the efficacy of sequential use of antiandrogens as second-line treatment following androgen deprivation monotherapy in patients with castration-resistant prostate cancer.

OBJECTIVE: We investigated whether serum testosterone after the failure of androgen deprivation monotherapy predicted the efficacy of antiandrogens added to androgen deprivation monotherapy as second-line treatments for patients with castration-resistant prostate cancer. METHODS: We reviewed 30 patients with castration-resistant prostate cancer who received maximal androgen blockade with addition of an antiandrogen (delayed maximal androgen blockade) (bicalutamide 80 mg daily for 21 patients and flutamide 375 mg daily for 9 patients) as the second-line treatment. The patients were divided into two groups by serum testosterone before delayed maximal androgen blockade: 22 in the testosterone ≥ 5 ng/dl group and 8 in the testosterone <5 ng/dl group. A prostate-specific antigen response was defined as a prostate-specific antigen decline of ≥ 50% from the pre-treatment level. RESULTS: The response rate was significantly higher in the testosterone ≥ 5 ng/dl group than in the testosterone <5 ng/dl group (77.3 vs. 37.5%, P =0.04). During the median follow-up period of 52.5 months, 24 patients (80.0%) developed prostate-specific antigen progression. A serum testosterone level of <5 ng/dl was an independent factor to predict prostate-specific antigen progression in a reduced and full model setting on multivariate analysis (hazard ratio 6.03, P =0.003 and 5.99, P =0.003, respectively). The 1-year prostate-specific antigen progression-free survival rate was significantly higher in the testosterone ≥ 5 ng/dl group than in the testosterone <5 ng/dl group (52.9 vs. 0%, P =0.002), as was cause-specific survival (5 years: 66.0 vs. 33.3%, P =0.007). CONCLUSIONS: Serum testosterone could play an important role when delayed maximal androgen blockade is indicated as the second-line treatment in patients with castration-resistant prostate cancer. Delayed maximal androgen blockade might be more beneficial in patients with a serum testosterone level of ≥ 5ng/dl.

A case with fistula formation between a perinephric retroperitoneal abscess and the duodenum: successful outcome after conservative management.

A 67-year-old woman diagnosed with pyonephrosis and perinephric abscess because of an impacted urinary stone in the pelvicoureteric junction was admitted to the hospital with a high-grade fever. Although construction of a right nephrostomy for drainage of the abscess improved her general condition, she had a fever again 2 weeks after the initial treatment. Computed tomography revealed a persistent perinephric retroperitoneal abscess and a second drainage procedure was performed. Then, imaging examination revealed fistula formation between the cavity of the perinephric retroperitoneal abscess and the duodenum. The patient received conservative management including percutaneous drainage, discontinuation of oral intake, and antimicrobial chemotherapy. Three days after the second drainage and discontinuation of oral intake, imaging examination revealed complete closure of the fistula. Fistula formation between a perinephric abscess and the duodenum is very rare but a favorable outcome was obtained by our conservative management.

Which Happens Earlier, Lower Urinary Tract Symptoms or Erectile Dysfunction?

INTRODUCTION: Although an association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) has been suggested, it was not clarified whether LUTS developed before ED or vice versa. AIM: To clarify whether LUTS develop before ED or vice versa and which symptoms predicted the onset of the other condition in a longitudinal community-based study. METHODS: We conducted a longitudinal community-based study on LUTS and ED in aged Japanese men. A follow-up study was conducted to determine their longitudinal changes of LUTS and ED after 15 years. Erectile function was evaluated using a validated questionnaire. LUTS were evaluated based on the International Prostate Symptom Score, quality of life index, and prostate volume. MAIN OUTCOME MEASURE: We evaluated the baseline symptoms among the participants who had LUTS and ED in the follow-up survey and what prior symptoms could predict the onset of the other condition using the data from a long-term longitudinal survey. RESULTS: A total of 108 men were enrolled in this study. Of the 47 men having both LUTS and ED in the follow-up study, men having only LUTS (n = 16) were more frequent than those having only ED (n = 6) in the initial study. Likewise, of the 38 men having both nocturia and ED at the time of the follow-up study, those having only nocturia (n = 12) were more frequent than those having only ED (n = 5) in the initial study. In multivariable analysis, age 60 years or older (odds ratio: 7.10, 95% CI: 2.09-24.13) and nocturia (odds ratio: 15.83, 95% CI: 3.05-82.15) were independent predictors for the onset of ED. CONCLUSION: There were more men with prior onset of LUTS, especially nocturia, than men with prior onset of ED among those with both ED and LUTS in this long-term longitudinal study. Nocturia may be a predictor of subsequent ED. Matsuda Y, Kobayashi K, Fukuta F, et al. Which Happens Earlier, Lower Urinary Tract Symptoms or Erectile Dysfunction?. J Sex Med 2021;9:100275.

Effect of delayed maximal androgen blockade therapy for patients with advanced prostate cancer who fail to respond to initial androgen deprivation monotherapy.

OBJECTIVES: We analyzed the efficacy of additional antiandrogens as second- and third-line treatments after the failure of initial androgen deprivation monotherapy. METHODS: This retrospective study included 53 patients with advanced prostate cancer initially treated with androgen deprivation monotherapy alone. An antiandrogen was added to androgen deprivation monotherapy as the second-line treatment after the failure of the initial androgen deprivation monotherapy. Another antiandrogen, estrogen or steroid was given as the third-line treatment after the second-line treatment failed. RESULTS: The initial androgen deprivation monotherapy was effective in all 53 patients for a median of 9.6 months. Thirty-three (62.3%) patients showed a prostate-specific antigen response to the second-line treatment for a median of 10.7 months. Of the 46 patients who received the third-line treatment, 16 (34.8%) showed a prostate-specific antigen response for a median of 6.0 months. Patients who responded to the second-line treatment had a significantly higher cancer-specific survival rate than those without a response. In multivariate analysis, a nadir prostate-specific antigen of 4.0 ng/ml or greater during androgen deprivation monotherapy and prostate-specific antigen doubling time of less than 10 months after androgen deprivation monotherapy failure were independent risk factors for prostate cancer death after androgen deprivation monotherapy failure, with hazards ratios of 5.59 and 8.00, respectively. The 5-year cancer-specific survival rates were 100%, 65.0% and 15.5% in patients with 0, 1 and 2 risk factors, respectively (P = 0.047). CONCLUSIONS: In this study, the second- and third-line treatments were effective for patients with advanced prostate cancer. Nadir prostate-specific antigen during androgen deprivation monotherapy and prostate-specific antigen doubling time just after the failure of androgen deprivation monotherapy are factors that can predict the prognosis.

[Neurotoxicity of valacyclovir in a peritoneal dialysis patient].

The patient was a 67-year-old man with a 2-year history of peritoneal dialysis for end-stage renal disease due to hypertensive nephropathy. He presented to a dermatologist with a complaint of pain in the right femoral region. He was diagnosed as having herpes zoster and valacyclovir, 1,000 mg/day, was prescribed. After 5 days of taking valacyclovir orally, he felt fretful and hallucinations appeared. He was admitted to our hospital and was hospitalized in our urology ward. We diagnosed his condition as neurotoxicity caused by an overdose of valacyclovir. As his general condition was stable, he was treated only by continuation of peritoneal dialysis. After 7 days of hospitalization, the neurotoxicity completely disappeared and he left the hospital. His serum acyclovir concentration at admission was 20.20 µg/l, and was reduced to 0.7 µg/l when he left the hospital. This supported our diagnosis of valacyclovir-induced neurotoxicity. In this case, valacyclovir should have been reduced to 500 mg/day, considering his renal function. Although we could treat the patient only by continuation of peritoneal dialysis, hemodialysis seems to be an effective treatment method in the case of unstable general condition or severe adverse effects, because it can eliminate the serum acyclovir.

[RENAL CELL CARCINOMA METASTASIS TO BLADDER DURING MOLECULAR TARGETED THERAPY WITH PAZOPANIB: REPORT OF TWO CASES].

Renal cell carcinoma (RCC) metastasis to the bladder is rare. We report two cases that occurred metachronously during pazopanib treatment for other metastases. To our knowledge, this is the first report to demonstrate bladder metastasis from RCC during molecular targeted therapy with pazopanib. (Case 1) A woman in her 60s was referred to our department for evaluation of an incidental right renal tumor. Dynamic CT showed a 6 cm renal cell carcinoma. In February 201X she underwent laparoscopic right radical nephrectomy, revealing clear cell carcinoma (grade 1>2), stage pT3aN0M0. In February 201X+1 she complained of left pelvic pain. She was found to have metastasis to two iliac bones and an occipital bone. She received pazopanib, in addition to a bone modifying agent and radiotherapy for the iliac bones. After 8 months, she complained of asymptomatic gross hematuria in spite of having stable disease for bone metastasis. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor on the posterior wall. She underwent transurethral resection of bladder tumor (TUR-BT). Histological examination showed metastatic RCC. Thereafter she received sequential therapies (axitinib, sunitinib, nivolumab). She remains alive without recurrence in the bladder 51 months after TUR-BT. (Case 2) A woman in her 60s presented to our department with a complaint of painless gross hematuria. A dynamic CT showed an 8.5 cm renal cell carcinoma and multiple lung metastases. In March 201Y she underwent right radical nephrectomy, revealing clear cell carcinoma (grade 2>3), stage pT2aN0M1. In June 201Y she started pazopanib. After 9 months CT showed a bladder tumor in addition to progression of lung metastases. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor at dome. She underwent TUR-BT. Histological examination showed metastatic RCC. She had no recurrence in the bladder during follow-up although she died of RCC.

Measurement of plasma concentration of gemcitabine and its metabolite dFdU in hemodialysis patients with advanced urothelial cancer.

OBJECTIVE: We investigated the pharmacokinetics of gemcitabine and its metabolite in two male patients (52 and 56-year-old) with advanced urothelial cancer receiving hemodialysis three times a week. METHODS: Gemcitabine, 1000 mg/m(2) in 100 ml of saline, was intravenously administered for 30 min. The concentration of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) was measured at several given time points using a high-pressure liquid chromatography assay. Pharmacokinetic parameters were determined using the two-compartment modeling program. RESULTS: Gemcitabine was rapidly eliminated from plasma even in patients with renal dysfunction. No obvious differences in pharmacokinetic parameters such as the t(1/2), AUC and C(max) of gemcitabine were observed between the patients on hemodialysis and those with normal renal function in previous reports. On the other hand, dFdU showed a sustained level until hemodialysis was initiated. Hemodialysis could reduce the plasma dFdU level by approximately 50%. CONCLUSIONS: According to the previous information, no dose modification of gemcitabine may be required for patients with renal impairment or hemodialysis. However, gemcitabine should be given with caution because only limited information is available, and the clinical effect of sustained and/or accumulated dFdU is unknown.