Contemporary management of renal tumors with venous tumor thrombus.

PURPOSE: Renal cell carcinoma with intravenous tumor thrombus remains one of the most intriguing and challenging topics in urological oncology. With better understanding of the biology of intravascular tumor invasion and improvements in overall survival, the surgical and medical treatment of these patients is being completely redefined. MATERIALS AND METHODS: We performed a MEDLINE(R) search for relevant articles on renal cell carcinoma with intravenous tumor thrombus. RESULTS: We describe the staging systems, prognostic factors and surgical techniques involved in the management of renal cell carcinoma with intravenous tumor thrombus. We also review long-term survival of local, advanced and metastatic renal cell carcinoma with tumor thrombus invasion. Finally, we propose a clinical algorithm for the treatment of patients with renal cell carcinoma invading the venous system. CONCLUSIONS: Management of a kidney cancer tumor invading the venous system should now consider the primary biology and natural behavior of a given tumor in that specific patient rather than only focusing on the level and extent of venous invasion. Treatment must be individualized for every patient based on performance status, tumor biology and risk of surgery.

Cytogenetic and molecular tumor profiling for type 1 and type 2 papillary renal cell carcinoma.

PURPOSE: The goal of this study was to evaluate immunohistochemical and cytogenetic features and their prognostic value in papillary renal cell carcinoma (PRCC) subtypes. EXPERIMENTAL DESIGN: One hundred fifty-eight cases of PRCC were identified and reclassified by subtype. Tumoral expression of 29 molecular markers was determined by immunohistochemistry. Cytogenetic analyses were done on a prospective series of 65 patients. Associations with clinicopathologic information and disease-specific survival were assessed. RESULTS: Fifty-one patients (32%) had type 1 and 107 (68%) type 2 PRCC. Type 2 patients had worse Eastern Cooperative Oncology Group performance status, higher T stages, nodal and distant metastases, higher grades, and a higher frequency of necrosis, collecting system invasion and sarcomatoid features. Type 2 showed greater expression of vascular endothelial growth factor (VEGF)-R2 in the tumor epithelium, and of VEGF-R3 in both tumor epithelium and endothelium. Loss of chromosome 1p, loss of 3p, and gain of 5q were exclusively observed in type 2, whereas type 1 more frequently had trisomy 17. Type 2 PRCC was associated with worse survival than type 1, but type was not retained as an independent prognostic factor. Lower PTEN, lower EpCAM, lower gelsolin, higher CAIX, and higher VEGF-R2 and VEGF-R3 expression, loss of 1p, 3p, or 9p, and absence trisomy 17 were all associated with poorer prognosis. CONCLUSIONS: Type 2 PRCC is associated with more aggressive clinicopathologic features and worse outcome. Molecular and chromosomal alterations can distinguish between PRCC subtypes and influence their prognosis. The effect of 3p loss on survival in PRCC is opposite to the relationship seen in clear cell RCC.

Intraoperative thrombus embolization during nephrectomy and tumor thrombectomy: critical analysis of the University of California-Los Angeles experience.

PURPOSE: Vascular invasion commonly occurs in renal cell carcinoma and intraoperative thrombus embolization is a known complication of tumor thrombectomy. We reviewed our experience with this complication to determine frequency, mortality, common factors and management strategies. MATERIALS AND METHODS: We retrospectively reviewed a prospective database of cases of open nephrectomy/tumor thrombectomy performed from 1989 to 2008. All cases were reviewed to identify clinicopathological variables, the thrombus extent and intraoperative complications. All cases with events were reviewed to identify preoperative pulmonary embolism, preoperative imaging, thrombus extent, presentation, management and outcome. RESULTS: A total of 282 cases of venous tumor thrombus were identified. Tumor thrombus level was 0 in 133 cases (47.2%), I to II in 85 (30.1%), III in 27 (9.6%) and IV in 29 (10.3%). Thrombus embolization was identified in 5 patients (1.8%). The incidence in level 0 vs I to IV was 0 of 133 cases (0%) vs 5 of 149 (3.4%), which was statistically significant (p = 0.04). Three patients (60%) died of the event. A review of recent series demonstrated a 1.49% incidence with 75% mortality. CONCLUSIONS: Intraoperative thrombus embolization is rare but when it occurs, mortality is extremely high. Strict attention to surgical principles is necessary to decrease risk. Extension into the vena cava, preoperative pulmonary embolism and a bland thrombus component may indicate increased risk. Adjunct procedures, such as preoperative filters and endoluminal occlusive balloons, may be justified in patients at high risk. Even with prompt recognition and embolectomy survival is rare.

Histologic evaluation of metastases in renal cell carcinoma with sarcomatoid transformation and its implications for systemic therapy.

BACKGROUND: Sarcomatoid features in renal cell carcinoma may represent an aggressive subclone arising from the primary tumor. The patterns of metastases for these tumors were evaluated to determine if sarcomatoid features were retained at metastasis and whether the percentage of sarcomatoid features in the primary tumor influenced spread. METHODS: All patients with sarcomatoid features found at nephrectomy with synchronous or metachronous resection of metastases were evaluated. The histology, grade, and percentage of sarcomatoid features in the primary and metastatic site were recorded. The association between percentage of sarcomatoid features, grade, histology, and pattern of metastases was evaluated. RESULTS: Thirty-two patients were identified with sarcomatoid features and resected metastases. Fifty-two metastatic sites were evaluated. A single histologic appearance (sarcomatoid or carcinomatoid) was present in 50 of 52 sites (96%). Thirty sites (58%) demonstrated only a sarcomatoid pattern, whereas 20 (38%) contained only a carcinoma pattern. Histology and carcinoma grade did not influence metastatic pattern; however, greater percentage of sarcomatoid features was associated with the presence of distant sarcomatoid histology. A cutoff of 30% sarcomatoid features in the primary tumor was useful in predicting systemic sarcomatoid histology. CONCLUSIONS: Sarcomatoid elements are frequently observed in the metastases of primary tumors with sarcomatoid features, and these metastases generally contain a solitary pattern supporting the subclone hypothesis. However, both components can metastasize in the same patient. The percentage of sarcomatoid features influences the pattern of spread, and patients with >30% sarcomatoid features in the primary tumor frequently have distant sarcomatoid histology. This cutpoint may be helpful for inclusion criteria for future clinical trials.

Cancer-specific survival outcomes among patients treated during the cytokine era of kidney cancer (1989-2005): a benchmark for emerging targeted cancer therapies.

BACKGROUND: The management of renal cell carcinoma (RCC) is evolving toward less extirpative surgery and the use of targeted therapy. The authors set out to provide a benchmark against which emerging therapies should be measured. METHODS: A prospective database including clinical and pathological variables for 1632 patients with RCC treated between 1989 and 2005 was queried. Patients were stratified using the University of California-Los Angeles Integrated Staging System (UISS) into low-, intermediate-, and high-risk groups. Disease-specific survival (DSS) was measured. Response to systemic therapy for patients with advanced disease was assessed. RESULTS: Nephrectomy was performed in 1492 patients. Overall 5-, 10-, and 15-year DSS was 55%, 40%, and 29%. For localized disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups was 97% and 92%, 81% and 61%, and 62% and 41%, respectively. For metastatic disease, 5- and 10-year DSS for UISS low-, intermediate-, and high-risk groups was 41% and 31%, 18% and 7%, and 8% and 0%, respectively. Patients with metastatic disease receiving immunotherapy (n=453) had complete response in 7% (median survival [MS], 120+ months), partial response in 15% (MS, 42.8 months), stable disease in 33% (MS, 38.6 months), and progressive disease in 45% (MS, 11.6 months). CONCLUSIONS: Most patients with localized RCC do well with surgery alone, but effective adjuvant therapy is needed for patients identified as at high risk for recurrence. For advanced disease, newer targeted and potentially less toxic treatments should be at least as effective as those achieved with aggressive surgical resection and immunotherapy.

A Survey of primary-care physicians and urologists regarding Peyronie's disease.

INTRODUCTION: Peyronie's disease (PD) is a connective tissue disorder with an uncertain etiology that causes penile deformity. The interest in PD and our understanding of the disorder has grown significantly in recent years. Data have shown that several previous beliefs regarding the prevalence, natural history, and treatment of PD were incorrect. The prevalence is significantly higher than the previously reported 1%, and most cases of PD do not spontaneously resolve. AIM: To determine the extent to which newer information about PD has reached physicians who are likely to encounter men with PD and to determine practice patterns regarding this disorder. METHODS: We created a survey of 20 questions and mailed it to primary-care physicians (PCPs) and urologists (UROs) in Illinois and Wisconsin. MAIN OUTCOME MEASURES: Responses to individual survey items were totaled. RESULTS: We received 152 responses from PCPs and 98 from UROs for response rates of 43% and 44%, respectively. Survey results revealed the following: 63% of PCPs and 41% of UROs thought the prevalence is less than 1%; 17% of PCPs and 38% of UROs believed PD spontaneously resolves in greater than 50% of cases; 17% of PCPs and 9% of UROs did not think PD occurs in men younger than 40 years of age; 48% of PCPs and 37% of UROs did not believe that PD is frequently associated with ED; 51% of PCPs and 1% of UROs were unsure if any effective medical or surgical treatment for PD existed. CONCLUSION: These data suggest that many physicians who are very likely to encounter men with PD have incorrect assumptions about the disease, and this can negatively affect diagnosis and treatment of men with PD.