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Abstract: Over the past 2 decades, a greater understanding of the basic biology and genetics of kidney cancer has occurred. Surgical techniques have also evolved, and technological advances have made possible new methods of managing renal tumors. The most extensively used system to provide prognostic information for renal cell carcinoma (RCC) is currently the tumor, nodes, metastasis (TNM) staging system. Emerging data over the last few years has questioned whether further revisions are needed and if improvements can be made with the introduction of new, more accurate and predictive prognostic factors. The recent discovery of molecular tumor biomarkers are expected to revolutionize the staging of RCC and potentially lead to the development of new therapies based on molecular targeting. This review will examine the current staging modalities and prognostic factors associated with RCC as well as the selection of patients most likely to benefit from clinical trials. [Copyright &y& Elsevier]

Purpose: We evaluated the prognosis, risk factors and relevance of the primary-free interval in a large cohort with metachronous bilateral renal cell carcinoma. Materials and Methods: We studied 120 patients with metachronous, bilateral renal cell carcinoma who were treated at 12 international academic centers. Logistic regression was performed to evaluate risk factors for contralateral metachronous renal cell carcinoma during followup. Disease specific survival was evaluated with univariate and multivariate analysis. Results: Median age at diagnosis of the first and second renal cell carcinomas was 54 and 62 years, respectively. The most common histological subtype was bilateral clear cell renal cell carcinoma (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was found in 81%. The 15-year disease specific survival rates for the first and second renal cell carcinomas were 66% and 44%, respectively. Logistic regression revealed von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age as independent risk factors for contralateral renal cell carcinoma after surgery for unilateral renal cell carcinoma. A longer primary-free interval was associated with a better prognosis. When calculating disease specific survival from the diagnosis of the first renal cell carcinoma, the primary-free interval was an independent prognostic factor. Conclusions: Long-term survival rates of metachronous, bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age are independent risk factors for contralateral renal cell carcinoma. These risk factors support close and extended abdominal surveillance following nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary-free interval have a more favorable prognosis. [Copyright &y& Elsevier]

OBJECTIVE To define the prognostic relevance of capsular involvement (invasion with no penetration) and collecting-system invasion in patients with stage I (pT1N0M0) and stage II (pT2N0M0) renal cell carcinoma (RCC), by evaluating the outcome of patients treated with nephrectomy. PATIENTS AND METHODS In all, 519 patients from a kidney cancer database treated with nephrectomy for stage I and II RCC between 1985 and 2005 were assessed retrospectively. The primary endpoint was recurrence-free survival time. The prognostic relevance of capsular involvement and collecting-system invasion were examined using univariate and multivariate survival analysis. RESULTS Capsular involvement and collecting-system invasion were evident in 112 (21.6%) and 39 (7.5%) patients, respectively. Capsular involvement was associated with higher Fuhrman grades and larger tumours. The incidence of collecting-system invasion was higher in patients with microvascular invasion. The median follow-up was 49 months. In univariate analysis, patients with capsular involvement and collecting-system invasion had a worse prognosis than patients without ( P = 0.007 and <0.001, respectively). In multivariate analysis, capsular involvement (hazard ratio 1.84, P = 0.036) and collecting-system invasion (3.78, P < 0.001) were independent prognostic factors of recurrence-free survival. Interestingly, there was no survival difference between patients with capsular involvement in stage I/II and patients with invasion of perinephric tissue (pT3aN0M0). CONCLUSIONS These findings suggest that capsular involvement and collecting-system invasion are poor prognostic findings in stage I and II RCC. They should both be considered when planning the follow-up. A revised pT3a stage including patients with capsular involvement could improve its prognostic validity. [ABSTRACT FROM AUTHOR]

It has been 35 years since the radical nephrectomy was standardized by the work of Robson et al. (J Urol 101:297–301, 1969). Despite being based on a retrospective review of only 88 cases operated upon over a span of 15 years, this publication was an important milestone in the attempt to create uniformity in the staging of Renal cell carcinoma (RCC), and the measurement of surgical outcomes for RCC. Although this manuscript forms the basis for our contemporary measurement of the long-term results of RCC surgery and set the standard to which the entire subsequent literature was compared, contemporary research subsequently has questioned many of Robson’s conclusions regarding RCC. In Robson’s era, the majority of patients presented with large, symptomatic tumors, pre-operative staging was imprecise, and many patients had locally advanced disease at the time of surgery: of the 88 patients in Robson’s series, 75% were managed through a thoracoabdominal incision. Since that time, advances in renal imaging and clinical staging have led to the increased detection of incidental, lower stage, organ-confined tumors more amendable to expanded surgical options. Surgical techniques have evolved and technological advances have made possible new methods of managing renal tumors in situ that have emphasized a transition from radical to less extirpative approaches. In addition, understanding of the basic biology and genetics of kidney cancer has led to improved prognostication and the development of effective immunotherapies for advanced disease. The current concepts and long-term outcomes of the surgical management of RCC will be reviewed to help elucidate some of these changes, from the evolution of open to laparoscopic to percutaneous, from radical to partial to ablative approaches. [ABSTRACT FROM AUTHOR]

Reports on the open surgical management of renal cell carcinoma in the era of minimally invasive kidney surgery. Evidence showing that nephron-sparing surgery (NSS) for patients with small tumors is equivalent to total radical nephroctomy in terms of long-term survival; Safety and efficacy of NSS; Clinical factors determining prognosis and survival in the management of the disease.

Abstract: Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of renal cell carcinoma (RCC) have paved the way for developments that may enhance early diagnosis, better predict prognosis, and improve survival. Reliable predictive factors are essential for the stratification of patients into clinically meaningful categories that can be used to provide patients with counseling regarding prognosis, select treatment modalities, and determine eligibility for clinical trials. The TNM (tumor, nodes, metastasis) staging system is currently the most extensively used staging system for RCC, but it has undergone systematic revisions as a result of emerging data. Comprehensive integrated staging systems that combine important clinical and pathological variables have been created in an attempt to improve prognostication. Although staging has improved with the development of integrated systems, the incorporation of molecular tumor markers are expected to revolutionize the staging of RCC. This article reviews the important molecular markers in RCC to date and discusses their role in the diagnosis, prognostication, and therapy of patients with RCC. [Copyright &y& Elsevier]

Reports on the adjuvant therapy of renal cell carcinoma in patient selection and therapeutic options. Renal cell carcinoma, survival and prognostic factors; Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma; Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma; Correlations with tumor oxygen measurements and prognostic in locally advanced carcinoma of the cervix.

The use of carbonic anhydrase IX as a promising molecular marker in RCC is described by authors from Los Angeles, who discuss the promise that molecular markers hold to improve diagnosis, staging, treatment surveillance and survival of patients with RCC. There is a whole range of new treatments being introduced in the management of metastatic renal cancer. The use of VEOF-targeted therapy has particular importance, especially as it has a strong genetically linked rationale for its potential success in this area. Authors from the USA show that substantial clinical activity has been reported in initial clinical trials. In prostate cancer, drugs targeting microtubules, such as taxanes, have already been introduced clinically, and their success has received widespread attention. A new group of drugs, the epothilones, have similar but not identical binding properties to microtubules, and authors from the USA describe how they have shown activity in hormone-refractory prostate cancer, and are moving to phase III testing. [ABSTRACT FROM AUTHOR]

Examines the staging of renal cell carcinoma (RCC). Use of local tumor growth, lymph node involvement and distant metastasis to categorize patients with RCC by the TNM system; Increase of the size threshold for T1 tumors to seven centimeters; Comparison between T3b and T3c classification of tumors with inferior vena caval involvement.

The foundations of the generally accepted principles underlying the surgical management of renal cell carcinoma (RCC) were best annunciated in 1969 by Robson in his classic description of the radical nephrectomy [J Urol 1969;101;297]. Since then, much has changed in our understanding of the basic biology and genetics of kidney cancer, advances in renal imaging and clinical staging have led to the increased detection of incidental, lower stage, organ-confined tumors more amendable to expanded surgical options, surgical techniques themselves have evolved, and surgical equipment technology has advanced to make possible new methods of managing renal tumors in situ. Thus, the management of both localized and metastatic RCC has changed dramatically in the last 20 years, predicated on these major advancements in renal imaging, surgical techniques, and the development of effective immunotherapies for advanced disease. In this review, the evolution in thinking regarding the tenets of the radical nephrectomy will be examined, including the necessity for removal of the entire kidney, the possibility of sparing the adrenal gland, when and how extensive a lymphadenectomy should be performed, the development of laparoscopic and percutaneous nephron-sparing surgery using ablative technologies, and the role of nephrectomy and metastasectomy in patients with metastatic RCC. Here, we review current concepts and outcomes on the surgical management of RCC to help elucidate some of these changes, from the evolution of open to laparoscopic to percutaneous, from radical to partial to ablative approaches. [Copyright &y& Elsevier]

Abstract: Objective: Anaemia and/or thrombocytosis were identified as independent predictors of poor survival in renal cell carcinoma (RCC). We tested the extent to which these markers worsen the prognosis in these patients. Methods: Analyses targeted 1828 patients with renal cell carcinoma. Univariable, multivariable, and predictive accuracy analyses addressed RCC-specific mortality (RCC-SM). Results: In univariable and multivariable analyses, both platelet count and preoperative haemoglobin level were statistically significant predictors of RCC-SM. However, neither platelet count nor preoperative haemoglobin level increased the combined multivariable accuracy of established RCC-SM (predictive accuracy gain=0.3%) predictors. Conclusions: Patients who present with severe anaemia or elevated platelets are at no higher risk of RCC-SM than that related to their stage, grade, histologic subtype, and Eastern Cooperative Oncology Group-Performance Status. [Copyright &y& Elsevier]

Objectives: Carbonic anhydrase-IX (CA-IX) is a cell surface tumor-associated antigen expressed by most clear cell renal cell carcinomas (RCCs). The specificity and the prognostic value of CA-IX provide impetus to create a mouse model of CA-IX-expressing RCC for testing CA-IX-targeted therapies against RCC. Methods: A retrovirus encoding the human CA-IX gene was used to transduce the murine RCC line, RENCA. In vivo growth kinetics and CA-IX expression were compared between RENCA and RENCA/CA-IX using heterotopic, metastatic, and orthotopic models. Results: Transduction of RENCA created the RENCA/CA-IX line with nearly 100% CA-IX surface expression. In the heterotopic model, subcutaneous injection of 500,000 and 50,000 cells led to tumor formation at 2 to 2.5 weeks after injection, with similar growth kinetics between the two cell lines at either cell number. In the pulmonary metastatic model, a similar number of metastases was noted after inoculation of RENCA and RENCA/CA-IX. In the orthotopic model, autopsy revealed a CA-IX-expressing renal tumor, as well as CA-IX-expressing metastases to the lungs, liver, contralateral kidney, intestines, and lymph nodes. In all the above models, the RENCA/CA-IX tumors retained expression of CA-IX, as demonstrated by immunohistochemistry staining. Conclusions: RENCA/CA-IX is the first tumor model that manifests in immunocompetent Balb/c mice and stably expresses a defined kidney cancer-associated antigen. It maintains antigen expression, forms metastases, and produces reliable tumor growth kinetics equivalent to that of its parental cell line. [ABSTRACT FROM AUTHOR]