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Risk stratification of kidney cancer patients after nephrectomy may tailor surveillance intensity and selection for adjuvant therapy. Transcriptomic approaches are effective in predicting recurrence, but whether they add value to clinicopathologic models remains unclear.Data from patients with clear cell renal cell carcinoma (ccRCC) was downloaded from The Cancer Genome Atlas. Clinicopathologic variables were used to calculate SSIGN (stage, size, grade, and necrosis) scores. The 16 gene recurrence score (RS) signature was generated using RNA-seq data. Transcriptomic risk groups were calculated using the original thresholds. SSIGN groups were divided into low, intermediate, and high risk. Disease-free status was the primary endpoint assessed.SSIGN and RS were calculated for 428 patients with non-metastatic ccRCC. SSIGN low-, intermediate-, and high-risk groups demonstrated 2.7%, 15.2%, and 27.5%, 3-year recurrence risk, respectively. On multivariable analysis, the RS was associated with disease-free status (sub-distribution hazard ratio (sHR) 1.43 per 25 RS [95% CI (1.00-1.43)], p = 0.05). By risk groups, RS further risk stratified the SSIGN intermediate-risk group (sHR 2.22 [95% CI 1.10-4.50], p = 0.03). SSIGN intermediate-risk patients with low and high RS had a 3-year recurrence rate of 8.0% and 25.2%, respectively. Within this risk group, the area under the curve (AUC) at 3 years was 0.69 for SSIGN, 0.74 for RS, and 0.78 for their combination.Transcriptomic recurrence scores improve risk prediction even when controlling for clinicopathologic factors. Utility may be best suited for intermediate-risk patients who have heterogeneous outcomes and further refinement for clinical utility is warranted.

Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab.After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined.The median follow-up was 8.3 months (range 0.2-29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased ( 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline.Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings.

Loss-of-function mutations in genes encoding the Krebs cycle enzymes Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) induce accumulation of fumarate and succinate, respectively and predispose patients to hereditary cancer syndromes including the development of aggressive renal cell carcinoma (RCC). Fumarate and succinate competitively inhibit αKG-dependent dioxygenases, including Lysine-specific demethylase 4A/B (KDM4A/B), leading to suppression of the homologous recombination (HR) DNA repair pathway. In this study, we have developed new syngeneic Fh1- and Sdhb-deficient murine models of RCC, which demonstrate the expected accumulation of fumarate and succinate, alterations in the transcriptomic and methylation profile, and an increase in unresolved DNA double-strand breaks (DSBs). The efficacy of poly ADP-ribose polymerase inhibitors (PARPis) and temozolomide (TMZ), alone and in combination, was evaluated both in vitro and in vivo. Combination treatment with PARPi and TMZ results in marked in vitro cytotoxicity in Fh1- and Sdhb-deficient cells. In vivo, treatment with standard dosing of the PARP inhibitor BGB-290 and low-dose TMZ significantly inhibits tumor growth without a significant increase in toxicity. These findings provide the basis for a novel therapeutic strategy exploiting HR deficiency in FH and SDH-deficient RCC with combined PARP inhibition and low-dose alkylating chemotherapy.

Recent studies have revealed that transurethral resection in one piece (TURBO) has several benefits over standard transurethral resection of bladder tumor (TUR-Bt), including a higher rate of containing the bladder muscle tissue and single-block resection. Five-aminolevulinic acid (5-ALA) was approved for the detection of bladder tumor treated with TUR-Bt. A 71-year-old male patient who received right nephroureterectomy developed bladder tumor recurrence on routine cystoscopy follow-up. We planned TURBO using fluorescent light-guided cystoscopy with 5-ALA. We herein report a case of bladder tumor successfully treated with TURBO using fluorescent light-guided cystoscopy with 5-ALA to detect the tumor surgical margin.

Introduction and Objectives. Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a simple marker of the systemic inflammatory response in critical care patients. We previously assessed the utility of NLR as a biomarker to predict tumor recurrence and cancer death in bladder cancer patients who underwent radical cystectomy. In this study, we evaluated the prognostic impact of NLR in bladder cancer patients who received gemcitabine and nedaplatin (GN) chemotherapy.Methods. A total of 23 patients who received GN chemotherapy for advanced bladder cancer were enrolled in this study. The cut-off point of NLR according to the sensitivity and specificity levels was derived from the area under receiver operator characteristics (AUROC) curve plotted for disease progression or overall mortality.Results. The NLR cut-off point was determined as 4.14 for both tumor progression and overall mortality. Median progression-free survival (PFS)/overall survival (OS) in the higher NLR group (NLR ≥ 4.14) and lower NLR group (NLR < 4.14) were 194/468 days versus 73/237 days, respectively. Kaplan-Meier analysis showed that higher NLR significantly correlated with poorer PFS (p=0.011) and OS (p=0.045).Conclusions. NLR may serve as a new biomarker to predict responses to GN-based chemotherapy in advanced bladder cancer patients and/or their prognosis.

BACKGROUND:Sarcopenia is defined as a low skeletal muscle volume. Recent studies have reported that sarcopenia is associated with a poor prognosis in various cancers. The purpose of this study is to evaluate the correlation between the psoas muscle volume and recurrence-free survival in patients with localized clear cell renal cell carcinoma (ccRCC). METHODS:A total of 316 male patients with localized ccRCC who underwent radical nephrectomy at Yokohama City University Hospital (Yokohama, JAPAN) and Kanagawa Cancer Center (Yokohama, JAPAN) between 2002 and 2018 were enrolled in this study. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area on the contralateral side of the tumor on axial CT, which was calculated at the level of L4 (mm2) divided by the square of the body height (m2). We divided patients into two groups based on the median PMI (409.64mm2/m2). RESULTS:The lower PMI group showed poorer recurrence-free survival (RFS) than the higher PMI group (p = 0.030). Regarding 5-year RFS, a lower PMI was a significant predictor of recurrence (p = 0.022, hazard ratio (HR): 2.306) and a multivariate analysis revealed that a lower PMI (4 cm (p = 0.044, HR: 2.341), and pathological stage >2 (p

Background The treatment of advanced or metastatic renal cell carcinoma (RCC) has drastically changed since the approval of immune checkpoint therapy. Nivolumab is a treatment option for patients with metastatic RCC, previously treated with targeted antiangiogenic therapy. The efficacy of nivolumab for patients with RCC was established by the Checkmate 025 clinical trial. Chromophobe RCC (CRCC) represents around 5% of RCC cases, but non-clear cell RCC (non-ccRCC) subtypes were excluded from the Checkmate 025 clinical trial. We report a case in which the use of nivolumab as the seventh-line therapy elicited a significant response in the treatment of metastatic CRCC with sarcomatoid differentiation. Case presentation We report a case of a 41-year-old woman with metastatic CRCC with sarcomatoid differentiation. She was treated with sunitinib, pazopanib, everolimus, sorafenib, axtinib, and temsirolimus, but treatment was discontinued because of disease progression or strong adverse events. Seventh-line treatment with nivolumab was initiated and significant clinical improvement was noted after 4 cycles. The treatment was well-tolerated with no significant side effects and the patient continues with nivolumab treatment at present. Conclusions Nivolumab may be an attractive treatment option for non-ccRCC patients with sarcomatoid differentiation that exhibited aggressive characteristics and poor prognosis. Further investigation is warranted.

Oxidative stress is a primary cause of vascular endothelial damage. In the prostate, ischemia increases the levels of reactive oxygen species, growth factors and cytokines, and induces the development of angiogenesis, which results in cancer progression. The expression levels of an oxidative stress marker, 8-hydroxyguanosine (8-OHdG), were compared between prostate cancer and non-neoplastic prostate tissues. A prostate tissue microarray composed of 10 cases of prostatic adenocarcinoma and 70 cases of benign prostatic hyperplasia was immunohistochemically stained for 8-OHdG. All cases expressed 8-OHdG. The levels of 8-OHdG expression in prostatic cancer (30.0% moderate and 70.0% strong) were significantly higher than those in benign prostatic hyperplasia (71.4% moderate and 28.6% strong; (p

Introduction.Horseshoe kidney is one of the most common congenital renal fusion anomalies. Due to its poor mobility and abnormal vasculature form, surgeons should pay close attention to all anatomical variations.Case Presentation.An 83-year-old woman was referred to our hospital because of left renal tumor in a horseshoe kidney incidentally found by her previous hospital. We performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell renal cell carcinoma. G2 INFαV-pT1a with a negative surgical margin. No evidence of recurrence has been noted, and the renal function is well preserved at 28 months after surgery.Conclusion.When performing laparoscopic partial nephrectomy for renal carcinoma, especially a horseshoe kidney, preoperative imaging is crucial for identifying the location of the renal vessels.

Background There is no reliable biomarker for predicting the prognosis of patients who undergo radical cystectomy for bladder cancer. Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) could function as a useful prognostic factor in several types of malignancies. This study aimed to assess the usefulness of NLR in bladder cancer. Methods A total of 74 patients who underwent radical cystectomy in our institutions from 1999 to 2014 were analyzed. The NLR was calculated using the patients’ neutrophil and lymphocyte counts before radical cystectomy. An immunohistochemical analysis was also performed to detect tumor infiltrating neutrophils (CD66b) and lymphocytes (CD8) in bladder cancer specimens. Results A univariate analysis showed that the patients with a high NLR (≥2.38; HR = 4.84; p = 0.007), high C-reactive protein level (>0.08; HR = 10.06; p = 0.030), or pathological lymph node metastasis (HR = 4.73; p = 0.030) had a significantly higher risk of cancer-specific mortality. Kaplan-Meier and log-rank tests further revealed that NLR was strongly correlated with overall survival (p = 0.018), but not progression-free survival (p = 0.137). In a multivariate analysis, all of these were found to be independent risk factors (HR = 4.62, 10.8, and 12.35, respectively). The number of CD8-positive lymphocytes was significantly increased in high-grade (p = 0.001) and muscle-invasive (p = 0.012) tumors, in comparison to low-grade and non-muscle-invasive tumors, respectively. Conclusions The NLR predicted the prognosis of patients who underwent radical cystectomy and might therefore function as a reliable biomarker in cases of invasive bladder cancer.

Objectives Recent studies have demonstrated that up-front docetaxel combined with androgen deprivation therapy (ADT) prolongs survival in some patients with metastatic hormone-naive prostate cancer (mHNPC). However, new biomarkers for selecting personalized treatment strategies for mHNPC are warranted. We evaluated the value of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression as a prognosticator in men with mHNPC. Methods and materials A total of 48 men with mHNPC diagnosed from 2003 to 2009 were enrolled in this study. Prostate cancer tissues obtained by needle biopsies were immunohistochemically stained for LMW-PTP. Correlations between LMW-PTP expression and clinicopathological characteristics were then assessed. Results At the time of analysis, 29 (60.4%) patients were alive, whereas 15 (31.3%) and 4 (8.3%) died of prostate cancer and nonprostate cancer, respectively. Of these, 29 (60.4%) had low LMW-PTP expression and 19 (39.6%) had high expression. Median overall survival (OS) for patients with high LMW-PTP expression was not reached and that for patients with low LMW-PTP expression was 23.8 months. High LMW-PTP expression was significantly correlated with a shorter OS compared with low LMW-PTP expression ( P = 0.01). Moreover, multivariate analysis showed that Gleason score (≥8 vs.≤7; HR = 5.8, 95% CI: 1.3–26.5, P = 0.02) and LMW-PTP expression (high vs. low; HR = 2.7, 95% CI: 1.0–7.2, P = 0.04) were independent prognostic factors for OS. Conclusions LMW-PTP is a potential biomarker to predict OS in patients with mHNPC.

e16098 Background: For patients with advanced prostate cancer, long-term treatment of androgen deprivation has been conventionally performed. Among the adverse events such as hormonal therapy, bone fracture due to osteoporosis or metastatsis is one of indispensable events. We assessed the frequency of bone fractures in Japanese patients received hormonal therapy. Methods: Between 2000 and 2010, 1,108 Japanese patients were treated with hormonal therapy including GnRH agonist plus anti-androgens or GnRH agonist alone at Yokohama City University Hospital. Of those patients, 48 patients (4.3%) had bone fractures during their treatment. In this retrospective study, we examined the association of bone fracture with the long-term hormonal therapy by investigating the duration of hormonal therapy, fracture sites, and the occurrence of fracture in castration resistant prostate cancer (CRPC) patients. Results: The median age of the patients with fracture was 77 (60-85) years; the median duration from the start of hormonal therapy to fracture was 29.4 (5.4-110.4) months. Eight patients with CRPC had pathological fractures at bone metastases. With respect of fracture sites, 22 patients (46%) had spinal fractures and 10 patients (21%) had fracture of lower legs. Of 8 CRPC patients, 7 patients had spinal fracture after long-term hormonal therapy (median: 38.6 months, range: 15.7-99.1 months). Conclusions: Japanese patients with prostate cancer treated with hormonal therapy have lower risk for bone fracture compared with those in western countries and USA, and interestingly, it is recognized that vertebral body is vulnerable to fracture in Japanese, especially in CRPC patients treated for long-term hormonal therapy. Because bone fracture in patients with prostate cancer endanger their prognosis, the bone management how to prevent bone fracture is very important during hormonal therapy. For the purpose of it, more detailed analysis in this retrospective study should be required.