J-AVENUE: A retrospective, real-world study evaluating patient characteristics and outcomes in patients with advanced urothelial carcinoma treated with avelumab first-line maintenance therapy in Japan.

OBJECTIVES: The JAVELIN Bladder 100 phase 3 trial showed that avelumab first-line maintenance + best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with advanced urothelial carcinoma who were progression-free following first-line platinum-based chemotherapy. We report findings from J-AVENUE (NCT05431777), a real-world study of avelumab first-line maintenance therapy in Japan. METHODS: Medical charts of patients with advanced urothelial carcinoma without disease progression following first-line platinum-based chemotherapy, who received avelumab maintenance between February and November 2021, were reviewed. Patients were followed until June 2022. The primary endpoint was patient characteristics; secondary endpoints included time to treatment failure and progression-free survival. RESULTS: In 79 patients analyzed, median age was 72 years (range, 44-86). Primary tumor site was upper tract in 45.6% and bladder in 54.4%. The most common first-line chemotherapy regimen was cisplatin + gemcitabine (63.3%). Median number of chemotherapy cycles received was four. Best response to chemotherapy was complete response in 10.1%, partial response in 58.2%, and stable disease in 31.6%. Median treatment-free interval before avelumab was 4.9 weeks. With avelumab first-line maintenance therapy, the disease control rate was 58.2%, median time to treatment failure was 4.6 months (95% CI, 3.3-6.4), and median progression-free survival was 6.1 months (95% CI, 3.6-9.7). CONCLUSIONS: Findings from J-AVENUE show the effectiveness of avelumab first-line maintenance in patients with advanced urothelial carcinoma in Japan in clinical practice, with similar progression-free survival to JAVELIN Bladder 100 and previous real-world studies, supporting its use as a standard of care.

The prognostic impact of peripheral blood eosinophil counts in metastatic renal cell carcinoma patients treated with nivolumab.

Although immune checkpoint inhibitors (ICIs) have gained approval for metastatic renal cell carcinoma (mRCC), the response rate is still limited. Therefore, it is urgent to explore novel markers of responses to ICIs that can help assess clinical benefits. Recently, it has been noted that peripheral blood eosinophil counts are an independent factor correlated with clinical outcome of ICIs in some types of cancer. We investigated peripheral blood absolute eosinophil counts (AECs) at baseline and 4 weeks after the initiation of nivolumab for mRCC patients between February 2016 and May 2022. In addition, we examined clinicopathological features including irAEs and analyzed the correlation between AECs and clinical efficacy of nivolumab. The median progression-free survival (PFS) and overall survival (OS) for all patients were 5.7 and 25.5 months, respectively. The median AECs in patients with irAEs were significantly higher at baseline and 4 weeks after the treatment compared to those without irAEs (p < 0.001 and p = 0.001). With the cutoff value of AECs of 329 cells/µL at 4 weeks after the treatment for prediction of irAEs, high-AECs groups had significantly higher number of responders compared with that in low-AECs group (p < 0.001). Accordingly, the PFS and OS were significantly better in patients with high-AECs group than those in low-AECs group (p = 0.03 and p = 0.009). High-AECs at 4 weeks after the treatment serve as the prominent surrogate marker associated with the incidence of irAEs and better clinical outcome in mRCC patients receiving nivolumab.

Relapsing cytokine release syndrome in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib therapy.

As immune checkpoint inhibitors become more widely available, the optimal management of immune-related adverse events (irAEs) is becoming increasingly important. Although irAEs are diverse, reports on cytokine release syndrome are rare. Here, we report a case of a 48-year-old man with relapsing cytokine release syndrome after receiving pembrolizumab and axitinib combination therapy for metastatic renal cell carcinoma. During dose reduction of prednisolone for immune-related hepatitis on day 33 after starting pembrolizumab plus axitinib, the patient suddenly developed abdominal pain, and a few hours later became hypotensive and poorly oxygenated. Despite the use of a ventilator and high doses of catecholamines, blood pressure and oxygenation could not be maintained. Extracorporeal membrane oxygenation and intra-aortic balloon pumping were also administered. The cytokine release syndrome (CRS) was treated with tocilizumab, and his general condition improved. Lower-grade CRS relapsed four times despite a moderate dose of oral prednisolone with mycophenolate mofetil or tacrolimus. After gradual reduction in prednisolone over 5 months, the patient was discharged from the hospital. Partial remission of renal cell carcinoma continued for 21 months, and salvage radical nephrectomy was performed. The patient remained disease-free without the need for further treatment 9 months after surgery.

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.

Progressive Spreading of DNA Methylation in the GSTP1 Promoter CpG Island across Transitions from Precursors to Invasive Prostate Cancer.

Glutathione S-transferase pi 1 (GSTP1) is lowly expressed in normal prostate luminal cells and becomes induced in most proliferative inflammatory atrophy (PIA) lesions. GSTP1 becomes silenced in prostatic intraepithelial neoplasia (PIN) and prostate adenocarcinoma (CaP) via cytosine-phospho-guanine (CpG) island promoter hypermethylation. However, GSTP1 methylation patterns in PIA and PIN, and their relationship to patterns in CaP are poorly understood. We used bisulfite genomic sequencing to examine patterns of GSTP1 promoter CpG island methylation in laser capture microdissected benign, PIA, PIN, and CaP regions from 32 subjects that underwent radical prostatectomy. We analyzed 908 sequence clones across 24 normal epithelium, 37 PIA, 18 PIN, and 23 CaP regions, allowing assessment of 34,863 CpG sites with allelic phasing. Normal and PIA lesions were mostly unmethylated with 0.52 and 1.3% of total CpG sites methylated, respectively. PIN and CaP lesions had greater methylation with 24% and 51% of total CpG sites methylated, respectively. The degree of GSTP1 methylation showed progression from PIA << PIN < CaP. PIN lesions showed more partial methylation compared with CaP lesions. Partially methylated lesions were enriched for methylation changes at AP1 and SP1 transcription factor binding sites. These results demonstrate that methylation density in the GSTP1 CpG island in PIN was intermediate relative to that in normal prostate epithelium/PIA and CaP lesions. These results are consistent with gradual spreading of DNA methylation centered at the SP1/AP1 transcription factor binding sites in precursor lesions, with subsequent spreading of methylation across the entire CpG island in transition to CaP. PREVENTION RELEVANCE: DNA hypermethylation at the GSTP1 promoter progressively spreads from being unmethylated in normal prostate to intermediate levels in precursor lesions to extensive methylation in cancer. This molecular progression of GSTP1 promoter methylation patterns in early prostate carcinogenesis could be useful for identification and interception of prostate cancer precursors.

[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.

Partial cooling of the upper body with a water-cooled vest in an environment exceeding body temperature.

OBJECTIVES: To evaluate the efficacy of water-cooled clothing that continuously cools restricted body areas to suppress body temperature increase as an anti-heatstroke measure for workers in hot environments that exceed body temperature. METHODS: Ten healthy men were placed in Room A (air temperature: 25°C, relative humidity: 50%) for 15 min. They were then transferred to Room B (air temperature: 40°C, relative humidity: 50%), where they rested for 10 min, then put on cooling clothing, and again rested for 15 min (the control group rested for 25 min). They then performed intense ergometer exercise for 40 min at 40% maximal oxygen consumption after which they rested for 10 min. The three trial conditions were CON (long-sleeved summer work clothes), VEST (cooling vest), and P-VEST (partial cooling vest). In VEST and P-VEST, water-cooled clothing continuously recirculated with 10°C water was used to cool the upper body. In P-VEST, only the neck, axillae, and heart areas were in contact with the cooled clothing. The measured indices were the rectal, esophageal, and external auditory canal temperatures; heart rate; estimated sweat volume; and subjective evaluations. RESULTS: Compared with the CON condition, the rectal, esophageal, and external auditory canal temperatures and the heart rate were significantly lower and the subjective indices were decreased in the VEST and P-VEST conditions. CONCLUSIONS: Partial cooling showed a body cooling effect similar to that of whole upper body cooling. Partial body cooling promoted the heat dissipation, suggesting that partial cooling is efficient for maintaining body cooling in hot environments.

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.

IMAGENE trial: multicenter, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy of niraparib with PD-1 inhibitor in solid cancer patients with homologous recombination repair genes mutation.

BACKGROUND: Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis. METHODS: Key eligibility criteria for this trial includes HRR gene-mutated tumor determined by any cancer gene tests; progression after previous ICI treatment; and Eastern Cooperative Oncology Group Performance Status ≤ 1. The primary endpoint is the confirmed objective response rate (ORR) in all patients. The secondary endpoints include the confirmed ORR in patients with HRR gene-mutation of ctDNA using the Caris Assure (CARIS, USA). The target sample size of the IMAGENE trial is 57 patients. Biomarker analyses will be performed in parallel using the Caris Assure, proteome analysis, and T cell repertoire analysis to reveal tumor immunosurveillance in peripheral blood. EXPECTED OUTCOME: Our trial aims to confirm the clinical benefit of PARPi plus ICI combination therapy in ICI-resistant patients. Furthermore, through translational research, our trial will shed light on which patients would benefit from the targeted combination therapy for patients with HRR gene-mutated tumor even after the failure of ICIs. TRIAL REGISTRATION: The IMAGENE trial: jRCT, Clinical trial no.: jRCT2051210120, Registered date: November 9, 2021.

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.

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.

Improvement in bladder volume reproducibility using A-mode portable ultrasound bladder scanner in moderate-hypofractionated volumetric modulated arc therapy for prostate cancer patients.

PURPOSE: This study introduced an A-mode portable ultrasound bladder scanner, the Lilium® α-200 (here after Lilium; Lilium Otsuka, Kanagawa, Japan), for the treatment of prostate cancer patients with hypofractionated volumetric modulated arc therapy to improve the reproducibility of bladder volume (BV). MATERIALS AND METHODS: Thirty patients were advised to maintain full BV prior to computed tomography (CT) simulation and daily treatment. Among these, the BV of 15 patients was measured using Lilium until a BV of 80% in the simulation was achieved (with the Lilium group). Daily cone-beam CT (CBCT) was performed for treatment. The correlation between BV measured by CBCT and Lilium was assessed. The differences in the BV and dosimetric parameters of the bladder in the CBCT versus planning CT were compared between the groups with and without Lilium. RESULTS: There was a significantly strong relationship (r = 0.796, p < 0.05) between the BVs measured using CBCT and Lilium. The relative BV ratios to simulation CT < 0.5 and > 2 were observed in 10.3% and 12.7%, respectively, of treatment sessions without Lilium group, while these ratios were 1% and 2.8%, respectively, in the Lilium group. The mean absolute difference in the range of V30Gy to V40Gy without Lilium sessions was significantly larger (p < 0.05) than that in the Lilium group. CONCLUSION: The use of the A-mode portable ultrasound bladder scanner significantly improved the reproducibility of the BV, resulting in few variations in the dosimetric parameters for the bladder.

Real-world Outcomes of Tyrosine Kinase Inhibitors Immediately After Immune Checkpoint Inhibitors in Renal Cell Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have demonstrated a survival benefit for patients with cancer. However, the clinical outcomes of subsequent tyrosine kinase inhibitors (TKIs) after ICI failure in patients with metastatic renal cell carcinoma (mRCC) remain unclear. PATIENTS AND METHODS: We retrospectively examined 38 patients with mRCC who started TKIs immediately after nivolumab with (combination group) or without ipilimumab (nivolumab group) between September 2016 and July 2019. RESULTS: Of the 38 patients, 16 and 11 achieved partial response and stable disease, respectively, resulting in a 42.1% objective response rate and 71.1% disease control rate. The median progression-free survival (PFS) from TKI initiation was 8.8 and 12.9 months in the nivolumab and combination groups, respectively. PFS and overall survival were significantly longer in patients with long-term responses to previous ICI treatment (p=0.0152 and p=0.0155, respectively). CONCLUSION: TKIs demonstrate adequate anti-tumour activity after treatment with ICIs in real-world settings.

A fan-attached jacket worn in an environment exceeding body temperature suppresses an increase in core temperature.

We examined whether blowing hot air above body temperature under work clothing may suppress core temperature. Nine Japanese men engaged in two 30-min bicycle ergometer sessions at a workload of 40% VO2max at 40 °C and 50% relative humidity. The experiment was conducted without wearing any cooling apparatus (CON), wearing a cooling vest that circulated 10.0 °C water (VEST), and wearing a fan-attached jacket that transferred ambient air underneath the jacket at a rate of 30 L/s (FAN). The VEST and FAN conditions suppressed the increases of rectal temperature (CON, VEST, FAN; 38.01 ± 0.19 °C, 37.72 ± 0.12 °C (p = 0.0076), 37.54 ± 0.19 °C (p = 0.0023), respectively), esophageal temperature (38.22 ± 0.30 °C, 37.55 ± 0.18 °C (p = 0.0039), 37.54 ± 0.21 °C (p = 0.0039), respectively), and heart rate (157.3 ± 9.8 bpm, 136.9 ± 8.9 bpm, (p = 0.0042), 137.5 ± 6.5 bpm (p = 0.0023), respectively). Two conditions also reduced the estimated amount of sweating and improved various subjective evaluations. Even in the 40 °C and 50% relative humidity environment, we may recommend wearing a fan-attached jacket because the heat dissipation through evaporation exceeded the heat convection from the hot ambient air.

Two cases of delayed onset of immune-related adverse events after discontinuation of nivolumab in patients with metastatic renal cell cancer.

INTRODUCTION: Delayed onset of immune-related adverse events following immune-checkpoint inhibitor discontinuation is underrecognized because of little available evidence. CASE PRESENTATION: A 50-year-old man with metastatic renal cell carcinoma (Case 1) and 58-year-old woman with renal cell carcinoma and retroperitoneal lymph node metastasis (Case 2) underwent nivolumab therapy. Case 1: Progressive disease forced nivolumab discontinuance after 18 months, and he underwent two courses of tyrosine kinase inhibitor therapy. immune-related adverse events of pneumonitis, hepatitis, and renal dysfunction were diagnosed 142 days after nivolumab discontinuation, and he recovered with immunosuppressive treatment. Case 2: The immune-related adverse event of pneumonitis forced nivolumab discontinuance after 14 months, and two courses of tyrosine kinase inhibitor therapy were administered. The immune-related adverse event of hepatitis was diagnosed 436 days after nivolumab discontinuation, and she recovered with immunosuppressive treatment. CONCLUSION: Two patients with delayed onset of immune-related adverse events after nivolumab discontinuation were recovered with immunosuppressive treatment.

Hospital volume and postoperative survival for three urological cancers: Prostate, kidney, and bladder.

OBJECTIVE: To examine the association between hospital volume and postoperative 5-year survival for patients with prostate, kidney, and bladder cancer. METHOD: Using Osaka Cancer Registry data, we identified 9285 patients who were diagnosed as having prostate, kidney, or bladder cancer and who underwent surgery between 2007 and 2011 in Osaka, Japan. The surgical hospital volume of each hospital was calculated and then divided into quartiles (high, medium, low, very low). We estimated the hazard ratios of hospital volume (quartiles) for 5-year survival using Cox proportional hazard models. RESULTS: For all three cancer sites, the mortality hazard of hospitals with the lowest hospital volume was significantly higher than that of hospitals with the highest volume. The difference in adjusted 5-year survival rates between hospitals with the highest and lowest hospital volume was 3.6% for prostate cancer, 6.6% for kidney cancer, and 13.3% for bladder cancer. CONCLUSION: Hospital surgical volume seems to affect 5-year survival for patients with urological cancers, especially kidney and bladder cancer.

Partial nephrectomy for a Bosniak IV cystic renal mass mimicking a simple renal cyst adjacent to a solid renal tumor.

INTRODUCTION: Renal tumors are often associated with renal cysts. Meanwhile, in some cases there are challenging issues of how to diagnose renal cystic tumors and to decide surgical procedures. CASE PRESENTATION: A 75-year-old man was referred to our department for a 21-mm tumor by his left kidney. Contrast-enhanced computed tomography showed an intense contrast uptake the tumor, which was adjacent to a 64-mm unilocular renal cyst with no contrasting effects. It was clinically diagnosed as renal cell carcinoma, stage T1aN0M0, and treated with robot-assisted partial nephrectomy, for both the solid tumor and the adjacent cyst. Pathological findings revealed a tumor cell clump within the cyst wall, concurrent with the renal cell carcinoma. The patient has remained free of disease at 1 year after surgery. CONCLUSION: A partial nephrectomy that includes the entire cyst wall should be considered for renal tumor associated with unilocular renal cyst.

Renal cell carcinoma with central nervous system demyelination caused by nivolumab.

INTRODUCTION: Central nervous system demyelination caused by immune checkpoint inhibitors is a very rare condition. CASE PRESENTATION: A 65-year-old man who received nivolumab for renal cell carcinoma developed abnormal behavior, such as disagreeable speech and sudden anger. Brain-enhanced magnetic resonance imaging revealed multiple lesions with partial contrast effects in the cerebral white matter. We tentatively diagnosed demyelination caused by nivolumab, and performed steroid pulse therapy twice. After that, his symptoms improved. For the next 2 years, his symptoms did not recur, nor did his cancer progress. CONCLUSION: Demyelination caused by immune checkpoint inhibitors can be fatal and requires early diagnosis and treatment.