[Show abstract][Hide abstract] ABSTRACT: Les thérapies ciblées sont utilisées dans le traitement du cancer du rein métastatique. Leur utilisation avant chirurgie pourrait réduire le volume tumoral, faciliter l’exérèse chirurgicale et traiter les micro-métastases. Nous exposons dans cette revue de la littérature les principaux résultats des études ayant évalué l’intérêt de l’utilisation néo-adjuvante des thérapies ciblées.
[Show abstract][Hide abstract] ABSTRACT: Background:
Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs.
Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression.
We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001).
RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.
No preview · Article · Nov 2015 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Objective:
To assess preoperative renal tumor biopsy (RTB) accuracy.
Materials and methods:
As part of the prospective NEPHRON study, data from 1,237 renal tumors were collected, including the use and results of RTB and final histology following nephrectomy. During the 6 months period of inclusion, 130 preoperative biopsies were performed. We used the kappa coefficient of the McNemar test to determine the concordance between the biopsy and the nephrectomy specimen (NS) regarding four parameters: malignant/benign status, histological subtype, Fuhrman grade and microscopic necrosis.
Preoperative biopsies were performed in 9.7 and 11.4 % of the 667 radical and 570 partial nephrectomies, respectively. Tumor biopsy was inconclusive in 7.7 % of the cases. In 117 cases, a comparison between RTB and NS was available. Benign tumors accounted for three (2.6 %) and five (4.3 %) of the RTB and NS, respectively (κ = 0.769, good). With seven (6 %) discordant results in terms of histological subtype characterization between RTB and final pathology, RTB accuracy was considered excellent (κ = 0.882). In 33 cases (31.7 %), Fuhrman grade was underestimated at biopsy resulting in an intermediate concordance level (κ = 0.498). Tumor microscopic necrosis was identified in 12 RTB (10.4 %) versus 33 NS (28.4 %) (κ = 0.357, poor).
RTB provides good to excellent diagnostic performance for discriminating malignancy and tumor histological subtype. However, its performance is intermediate or even poor when considering prognostic criteria like Fuhrman grade or microscopic necrosis. Thus, this possible inaccuracy should be taken into consideration when using RTB for accurate guidance of treatment strategy.
No preview · Article · Jul 2015 · World Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: To evaluate the oncological outcomes of papillary renal cell carcinoma (pRCC) following nephron sparing surgery (NSS) and to determine whether the subclassification type of pRCC could be a prognostic factor for recurrence, progression, and specific death.
An international multicentre retrospective study involving 19 institutions and the French network for research on kidney cancer was conducted after IRB approval. We analyzed data of all patients with pRCC who were treated by NSS between 2004 and 2014.
We included 486 patients. Tumors were type 1 pRCC in 369 (76 %) cases and type 2 pRCC in 117 (24 %) cases. After a mean follow-up of 35 (1-120) months, 8 (1.6 %) patients experienced a local recurrence, 12 (1.5 %) had a metastatic progression, 24 (4.9 %) died, and 7 (1.4 %) died from cancer. Patients with type I pRCC had more grade II (66.3 vs. 46.1 %; p < 0.001) and less grade III (20 vs. 41 %; p < 0.001) tumors. Three-year estimated cancer-free survival (CFS) rate for type 1 pRCC was 96.5 % and for type 2 pRCC was 95.1 % (p = 0.894), respectively. Three-year estimated cancer-specific survival rate for type 1 pRCC was 98.4 % and for type 2 pRCC was 97.3 % (p = 0.947), respectively. Tumor stage superior to pT1 was the only prognostic factor for CFS (HR 3.5; p = 0.03).
Histological subtyping of pRCC has no impact on oncologic outcomes after nephron sparing surgery. In this selected population of pRCC tumors, we found that tumor stage is the only prognostic factor for cancer-free survival.
Full-text · Article · Apr 2015 · World Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION AND OBJECTIVES: The aim of this study was to evaluate the oncological outcome of non-clear cell renal cell carcinoma (nCC-RCC) following nephron sparing surgery (NSS)
METHODS: We retrospectively analyzed data of all patients with nCC-RCC who were treated by NSS between 2004 and 2014 at 19 institutions. Histological subtypes were recorded according to the WHO classification of kidney tumors. Oncologic outcomes for cancer-specific survival (CSS), and cancer-free survival (CFS) were estimated using the Kaplan-Meier method. Univariate and Multivariable Cox proportional hazards regression models evaluated prognostic factors for CSS and CFS.
RESULTS: We included 808 patients. Tumors were type 1 papillary RCC in 369 cases (45.7%), type 2 papillary RCC in 117 cases (14.5%), Chromophobe RCC in 234 cases (29%), multilocular clear cell RCC in 21 cases (2.6%), unclassified subtype of papillary RCC in 13 cases (1.6%), Xp11 translocation carcinomas in 9 cases (1.1%), sarcomatoide carcinomas in 4 cases (0.5%), mucinous tubular and spindle cell carcinoma in 3 cases (0.5%), carcinoma of the col- lecting ducts of Bellini in 1 case (0.1%), and unclassified RCC in 37 cases (4.6%). Mean tumor size was 3.5 (0.6-17) cm. NSS were per- formed for imperative indications in 120 (14.9%) cases. A positive surgical margin was identified in 45 specimens (5.6%). Pathologic stages were T1a, T1b, T2a, T2b and T3a in 559 (69.2%), 165 (20.4%), 24 (3%) and 53(6.5%) cases, respectively. Fuhrman grade were respectively I, II, III, IV in 70 (8.7%), 459 (56.8%), 201 (24.9%), and 17 (2.1%) cases. After a mean follow-up of 33 (1-120) months, 12 (1.5%) patients experienced a local recurrence, 16 (2%) had a metastatic progression and 12 (1.5%) died from cancer. In multivariate analysis, pT3a stage (HR: 5.2, p1⁄40.011), tumor size (HR: 1.13, p1⁄4 0.043), and chromophobe histological subtype (HR: 0.186, p1⁄40.026) were prog- nostic factors for CFS whereas imperative indication (HR: 4.6; p1⁄40.036) and pT3a stage (HR: 9.8; p1⁄40.003) were prognostic factor for CSS. For the entire cohort five-years estimated CFS and CSS rates were 94%, and 95%. For type 1 papillary RCC, type 2 papillary RCC and chromophobe RCC five-year estimated CFS were respectively 91%, 95% and 97.8%. For type 1 papillary RCC, type 2 papillary RCC and chromophobe RCC five-year estimated CSS were 94%, 97% and 100%, respectively.
CONCLUSIONS: NSS has achieved excellent oncological outcomes for nCC-RCC. Chromophobe carcinomas had a significant better outcome whereas pT3a stage was associated with an increasing risk of cancer recurrence and death.
[Show abstract][Hide abstract] ABSTRACT: Le diagnostic d’angiomyolipome avec thrombus de la veine rénale et de la veine cave inférieure est rare, en particulier pendant la grossesse. Nous rapportons le cas d’une femme de 31 ans, enceinte à 24 semaines d’aménorrhée, chez qui a été diagnostiqué un angiomyolipome de 9 cm du rein droit avec thrombus cave, géré par une surveillance active pendant la grossesse et un traitement chirurgical différé après l’accouchement.
No preview · Article · Jan 2015 · Progrès en Urologie
[Show abstract][Hide abstract] ABSTRACT: Objective
Quantify the rate of residual bladder tumor following systematic second look resection of pTa high-grade versus pT1 high-grade patients.
Material and methods
From January 2010 to July 2013, 53 patients with a non-muscle-invasive bladder cancer with high-risk of recurrence and progression underwent a second systematic resection in accordance with the current guidelines of the French Association of Urology (AFU).
Among the 53 patients with a high-risk non-muscle-invasive bladder cancer, histological examination of the initial resection identified: 17 pTa high-grade (32.1%) and 36 pT1 high-grade (67.9%). There was a significant difference between the 2 groups of patients (Ta high-grade versus T1 high-grade) concerning the rate of residual tumor on second look resection (11.8% versus 66.7%, P = 0.0002). The predictive factors of residual tumor after second resection were the pT1 stage (P = 0.0002), tumor multifocality (P = 0.02) and presence of associated Cis (P = 0.0005).
The high rate of residual tumor in our series confirmed the importance of a systematic second look resection for high-risk non-muscle-invasive bladder cancers. However, for the pTa tumors without associated Cis, the interest of this second look seemed of less concern.
Level of evidence
No preview · Article · Sep 2014 · Progrès en Urologie
[Show abstract][Hide abstract] ABSTRACT: Introduction
Upper tract urinary carcinoma (UTUC) pT3 tumors are a heterogeneous entity including tumors invading the renal parenchyma, tumors with peripelvic fat invasion or peri-ureteral fat invasion. The aim of this study was to evaluate the prognostic significance of these three different groups of pT3 tumors.
Patients and methods
Between 1998 and 2012, 205 patients with UTUC were operated in two centers, including 52 patients with pT3 tumor stage. pT3 tumors were divided into three groups: peri-ureteral fat invasion (pT3U, n = 16), peripelvic fat invasion (pT3G, n = 21), and renal parenchyma invasion (pT3P, n = 15). The prognostic significance of the type of tumor infiltration was evaluated on specific and disease-free survival.
Median follow-up was 18.9 months [6–133.4]. In univariate analysis, renal parenchyma invasion was associated with a better prognostic in both specific (P = 0.026) and disease-free survival (P = 0.031) compared with peripelvic or peri-ureteral fat invasion. Mutivariate analysis retained the pT3 subgroup as an independant prognostic factor in both specific and disease-free survival (P = 0.02).
pT3 tumors with renal parenchyma invasion had a better prognosis than those with peripelvic or peri-ureteral fat invasion. The heterogeneity of the pT3 group should be taken into account to improve the care of patients.
No preview · Article · Jul 2014 · Progrès en Urologie
[Show abstract][Hide abstract] ABSTRACT: Surgery remains the treatment of choice for locally advanced or metastatic renal cell carcinoma. However, the contribution of targeted therapies has recently significantly impacted recurrence-free survival in metastatic patients, challenging in some cases the real interest of nephrectomy. Waiting for the results of CARMENA trial, assessing the impact of cytoreductive nephrectomy on survival, neoadjuvant and adjuvant strategies are emerging. In locally advanced disease, adjuvant therapy should be considered if the patient is considered at high risk of progression, and therefore require its inclusion in a prospective randomized trial. Neo-adjuvant anti-angiogenic strategies show a quite modest improvement in resectability of primary tumor, while allowing performing translational research. However, many questions remain on hold in terms of precise indications, choice of drugs, toxicity and optimal dosing schedule. All these questions explain the current development of phase III trials.
No preview · Article · Mar 2014 · Minerva urologica e nefrologica = The Italian journal of urology and nephrology
[Show abstract][Hide abstract] ABSTRACT: Objective
To assess the influence of vascular clamping and ischemia time on long-term post-operative renal function following partial nephrectomy (PN) for cancer in a solitary kidney.
Patients and methods
This is a retrospective study including 259 patients managed by PN between 1979 and 2010 in 13 centers. Clamping use, technique choice (pedicular or parenchymal clamping), ischemia time, and peri-operative data were collected. Pre-operative and last follow-up glomerular filtration rates were compared. A multivariate analysis using a Cox model was performed to assess the impact of ischemia on post-operative chronic renal failure risk.
Mean tumor size was 4.0 ± 2.3 cm and mean pre-operative glomerular filtration rate was 60.8 ± 18.9 mL/min. One hundred and six patients were managed with warm ischemia (40.9%) and 53 patients with cold ischemia (20.5%). Thirty patients (11.6%) have had a chronic kidney disease. In multivariate analysis, neither vascular clamping (P = 0.44) nor warm ischemia time (P = 0.1) were associated with a pejorative evolution of renal function. Pre-operative glomerular filtration rate (P < 0.0001) and blood loss volume (P = 0.02) were significant independent predictive factors of long-term renal failure.
Renal function following PN in a solitary kidney seems to depend on non-reversible factors such as pre-operative glomerular filtration rate. Our findings minimize the role of vascular clamping and ischemia time, which were not significantly associated with chronic renal failure risk in our study.
Level of evidence
No preview · Article · Jan 2014 · Progrès en Urologie
[Show abstract][Hide abstract] ABSTRACT: To investigate the impact of hospital volume on partial nephrectomy indications and outcomes.
Data were extracted from the National Observational Registry on the Practice and Hemostasis in Partial Nephrectomy registry. Four groups were created according to the number of partial nephrectomy (PN) performed: very high (VH, ≥19 PN), high (H, 10-18 PN), moderate (M, 4-9 PN) and low (L, <4 PN) PN activity. Indications and surgical outcomes were compared among all groups. The effect of hospital volume on postoperative complications and positive margin rate was examined by a multivariable analysis.
Fifty-three centers included a total of 570 PN. There were 9 VH, 13 H, 12 M and 19 L volume centers which performed 270 (47.4 %), 179 (31.4 %), 74 (13 %) and 47 (8.2 %) PN, respectively. Patients in higher volume centers were significantly younger (p = 0.008), had a lower BMI (p = 0.002) and decreased ASA score (p < 0.001). PN was more frequently performed in higher volume centers (p = 0.006) particularly in case of renal masses <4 cm (p = 0.005). Open surgery was the most common approach in all groups, but laparoscopic PN was more frequent in M volume hospitals (p < 0.001). Positive margin (p = 0.06) and complications (p = 0.022) rates were higher in M group. In multivariable analysis, renal chronic disease was an independent predictor of positive margin rate (p < 0.001, OR 3.91).
PN is more frequently performed in high volume institutions particularly for small renal masses. We observed increase positive margin and complication rates in moderate volume centers that might be explained by an increased use of laparoscopy.
Full-text · Article · Nov 2013 · World Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: To identify the predictive factors of hemorrhagic complications (HC) in a contemporary cohort of patients who underwent partial nephrectomy (PN).
Records of 199 consecutive patients who underwent PN between 2008 and 2012 at our institution were retrospectively analyzed. HC was defined as a hematoma requiring transfusion, an arterio-veinous fistula, a false aneurysm or a post-operative decrease of hemoglobin >3 g/dl. Patients with or without HC were compared using Wilcoxon and Fisher exact tests for continuous and categorical variables, respectively. We performed a univariate and multivariate analysis with a logistic regression model using the occurrence of an HC as the dependent variable.
54% of the patients were male with a median age of 61 (22-86) years. Median BMI was 26 (18-47) kg/m(2). Surgery was done open, laparoscopically or with robotic assistance in 106, 54 and 39 cases, respectively. Global complication rate was 40% including 21.6% HC. There were more complex tumors (75.6% vs. 66.5%, p = 0.04) and median length of stay was increased (11 days compared to 7 days, p < 0.0001) in case of a HC. In univariate analysis, imperative indication (p = 0.08), RENAL score (p = 0.07), operating time (p = 0.07) and operative blood loss > 250 ml (p = 0.002) were statistically relevant. In multivariate analysis, only operative blood loss >250 ml was identified as a predictive factor of HC (p = 0.0007).
Patients who underwent a procedure with estimated blood loss >250 ml should be carefully monitored in the postoperative course.
Full-text · Article · Nov 2013 · European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology