Conventional Renal Cell Carcinoma Research Articles

Immunoreactivity of p27(Kip1), cyclin D3, and Ki67 in conventional renal cell carcinoma

The goal of the study was to evaluate expression of the cell-cycle regulatory proteins (p27(Kip1) and cyclin D3) and proliferation marker Ki67 in normal human kidneys and renal cell carcinoma (RCC) tissues. Intensity of the markers' expression was prospectively studied and compared between normal and RCC tissue samples. Association was analyzed with cancer clinical parameters. p27(Kip1) was significantly upregulated in normal compared with in RCC samples. Immunoreactivity of the protein negatively correlated with tumor size and was associated with pathological stage and grade. Patients with symptomatic disease had significantly less marker expression than those with incidentally discovered tumors. Intensity of Ki67 staining positively correlated with primary tumor size and associated with disease stage and grade. Cyclin D3 immunoreactivity positively correlated with tumor size. Loss of p27(Kip1) expression, pathological stage, grade, and tumor size were risk factors for disease recurrence (P = 0.0072, 0.0011, and 0.0467, and P < 0.0001, respectively) and patient death (P = 0.0021, 0.0106, 0.0151, and 0.0021, respectively). With Cox multivariate analysis loss of p27(Kip1) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. In conclusion, intensity of the markers' expression in RCC is associated with tumour clinical parameters (size, stage, grade, and disease presentation type). Loss of p27(Kip1) expression is a risk factor for the disease recurrence and cancer-related patient death.

Chromophobe renal cell carcinoma with calcification: Report of a case with rare finding on aspiration smears

Chromophobe renal cell carcinoma (ChRCC) is a distinct variant of renal cell carcinoma. It is important to identify this entity because it has a significantly better prognosis than clear cell (conventional) renal cell carcinoma. We report the case of a 56-year-old male who presented with 10 days history of painless hematuria. There was no palpable swelling or systemic symptoms. On radiological examination the possibility of a right renal neoplasm was considered. Ultrasound guided aspiration was done and cytological features of ChRCC were noted. In addition, numerous foci of calcification were seen, which was an unusual cytological feature for ChRCC. The characteristic cytomorphology of ChRCC makes it possible to render a preoperative diagnosis on fine needle aspiration cytology (FNAC). We report the case to emphasize the importance and possibility of diagnosing of ChRCC on cytology. In addition, the extensive calcification as seen in our case is an unusual cytological finding not previously reported in cytology smears.

Microarray-based identification of CUB-domain containing protein 1 as a potential prognostic marker in conventional renal cell carcinoma

Renal cell carcinoma (RCC) is characterized by a variable and unpredictable clinical course. Thus, accurate prediction of the prognosis is important in clinical settings. We conducted microarray-based study to identify a novel prognostic marker in conventional RCC. The present study included the patients surgically treated at Kyoto University Hospital. Gene expression profiling of 39 samples was carried out to select candidate prognostic markers. Quantitative real-time PCR of 65 samples confirmed the microarray experiment results. Finally, we evaluated the significance of potential markers at their protein expression level by immunohistochemically analyzing 230 conventional RCC patients. Using expression profiling analysis, we identified 14 candidate genes whose expression levels predicted unfavorable disease-specific survival. Next, we examined the expression levels of nine candidate genes by quantitative real-time PCR and selected CUB-domain containing protein 1 (CDCP1) for further immunohistochemical analysis. Positive staining for CDCP1 inversely correlated with disease-specific and recurrence-free survivals. In multivariate analysis including clinical/pathological factors, CDCP1 staining was a significant predictor of disease-specific and recurrence-free survivals. We identified CDCP1 as a potential prognostic marker for conventional RCC. Further studies might be required to confirm the prognostic value of CDCP1 and to understand its function in RCC progression.

Unusual solitary metastasis of the ciliary body in renal cell carcinoma

Renal cell carcinoma (RCC) usually metastasizes to the lung, liver, bone; ocular metastasis is uncommon. We describe a rare case of metachronous ciliary RCC metastasis in a 42-year-old man who had undergone left radical nephrectomy for conventional RCC (pT3aN0M0, G2 Fuhrman) 6 years earlier. Solitary metastasis of the left eye presented with inflammatory symptoms, but examination of the fundus and bulbar ultrasound revealed a small mass of the ciliary body. Initial radiotherapy was unsuccessful and definitive treatment consisted of ocular enucleation with radical result and no further evidence of local and distant disease. Ocular metastasis of RCC is rare, can appear years after treating the primary tumor and should not be excluded in RCC follow-up. As for other RCC solitary metastasis, the best option remains the radical surgical approach.

Prognostic Factors in Renal Cell Carcinoma: Association of Preoperative Sodium Concentration with Survival

Conventional renal cell carcinoma (RCC) has a variable natural history, and determining individual prognosis is important to guide management. We have examined the prognostic significance of a large number of hematologic and biochemical variables, as well as traditional tumor-related factors in patients with RCC. Patients undergoing nephrectomy for newly diagnosed RCC between September 1998 and March 2005 were invited to participate. Clinical, pathologic, and laboratory data were recorded in each case, and immunophenotyping was carried out on a subset of patients. A planned subset analysis of patients presenting with N0M0 disease was done. Two hundred twelve patients with RCC formed the study population. In addition to tumor-related factors, multivariate analyses revealed preoperative serum sodium concentration to be independently and significantly associated with overall survival and disease-free survival when considered as both a continuous variable and when dichotomized to above and below the median value [139 mmol/L; reference range 135-145 mmol/L, hazard ratio 0.44, 95% confidence interval (95% CI) 0.22-0.88, P = 0.014]. Five-year overall survival estimates for patients above and below the median serum sodium were 67.6% (95% CI 54.2-80.9) and 44.3% (95% CI 32.8-55.8), respectively. These findings persisted in the N0M0 subgroup analysis. We have confirmed the prognostic value of traditional tumor-related factors but, to our knowledge, these are the first data to show that low preoperative sodium concentration may be an important factor associated with reduced survival in patients with RCC, suggesting that serum sodium should be considered with established prognostic variables in modeling survival in RCC.

VEGF, COX-2, and PCNA expression in renal cell carcinoma subtypes and their prognostic value

To evaluate the prognostic value of new markers such as VEGF (vascular endothelial growth factor), COX-2 (cyclooxygenase-2), and PCNA (proliferating cell nuclear antigen) and review their differences in expression by histological subtype in patients with renal cell carcinoma (RCC). About 99 patients who underwent radical (n = 79) or partial nephrectomy (n = 20) were included in this study. Histopathological specimens from the subjects were retrospectively analyzed immunohistochemically for the presence of VEGF, COX-2, or PCNA. Mean staining ratios for VEGF, COX-2, and PCNA were 16.5, 16.8, and 31%, respectively. Correlations were evaluated among these three prognostic factors. There was no correlation between PCNA and VEGF (P = .068), but there were significant correlations between COX-2 and both PCNA and VEGF (P = .005 and P = .000, respectively). A significant correlation was found between the expression of VEGF and both pathologic stage and vascular invasion (P = .018 and P = .025, respectively). In addition, patients with conventional RCC had significantly lower VEGF and COX-2 levels than those with papillary RCC (P < .012). It is obvious that prognostic factors such as VEGF, COX-2, and PCNA may vary depending on histological subtype. The level of expression of these factors together with histological subtype may provide valuable predictive information about the outcome of treatment.

Lymphangiogenesis and Angiogenesis in Conventional Renal Cell Carcinoma: Association with Vascular Endothelial Growth Factors A to D Immunohistochemistry

Lymphangiogenesis is associated with tumor progression in various cancers and is regulated by vascular endothelial growth factors (VEGFs). However, little is known about the pathologic roles of lymphangiogenesis in renal cell carcinoma (RCC). We investigated the relationships between various clinicopathologic features and lymphangiogenesis, angiogenesis, and expression of VEGFs in RCC. The TNM stage and grade of 107 conventional RCC were reviewed. Lymph vessel density (LVD) and microvessel density (MVD) were measured by quantitative immunohistochemistry using anti-D2-40 antibody and anti-CD34 antibody, respectively. Expression levels of VEGF-A, B, C, and D were examined by immunostaining. D2-40-positive lymphatic vessels were detected mainly in the peritumoral area. However, no significant difference was found between LVD in peritumoral areas of the RCC tissues and the normal kidney (P = 0.238). Intratumoral D2-40-positive lymphatic vessels were detected in only six specimens, and neither intratumoral nor peritumoral LVD correlated with the clinicopathologic features. VEGF-A expression correlated with MVD (r = 0.50, P <0.001), but not with LVD, and was also associated with pT stage, the presence of metastasis, and tumor grade. No other members of the VEGF family showed any correlation with LVD, MVD, or the clinicopathologic features. Lymphangiogenesis seems to play a minimal role in the progression of human RCC. Only VEGF-A, but not B, C, or D, was associated with the histopathologic features and MVD of RCC.

Useful markers for differential diagnosis of oncocytoma, chromophobe renal cell carcinoma and conventional renal cell carcinoma

Renal oncocytoma, conventional RCC (granular cell type) and chromophobe RCC have different prognosis. Sometimes differentiation between them is difficult in HandE slides. In a 5-year study of 128 renal tumors, we selected 76 cases [30 conventional RCC (CRCC), 16 papillary RCC, 21 chromophobe RCC (ChRCC), 8 oncocytoma, 1 collecting duct carcinoma (cdc)] and staining with Hale's colloidal iron, CK7, CK8, CK18, CK19, CK20, Vimentin, EMA, CD10 and RCC marker were done. No significant difference was seen between renal tumor subtypes with CK8, CK18, CK19, CK20 and EMA. The most useful markers were Vimentin, CK7, CD10, RCC marker and Hale's colloidal iron. Hale's colloidal iron staining with diffuse reticular fine cytoplasmic pattern was present in ChRCCs, but was absent in other subtypes and oncocytomas. Vimentin, CK7, CD10, RCC marker and Hale's colloidal iron can be used for the differential diagnosis of problematic epithelial tumors of kidney (CRCC, ChRCC and oncocytoma) - i.e. ChRCC: Vimentin, CD10 and RCC marker - negative, CK7 - positive and positive diffuse fine reticular cytoplasmic pattern of Hale's colloidal iron; oncocytoma: Vimentin, CK7, RCC marker and CD10 - negative and Hale's colloidal iron - negative; CRCC: CK7 - negative, Vimentin, CD10 and RCC marker - positive and Hale's colloidal iron - negative.

Clinical Characteristics of Renal Cell Carcinoma in Korean Patients with von Hippel-Lindau Disease

Purpose: To analyze the clinical characteristics of renal cell carcinoma (RCC) in Korean patients with von Hippel-Lindau (VHL) disease. Materials and Methods: The clinical characteristics of 21 patients who were diagnosed with VHL disease were analyzed. In patients with RCC related to VHL disease, the clinical characteristics of the tumor, type of pathology and survival were investigated. Results: There were 1,396 patients diagnosed with RCC during the same period. A total of 21 patients were diagnosed with VHL disease. Among the 21 patients with VHL disease, 6 (28.6%) patients had retinal angioma, 18 (85.7%) had cerebellar hemangioblastoma, 15 had pancreatic lesions, including 13 with a pancreatic cyst and two with a pancreatic mass. The mean age of the patients diagnosed with VHL disease was 39.1±13.5 years and for those that were diagnosed with VHL disease with RCC it was 42.5±11.5 years. Thirteen patients (61.9%) had renal lesions and nine (42.9%) had RCC. Five had bilateral RCC and four had unilateral RCC. The presenting symptoms were gross hematuria and flank pain in two patients. The treatment of the RCC included radical nephrectomy in two, radical nephrectomy and target therapy in one, partial nephrectomy in two, IL-2 immunotherapy in one, and target therapy in one. Two were observed without treatment because of severe complications of a cerebellar hemangioblastoma. The pathology of the seven patients that had surgery or a biopsy was that of the conventional type RCC. The survival of the patients with VHL with and without RCC was not significantly different. Conclusions: The incidence of RCC in patients with VHL disease was 42.9%, and the incidence of VHL disease in RCC patients was 0.64% in Korea. However, VHL disease in Korea is rare; further extended multiinstitutional studies are needed to determine the characteristics of VHL disease in Korea. (Korean J Urol 2008;49:863-867) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Expression of cyclin D1 and p27kip1 in renal cell carcinoma and its significance

To investigate the role of cyclin D1 and p27(kip1) in the occurrence and development of conventional renal cell carcinoma(CRCC). RT-PCR and Western-blot were used to detect mRNA and protein contents of cyclin D1 and p27(kip1) in 25 CRCCs and 10 normal renal tissue distant to tumor. Immunohistochemistry was used to investigate the expression of cyclin D1 and p27(kip1) in pathological tissue sections of 76 CRCCs. The relationship between those index and clinicopathological parameters was analyzed statistically. In CRCC, the expression of cyclin D1 was higher than that of the control group. The higher cyclin D1 content was related to big tumor size (P<0.05); The expression of p27(kip1) was lower than that of the control group, and the lower p27(kip1) was related to higher nuclear grade and TNM stage (P<0.01). The 5-year cumulative survival rate of the p27(kip1) high expression group is longer than that of the low group (P<0.01). The excessive expression of cyclin D1 and lower expression of p27(kip1) play an important role in the carcinogenesis of CRCC. The lower expression of p27(kip1) may affect the progression of the tumors. The detection of p27(kip1) may be as a reference marker in the prognosis of CRCC.

311 POSTER Early discovery of genomic correlates of drug response by high-resolution gene copy number profiling

Loss of heterozygosity (LOH) is frequently associated with the inactivation of tumor suppressor genes. 18q LOH has been frequently reported in colorectal cancer and lung cancer; however, allelic loss on 18q has not been investigated in renal cell carcinoma (RCC). We evaluated LOH on 18q using nine microsatellite markers in 126 with conventional RCC (cRCC). LOH was observed in more than one 18q microsatellite locus in 24 cRCC (19%). We found the highest frequency of LOH (13.5%) at 18q21.3, where the DCC gene is located. We also assessed the relationship between LOH frequency and patient clinical parameters. Patients with a family history of cancer had a significantly higher frequency of 18q LOH than those without such a history (P = 0.0017). No associations were found with other parameters, including gender, tumor grade, tumor stage, smoking status, and body mass index. The results suggest that inactivation of tumor suppressor genes at 18q21.3, including DCC and SMAD4 as candidates, may be involved in the tumorigenesis of some conventional RCCs.

Alpha4 chain laminins are widely expressed in renal cell carcinomas and have a de-adhesive function

Laminin (Lm) α4 chain, a constituent of Lm-411 and Lm-421, is mainly localized to mesenchyme-derived tissues, and is suggested to have a role in formation and function of endothelium, transmigration of inflammatory cells through endothelium, and invasion of certain tumors. In this study, we evaluated the distribution of α4 chain Lms in 33 conventional (clear cell) renal cell carcinomas (RCCs) (31 primary tumors, two metastases), two papillary RCCs, and two oncocytomas by immunohistochemistry. In all tumors, immunoreactivity for Lm α4 chain was found in vasculature and stroma. Basement membranes were detected around tumor cell islets in 34/37 tumors. They showed immunoreactivity for Lm α4 chain in 28/34 cases. Northern blotting, inhibition of protein secretion with monensin, and immunoprecipitation combined with Western blotting showed that Caki-2, ACHN, and Caki-1 renal carcinoma cell lines produce α4 chain Lms. In cell adhesion assay, recombinant human Lm-411 did not promote adhesion of renal carcinoma cells but inhibited adhesion to fibronectin (Fn). In cell migration assay, the cells migrated more on Lm-411 than on Fn. The results suggest that α4 chain Lms have a de-adhesive function and could thus play a role in detachment, migration and invasion of renal carcinoma cells in vivo.

Prognostic impact of carbonic anhydrase IX expression in human renal cell carcinoma

To evaluate the prognostic information of carbonic anhydrase (CA) IX expression in patients with renal cell carcinoma (RCC), as increased expression of CA IX is correlated with a worse prognosis in several malignancies. CA IX expression was assessed in RCC tumours from 228 patients, using a tissue microarray technique on archival material. The expression was related to RCC cell type, Tumour-Node-Metastasis (TNM) stage, nuclear grade and survival. CA IX expression was significantly higher (P < 0.001) in 183 conventional than in 31 papillary RCC and 14 chromophobe RCC. For conventional RCC there was no correlation of CA IX expression with TNM stage or nuclear grade. To evaluate the prognostic information conventional RCC tumours were subdivided arbitrarily into three groups according to the CA IX expression, of 0-10%, 11-90% and 91-100% expression, respectively. Patients with tumours with 0-10% expression had a less favourable prognosis than those with 11-90% and 91-100% expression (P = 0.012, and 0.001), respectively. A multivariate analysis of prognostic factors for patients with conventional RCC showed that TNM stage, nuclear grade and CA IX were independent predictors of prognosis. These results show that CA IX expression is higher in conventional than other RCC cell types; furthermore, patients with conventional RCC with low CA IX expression had a less favourable prognosis.

Pigmented microcystic chromophobe renal cell carcinoma

We report a case of a 60-year-old female with a pigmented microcystic chromophobe renal cell carcinoma (PMCRCC). The tumor was 4.5 cm in diameter, and was located in the right kidney. Grossly, on cross section, the tumor was light gray with multiple small brown to black pigmented foci up to 0.2 cm in diameter. Histologically, the tumor showed a microcystic arrangement with cribriform areas and formation of adenomatous structures. The microcystic and cribriform areas were composed of larger pale cells and smaller eosinophilic cells, with cytological features of conventional chromophobe renal cell carcinoma (CRCC). The cytological features of the cells within the adenomatous structures were different. These cells were mostly columnar with nuclei at the base, and had a variable amount of pale to eosinophilic cytoplasm. There were foci of ample brown pigmentation located in the cytoplasm of the tumor cells and extracellularly. In addition, microscopic calcifications were present. Immunohistochemically, the tumor cells were positive for EMA, E-cadherin, cytokeratin CAM5.2, and cytokeratin AE1/AE3. Cytokeratin 7 was positive only focally. S-100 protein, melan A, HMB 45, vimentin, and CD117 were negative. PMCRCC is a rare tumor. To the best of our knowledge, only one series containing 20 cases of this variant of CRCC has been described to date. The important feature is that PMCRCC seems to have a relatively benign biological behavior, and distant metastases and sarcomatoid transformation are absent.

Response from authors of “Extracellular matrix alterations in conventional renal cell carcinomas by tissue microarray profiling influenced by the persistent, long-term, low-dose ionizing radiation exposure in humans”

Response from authors of “Extracellular matrix alterations in conventional renal cell carcinomas by tissue microarray profiling influenced by the persistent, long-term, low-dose ionizing radiation exposure in humans”

Plasma level and tissue expression of vascular endothelial growth factor in renal cell carcinoma: a prospective study of 50 cases

Vascular endothelial growth factor (VEGF) is the major factor involved in angiogenesis. Although it is known that one of the functions of VEGF is to regulate neovascularization in renal cell carcinomas, the relationship between the production of VEGF in tumor tissue and its concentration in blood has not yet been studied. The aims of this study were to determine, in a series of conventional renal cell carcinoma (CRCC) cases, (1) VEGF expression and VEGF pattern in tumor cells, (2) the relationship between VEGF expression/pattern and VEGF levels in plasma (pVEGF), and (3) the association with usual clinical and pathologic prognostic factors. Fifty patients operated on for CRCC by radical nephrectomy were included. Clinical and histologic parameters were studied. VEGF expression and VEGF pattern in tumor cells was immunohistochemically recorded. pVEGF levels and platelet count were analyzed in relation to clinical and histologic parameters. Intratumoral VEGF expression associated with a cytoplasmic VEGF pattern was significantly higher in patients with high pVEGF levels (P = .01). Both VEGF expression and pVEGF levels were significantly correlated with Fuhrman grade (P = .002 and P = .01, respectively) and tumor stage (P = .006 and P = .008, respectively). In addition, VEGF expression was also correlated with tumor necrosis (P = .001) and progression (P = .001). We demonstrated that in CRCC with tumor necrosis, VEGF expression, pVEGF levels, and platelet count were significantly higher than in CRCC with no tumor necrosis (P = .001, P = .03, and P = .001, respectively). Our results revealed that cytoplasmic VEGF expression and pVEGF levels are associated with usual prognostic factors and progression in CRCC, which may allow VEGF to be used as a prognostic marker for CRCC, especially in patients with VEGF-targeted therapy.

Von Hippel-Lindau gene mutation status is associated with a dichotomous response in primary and metastatic tumors in patients receiving bevacizumab and erlotinib for metastatic renal cell carcinoma

15522 Background: A single arm phase II study is underway evaluating the safety and clinical benefit of presurgical bevacizumab and erlotinib in the management of patients with untreated conventional renal cell carcinoma (RCC). It is not known how the presence or absence of von Hippel Lindau (VHL) mutations affect the response to therapy in the primary or metastatic site, and whether VHL mutational status is predictive for either. Methods: Patients enrolled had conventional RCC, measurable metastatic disease, a primary tumor in place, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. A total of 35 patients were enrolled as of January 8, 2007. Patients were treated with bevacizumab for 4 cycles and erlotinib for 8 weeks, and underwent cytoreductive nephrectomy at week 10 (4 weeks after the last dose of bevacizumab). A VHL gene mutation and methylation analysis was completed on nephrectomy specimens from the first 18 evaluable patients. Patients were grouped according to the presence or absence of functional VHL gene inactivation (mutation and/or methylation). Two-sample T-test and Fisher’s exact test were performed. Results: Ten patients (55%) demonstrated either VHL mutation or methylation ( table 1 ). Patients with no VHL gene inactivation demonstrated more robust primary tumor shrinkage, but did not demonstrate partial responses (PRs). Table 1 . Conclusions: These findings, although preliminary, suggest a dichotomous response in the primary and metastatic disease sites according to VHL functional status. Ongoing evaluation of new treatment strategies using antivascular/targeted agents in RCC may benefit from molecular stratification. [Table: see text] No significant financial relationships to disclose.

Preoperative sodium concentration as a possible predictor of survival in patients with renal cell carcinoma

10601 Background: Conventional renal cell carcinoma (RCC) has a variable natural history, and determining individual prognosis is important to guide management. In this cross-sectional study of RCC, a large number of parameters including hematological and biochemical as well as traditional tumor-related factors have been assessed for their prognostic significance. Methods: Consecutive, unselected patients undergoing nephrectomy for newly diagnosed RCC were invited to participate. Primary end-points were overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). A subset analysis of patients presenting with localized N0 disease was planned. Univariate and multivariate Cox's proportional hazards models were used. Results: 212 patients with RCC formed the study population. Tumor-related factors including grade, stage, presence of necrosis and vascular invasion were prognostic for survival on multivariate testing, in agreement with previous reports. In multivariate analyses pre-operative serum sodium (sNa) was found to be independently and significantly associated with OS and DFS when considered as a continuous variable (see table ). In a further exploratory analysis for all patients when sNa was dichotomized into above/below the median value (139 mmol/l; normal range: 135–145 mmol/l), 3-year OS estimates above and below the median were 74%, 95% CI [64%, 85%] and 54%, 95% CI [44%, 64%]; corresponding figures for 5 years were 68%, 95% CI [54%, 81%] and 44%, 95% CI [33%, 56%]. Conclusions: We have confirmed the prognostic value of traditional tumor-related factors but, to our knowledge, these are the first data to demonstrate that pre-operative sodium concentration may be an important factor associated with survival in patients with RCC. This result suggests that sNa should be considered with established prognostic parameters in modeling survival in RCC. [Table: see text] No significant financial relationships to disclose.

Randomized phase II study of sorafenib with or without low-dose IFN in patients with metastatic renal cell carcinoma

5104 Background: An 80 patient randomized open label phase II study is underway evaluating the safety and clinical benefit of sorafenib with or without low-dose interferon (LD IFN) in patients with untreated metastatic conventional (clear cell) renal cell carcinoma (mRCC). Prior studies combining sorafenib and conventional dose IFN demonstrated a response rate (RR) in the 20–30 percent range, higher than the 2–10 percent RR seen with sorafenib monotherapy, but with increased toxicity. Prior data suggest equivalent efficacy between LD and conventional dose IFN with fewer side effects. We postulated that low-dose IFN will add to the clinical benefit of sorafenib in patients with mRCC with minimal additional toxicity. Methods: Eligibility included conventional mRCC, measurable disease, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. Patients were treated with sorafenib 400mg PO BID or sorafenib at the same dose plus interferon alfa 0.5 million units SC BID. Primary endpoints included response rate and progression free survival (PFS). The probabilities of PFS and overall survival (OS) were estimated for each arm using Kaplan-Meier methods. Median PFS and OS were summarized, along with the 95% confidence intervals for each arm separately. Results: A total of 60 patients were enrolled as of January 8, 2007. Five patients were inevaluable, and 5 patients had not undergone first restaging. Treatment was well tolerated in both groups. Best response and PFS are summarized below. In the sorafenib arm, 13 out of 25 patients progressed or died. The median time to progression was 9.3 months (95% CI 5.8- not reached). In the sorafenib + IFN arm, 13 out of 25 patients progressed or died. Median time to progression was 9.3 months (95% CI 5.2- not reached). Median OS was not reached in either arm. Conclusions: These findings, although preliminary, suggest that adding low dose interferon therapy to sorafenib therapy does not provide superior cytoreduction of metastatic RCC, but provides equivalent PFS. [Table: see text] No significant financial relationships to disclose.

A Preoperative Prognostic Nomogram for Solid Enhancing Renal Tumors 7 cm or Less Amenable to Partial Nephrectomy

Small renal masses are increasing in incidence. Most tumors 7 cm or less are treated with radical or partial nephrectomy but clinicians are increasingly relying on ablative therapies and observation for some small renal masses. We present novel nomograms that predict the likelihood of benign, likely indolent or potentially aggressive pathological findings based only on readily identifiable preoperative factors. Information on all partial nephrectomies performed at a single institution was collected in an institutional review board approved registry. Using retrospectively collected data on all 862 patients who underwent partial nephrectomy for a single, solid, enhancing, clinical T1 (7 cm or less) tumor between 1999 and 2005 tumors were classified as benign or malignant. Grade 3 clear cell renal cell carcinoma, grade 4 renal cell carcinoma of any type and any renal cell carcinoma with vascular, fat or collecting system invasion were considered potentially aggressive. The likelihood of benign, likely indolent or potentially aggressive pathological findings was modeled using multivariable logistic regression models based on age, gender, radiographic tumor size, symptoms at presentation and smoking history. Of 862 small renal masses 20% were benign and 80% were malignant but only 30% of cancers (24% of small renal masses) were potentially aggressive. All 11 patients with systemic symptoms had cancer. The remaining 851 patients underwent further analysis. Factors that were most strongly associated with the likelihood of benign pathology were age, gender, tumor size and smoking history. A nomogram constructed to predict benign histology proved to be relatively accurate and discriminating (bootstrap corrected concordance index 0.644) and calibrated. Small renal masses in older men and younger women were more likely to be benign. With regard to differentiating indolent from potentially aggressive cancers, only advanced age was independently significant on multivariate analysis (p <0.005). The nomogram for this outcome performed with limited ability (concordance index 0.557). Clinical factors provide substantial predictive ability to predict benign vs malignant pathology for small renal masses amenable to partial nephrectomy. Although most of these small renal masses are benign or indolent, our ability to predict potentially aggressive cancer in this population remains limited.