Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

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.

Study Type – Therapy (multi‐centre retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UUT‐UCs) are rare tumours. Because of the aggressive pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains the ‘gold‐standard’ treatment. However, conservative strategies, such as segmental ureterectomy (SU) or endourological management, have also been developed in patients with imperative indications. Some teams are now advocating the use of conservative management more commonly in cases of elective indications of UUT‐UCs. Due to the paucity of cases of UUT‐UC, only limited data are available on the oncological outcomes afforded by conservative management. We retrospectively investigated the oncological outcomes after SU and RNU in a large multi‐institutional database. Overall, 52 patients were treated with SU and 416 with RNU. There was no statistical difference between the RNU and SU groups for the 5‐year probability of cancer‐specific survival, recurrence‐free survival and metastasis‐free survival. The type of surgery was not a significant prognostic factor in univariate analysis. The results were the same in a subgroup analysis of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low stage (≤T2). Our results suggest that oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases. OBJECTIVE To compare recurrence‐free survival (RFS), metastasis‐free survival (MFS) and cancer‐specific survival (CSS) after segmental ureterectomy (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the upper urinary tract (UUT‐UC) located in the ureter. PATIENTS AND METHODS We performed a multi‐institutional retrospective review of patients with UUT‐UC who had undergone RNU or SU between 1995 and 2010. Type of surgery, Tumour‐Node‐Metastasis status, tumour grade, lymphovascular invasion and positive surgical margin were tested as prognostic factors for survival. RESULTS In all, 52 patients were treated with SU and 416 with RNU. The median (range) follow‐up was 26 (10–48) months. The 5‐year probability of CSS, RFS and MFS for SU and RNU were 87.9% and 86.3%, respectively (P= 0.99); 37% and 47.9%, respectively (P= 0.48); 81.9% and 85.4%, respectively (P= 0.51). In univariable analysis, type of surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P= 0.94, 0.42 and 0.53, respectively). In multivariable analyses, pT stage and pN stage achieved independent predictor status for CSS (P= 0.005 and 0.007, respectively); the positive surgical margin and pT stage were independent prognostic factors of RFS and MFS (P= 0.001, 0.04, 0.009 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of the disease. CONCLUSIONS Short‐term oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases and should...

De novo tumors in renal allografts are rare and their prevalence is underestimated. We therefore analyzed renal cell carcinomas arising in renal allografts through a retrospective French renal transplant cohort. We performed a retrospective, multicentric survey by sending questionnaires to all French kidney transplantation centers. All graft tumors diagnosed after transplantation were considered as de novo tumors. Thirty-two centers participated in this study. Seventy-nine tumors were identified among 41 806 recipients (Incidence 0.19%). Patients were 54 men and 25 women with a mean age of 47 years old at the time of diagnosis. Mean tumor size was 27.8 mm. Seventy-four (93.6%), 53 (67%) and 44 tumors (55.6%) were organ confined (T1-2), low grade (G1-2) and papillary carcinomas, respectively. Four patients died of renal cell carcinomas (5%). The mean time lapse between transplantation and RCC diagnosis was 131.7 months. Thirty-five patients underwent conservative surgery by partial nephrectomy (n = 35, 44.3%) or radiofrequency (n = 5; 6.3%). The estimated 5 years cancer specific survival rate was 94%. Most of these tumors were small and incidental. Most tumors were papillary carcinoma, low stage and low grade carcinomas. Conservative treatment has been preferred each time it was feasible in order to avoid a return to dialysis.

In this study, RPN was less morbid than OPN, with lower complications, less blood loss, and a shorter hospital of stay. The intermediate-term oncologic outcomes were similar in the two groups.

No abstract

BACKGROUND: Urothelial carcinoma of the upper urinary tract (UUT-UC) was a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. High-risk patients had poor outcomes. Because of the rarity of these tumors, randomized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable. Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high-risk, postsurgical UUT-UC patients. METHODS: Using a multi-institutional, international retrospective database, identified were 627 patients with high risk UUT-UCs (pT3N0, pT4N0 and/or Nþ and/or Mþ) who underwent surgical removal. Only patients who received adjuvant chemotherapy were included. RESULTS: Overall, 140 patients (22.6%) with a median age of 67 years were included. The median follow-up was 22.5 months. The 5-year, overall survival for the entire cohort was 43%, the 5-year recurrencefree survival was 54%, and metastasis-free survival was 53% at 5 years. Positive surgical margins were an independent prognostic factor for recurrence (P ¼ .06), cancer-specific mortality (P ¼ .05), and overall mortality (P ¼ .02) of any cause. Adjuvant chemotherapy was not linked with overall or cancer-specific survival in patients with high risk disease (adjuvant chemotherapy [n ¼ 140] vs no treatment [n ¼ 487]) (P >.5). CONCLUSIONS: Adjuvant postoperative chemotherapy did not offer any significant benefit to overall survival in our population. Additional data were necessary, and studies enrolling patients at high risk in clinical trials investigating neoadjuvant chemotherapy in conjunction with chemotherapy should have been highly encouraged. Cancer 2011;117:5500-8.

There is no evidence that oncological outcomes for LNU are inferior to those for open surgery, provided that the appropriate precautionary measures are taken.