Real-world outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma in Japanese patients: data with a minimum of 3 years of follow-up.

BACKGROUND: Long-term follow-up data regarding treatment outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma as a first-line therapy are limited in real-world Japanese populations. METHODS: We retrospectively evaluated data of 56 advanced renal cell carcinoma patients treated with nivolumab plus ipilimumab, with a follow-up of at least 3 years. Survival, tumour response and adverse event profiles were assessed. RESULTS: A total of 41 patients (73%) were histopathologically diagnosed with clear-cell renal cell carcinoma, and 34 (61%) were categorized into the International Metastatic renal cell carcinoma Database Consortium intermediate-risk group. The median follow-up period was 34.4 months. Regarding an effectiveness profile, median progression-free survival, time to treatment failure and overall survival were 9.01, 12.5 and 49.0 months, respectively. Objective response was observed in 27 patients (48%), including eight patients with complete response (14%), and the median duration of response was 30.8 months. Multivariate analyses showed that clear-cell histology was an independent factor of longer overall survival (hazard ratio: 0.23, P = 0.0013). Regarding safety profiles, adverse events of any grade and those with grade ≥3 developed in 40 (71%) and 25 patients (45%), respectively. Median time to adverse event development was 1.68 months. Treatment was interrupted in 28 patients (50%), and corticosteroid administration was needed in 25 (45%). CONCLUSION: The 3-year follow-up data showed that nivolumab plus ipilimumab combination therapy exhibited a feasible effectiveness in real-world Japanese patients with advanced renal cell carcinoma. Accordingly, the high risk of adverse event development, which often requires treatment withdrawal and corticosteroid administration, should be considered.

Changes in outcome of patients with advanced non-clear cell renal cell carcinoma from the tyrosine kinase inhibitor era to the immuno-oncology era.

BACKGROUND: The therapeutic benefit of immuno-oncology (IO) therapy for patients with advanced non-clear-cell renal cell carcinoma (nccRCC) remains unclear. PATIENTS AND METHODS: We reviewed clinical data from 93 patients with advanced nccRCC who received first-line systemic therapy including IO combination therapy and tyrosine kinase inhibitor (TKI) monotherapy at our affiliated institutions. Patients were divided based on the period when the treatment was implemented as the standard of care into the IO and TKI eras. Survival and tumor response outcomes were compared between the IO and TKI eras. RESULTS: Of the 93 patients, 50 (54%) and 43 (46%) were categorized as IO era and TKI era groups, respectively. Progression-free survival (PFS) and overall survival (OS) were significantly longer in the IO era than in the TKI era (median PFS: 8.97 vs. 4.96 months, p = 0.0152; median OS: 38.4 vs. 13.5 months, p = 0.0001). After the adjustment using other covariates, the treatment era was an independent factor for PFS (hazard ratio: 0.59, p = 0.0235) and OS (hazard ratio: 0.27, p < 0.0001). Objective response and disease control rates was not significantly different between the treatment eras (26% vs. 16.3%, p = 0.268; 62% vs. 62.8%, p = 0.594). CONCLUSION: The implementation of IO therapy was significantly associated with longer survival in the nccRCC population. Further studies are needed to establish a more effective treatment strategy in this population using multiple regimens of IO combination therapy.

First-line dual immune checkpoint inhibitor therapies versus combination therapies comprising immune checkpoint inhibitors and tyrosine kinase inhibitors for advanced renal cell carcinoma: a comparative analysis of the effectiveness using real-world data.

BACKGROUND: There are few comparative studies on dual immune checkpoint inhibitors (ICIs) (i.e., IO-IO) and combination therapies comprising ICIs plus tyrosine kinase inhibitors (TKIs) (i.e., IO-TKI) for advanced renal cell carcinoma (RCC), especially in real-world settings. METHODS: We retrospectively evaluated data of 175 patients with IMDC intermediate-risk or poor-risk RCC; as first-line therapy, 103 received IO-IO, and 72 received IO-TKI. An inverse probability of treatment weighting (IPTW) analysis was conducted to balance patients' backgrounds in the IO-IO and IO-TKI groups. RESULTS: Based on the IPTW analysis, progression-free survival (PFS) was longer in the IO-TKI group than in the IO-IO group (median: 15.6 vs. 8.3 months; p = 0.0386). In contrast, overall survival was not different between groups (median: 46.7 vs. 49.0 months; p = 0.465). Although the IPTW-adjusted objective response rate was not significantly different (51.2% vs. 43.9%; p = 0.359), the progressive disease rate as the best overall response was lower in the IO-TKI group than in the IO-IO group (3.3% vs. 27.4%; p < 0.0001). Regarding the safety profile, the treatment interruption rate was higher in the IO-TKI group than in the IO-IO group (70.3% vs. 49.2%; p = 0.005). In contrast, the IO-IO group had a higher corticosteroid administration rate (43.3% vs. 20.3%; p = 0.001). CONCLUSION: IO-TKI therapy exhibited superior effectiveness over IO-IO therapy in terms of PFS improvement and immediate disease progression prevention and was associated with a higher risk of treatment interruption and a lower risk of needing corticosteroids.

Impact of sex on prognosis in patients with advanced renal cell carcinoma treated with immune checkpoint inhibitors.

BACKGROUND: Prognostic impact of sex in patients with malignancies treated with immune checkpoint inhibitors has been intensively discussed but remains unclear, especially in advanced renal cell carcinoma. METHODS: We retrospectively evaluated a total of 184 patients with advanced renal cell carcinoma treated with either nivolumab plus ipilimumab combined treatment as first-line therapy (n = 73) or nivolumab as later-line therapy (n = 111) at our affiliated institutions. Progression-free survival, overall survival and objective response rate as well as adverse event profile were compared between sexes. RESULTS: Of the total 184 patients, 48 (26%) were female. Female patients had a significantly shorter progression-free survival than male patients (median: 3.8 vs. 8.3 months, P = 0.0005), but overall survival (median: 39.2 vs. 45.1 months, P = 0.283) and objective response rate (29% vs. 42%, P = 0.119) were not different between them. Similar findings were observed when analyzing within each treatment; in both patient groups treated with nivolumab plus ipilimumab combined therapy and nivolumab monotherapy, progression-free survival was significantly shorter in female than in male patients (P = 0.007, P = 0.017), but overall survival (P = 0.914, P = 0.117) and objective response rate (P = 0.109, P = 0.465) were comparable between them. Moreover, in a more restricted cohort consisting of patients with clear-cell renal cell carcinoma, a shorter progression-free survival in female patients was also observed (3.8 vs. 11.0 months, P < 0.0001). CONCLUSIONS: This retrospective study showed that immune checkpoint inhibitors-based treatment for renal cell carcinoma exhibited less marked effects in female than in male patients. Thus, sex may be an important factor for decision-making on systemic therapy as renal cell carcinoma treatment, although further studies are required to validate the present findings.

Real-world efficacy and safety of cabozantinib following immune checkpoint inhibitor failure in Japanese patients with advanced renal cell carcinoma.

BACKGROUND: Real-world data of cabozantinib after failure of immune checkpoint inhibitors for advanced renal cell carcinoma in Japanese population are limited. Additionally, prognostic factors of cabozantinib in this setting are still unknown. METHODS: We retrospectively evaluated data of 56 patients treated with cabozantinib subsequent to failed immune checkpoint inhibitors at four institutions. Regarding the efficacy profile, progression-free survival, overall survival and objective response rate were assessed. In terms of the safety profile, rate of adverse events, dose reduction and treatment interruption were assessed. Furthermore, risk factors of progression-free survival were analyzed. RESULTS: Twenty-nine patients (52%) were treated with cabozantinib as second-line therapy. Most frequent prior immune checkpoint inhibitor treatment was nivolumab plus ipilimumab combination therapy as first-line therapy (n = 30, 54%). Median progression-free survival and overall survival were 9.76 and 25.5 months, respectively, and objective response rate was 34%. All patients experienced at least one adverse event, and grade ≥ 3 adverse events were observed in 31 patients (55%). Forty-four (79%) and 31 (55%) patients needed dose reduction and treatment interruption, respectively. Multivariate analysis showed that reduced initial dose (i.e. <60 mg) (hazard ratio: 2.50, P = 0.0355) and presence of lymph node metastasis (hazard ratio: 2.50, P = 0.0172) were independent factors of shorter progression-free survival. CONCLUSION: Cabozantinib in Japanese patients with advanced renal cell carcinoma who failed immune checkpoint inhibitors was efficacious and had a manageable safety profile. These results appear to be similar to those of previous clinical trials.

Association between lung immune prognostic index and survival of patients with metastatic urothelial carcinoma treated with pembrolizumab.

INTRODUCTION AND OBJECTIVE: Lung immune prognostic index score (LIPI), calculated using the derived neutrophil-lymphocyte ratio and lactate dehydrogenase level, is reported for use in numerous malignancies, while its role on metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains limited. We aimed to investigate association between LIPI and outcomes in this setting. METHODS: We retrospectively evaluated 90 patients with mUC treated with pembrolizumab at four institutions. The associations between three LIPI groups and progression-free survival (PFS), overall survival (OS), objective response rates (ORRs) or disease control rates (DCRs) were assessed. RESULTS: Based on the LIPI, good, intermediate, and poor groups were observed in 41 (45.6%), 33 (36.7%), and 16 (17.8%) patients, respectively. The PFS and OS were significantly correlated with the LIPI (median PFS: 21.2 vs. 7.0 vs. 4.0 months, p = 0.001; OS: 44.3 vs. 15.0 vs. 4.2 months, p < 0.001 in the LIPI good vs. intermediate vs. poor groups). Multivariable analysis further revealed that LIPI good (vs. intermediate or poor, hazard ratio: 0.44, p = 0.004) and performance status = 0 (p = 0.015) were independent predictors of a longer PFS. In addition, LIPI good (hazard ratio: 0.29, p < 0.001) were shown to be associated with a longer OS together with performance status = 0 (p < 0.001). The ORRs tended to be different among patients with Good LIPI compared with Poor, and DCRs were significantly different among the three groups. CONCLUSIONS: LIPI, a simple and convenient score, could be a significant prognostic biomarker of OS, PFS, and DCRs for mUC treated with pembrolizumab.

Outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma: a real-world multi-institution data with a minimum of 2 years of follow-up.

OBJECTIVES: To investigate the long-term follow-up outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma, using real-world data. METHODS: A total of 121 patients were treated with nivolumab monotherapy as subsequent therapy after the failure of prior tyrosine kinase inhibitor therapy between January 2013 and December 2021 at four affiliated institutions. To evaluate the outcome after 2 years or more, we selected patients in whom nivolumab therapy was started in December 2019 or earlier because data collection was performed until the end of December 2021. RESULTS: Seventy-four patients were evaluated. During the median follow-up period of 25.8 months, 62 (84%) and 40 (54%) patients had disease progression and died, respectively. Nivolumab was administered as second-line therapy in 43 patients (58%). The median progression-free survival and overall survival were 5.52 and 31.1 months, respectively, and objective response rate was 36%. There was no difference in progression-free survival or overall survival based on the treatment line of nivolumab (P = 0.915, P = 0.559). The magnitude of tumor response and development of immune-related adverse events were significantly associated with progression-free survival (P < 0.0001, P < 0.0001, respectively) and overall survival (P < 0.0001, P = 0.0002, respectively). Treatment-related adverse events developed in 38 patients (51%), including 33 (45%) who had immune-related adverse events. Steroid administration was needed in nine patients (12%). CONCLUSIONS: The present real-world multi-institution study with long-term follow-up data demonstrates that nivolumab monotherapy is effective for previously treated metastatic renal cell carcinoma, prolonging survival, improving tumor response and has a manageable safety profile.

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

OBJECTIVES: To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. PATIENTS AND METHODS: Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared. RESULTS: During a median follow-up period of 12.0 months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4 months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P = 0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P = 0.0613). CONCLUSIONS: The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma.

Association of tumor burden with outcome in first-line therapy with nivolumab plus ipilimumab for previously untreated metastatic renal cell carcinoma.

OBJECTIVES: To investigate the prognostic impact of tumor burden in patients receiving nivolumab plus ipilimumab as first-line therapy for previously untreated metastatic renal cell carcinoma (mRCC). METHODS: We retrospectively evaluated 62 patients with IMDC intermediate- or poor-risk mRCC, treated with nivolumab plus ipilimumab as first-line therapy at five affiliated institutions. Tumor burden was defined as the sum of diameters of baseline targeted lesions according to the RECIST version.1.1. We categorized the patients into two groups based on the median value of tumor burden (i.e., high vs. low). The association of tumor burden with progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) with nivolumab plus ipilimumab treatment was analyzed. RESULTS: The median tumor burden was 63.0 cm (interquartile range: 34.2-125.8). PFS was significantly shorter in patients with high tumor burden (n = 31) than in those with low tumor burden (n = 31) (median: 6.08 [95% CI: 2.73-9.70] vs. 12.5 [4.77-24.0] months, P = 0.0134). In addition, OS tended to be shorter in patients with high tumor burden; however, there was no statistically significant difference (1-year rate: 77.3 vs. 96.7%, P = 0.166). ORR was not significantly different between patients with high and low tumor burden (35 vs. 55%, P = 0.202). Multivariate analysis of PFS further showed that tumor burden was an independent factor (HR: 2.22 [95% CI: 1.11-4.45], P = 0.0242). CONCLUSIONS: Tumor burden might be a useful factor for outcome prediction, at least for PFS prediction, in patients receiving nivolumab plus ipilimumab for mRCC. Further prospective studies are warranted to confirm our findings.

Prognostic impact of sarcopenia in patients with metastatic hormone-sensitive prostate cancer.

BACKGROUND: Cancer cachexia is associated with a poor prognosis. This study aimed to investigate the association between sarcopenia and survival in patients with metastatic hormone-sensitive prostate cancer. METHODS: We retrospectively evaluated 197 patients diagnosed with metastatic hormone-sensitive prostate cancer in our department and its affiliated institution between January 2008 and December 2015. Sarcopenia was diagnosed according to the sex-specific consensus definition. Castration-resistance prostate cancer-free survival, cancer-specific survival and overall survival from the metastatic hormone-sensitive prostate cancer diagnoses were calculated using the Kaplan-Meier method and compared using the log-rank test. Risk factors affecting the survival outcomes were analyzed using the Cox proportional regression analysis. RESULTS: In total, 163 patients (82.7%) had sarcopenia. Cancer-specific survival and overall survival were significantly shorter in sarcopenic patients than in non-sarcopenic patients (median cancer-specific survival: 77.0 months vs. not reached, P = 0.0099; overall survival: 72.0 months vs. not reached, P = 0.0465), whereas castration-resistance prostate cancer-free survival did not significantly differ between the groups (P = 0.6063). Multivariate analyses showed that sarcopenia was an independent factor for cancer-specific survival (hazard ratio: 2.18, P = 0.0451), together with the Gleason score (hazard ratio: 1.87, P = 0.0272) and LATITUDE risk classification (hazard ratio: 2.73, P = 0.0008). Moreover, the prognostic association of sarcopenia was remarkable in patients aged <73.0 years (cancer-specific survival: 82.0 months vs. not reached, P = 0.0027; overall survival: 72.0 months vs. not reached, P = 0.0078 in sarcopenic vs. non-sarcopenic patients), whereas the association was not significant in patients aged ≥73.0 years (cancer-specific survival: 76.0 and 75.0 months, respectively, P = 0.7879; overall survival: 67.0 and 52.0 months, respectively, P = 0.7263). CONCLUSION: Sarcopenia was an independent risk factor of cancer-specific survival in patients with metastatic hormone-sensitive prostate cancer, especially in younger patients.

Sarcopenia predicts survival outcomes among patients with urothelial carcinoma of the upper urinary tract undergoing radical nephroureterectomy: a retrospective multi-institution study.

BACKGROUND: We aimed to evaluate the effect of sarcopenia, a condition of low muscle mass, on the survival among patients who were undergoing radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUT). METHODS: We retrospectively reviewed consecutive patients with UCUT (cT[any]N0M0) who underwent RNU between 2003 and 2013 at our department and its affiliated institutions. Preoperative computed tomography images were used to calculate each patient's skeletal muscle index, an indicator of whole-body muscle mass. Sarcopenia was defined according to the sex-specific consensus definitions, based on the patient's skeletal muscle and body mass indexes. We analyzed the relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU to identify factors that predicted patient survival. RESULTS: A total of 137 patients were included, and 90 patients (65.7 %) were diagnosed with sarcopenia. Compared to the non-sarcopenic patients, the sarcopenic patients had a significant inferior 5-year RFS (48.8 vs. 79.6 %, p = 0.0002), CSS (57.1 vs. 92.6 %, p < 0.0001), and OS (48.2 vs. 90.6 %, p < 0.0001). Multivariate analyses revealed that sarcopenia was an independent predictor of shorter RFS, CSS, and OS (all, p < 0.0001). CONCLUSIONS: Sarcopenia was an independent predictor of survival among patients with UCUT who were undergoing RNU.

Template-based lymphadenectomy reduces the risk of regional lymph node recurrence among patients with upper/middle ureteral cancer.

BACKGROUND: Our previous nonrandomized prospective study showed that template-based lymphadenectomy improved survival among patients with renal pelvic cancer but not among patients with ureteral cancer. However, regional node sites vary according to the tumor's location in relation to the ureter. Therefore, this retrospective study examined the therapeutic role of lymphadenectomy for ureteral cancer according to tumor location. METHODS: Between January 1988 and September 2015, we performed nephroureterectomy for 154 patients with nonmetastatic urothelial carcinoma of the ureter at two Japanese institutions. The tumors' locations were classified as the lower ureter or the upper/middle ureter (before the cranial crossing of the common iliac artery). The appropriate regional nodes were identified based on our previous mapping study. Dissection was classified as complete lymphadenectomy (all regional sites were dissected), incomplete lymphadenectomy (not all sites were dissected), or no lymphadenectomy. We focused the analyses on patients with ≥pT2 disease to clarify the effect of the lymphadenectomy. RESULTS: Among the 48 patients with upper/middle ureteral cancer, recurrence-free and cancer-specific survival were significantly higher in the complete lymphadenectomy group (vs. the incomplete or no lymphadenectomy groups). However, there were no differences in recurrence-free and cancer-specific survivals among the 56 patients with lower ureteral cancer. In the patients with upper/middle ureteral cancer, multivariate analysis revealed that template-based lymphadenectomy was independently associated with a reduced risk of cancer-specific mortality. CONCLUSIONS: Template-based lymphadenectomy has a therapeutic benefit for treating patients with upper/middle ureteral cancer but not for treating patients with lower ureteral cancer.

Comparison of survival rates in stage 1 renal cell carcinoma between partial nephrectomy and radical nephrectomy patients according to age distribution: a propensity score matching study.

OBJECTIVE: To assess differences in overall survival (OS) between patients receiving partial nephrectomy (PN) and radical nephrectomy (RN) for stage 1 renal cell carcinoma (RCC) according to age distribution, as the survival advantage of PN vs RN has been unclear owing to conflicting data. PATIENTS AND METHODS: We studied 952 patients with stage 1 RCC who underwent either PN or RN. Patients were divided into three groups according to age: Group 1 (≤54 years), Group 2 (55-64 years), and Group 3 (≥65 years). Patient variables including age, body mass index, sex, presence of hypertension (HT) and/or diabetes mellitus (DM), performance status, tumour size, pathological diagnosis, nuclear grade, and preoperative estimated glomerular filtration rate (eGFR), were adjusted using 1:1 propensity score matching between PN and RN. RESULTS: Group 1 included 66 matched patients; Group 2, 72; and Group 3, 70. Group 1 tended to have higher preoperative eGFR values and lower rates of HT and DM compared with Groups 2 and 3. Postoperative eGFR dropped by 11-13% in PN patients and by 34-36% in RN patients. In Group 3, PN patients had longer OS than RN patients (5-year OS: PN 96%, RN 81%, P = 0.043); however, there was no significant difference in Group 1 (5-year OS: PN 100%, RN 93%, P = 0.302) or Group 2 (5-year OS: PN 94%, RN 87%, P = 0.358). CONCLUSIONS: Only the oldest group of patients showed significantly better OS for PN compared with RN; however, we still recommend PN in young patients.

Efficacy and safety of sorafenib for treatment of Japanese metastatic renal cell carcinoma patients undergoing hemodialysis.

BACKGROUND: Little information has been published on the use of tyrosine kinase inhibitors for treatment of patients undergoing hemodialysis (HD). We investigated the efficacy and safety of sorafenib for metastatic renal cell carcinoma (mRCC) patients undergoing HD. METHODS: Twenty patients undergoing HD were treated with sorafenib as first-line therapy for mRCC at our hospital between April 2008 and August 2014. Patient medical records were retrospectively reviewed to evaluate the response to sorafenib and treatment-related toxicity. RESULTS: Fifteen and 5 patients were classified in the intermediate and poor risk groups, respectively, of the Memorial Sloan-Kettering Cancer Center risk model. Eighteen patients had 3 or more metastatic lesions, and 7 patients had metastases in 2 or more organs. Of 16 patients who had previously undergone nephrectomy, 8 were pathologically diagnosed with non-clear-cell carcinoma. The median duration of sorafenib therapy was 4.7 months. Sorafenib was discontinued owing to progressing disease for 15 patients and because of serious adverse events (AE) (≥grade 3) for 4 patients, i.e. subarachnoid hemorrhage, cerebral hemorrhage, sepsis, and syncope for 1 patient each. Median time to progression was 6.3 months, and median overall survival was 14.2 months. CONCLUSIONS: In this study, many patients had unfavorable clinical features, for example poor risk classification and metastases in multiple organs. Although sorafenib treatment of HD patients seems feasible, careful monitoring is needed because of the tendency for a high incidence of serious AE, even when a reduced dose is administered.

Comparison of prognosis between patients with renal cell carcinoma on hemodialysis and those with renal cell carcinoma in the general population.

OBJECTIVE: We compared the clinical features and prognosis of renal cell carcinoma (RCC) between patients on hemodialysis (RCC-HD) and those in the general population (RCC-general). METHODS: We included a total of 1,794 patients who underwent surgery (RCC-HD, 408; RCC-general, 1,386) and analyzed the clinical characteristics and oncological outcomes using a stage-for-stage analysis between the two groups. RESULTS: In the RCC-HD group, the mean duration of dialysis before surgery was 120 months. Compared to the RCC-general group, the RCC-HD group tended to be younger (55 vs. 60 years, p < 0.0001) and more predominately male (84 % vs. 70 %, p < 0.0001), and the tumor size was smaller in this group (39 vs. 49 mm, p < 0.0001). The pathological characteristics of the RCC-HD group included a higher frequency of papillary tumors (22 % vs. 5 %, p < 0.0001) and stage I tumors (82 % vs. 68 %, p < 0.0001). During the follow-up period, 39 of patients (10 %) in the RCC-HD group and 193 patients (14 %) in the RCC-general group died of cancer. The patients on hemodialysis had better cancer-specific survival (CSS) than their counterparts (p = 0.0292) in the univariable analysis, but no significance was found in the multivariable analysis. In the stage-for-stage analysis, the 5-year CSS was similar between the two groups for each stage. CONCLUSIONS: CSS appeared to be better in the RCC-HD group than in the RCC-general group, which may be associated with the higher incidence of stage I disease in the RCC-HD group. The comparable CSS between the groups in the stage-for-stage analysis supports this finding.

Early unclamping might reduce the risk of renal artery pseudoaneurysm after robot-assisted laparoscopic partial nephrectomy.

OBJECTIVES: To determine the influence of the early unclamping technique on the risk of renal artery pseudoaneurysm during robot-assisted laparoscopic partial nephrectomy. METHODS: From January 2013 to October 2014, 96 patients underwent robot-assisted laparoscopic partial nephrectomy for renal masses at Tokyo Women's Medical University Hospital, Tokyo, Japan. Computed tomography angiography was carried out 3-4 days after surgery. Early in the series, renal hilum was left unclamped and renorrhaphy was subsequently carried out (conventional unclamping technique). An early unclamping technique has been used since November 2013. RESULTS: A total of 61 patients underwent robot-assisted laparoscopic partial nephrectomy with early unclamping, and 35 patients underwent robot-assisted laparoscopic partial nephrectomy with conventional unclamping. Ischemia time was significantly shorter in the early unclamping group (16.5 vs. 23.1 min; P < 0.01). The early unclamping group showed a significantly lower incidence of asymptomatic renal artery pseudoaneurysm relative to the conventional unclamping group (11.4% vs. 28.6%; P = 0.03). Multivariate analysis showed that the early unclamping technique was a significant independent factor in reducing the risk of renal artery pseudoaneurysm (hazard ratio 0.27; P = 0.01). CONCLUSIONS: The present findings suggest that an early unclamping technique might reduce ischemic time and risk of renal artery pseudoaneurysm. The absence of arterial bleeding before renorrhaphy is likely to be a key step in preventing renal artery pseudoaneurysm during robot-assisted laparoscopic partial nephrectomy.

Renal sinus exposure as an independent factor predicting asymptomatic unruptured pseudoaneurysm formation detected in the early postoperative period after minimally invasive partial nephrectomy.

OBJECTIVES: To investigate the incidence of asymptomatic unruptured renal artery pseudoaneurysm detected by 3-D computed tomography arteriography in the early period after minimally invasive partial nephrectomy, including laparoscopic and robotic partial nephrectomy. METHODS: From February 2012 to November 2013, 101 patients underwent minimally invasive partial nephrectomy for renal masses. Computed tomography arteriography was carried out 3-4 days after surgery; radiologists diagnosed renal artery pseudoaneurysm in a blinded manner. Factors influencing the occurrence of renal artery pseudoaneurysm were analyzed with the logistic regression model. RESULTS: The incidence of renal artery pseudoaneurysm was unexpectedly high at 21.7% when detected by computed tomography arteriography during the early period after minimally invasive partial nephrectomy. The renal artery pseudoaneurysm group showed a significantly larger tumor size (P = 0.02), significantly higher N component score (P = 0.01) and higher incidence of renal sinus exposure or opening of the collecting system (P < 0.01) compared with the no renal artery pseudoaneurysm group. Although these aforementioned factors were found to be significant by univariate analysis, multivariate analysis showed that renal sinus exposure was the only significant independent predictive factor for occurrence of renal artery pseudoaneurysm. Tumor-related factors, such as the N component of the nephrometry scoring system or tumor size, did not show an independent influence on the occurrence of renal artery pseudoaneurysm. CONCLUSIONS: The present study shows an unexpectedly high incidence of asymptomatic unruptured renal artery pseudoaneurysm detected by computed tomography arteriography in the early period after minimally invasive partial nephrectomy. Renal sinus exposure is an independent significant factor predicting the occurrence of renal artery pseudoaneurysm. Avoidance of deep excision into the renal sinus could reduce the risk of renal artery pseudoaneurysm.

Clinical symptoms predict poor overall survival in chronic-dialysis patients with renal cell carcinoma associated with end-stage renal disease.

OBJECTIVE: To evaluate which clinical symptoms predict the survival of patients with renal cell carcinoma associated with end-stage renal disease under chronic dialysis. METHODS: We retrospectively evaluated 401 patients with renal cell carcinoma associated with end-stage renal disease who underwent radical nephrectomy at our institute up through December 2012. Patients were divided into two groups: the symptomatic group and the incidental group, by diagnosis. We compared the clinicopathologic features and patient survival of the two groups and investigated prognostic factors using Cox multivariate analysis. RESULTS: Of the 401 patients, 124 (30.9%) were in the symptomatic group and 277 (69.0%) in the incidental group. The symptomatic group included more advanced tumors in terms of larger tumor size, higher stage and higher grade compared with the incidental group. The 5-year cancer-specific survival and overall survival of the symptomatic and incidental groups were 76.9 vs. 95.3% (P < 0.001) and 64.2 vs. 84.9% (P < 0.001), respectively. On multivariate analysis, the presence of symptoms, higher age, higher stage, diabetic nephropathy and longer hemodialysis duration were independent prognostic factors. CONCLUSIONS: Symptomatic detection was significantly associated with worse overall survival in patients with renal cell carcinoma associated with end-stage renal disease as well as sporadic renal cell carcinoma. The high incidence of renal cell carcinoma as well as the poor oncologic outcome in patients with longer dialysis therapy may suggest an important role for routine screening in these patients.