G. Verhoest

Prognostic Value of Renal Vein and Inferior Vena Cava Involvement in Renal Cell Carcinoma

BACKGROUND The prognostic significance of venous tumor thrombus extension in patients with renal cell carcinoma (RCC) is a matter of many controversies in the current literature. OBJECTIVE To evaluate the prognostic role of inferior vena cava (IVC) involvement in a large series of pT3b and pT3c RCCs. DESIGN, SETTING, AND PARTICIPANTS A total of 1192 patients from 13 European institutions underwent a radical nephrectomy for pT3b and pT3c RCC between 1982 and 2003. The patients were evaluated in a retrospective manner. Age, gender, clinical symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, TNM stage, tumor size, adrenal invasion, perinephric fat invasion, histological type, and Fuhrman grade were reviewed. The log-rank and Cox uni- and multivariate regression analyses were used to evaluate prognostic factors for overall survival. MEASUREMENTS Overall survival and prognostic factors for overall survival in patients with RCC extending to the renal vein (RV) or to the IVC. RESULTS AND LIMITATIONS The median follow-up was 61.4 mo (56.3-66.5 mo). The mean age was 63.2 yr. The mean tumor size was 8.9 cm. Group 1 (Gr 1) included 933 patients with a renal vein tumor thrombus (78.3%), Group 2 (Gr 2) included 196 patients with a subdiaphragmatic IVC tumor thrombus (16.4%), and Group 3 (Gr 3) included 63 patients with a supradiaphragmatic IVC tumor thrombus (5.3%). Median survival was 52 mo for Gr 1, 25.8 mo for Gr 2, and 18 mo for Gr 3. In univariate analysis, Gr 1 had a significantly better overall survival than Gr 2 (p<0.001) and Gr 3 (p<or=0.001). No significant difference in survival was noted between Gr 2 and Gr 3 (p=0.613). Prognostic factors for overall survival in univariate analysis were clinical symptoms (p<0.001), tumor size (p<0.001), perinephric fat invasion (p<0.001), Fuhrman grade (p<0.001), histological type (p=0.021), lymph node invasion (p<0.001), and distant metastasis (p<0.001). Independent prognostic factors in multivariate analysis were tumor size (p=0.013), perinephric fat invasion (p=0.003), lymph node invasion (p<0.001), distant metastasis (p<0.001), and IVC invasion (p=0.008). CONCLUSIONS The level of tumor thrombus in the IVC does not significantly affect long-term overall survival in patients with renal cell carcinoma. The overall survival was statistically different for patients with a tumor thrombus in the RV compared to those with IVC involvement. This has to be considered for the next revision of the TNM system, and the pT3b and pT3c stages have to be redesigned.

Tumor Size Does Not Predict Risk of Metastatic Disease or Prognosis of Small Renal Cell Carcinomas

PURPOSE We characterized the clinicopathological features and the prognosis of small solid renal tumors defined as tumors 4 cm or smaller. MATERIALS AND METHODS We identified 1,208 patients who were treated with nephrectomy at 5 international academic centers for small solid renal tumors. Clinicopathological parameters and outcome data were collected for each patient and analyzed. RESULTS Of the tumors 88% were renal cell carcinoma and 12% were benign. Of those with renal cell carcinoma 995 (93%) were localized (N0M0) and 72 (7%) presented with metastatic disease. Tumor size did not predict synchronous metastatic disease. The incidence of metastatic disease in the tumor size ranges 0.1 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 cm was 7%, 6%, 5% and 8%, respectively (p = 0.322). Survival rates were excellent. The majority of patients who died of renal cell carcinoma (54%) presented with synchronous metastatic disease, but 3% of patients with localized disease also died of renal cell carcinoma. In patients with localized disease there was a 7% chance of recurrence post nephrectomy at 5 years. Progression-free survival (28 months) was better than for patients with metastatic disease having a primary tumor greater than 4 cm (8 months). Tumor size was not retained as an independent prognostic factor of survival in multivariate analyses. The University of California Integrated Staging System and the Karakiewicz nomogram were the best predictors of cancer specific survival for all renal cell carcinoma stages (c-index 0.87). CONCLUSIONS More than 85% of small solid renal tumors are renal cell carcinoma. The majority of localized small renal tumors can be cured with existing surgical approaches. However, there is a small but not insignificant risk of synchronous and metachronous metastatic disease and cancer associated death. Patients considering experimental therapies such as ablation and surveillance should be aware of this. Tumor size alone is not sufficient to distinguish renal cell carcinoma with benign behavior from aggressive small renal cell carcinoma. Survival of patients with small metastatic renal cell carcinoma is better then expected. The biology of these unique tumors should be further studied.

Sunitinib combined with angiotensin-2 type-1 receptor antagonists induces more necrosis: a murine xenograft model of renal cell carcinoma.

Background. Angiotensin-2 type-1 receptor antagonists not are only antihypertensive drugs but also can inhibit VEGF production. We hypothesised that adding telmisartan to sunitinib could potentiate the antiangiogenic effects. Material and Methods. 786-O cell lines were injected in nude mice. After tumor development, mice were divided into 4 groups: the first was the control group (DMSO), the second group was treated with sunitinib alone, the third group was treated with telmisartan alone, and the fourth group was treated with the combination. Drugs were orally administered every day for four weeks. Animals were sacrificed after treatment. Blood and tumor tissues were collected for analysis by immunohistochemistry, Western Blot, and ELISA methods. Results. All animals developed a ccRCC and ten in each group were treated. Using a kinetic model, tumors tended to grow slower in the combination group compared to others (P = 0.06). Compared to sunitinib alone, the addition of telmisartan significantly increased tissue necrosis (P = 0.038). Central microvascular density decreased (P = 0.0038) as well as circulating VEGF (P = 0.003). There was no significant variation in proliferation or apoptosis markers. Conclusion. The combination of sunitinib and telmisartan revealed an enhancement of the blockage of the VEGF pathway on renal tumor resulting in a decrease in neoangiogenesis and an increase in necrosis.

Prognostic factors for upper urinary tract urothelial carcinoma

Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, which means there are little evidence-based data available to guide clinical decision-making. Although diagnosis and treatment of UTUC have improved significantly over the last 5 years, accurate risk stratification remains a challenge owing to the difficulty of clinical staging. A number of potential prognostic factors have been identified, encompassing clinical characteristics, pathological factors and molecular markers. Tumor stage and lymph node status are the most important predictors of survival in patients with UTUC. Preoperative evaluation for hydronephrosis can identify patients at risk of non-organ-confined disease. In the subgroup of patients with stage ≥pT2 disease, a longer interval between diagnosis and radical nephroureterectomy is associated with a higher risk of disease recurrence and cancer-specific mortality. Extensive tumor necrosis, sessile tumor architecture and lymphovascular invasion are independent predictors of clinical outcomes for patients with UTUC treated with radical nephroureterectomy. The incorporation of such prognosticators into clinical prediction models might help to guide decision-making with regard to timing of surveillance, type of treatment, performance of lymphadenectomy, and consideration of neoadjuvant or adjuvant systemic therapies.

The use of partial nephrectomy in European tertiary care centers.

PURPOSE The objective was to define the trends of PN use over time at six tertiary care European centers. METHODS Data were retrieved from institutional databases for patients treated with either PN or radical nephrectomy (RN) for stages T(1-2)N(0)M(0) renal cell carcinoma (RCC) between 1987 and 2007. For purpose of temporal trend analyses patients were divided into five equally sized groups according to the date of surgery. Categorical and multivariable logistic regression analyses assessed predictors of PN use. RESULTS Overall 597 (31.7%) patients were treated with PN. Overall, a 4.5-fold increase of PN was recorded. The absolute increases were 41.7-86.3%, 14.9-69.3% and 8.1-35.3% for lesions < or = 2 cm, 2.1-4 cm and 4.1-7 cm (chi-square trend test p<0.001), respectively. In multivariable logistic regression models, decreasing tumor size, younger age, more contemporary date of surgery, male gender and institutional PN rate represented independent predictors of the individual probability of treatment with PN. Lack of data from community hospitals limits the generalizability of our findings. CONCLUSION Based on data from six tertiary care centers, the contemporary rate of PN ranges from 86 to 35% for renal masses < or = 2 cm to 4.1-7 cm and is indicative of excellent quality of care.

Patients with renal cell carcinoma nodal metastases can be accurately identified: external validation of a new nomogram.

Outcome of patients with renal cell carcinoma nodal metastases (NM) is substantially worse than that of patients with localized disease. This justifies more thorough staging and possibly more aggressive treatment in those at risk of or with established NM. We developed and externally validated a nomogram capable of highly accurately predicting renal cell carcinoma NM in patients without radiographic evidence of distant metastases. Age, symptom classification, tumour size and the pathological nodal stage were available for 4,658 individuals. The data of 2,522 (54.1%) individuals from 7 centers were used to develop a multivariable logistic regression model‐based nomogram predicting the individual probability of NM. The remaining data from 2,136 (45.9%) patients from 5 institutions were used for external validation. In the development cohort, 107/2,522 (4.2%) had lymph node metastases vs. 100/2,136 (4.7%) in the external validation cohort. Symptom classification and tumour size were independent predictors of NM in the development cohort. Age failed to reach independent predictor status, but added to discriminant properties of the model. A nomogram based on age, symptom classification and tumour size was 78.4% accurate in predicting the individual probability of NM in the external validation cohort. Our nomogram can contribute to the identification of patients at low risk of NM. This tool can help to risk adjust the need and the extent of nodal staging in patients without known distant metastases. More thorough staging can hopefully better select those in whom adjuvant treatment is necessary.

Urinary Collecting System Invasion is an Independent Prognostic Factor of Organ Confined Renal Cell Carcinoma

PURPOSE We evaluated urinary collecting system invasion as a prognostic parameter of renal cell carcinoma. MATERIALS AND METHODS A total of 1,124 patients who underwent nephrectomy for a renal tumor at 5 European centers were included in this retrospective study. Several variables were analyzed including urinary collecting system invasion, age, sex, TNM stage, Fuhrman grade, histological subtype, Eastern Cooperative Oncology Group performance status and cancer specific survival. RESULTS There were 771 males (68.6%) and 353 females (31.4%) in this study, and median age was 61 years (range 14 to 88). Median tumor size was 6 cm (range 1 to 24). Tumors were organ confined and Fuhrman grade was recorded as 1 or 2 in 67.1% and 62.3% of cases, respectively. Symptoms were present at diagnosis, and Eastern Cooperative Oncology Group performance status was 1 or more in 50.3% and 16.1% of the cases, respectively. Median followup was 43 months (range 1 to 299). At the end of followup 246 patients (21.9%) died of cancer. In 132 cases (11.7%) urinary collecting system invasion was noted. Urinary collecting system invasion was associated with symptoms, TNM stage, Fuhrman grade, tumor size (p <0.001) and Eastern Cooperative Oncology Group performance status (p = 0.003), but not with histological subtype (p = 0.7). On univariate analysis TNM stage, Fuhrman grade, symptoms, Eastern Cooperative Oncology Group performance status, tumor size and urinary collecting system invasion (p = 0.0001) were significant predictors of cancer specific survival. Urinary collecting system invasion was an independent prognostic parameter only in the setting of pT1-T2 tumors. When the urinary collecting system was invaded the 5 and 10-year probabilities of survival were 43% and 41%, respectively. CONCLUSIONS Urinary collecting system invasion appears to be an independent prognostic parameter of organ confined renal cell carcinoma. Our data support the need to integrate this parameter in further TNM revisions.

Predictive factors of recurrence and survival of upper tract urothelial carcinomas

ObjectiveUTUCC is a rare tumor, and most reports on prognostic factors come from small single-center series. The objective of this article was to provide an updated overview of current clinical, pathological and biological prognostic factors of UTUC.MethodsPubMed was searched for records from 2002 to 2010 using the terms “prognostic factors”, “recurrence”, “survival”, and “upper tract urothelial carcinoma”. Among identified citations, papers were selected based on their clinical relevance.ResultsClassical clinical factors that influence UTUC prognosis include age, presence of symptoms, hydronephrosis, and interval from diagnosis. Many biomarkers have shown promises to better appraise the natural course of UTUC although none is currently used in clinical practice. Stage, grade, lymph node metastases, lymphovascular invasion, tumor necrosis, and tumor architecture are strong pathological parameters. RNU is the standard treatment of localized UTUC. Both laparoscopic and open approaches seem to offer similar cancer control. Lymph node dissection increases staging accuracy and might confer a survival benefit.ConclusionRNU is the standard treatment for most patients with UTUC. Recent multicenter studies confirmed the prognostic value of classical prognostic parameters. Better survival prediction might be obtained with prognostic systems including clinical data and new biomarkers.

Prognostic variables to predict cancer‐related death in incidental renal tumours

To identify, in a large multicentre series of incidental renal tumours, the key factors that could predict cancer‐related deaths, as such tumours have a better outcome than symptomatic tumours and selected patients are increasingly being included in watchful‐waiting protocols.

Predictive factors of complications after robot-assisted laparoscopic partial nephrectomy: a retrospective multicentre study

To analyse the predictive factors of complications after robot‐assisted laparoscopic partial nephrectomy (RALPN).