Julien Berger

Detailed analysis of morbidity following nephrectomy for renal cell carcinoma in octogenarians.

PURPOSE We evaluated the morbidity of nephrectomy in patients older than age 80 years. MATERIALS AND METHODS Between June 2002 and March 2011, 2,530 patients underwent surgery for renal tumor at 5 French academic centers. Of these patients 180 (7.1%) were age 80 years or older, including 22 (12%) and 158 (88%) who underwent partial and radical nephrectomy, respectively, and 47 (26.1%) who were treated with a laparoscopic approach. RESULTS Mean patient age was 82.3 years. Median Charlson score was 4. Mean preoperative glomerular filtration rate was 47 ml/minute. A total of 136 complications were recorded in 70 patients (38.8% of all patients). Of the patients 28 (15.5%), 25 (13.9%) and 17 (9.4%) experienced 1, 2 and 3 or more complications, respectively. According to the modified Clavien classification grade I, II, III, IV and V complications were observed in 7, 81, 19, 23 and 6 patients, respectively. The transfusion rate was 31.1% (56). On logistic regression analysis the parameters of Eastern Cooperative Oncology Group Performance Status 2 to 4 (p = 0.035) and preoperative glomerular filtration rate less than 30 ml/minute (p = 0.03) were independent predictive factors of morbidity. CONCLUSIONS Morbidity and mortality are significant in the octogenarian population. The risk of complications should be considered in decision making for patients with renal cell carcinoma older than age 80 years.

Nephrectomy improves overall survival in patients with metastatic renal cell carcinoma in cases of favorable MSKCC or ECOG prognostic features

OBJECTIVES The role of cytoreductive nephrectomy (CN) in the treatment of patients harboring metastatic renal cell carcinoma (mRCC) has become controversial since the emergence of effective targeted therapies. The aim of our study was to compare the overall survival (OS) between CN and non-CN groups of patients presenting with mRCC in the era of targeted drugs and to assess these outcomes among the different Memorial Sloan-Kettering Cancer Center (MSKCC) and The Eastern Cooperative Oncology Group (ECOG) performance status subgroups. METHODS AND MATERIALS A total of 351 patients with mRCC at diagnosis recruited from 18 tertiary care centers who had been treated with systemic treatment were included in this retrospective study. OS was assessed by the Kaplan-Meier method according to the completion of a CN. The population was subsequently stratified according to MSKCC and ECOG prognostic groups. RESULTS Median OS in the entire cohort was 37.1 months. Median OS was significantly improved for patients who underwent CN (16.4 vs. 38.1 months, P<0.001). However, subgroup analysis demonstrated that OS improvement after CN was only significant among the patients with an ECOG score of 0 to 1 (16.7 vs. 43.3 months, P = 0.03) and the group of patients with good and intermediate MSKCC score (16.8 vs. 42.4 months, P = 0.02). On the contrary, this benefit was not significant for the patients with an ECOG score of 2 to 3 (8.0 vs. 12.6 months, P = 0.8) or the group with poor MSKCC score (5.2 vs. 5.2, P = 0.9). CONCLUSIONS CN improves OS in patients with mRCC. However, this effect does not seem to be significant for the patients in ECOG performance status groups of 2 to 3 or poor MSKCC prognostic group.

Efflux pump ABCB1 single nucleotide polymorphisms and dose reductions in patients with metastatic renal cell carcinoma treated with sunitinib

Abstract There is growing evidence that sunitinib plasma levels have an impact on treatment outcome in patients with metastatic renal cell carcinoma (mRCC). We studied the impact of single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics, and additionally, sunitinib pharmacodynamics on dose reductions of the tyrosine kinase inhibitor. Methods. We retrospectively analyzed germ-line DNA retrieved from mRCC patients receiving sunitinib as first-line therapy. We genotyped 11 key SNPs, respectively, in ABCB1, NR1/2, NR1/3 and CYP3A5, involved in sunitinib pharmacokinetics as well as VEGFR1 and VEGFR3, which have been suggested as regulators of sunitinib pharmacodynamics. Association between these SNPs and time-to-dose-reduction (TTDR) was studied by Cox regression. Results. We identified 96 patients who were treated with sunitinib and from whom germ-line DNA and data on dose reductions were available. We observed an increased TTDR in patients carrying the TT-genotype in ABCB1 rs1125803 compared to patients with CC- or CT-genotypes (19 vs. 7 cycles; p = 0.031 on univariate analysis and p = 0.012 on multivariate analysis) and an increased TTDR in patients carrying the TT/TA-variant in ABCB1 rs2032582 compared to patients with the GG- or GT/GA-variant (19 vs. 7 cycles; p = 0.046 on univariate analysis and p = 0.024 on multivariate analysis). Conclusion. mRCC patients carrying the rs1128503 TT-variant or the TT/TA-variant in rs2032582 in ABCB1, which encodes for an efflux pump, do require less dose reductions due to adverse events compared to patients with the wild type or heterozygote variants in these genes.

National prospective study on the use of local haemostatic agents during partial nephrectomy

To assess the use of local haemostatic agents (HAs) in a prospective multicentre large series of partial nephrectomies (PNs).

Overall mortality after radical nephrectomy in patients aged over 80 years with renal cancer : A retrospective study on preoperative prognostic factors

Objectives:  To evaluate the overall survival postnephrectomy for renal cancer for patients aged over 80 years, and to identify preoperative prognostic factors that might influence therapeutic strategies.

Safety and Feasibility of Laparoscopic Nephrectomy for Big Tumors (≥ 10 cm): A Retrospective Multicentric Study

OBJECTIVE Evaluate the feasibility of laparoscopic nephrectomy for big tumors. MATERIAL AND METHODS Data from 116 patients were retrospectively collected from 16 tertiary centres. Clinical and operative parameters, tumor characteristics, pre- and postoperative parameters, and renal function before and after surgery were analyzed. RESULTS Mean age and body mass index were 61 years and 27.8 kg/m(2), respectively. Males represented 63.8% of patients, and 54.4% presented symptoms at diagnosis. Median tumor size was 11 cm, and 75% of the cases were performed by expert surgeons. Median operative time and blood loss were 180 minutes and 200 mL respectively. Conversion to open surgery was necessary in 20.7% of cases. Intraoperative complications related to massive hemorrhage occurred in 16.4% of patients, resulting in open conversion in 62.5%. Major postoperative complications occurred in only 10 patients (8.6%). In univariate analysis, intraoperative complications, age, and blood loss were predictive factors of conversion to open surgery. Positive surgical margins occurred in 6 patients (5.2%). None of them presented a local recurrence. Predictive factors of recurrence or progression were lymph node invasion, metastases, and Furhman grade. CONCLUSION Laparoscopic nephrectomy for tumors > 10 cm can be performed safely. Complication rate and positive surgical margins are similar to open surgery. In experienced hands, the benefit of a mini invasive surgery remains evident.

Continence urinaire après prostatectomie radicale : comparaison des voies rétropubienne, laparoscopique et robot-assistée

AIM To compare urinary continence following radical prostatectomy (RP) between open (Op), laparoscopic (Lap), and robotic (Ro) approaches. METHOD Urinary continence of the first 59 patients operated by Ro RP between May 2008 and August 2009 was evaluated by self-questionnaires. Results were compared to those obtained in 2006 using the same questionnaire from patients operated by Lap RP or Op RP in the same institution. Patients treated by radiotherapy were excluded from the analysis. RESULTS Fifty-one of the 59 operated by RP Ro answered the questionnaire. Op and Lap groups included 82 and 100 patients respectively. No significant difference was observed between the three groups in terms of age, body mass index, preoperative PSA, prostate gland weight, and TNM stage on pathology. Overall incontinence rate was 8%, 32%, and 21% for Ro, Lap, and Op RP, respectively. Median duration to recover continence after surgery was three weeks in the Ro group, versus eight weeks in the two other groups. CONCLUSION In our experience, patients operated by a Ro approach had a lower risk of incontinence and a shorter duration to recover continence compared to those operated by Op and Lap RP. Our previous experience of laparoscopy might explain these findings. Evaluation of overall functional and oncological results is necessary before concluding to a possible superiority of Ro RP.

1775 COMPARISON OF TWO MAJOR PROGNOSTIC MODELS FOR PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED IN THE CONTEMPORARY ERA OF TARGETED THERAPIES

4660 Background: The 2 most popular prognostic systems for patients with metastatic renal cell carcinoma (mRCC) are MSKCC and French Group of Immunotherapy (FGI) models. Both systems have initially been established by using cohorts of patients treated with cytokines. No direct comparison of these 2 models has been published so far in the modern era of targeted therapies. Our goal was to compare their effectiveness in predicting overall survival (OS) in mRCC patients treated with anti-angiogenic drugs. METHODS Based on an international cohort of 965 mRCC patients from 18 tertiary care centers treated with systemic treatment, we assessed OS in univariate Cox regression according to both prognostic models stratification. Then, variables of each model were compared in multivariate Cox regression. Area under the curve (AUC) of both model was also calculated. RESULTS Median OS for the entire population was 31.8 months. Both systems were able to distinguish 3 groups with statistically significantly different survivals. Median OS in good, intermediate and poor prognostic group were 45.9, 23.5, 13.5 months and 50.9, 33.4, 13.5 months in MSKCC and FGI models, respectively. In multivariate Cox regression analysis, 3 out of the 5 variables of MSKCC model achieved independent prognostic value (haemoglobin level (HR=1.79, p=0.001), LDH elevation (HR=4.3; p=0.001) and Performance Status (HR=1.71; p=0.006). Similarly, 3 out of the 5 variables of the FGI model achieved independent prognostic status (haemoglobin level (HR=1.74; p=0.04); number of metastasis (HR=2.2; p=0.008) and performance status (HR=2.12; p=0.006). AUC of MSKCC and FGI models were 0.57 and 0.65, respectively. When focusing on 369 patients who received sunitinib as first line treatment, AUC of MSKCC and FGI models were 0.66 and 0.75, respectively. CONCLUSIONS MSKCC and FGI are both effective prognostic models in predicting OS in mRCC patients treated in the contemporary period. However, based on our data, FGI model seems to exhibit a better predictive accuracy than MSKCC model. The prognostic role of FGI model should be therefore revisited in the era of targeted therapies.