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.
Objectives: The benefit of lymphadenectomy (LND) in patients with urothelial carcinoma of the upper urinary tract (UCUUT) has remained controversial. The aim of this study was to examine the ...influence of the LND template and the total number of lymph nodes (LN) when increasing the number of patients undergoing complete dissection of regional nodes (CompLND).
Methods: A total of 109 UCUUT patients with clinically negative nodes underwent nephroureterectomy with concomitant lymphadenectomy at our center. Patients' survival was examined according to the type of LND and the number of removed LN. Univariate analysis was performed to find the cut‐off value of LN influencing survival.
Results: Seventy‐eight patients underwent CompLND. Incomplete lymphadenectomy was performed in an additional 41 patients. In the patients with pT2 or higher who were clinically negative for nodal metastasis, any cut‐off value for the total number of LN removed showed no statistical significance. In contrast, CompLND had a significant impact on patient survival. The Cox proportional hazard model showed that CompLND was a significant factor after adjusting for adjuvant chemotherapy. The total number of removed LN was not significant.
Conclusions: In patients with muscle‐invasive clinical node‐negative UCUUT, the number of LN removed shows minimal influence on their survival. In contrast, the influence of the particular type of lymphadenectomy is statistically significant. These findings suggest that the extent of lymphadenectomy should be determined by the template and not by the number of removed LN.
We investigated the prognostic nutritional index (PNI), comprised of lymphocytes and albumin, as a potential prognosticator of metastatic urothelial carcinoma (mUC) patients receiving pembrolizumab.
...Sixty-five patients were retrospectively enrolled and classified as low (<40) and high (≥40) based on pretreatment PNI. Progression-free survival (PFS), overall survival (OS) and response rates were evaluated.
In the low PNI group, significantly shorter PFS and OS were observed. PNI was shown to be an independent predictor of PFS and OS in the multivariate analysis. C-index for both PFS and OS improved with the addition of PNI to the model described in the KEYNOTE-045 study. Significantly more patients experienced initial disease progression in the low PNI group.
PNI is a useful predictor of prognosis and disease progression in mUC patients receiving pembrolizumab.
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.
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.
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).
Sarcopenia was an independent risk factor of cancer-specific survival in patients with metastatic hormone-sensitive prostate cancer, especially in younger patients.
Objectives
Recent studies showed the therapeutic benefit of lymphadenectomy in advanced stage urothelial carcinoma of the upper urinary tract, but there is still a lack of prospective studies and ...standardization of the extent of lymphadenectomy. The aim of this multi‐institutional study was to examine the role of lymphadenectomy in urothelial carcinoma of the upper urinary tract.
Methods
From January 2005 to September 2012, 77 patients undergoing nephroureterectomy and lymphadenectomy for non‐metastatic (cN0M0) urothelial carcinoma of the upper urinary tract were included in a prospective study at two Japanese institutions (lymphadenectomy group). Lymphadenectomies were carried out according to definite anatomical template. Results from this group were compared with those from a control group of 89 patients who did not receive lymphadenectomy during the study period (no lymphadenectomy group).
Results
In patients with urothelial carcinoma of the upper urinary tract in the renal pelvis of pathological stage 2 or higher, template‐based lymphadenectomy resulted in significantly higher cancer‐specific survival (89.8% and 51.7%, P = 0.01) and overall survival (86.1% and 48.0%, P = 0.01). Disease‐free survival tended to be higher in the lymphadenectomy group (77.8% and 50.0%, P = 0.06). Template‐based lymphadenectomy was a significant independent factor for reducing the risk of cancer death in patients with renal pelvic cancer of ≥pT2 by multivariate analysis. In contrast, cancer‐specific survival of patients with ureteral urothelial carcinoma of the upper urinary tract was not significantly different between the lymphadenectomy and no lymphadenectomy groups.
Conclusions
This multi‐institutional prospective study further supports the therapeutic role of template‐based lymphadenectomy in patients with advanced‐stage urothelial carcinoma of the upper urinary tract in the renal pelvis. This is not the case for patients with ureteral urothelial carcinoma of the upper urinary tract.
•Antibiotics alter the gut microbiota and affect the efficacy of immune therapies.•Antibiotics were associated with a decreased progression-free and overall survival in metastatic urothelial ...carcinoma patients treated with pembrolizumab.•Antibiotics were also associated with disease progression.•As baseline performance status was worse in patients with antibiotics, associations between antibiotic use, bacterial infection for which it was indicated or its influence on performance status, on treatment outcomes needs further analysis.
The use of antibiotics alters gut microbiota and has been reported to impact outcomes in immune checkpoint inhibitor (ICI) treatment in various types of cancer. We investigated the impact of antibiotics on patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab.
The data of 67 patients with chemotherapy-resistant mUC who were treated with pembrolizumab were retrospectively evaluated. The patients were classified into groups according to antibiotic status (with-antibiotic and without-antibiotic), and the progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were compared between the 2 groups.
PFS (median: 1.1 vs. 8.9 months; P < 0.001) and OS (median: 2.3 vs. 19.5 months; P < 0.001) were significantly shorter in the with-antibiotic group (n = 15, 22%) than in the without-antibiotic group (n = 52, 78%). Patients in the with-antibiotic group had significantly higher Eastern Cooperative Oncology Group performance status scores (P = 0.042). Multivariable analyses revealed antibiotic use as an independent predictor of PFS (P < 0.001) and OS (P = 0.002). No patients in the with-antibiotic group achieved a complete response to pembrolizumab. The ORR (complete response (CR) + partial response (PR)) was higher among patients not treated with antibiotics than among patients treated with antibiotics, though the difference was not significant (34.6% vs. 13.3%, P = 0.093). The DCR (CR + PR + stable disease) was also higher among patients in the with-antibiotic group than in the without-antibiotic group (57.7% vs. 20.0%, P = 0.008).
The use of antibiotics was negatively associated with outcomes in patients with mUC who are administered pembrolizumab. Baseline performance status was worse for these patients. Further analyses are required to identify associations between antibiotic use, bacterial infection for which it was indicated or its influence on performance status, on treatment outcomes.
Abstract
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.
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).
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.
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).
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.
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