Pierre Bigot

Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib

Background:There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients.Methods:We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates.Results:In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013).Conclusion:Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required.

Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study.

Study Type – Therapy (multi‐centre retrospective cohort)

Renal Cell Carcinoma (RCC) in Patients With End-Stage Renal Disease Exhibits Many Favourable Clinical, Pathologic, and Outcome Features Compared With RCC in the General Population

BACKGROUND Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.

Recommandations en onco- urologie 2013 du CCAFU : Cancer du rein

Resume Introduction L’objectif de ce travail a ete d’etablir par le sous-comite rein du CCAFU des recommandations pour le diagnostic, le bilan, les traitements et la prise en charge des tumeurs du rein. Methodes Le sous-comite a remis a jour les recommandations de 2010 en s’appuyant sur une revue exhaustive de la litterature effectuee sur PubMed, en evaluant les references et leur niveau de preuve. Resultats Le scanner renal multiphasique est le standard diagnostique pour les tumeurs renales. Les biopsies renales sont d’importance croissante dans la mesure ou elles peuvent modifier la prise en charge. La nephrectomie partielle est a envisager systematiquement pour les tumeurs cT1. La voie incisionnelle reste le standard pour les cancers du rein localement avances. Le traitement des cancers du rein metastatiques inclut de nouvelles drogues. Le role de la nephrectomie en situation metastatique reste a demontrer dans le cadre de l’essai Carmena. Conclusions Les therapies mini-invasives et conservatrices prennent une part croissante dans les cancers du rein localises. L’arsenal therapeutique continue a s’enrichir pour les formes metastatiques.

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.

Influence of previous or synchronous bladder cancer on oncologic outcomes after radical nephroureterectomy for upper urinary tract urothelial carcinoma

OBJECTIVE The objective of the study was to evaluate the effect of a history of bladder cancer (BC) or synchronous BC on the prognosis and survival of patients who have undergone radical nephroureterectomy (RNU). METHODS AND MATERIALS Using a multi-institutional, retrospective database, we identified 662 patients with upper urinary tract urothelial carcinoma (UUT-UC) treated by radical nephroureterectomy, between 1995 and 2010. We analyzed clinicopathologic characteristics and outcomes according to the history of BC or concomitant BC or both, at the time of diagnosis. BC was evaluated as a prognostic factor for bladder recurrence and survival. RESULTS Overall, 83 (12.5%) patients had previous BC, 62 (9.4%) exhibited concomitant BC, and 75 (11.3%) presented with both previous and current BC. A history of BC was less seen in women and nonsmokers (P<0.0001 and P = 0.013, respectively). The patients with associated BC had more tumors located in the ureter (P<0.0001), as well as more multiple locations in the upper tract (P<0.0001). The tumors without concomitant BC were more likely to be associated with locally advanced stages (P = 0.024). At a median follow-up time of 37.3 months, 31.4% of patients experienced BC recurrence and 2.9% developed contralateral upper tract tumor. Using multivariate analyses, the previous or synchronous BC (P = 0.01) and positive surgical margins (P = 0.03) are independent prognostic factors for BC recurrence. The metastasis-free survival and cancer-specific survival rates did not significantly differ according to the associated BC status. CONCLUSIONS In patients without previous or concomitant BC, the upper tract tumors are more frequently localized in the renal pelvis and are associated with a more invasive status at the time of diagnosis. Nevertheless, the presence of UUT-UC without previous or synchronous BC did not significantly affect the survival rates after nephroureterectomy.

The role of American Society of Anesthesiologists scores in predicting urothelial carcinoma of the upper urinary tract outcome after radical nephroureterectomy: results from a national multi-institutional collaborative study

Study Type – Prognosis (cohort)

Positive surgical margins and their locations in specimens are adverse prognosis features after radical cystectomy in non-metastatic carcinoma invading bladder muscle: results from a nationwide case–control study

Positive surgical margin (PSM) frequency after radical cystectomy has been estimated to be 4–15%. Studies that have not distinguished between the different sites of PSM have failed to show that they are an independent prognostic factor for disease‐free survival. Only perivesical soft tissue PSMs have been associated with an increased risk of cancer recurrence and cancer‐specific death. This is the first comprehensive published analysis of PSMs occurring during radical cystectomy for pTx pN0 M0 bladder cancer according to their location, comparing their cancer‐specific survival (CSS) and other outcomes with those of a control group paired according to TNM status, age, sex and urinary diversion method. Local recurrence‐free survival rates were found to be lower in patients with both soft tissue and urethral PSMs. Moreover, soft‐tissue PSMs were associated with lower metastatic recurrence‐free and CSS rates.

Formation et avenir des internes et chefs de clinique d’urologie en France : résultats d’une enquête nationale auprès de 154 urologues en formation

PURPOSE To raise an appraisal of French urologist resident and chief residents demographic characteristics, activity, post-residency project, career desires and factors associated with obtaining a fellowship. METHODS An electronic questionnaire was sent by email between June 2009 and January 2010 to the 288 French urologists currently in training. Items analysed included demographics, achievement of academic works and post-residency projects. RESULTS Overall, we obtained 156 answers (response rate of 54%). Our population was composed by 47 (27%) fellows and 114 (73%) residents. They work 68.1 hours per week and 31 (20%) leave the hospital after an on-call night. Thirty-two (20.5%) have validated a master 2. Among the resident, 54 (47.3%) are certain to have the opportunity to be a chief resident. Regarding residents, factors significantly associated with the fact to obtain a fellowship in multivariate analysis were: to gain a master 2, working more than 65 hours per week and achieving academics works. Installation in a general hospital, a university hospital and a private clinic was considered by respectively 21.7%, 41.6% and 67.3% of young urologists. CONCLUSION French urologist resident and chief residents work an average 68 hours per week. The determining factors in obtaining a fellowship are the realization of a master 2, a workweek exceeding 68 hours and the achievement of academic work. After completing their academic training, a majority of young urologists are attracted by private practice.