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The most important and widely utilized system for providing prognostic information following surgical management for renal cell carcinoma (RCC) is currently the tumor, nodes, and metastasis (TNM) staging system. An accurate and clinically useful staging system is an essential tool used to provide patients with counseling regarding prognosis, select treatment modalities, and determining eligibility for clinical trials. Data published over the last few years has led to significant controversies as to whether further revisions are needed and whether improvements can be made with the introduction of new, more accurate predictive prognostic factors. Staging systems have also evolved with an increase in the understanding of RCC tumor biology. Molecular tumor biomarkers are expected to revolutionize the staging of RCC by providing more effective prognostic ability over traditional clinical variables alone. This review will examine the components of the TNM staging system, current staging modalities including comprehensive integrated staging systems, and predictive nomograms, and introduce the concept of molecular staging for RCC. [ABSTRACT FROM AUTHOR]

Abstract: Patient''s history, physical examination, laboratory tests, and radiographic evaluation are the cornerstones of postoperative surveillance. It has been shown that localized renal cell carcinoma (RCC) can recur in nearly all organs of the body, but most commonly in the lung, bone, liver, brain, and renal fossa. Lung metastases can be sensitively detected through radiographic evaluation. Treatment of lung metastases might prolong survival, which supports surveillance x-ray or computed tomography scans. Surgical treatment of early detected liver metastases and local recurrences may also prolong survival, which supports a close abdominal surveillance program. Brain and bone metastases are usually symptomatic when they occur, and their treatment is generally palliative. Hence, surveillance protocols do not usually include their routine radiographic evaluation. Because partial nephrectomy does not increase the risk of local recurrence over radical nephrectomy, we recommend identical surveillance for completely resected tumors regardless of surgical approach. The risk of recurrence after nephrectomy is generally related to tumor stage, tumor grade, and patient performance status. The majority of recurrences occur within the first 5 years after surgery, supporting a more intense surveillance strategy within the first 5 years. The University of California Integrated Staging System (UISS) combines TNM stage, Fuhrman grade, and performance status, and categorizes patients into 3 different risk groups. The current surveillance protocol at our institution is based on the UISS. It is expected that molecular markers such as p53 will allow more individualized surveillance strategies in the future. [Copyright &y& Elsevier]

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: The treatment of small renal tumors continues to evolve in parallel with advances in ablative technology. We compared the lesion geometry of 3, 17 gauge cryoneedles to determine the most effective distance and configuration of the cryoneedles in an in vivo porcine kidney model. Materials and Methods: Argon gas based renal cryoablation was performed in 6 pigs using a laparoscopically assisted percutaneous approach. Cryoablation using a single cryoneedle and a template of 3 cryoneedles with various ice ball shapes, including elliptical, bulb-shaped and standard 17 gauge cryoneedles (Galil Medical, Plymouth Meadow, Pennsylvania) was performed in 3 pigs. Three additional pigs underwent renal cryoablation using elliptical cryoneedles in 3 triangular template configurations with the cryoneedles spaced 1, 1.5 and 2 cm apart, respectively. The animals were sacrificed a minimum of 2 weeks following treatment. Results: Elliptical cryoneedles achieved the largest area of necrosis when used in single and template configurations. When used in a template configuration of 3 needles 1, 1.5 and 2 cm apart from each other the calculated volume of necrosis was 4.3 × 4.5 × 2.5, 4.9 × 4.1 × 2.5 and 4.0 × 4.5 × 2.5 cm, respectively. Conclusions: Using a single 17 gauge cryoneedle is inadequate for treating most small renal tumors. Cryoneedles with an elliptical ice ball are most effective for achieving consistent and reliable tissue destruction. The 1.5 cm template configuration generated the largest area of necrosis. Our data suggest that with the current technology renal cryoablation should be limited to lesions not greater than 4 cm. [Copyright &y& Elsevier]

OBJECTIVES To compare cancer-specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype. PATIENTS AND METHODS Eighty-five patients with URCC and 4322 with CRCC were identified within 6530 patients treated with either radical or partial nephrectomy at 18 institutions. Of 85 patients with URCC, 55 were matched with 166 of 4322 for grade, tumour size, and Tumour, Node and Metastasis stages. Kaplan-Meier and life-table analyses were used to address RCC-specific survival. Subsequently, multivariate Cox regression analyses were used to test for differences in RCC-specific survival in unmatched samples. RESULTS Of patients with URCC, 80% had Fuhrman grades III or IV, vs 37.8% for CRCC. Moreover, 36.5% of patients with URCC had pathologically confirmed nodal metastases, vs 8.6% with CRCC. Finally, 54.1% of patients with URCC had distant metastases at the time of nephrectomy, vs 16.8% with CRCC. Despite these differences in the overall analyses, after matching for tumour characteristics, the URCC-specific mortality rate was 1.6 times higher ( P = 0.04) in matched analyses and 1.7 times higher ( P = 0.001) in multivariate analyses. CONCLUSIONS These findings indicate that URCC presents with a higher stage and grade, and even after controlling for the stage and grade differences, predisposes patients to 1.6–1.7 times the mortality of CRCC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the prognostic role of tumour size in pathological stage T3a renal cell carcinoma (RCC) with fat invasion only and to assess whether this subgroup maintains its relevance over the other pathological stages. Methods: We retrospectively studied 2113 patients from eight international institutions who were treated by surgical resection for T2–4 RCC. Disease-specific survival (DSS) was evaluated with univariate and multivariate analyses. Results: Univariate analysis of patients with T3a RCC showed that tumour size was significantly associated with DSS (HR: 1.09, 95% CI: 1.05–1.12, p <0.001). An ideal cut-off of 7cm for these patients was identified with a scatter plot of Martingale residuals and tumour size. The two T3a groups were distinctly different with respect to clinicopathologic parameters (performance status, metastases, grade, histological subtype) and survival (p <0.001). Median survival time was not reached for patients with T2 and T3a≤7cm disease with a 5- and 10-yr DSS rate of 70% and 59% and 63% and 53%, respectively. Median survival time for patients with T3a>7cm, T3b, T3c, and T4 disease was 54, 46, 21, and 11 mo, respectively, with 5- and 10-yr DSS rates of 46% and 36%, 46% and 36%, 34% and 0%, and 16% and 14%, respectively. Conclusions: Our data indicate that tumour size is an important factor for predicting outcome of patients with T3a RCC with fat invasion only. Our findings should merit consideration during the next revision of the TNM classification. [Copyright &y& Elsevier]

An interesting group of papers in this section is headed by two papers on synchronous bilateral renal tumours, one from an international group of authors and one from Germany. The large series of patients are examined carefully by both groups, and the findings should be useful for all who are interested in this area. Authors from the UK examine the role of lactate dehydrogenase as a prognostic factor for testicular cancer. They found that it had limited sensitivity, specificity and positive predictive value for detecting relapse, with false-positive elevations being common. OBJECTIVE To present a multicentre experience and the largest cohort to date of nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because it is rare the single-institutional experience is limited. PATIENTS AND METHODS We retrospectively studied 10 337 patients from 12 urological centres to identify patients with N0M0 synchronous bilateral RCC; the clinicopathological features and cancer-specific survival were compared to a cohort treated for N0M0 unilateral RCC. RESULTS In all, 153 patients had synchronous bilateral solid renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell RCC was the major histological subtype (76%), and papillary RCC was the next most frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group performance status (ECOG PS) and T classification, but bilateral RCCs were more frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19% vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC had a similar prognosis ( P = 0.63); multifocality did not affect survival ( P = 0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman grade, but not laterality, as independent prognostic factors for cancer-specific survival. CONCLUSIONS Patients with N0M0 synchronous bilateral RCC and N0M0 unilateral RCC have a similar prognosis. The frequency of a familial history for RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in bilateral synchronous than in unilateral RCC. The significant pathological findings in synchronous bilateral RCC are papillary subtype and multifocality. [ABSTRACT FROM AUTHOR]

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]

Renal cell carcinoma (RCC) remains one of the most lethal urologic malignancies, with up to 40% of patients eventually dying of cancer progression. Despite advances in the diagnosis, staging and treatment of patients with RCC, approximately a third of patients who undergo surgery for clinically localized RCC will suffer a recurrence. Timely identification of recurrences following surgical extirpation is imperative in the treatment of these patients. RCC is known to metastasize through hematogenous routes of spread to distant organ sites and via lymphatic channels to regional lymph nodes. The path of tumor escape is associated with diverse clinical outcomes and a unique tumor biology. A consensus on surveillance regimens for patients following surgical resection of localized disease is lacking. The most extensively used system for providing prognostic information regarding survival and recurrence of disease has historically been the tumor-node-metastasis (TNM) classification system. As a result, most contemporary surveillance protocols have tailored follow-up regimens according to stage-based stratifications. Numerous studies have recently demonstrated that certain clinical and histopathological factors can improve the prediction of tumor recurrence. The incorporation of these prognostic factors into stage-based stratification models should be better than stage alone in attempting to provide a rational approach to identifying treatable recurrences while minimizing unnecessary exams and tests, as well as patient anxiety. Advances in the understanding of the pathogenesis, behavior and molecular biology of RCC have paved the way for developments that may enhance early diagnosis and prognostication, and improve survival for patients. Lastly, molecular markers should, in the future, revolutionize surveillance protocols for RCC by tailoring follow-up to specific molecular classifications. [ABSTRACT FROM AUTHOR]

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]