Pathobiology and prognosis of chromophobe renal cell carcinoma.

OBJECTIVES: To analyze pathobiology and prognosis of chromophobe renal cell carcinoma (CRCC). PATIENTS AND METHODS: We studied 124 patients with CRCC who underwent nephrectomy from 1989 to 2006 at two institutions. Clinicopathological characteristics and survival were compared with 1,693 consecutive patients with clear-cell RCC. RESULTS: Compared with clear cell RCC, patients with CRCC presented with less advanced tumors, but had a higher prevalence of concomitant sarcomatoid features (15% vs. 6%, P < 0.001). Metastatic CRCC showed a high incidence of sarcomatoid features (50%) and a predilection for liver metastases. The 5-year DSS rate for all patients with CRCC was 78% compared with 60% for patients with clear-cell RCC (P = 0.008). When adjusted for metastatic status, this survival difference disappeared. Nonmetastatic RCCs had similar prognosis (P = 0.157), whereas survival of metastatic CRCC was inferior to that of patients with metastatic clear-cell tumors (median: 6 vs. 19 months, P = 0.0095). In multivariate analysis, ECOG PS, symptomatic presentation, T stage, N stage, M stage, nuclear grade, and presence of sarcomatoid features, but not histological sub-type, were independent prognostic factors of DSS. Ten patients received immunotherapy, none of whom were responders. CONCLUSIONS: Compared with clear-cell RCC, patients with CRCC present with less advanced tumors, which lead to better survival rates on the whole. However, adjustment for metastatic status negates this difference. Patients with metastatic CRCC show a high prevalence of sarcomatoid features, predilection for liver metastases, no response to immunotherapy, and exhibit poor prognosis.

Feasibility of nerve-sparing prostate cryosurgery: applications and limitations in a canine model.

BACKGROUND AND PURPOSE: In a canine model, we evaluated the feasibility of nerve-sparing cryosurgery by active warming of the neurovascular bundle (NVB). Furthermore, our aim was to determine if NVB warming increases the risk of acinar gland and stromal-tissue preservation in adjacent areas of the prostate. The effects of a single versus double freeze-thaw cycle on prostate tissue were also assessed. MATERIALS AND METHODS: Ten prostate lobes from five dogs were evaluated. Nine lobes from five dogs were treated with cryoablation using 17-gauge gas-driven cryoneedles. Seven lobes wre treated with active warming of the NVB using helium gas, and two lobes were treated without active warming. A single or double freeze-thaw cycle was utilized. Prostate tissue ablation and NVB preservation were evaluated in histologic sections. RESULTS: All seven prostate lobes treated with active warming demonstrated complete or partial NVB preservation. Four of these lobes had adjacent gland preservation. All lobes treated with a double freeze-thaw cycle showed complete and uniform ablation of prostate tissue. One of the three lobes treated with a single freeze-thaw cycle demonstrated incomplete ablation of the tissue. CONCLUSIONS: This is the first study investigating the feasibility of NVB preservation under controlled experimental conditions. In our canine model, NVB preservation with active warming was possible but not consistently reproducible. In some cases, NVB preservation with active warming may result in incomplete peripheral tissue ablation. A double, but not a single, freeze-thaw cycle induces complete and effective necrosis of prostatic tissue. These results have significant clinical applications when attempting nerve-sparing cryosurgical ablation of the prostate.

The effects of intentional cryoablation and radio frequency ablation of renal tissue involving the collecting system in a porcine model.

PURPOSE: Ablative techniques for the treatment of urological malignancy are gaining acceptance and they are likely to become more widely used in clinical practice. Indications and limitations of the technologies are still evolving. In a porcine model we evaluated the safety and efficacy of cryotherapy and radio frequency ablation (RFA) of cortical and deep renal tissue. MATERIALS AND METHODS: In 11 swine argon gas based cryoablation or RFA of renal tissue adjacent to the collecting system was performed using a laparoscopic or percutaneous approach. Lesions created in renal units 30 days or 2 hours prior to harvest were termed chronic or acute. Using single or multiple 17 gauge cryoneedles or 3.0 mm cryoprobes and 2 freeze-thaw cycles (10-minute freeze and 5-minute thaw) 13 acute and 10 chronic cryolesions were made. Using a single 16 gauge umbrella-shaped RFA probe and 2 heating cycles to maximum impedance 13 acute and 4 chronic RFA lesions were made. Gross and microscopic tissue analysis was performed to assess lesion size and renal parenchymal, collecting system and arterial effects. Acute cryolesion size estimation by laparoscopic or transcutaneous ultrasound (US) was compared with pathological lesion size. RESULTS: Acute cryolesions on hematoxylin and eosin staining demonstrated uniform coagulative necrosis of renal parenchyma and chronic cryolesions demonstrated uniform necrosis with fibrous scar formation. Interlobar artery (adjacent to renal pyramid) preservation occurred in 7 of 13 acute and 5 of 9 chronic cryolesions. Urothelial architecture was preserved in 8 of 13 acute and 7 of 9 chronic cryolesions. Acute and chronic RFA lesions demonstrated indeterminate necrosis on hematoxylin and eosin staining, although triphenyl tetrazolium chloride staining of gross specimens confirmed necrosis most definitively in renal cortex. Interlobar artery preservation occurred in 6 of 13 acute and 3 of 4 chronic RFA lesions. Urothelial architecture was preserved in 1 of 13 acute and 2 of 4 chronic RFA lesions. Acute cryolesion dimensions measured by laparoscopic US equaled or underestimated lesion size measured grossly in all 6 cases. Lesion dimensions measured by transcutaneous US equaled or underestimated true lesion size in 3 of 6 cases. In 3 of 6 lesions transcutaneous US overestimated true lesion size by 20%, 76% and 260%, respectively. CONCLUSIONS: Renal cortical tissue can be effectively destroyed by cryoablation or RFA. However, treatment of deep parenchymal lesions with either modality may result in incomplete ablation. Cryosurgery but not RFA spares the collecting system in an acute setting. However, healing or regrowth of the urothelium may occur with time after RFA. Laparoscopic US is more accurate for cryolesion monitoring than transcutaneous US.

Cystic renal cell carcinoma: biology and clinical behavior.

The purpose of the study was to evaluate unilocular and multilocular cystic renal cell carcinoma (cRCC). These tumors are a rare entity, comprising approximately 1 to 2% of all renal tumors, and their true biologic behavior is not well-known. Initial review of renal cell carcinoma (RCC) cases treated at our institution between 1989 and 2001 identified 39 cases of cRCC. However, histopathologic review of these cases by 2 pathologists revealed that only 18 cases met the criteria that all tumors have a cystic component that constitutes at least 75% of the total lesion without evidence of necrosis. These cases were compared to 614 conventional clear cell RCC cases with regards to clinical outcomes. All 18 patients presented with localized (N0M0) disease. Thirteen (72%) of the tumors were Fuhrman Grade 1, while the remaining 5 (28%) were Fuhrman Grade 2. By comparison, only 60% of the clear cell RCC tumors were Grade 1 or 2. Similarly, 83% of cRCC were pT1 tumors compared to only 35% of conventional clear cell tumors. Mean tumor size for the cRCC tumors was 4.9 cm compared to 7.4 cm for conventional clear cell tumors. Cystic RCC patients had an 82% four-year disease-specific survival (DSS). Unilocular and multilocular cRCC is a distinct subtype of clear cell RCC. Its biology appears to be more favorable with regards to important prognostic factors such as metastatic presentation, Fuhrman grade, 1997 T stage, and tumor size. These findings suggest that cRCC patients may benefit from nephron sparing surgery.

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE: To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS: 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS: The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION: This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Eastern Cooperative Oncology Group performance status predicts bone metastasis in patients presenting with renal cell carcinoma: implication for preoperative bone scans.

PURPOSE: We identified a subset of patients with renal cell carcinoma (RCC) who have a high likelihood of presenting with bone metastasis and would most benefit from a preoperative bone scan. MATERIALS AND METHODS: A database of 1,357 patients undergoing nephrectomy and/or immunotherapy for RCC at our institution was queried. Patients presenting with metastasis to the bones were identified and stratified according to T stage, Eastern Cooperative Oncology Group (ECOG) score, musculoskeletal symptoms and alkaline phosphatase. RESULTS: Of the patients 37% presented with metastasis. Bone metastasis was identified in 14% of patients. The incidence of bone metastasis was 5.4%, 13.8%, 15.4% and 28.2% in patients with T1 to T4 lesions, and 1.4%, 19% and 41% in those with an ECOG score of 0 to 2 and greater, respectively. T stage and ECOG score were then integrated. Bone metastasis was confirmed in 0.046%, 3.8%, 1.4% and 0% of patients with T1 to T4/ECOG 0 disease, and in 13.4%, 20%, 21.5% and 31% of those with T1 to T4/ECOG greater than 0 disease, respectively (p < 0.0001). Only 1.4% of patients with an ECOG score of 0 harbored bone metastasis, of whom 71% complained of musculoskeletal pain, 100% manifested extraosseous metastases and 25% had increased alkaline phosphatase at presentation. CONCLUSIONS: Performance status is an important predictor of bone metastasis in patients presenting with presumed RCC lesions. Bone scan should be performed in patients with an ECOG score of greater than 0 regardless of T stage but is unnecessary in those presenting with an ECOG score of 0, particularly when lacking symptoms and extraosseous metastasis.

Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience.

PURPOSE: We compared cancer specific survival of patients undergoing partial and radical nephrectomies for T1N0M0 renal tumors according to tumor size in a large multicenter series. MATERIALS AND METHODS: A retrospective analysis of 1454 patients undergoing partial or radical nephrectomy for T1N0M0 renal tumors from 7 international academic centers was performed. Data were obtained for each patient including TNM stage (determined according to the 2002 TNM criteria), tumor size, type of surgery (partial versus radical nephrectomy) and cancer specific survival. Recurrence events were recorded when available. RESULTS: Partial and radical nephrectomies were performed in 379 (26.1%) and 1075 (73.9%) cases, respectively. Mean followup +/- SD was 62.5 +/- 51.8 months. Recurrence data were available on 544 patients. There were no significant differences in local or distant recurrence rates between patients undergoing partial or radical nephrectomy for either T1a (p = 0.6) or T1b tumors (p = 0.5). For patients with T1a tumors, there was no significant difference in the rate of cancer specific deaths between the partial (314) and radical (499) nephrectomy groups (2.2% versus 2.6%, respectively, p = 0.8). For patients with T1b tumors there was also no significant difference in the rate of cancer specific deaths between patients undergoing partial (65) and patients undergoing radical (576) nephrectomy (6.2% versus 9%, respectively, p = 0.6). CONCLUSIONS: Partial nephrectomy is becoming the gold standard for renal tumors less than 4 cm but this treatment is much more controversial for larger T1 tumors. This large multicenter study suggests that it is safe to expand the indications of partial nephrectomy to include patients with T1N0M0 tumors up to 7 cm. However, careful patient selection remains necessary.

Prognostic value of carbonic anhydrase IX and KI67 as predictors of survival for renal clear cell carcinoma.

PURPOSE: The natural history of renal cell carcinoma (RCC) is complex and not entirely explained by conventional prognostic factors. In this study we evaluated the prognostic value of carbonic anhydrase IX (CAIX) and Ki67 to predict survival in RCC. MATERIALS AND METHODS: Immunohistochemical analysis using a CAIX and a Ki67 monoclonal antibody was performed on tissue microarrays constructed from paraffin embedded specimens from 224 patients treated with nephrectomy for clear cell renal carcinoma. CAIX and Ki67 staining were correlated with clinical factors, pathological features and survival. Median followup was 34 months (range 0.3 to 117) and disease specific survival was the primary end point assessed. RESULTS: Univariate statistical analysis showed that high Ki67 staining and low CAIX staining correlated significantly with poor median survival (21 months, p < 0.001 and 22 months, p = 0.011, respectively). Each marker was highly significant for stratifying patient groups defined by T stage, Fuhrman grade, nodal status, metastatic status and performance status. On multivariate analysis CAIX and Ki67 were significant predictors of survival with an HR of 1.78 (p = 0.014) and 1.75 (p = 0.009), respectively. Although CAIX and Ki67 staining were inversely correlated (p = 0.009), Ki67 significantly substratified patient subgroups defined by high or low CAIX staining (p = 0.001 and 0.003, respectively). When Ki67 and CAIX were combined into a single parameter, RCC tumors could be stratified into low, intermediate and high risk groups with a median survival of greater than 101, 31 and 9 months, respectively (p <0.001). On multivariate analysis the combined parameter consisting of Ki67 and CAIX was a significant predictor of survival (p <0.001) and it was able to displace histological grade. CONCLUSIONS: Ki67and CAIX are useful prognostic biomarkers for RCC that improve the survival prediction and classification of kidney cancer.

Use of American Society of Anesthesiologists physical status classification to assess perioperative risk in patients undergoing radical nephrectomy for renal cell carcinoma.

OBJECTIVES: To perform a retrospective analysis to determine the operative morbidity in patients with substantial comorbidities requiring renal surgery. Increasing numbers of patients requiring renal surgery are presenting with substantial comorbidities, such as diabetes mellitus, chronic obstructive pulmonary disease, and cardiovascular disease. METHODS: The American Society of Anesthesiologists (ASA) physical status classification was used to define perioperative risk. Of 1087 patients who underwent nephrectomy between 1989 and 2001, 237 patients were classified as ASA classification 1 or 2 (low risk), 297 were ASA classification 3 (intermediate risk), and 17 were ASA classification 4 (high risk). RESULTS: No statistically significant differences were found among the low-risk, intermediate-risk, or high-risk patients with regard to 1997 T stage distribution, mean tumor size, vascular and/or inferior vena cava involvement, percentage of partial nephrectomy, adjacent organ resection, or preoperative hemoglobin. Intermediate-risk patients did have a greater estimated blood loss (946 versus 739 mL, P = 0.05), leading to greater transfusion rates (42% versus 28%, P = 0.001). However, no increase occurred in intraoperative or postoperative morbidity. High-risk patients also had greater transfusion rates, as well as a greater rate of complications occurring more than 24 hours after surgery. CONCLUSIONS: Partial or radical nephrectomy can be offered to patients with comorbid conditions. ASA classification 3 patients are more likely to require transfusion. This may have been a result of a lower threshold to transfuse patients with preoperative morbidities. However, the perioperative and postoperative complication rates were similar to those of low-risk patients. Not surprisingly, high-risk patients had greater rates of transfusions and complications.

Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma.

PURPOSE: Epithelial cell adhesion molecule (EpCAM) is a widely expressed adhesion molecule in epithelial cancers. The purpose of this study is to determine the protein expression patterns of EpCAM in renal cell carcinoma (RCC) using tissue arrays linked to a clinicopathological database to evaluate both its predictive power in patient stratification and its suitability as a potential target for immunotherapeutic treatment strategies. EXPERIMENTAL DESIGN: The University of California, Los Angeles kidney cancer tissue microarray contains specimens from 417 patients treated with nephrectomy. EpCAM protein expression in tumors and matched morphologically normal renal tissues was evaluated using anti-EpCAM immunohistochemistry. The resultant expression reactivity was correlated with clinicopathological variables. RESULTS: EpCAM is consistently expressed in the distal nephron on normal renal epithelium. Clear cell RCCs show minimal and infrequent EpCAM expression, whereas chromophobe and collecting duct RCCs both demonstrate intense and frequent expression. Of 318 clear cell carcinomas used in the analysis, 10% were EpCAM positive in > or = 50% of cells, and 8% of patients would be considered candidates for EpCAM-based therapy, based on high expression [> or = moderate intensity and frequent (> or = 50%) expression] and the need for systemic treatment. EpCAM expression was an independent prognostic factor for improved disease-specific survival, with a multivariate hazard ratio of 0.63 (P = 0.017; 95% confidence interval, 0.43-0.92). CONCLUSIONS: EpCAM is a novel prognostic molecular marker in RCC patients, and its positive expression is an independent predictor associated with improved survival. However, high expression in morphologically normal renal tissues and minimal or absent expression in clear cell carcinomas will likely limit the utility of this epithelial marker in targeted treatments of this most common RCC type.

Cachexia-like symptoms predict a worse prognosis in localized t1 renal cell carcinoma.

PURPOSE: Although cachexia is a common sequela of advanced and metastatic renal cell carcinoma (RCC), cachexia-like symptoms may also represent a paraneoplastic finding. We assessed the prognostic significance of these symptoms in patients with stage T1 RCC. MATERIALS AND METHODS: Using the kidney cancer database at our institution 250 patients were identified who underwent partial or radical nephrectomy for T1N0M0 RCC between 1989 and 2001. The prognostic significance of the symptoms present at diagnosis and findings on preoperative laboratory evaluation were examined. RESULTS: Mean and median followup was 33 and 43 months, respectively. Malaise, weight loss, anorexia and hypoalbuminemia were cachexia related findings that were significant predictors of worse disease specific survival (DSS). DSS in patients with 1 vs greater than 1 cachexia related symptoms was not significantly different (p = 0.077). Therefore, any patient with at least 1 cachexia related finding was considered to be positive for cachexia and cachexia occurred in 37 (14.8%). Cachexia was associated with significantly worse recurrence-free survival (HR 3.03, p = 0.032) and DSS (HR 4.39, p = 0.011) even after controlling for tumor size, grade and performance status. The 5-year survival rate in patients with low grade (1 or 2) tumors with and without cachexia was 91% and 81%, respectively. The 5-year survival rate in patients with high grade (3 or 4) tumors with and without cachexia was 75% and 55%, respectively. CONCLUSIONS: Cachexia-like symptoms independently predict a worse prognosis in patients with T1 RCC. Patients with cachexia (malaise, weight loss, anorexia and hypoalbuminemia), especially when associated with high grade tumors, should be considered for clinical trials of adjuvant therapies.

Routine pouchograms are not necessary after continent urinary diversion.

OBJECTIVES: Pouchograms are routinely performed before catheter removal after continent urinary diversion at our institution. Our aim was to determine the necessity of pouchograms based on a review of our experience. METHODS: A retrospective review of patient records and radiographic studies was done for patients undergoing radical cystectomy and continent urinary diversions between 1991 and 2001. RESULTS: Seventy-two patients underwent continent urinary diversion (orthotopic, n = 59; cutaneous, n = 13) during the study period. All underwent pouchogram postoperatively (median 22 days; range 20 to 27). Six patients (8.3%) had a demonstrable radiographic leak; in 5 of the 6 patients, the urine leak was suspected on clinical grounds. Three patients (4.7%) developed urosepsis after pouchogram. CONCLUSIONS: Our findings indicate that routine pouchograms before pouch activation after continent urinary diversion may not be necessary.

Prostate stem cell antigen expression is associated with gleason score, seminal vesicle invasion and capsular invasion in prostate cancer.

PURPOSE: Few successful therapeutic options exist for men who present with metastatic prostate cancer (CaP) or for the 30% with recurrence. The development and characterization of molecular markers are vital to the development of prognostic and therapeutic modalities in CaP. We investigated the expression and potential clinical usefulness of prostate stem cell antigen (PSCA) in CaP using tissue microarrays. MATERIALS AND METHODS: Immunohistochemical analysis using a PSCA monoclonal antibody was performed on tissue microarrays constructed from paraffin embedded specimens from 246 patients who underwent radical retropubic prostatectomy. PSCA staining was correlated with established prognostic factors, such as Gleason score, prostate specific antigen (PSA), and seminal vesicle invasion. In addition, recurrence-free survival was analyzed. RESULTS: A high PSCA intensity of 3 was associated with adverse prognostic features, such as Gleason score 7 and above (p = 0.001), seminal vesicle invasion (p = 0.005) and capsular involvement (p = 0.033). On univariate analysis tumors with a PSCA intensity of 3 carried an increased risk of PSA recurrence (p = 0.031, HR 1.77, 95% CI 1.05 to 2.96). However, after adjusting for these variables a PSCA intensity of 3 was no longer an independent predictor of PSA recurrence. CONCLUSIONS: We found that high PSCA intensity is significantly associated with adverse prognostic features such as high Gleason score and extra-organ disease. The results of this study suggest that PSCA is a promising tumor marker for the selection of patients at high risk but additional studies are necessary to assess the usefulness of PSCA in patient biopsies.

Prognostic significance of venous thrombus in renal cell carcinoma. Are renal vein and inferior vena cava involvement different?

PURPOSE: The prognostic significance of the level of venous involvement in renal cell carcinoma (RCC) is controversial. It has been suggested that the 1997 TNM classification of venous involvement system should be revised. MATERIALS AND METHODS: The records of 226 patients who underwent a nephrectomy and tumor thrombectomy, 117 for renal vein (RV) and 109 for inferior vena cava (IVC) involvement, between 1989 and 2001 were reviewed and compared to those of 654 patients undergoing nephrectomy without venous involvement. RESULTS: In patients with localized RCC (N0M0), the risk of recurrence after nephrectomy was significantly increased in patients with venous thrombus compared to patients without venous thrombus (p = 0.005). However, the difference was not significant in a multivariate analysis including T stage (1, 2, 3 or 4), Fuhrman grade and Eastern Cooperative Oncology Group performance status. In patients with localized RCC disease specific survival was similar (p = 0.536) in patients with RV (T3b) and IVC involvement below the diaphragm (T3b). However, patients with IVC involvement above the diaphragm (T3c) had a significantly worse survival rate even after controlling for Fuhrman grade and Eastern Cooperative Oncology Group performance status in a multivariate analysis (p = 0.020). All patients treated for metastatic RCC had a similar prognosis regardless of the level of venous involvement. CONCLUSIONS: For patients with pT3b disease, local tumor stage and grade are better predictors of prognosis than extent of venous involvement. Based on our data we support the current TNM classification of venous involvement with RV and IVC invasion categorized as T3b and IVC involvement above the diaphragm categorized as T3c.

Primary leiomyosarcoma of the inferior vena cava presenting as a renal mass.

Leiomyosarcoma of the inferior vena cava (IVC) is an extremely rare entity. We present the case of a 62-year-old woman who was found to have a large right upper quadrant mass upon examination by her primary care physician in evaluation for diffuse abdominal pain accompanied by anorexia and weight loss. A computed tomographic scan and magnetic resonance imaging demonstrated a 13-cm retroperitoneal lesion that appeared to stem from the right kidney and yielded a tumor thrombus up to the level of the hepatic venous confluence. The patient underwent a right radical nephrectomy and IVC thrombectomy for treatment of a presumed renal cell carcinoma. Instead, pathology revealed the tumor to be a leiomyosarcoma of the IVC. We document this unusual presentation of an extremely rare tumor entity.

Emerging technologies in uroradiologic imaging.

Advances in imaging technologies have readily been incorporated into the practice of urology and have led to important advances in patient care and outcomes. In the area of oncology, advances in radiologic imaging are improving the ability of the urologist to diagnose and monitor urologic malignancies. Some of these technologies include positron emission tomography (PET), intraoperative ultrasound (IUS), 3-dimensional computerized tomography (3D-CT), and magnetic resonance spectroscopy (MRS). We provide an overview of these four emerging imaging modalities and their potential applications and limitations in the diagnosis and management of urologic malignancy.

Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: a stratification tool for prospective clinical trials.

BACKGROUND: The objective of this study was to develop an algorithm capable of stratifying the survival of patients with metastatic renal cell carcinoma (RCC) after nephrectomy and immunotherapy. METHODS: The medical records of 173 patients who underwent radical nephrectomy for metastatic RCC and received recombinant interleukin-2 (IL-2)-based immunotherapy between 1989 and 2000 were evaluated. Survival was the primary endpoint and was assessed based on clinical, surgical, and pathologic parameters. The clinical parameters included age, gender, performance status, existing hypertension, thyroid-stimulating hormone (TSH) levels, location of metastases, and presenting symptomatology. The surgical features included the requirement for blood transfusion or adrenalectomy. The pathologic factors involved tumor stage, tumor size, nuclear grade, lymph node status, and histologic subtype. Disease-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to determine associations between clinical and pathologic features and survival. RESULTS: The median follow-up was 3.2 years (range, 0.2-9.3 years). Death due to RCC occurred in 123 patients (71%) at a median of 13 months (range, from 0.1 months to 8.4 years) after nephrectomy. Multivariate analysis revealed that the following features were associated with survival: lymph node status (P = 0.002), constitutional symptoms (P = 0.005), location of metastases (P < 0.001), sarcomatoid histology (P = 0.003), and TSH level (P = 0.038). A scoring system based on the features in the multivariate model was created to stratify patients into low-risk, intermediate-risk, and high-risk groups. Estimated survival rates at 1 years, 3 years, and 5 years were 92%, 61%, and 41%, respectively, for the low-risk group and 66%, 31%, and 19%, respectively, for the intermediate risk group. The high-risk group had 1% survival at 1 year and no survivors at 3 years. CONCLUSIONS: In patients with metastatic RCC who were treated with nephrectomy and IL-2 immunotherapy, regional lymph node status, constitutional symptoms, location of metastases, sarcomatoid histology, and TSH levels were associated with survival. The authors present a scoring algorithm based on these features that can be used to predict survival in patients who present with metastatic RCC and to stratify such patients for prospective clinical trials.

Validation of an integrated staging system toward improved prognostication of patients with localized renal cell carcinoma in an international population.

PURPOSE: Outcome prediction for patients with renal cell carcinoma is based on a combination of factors. In this study a previously published clinical outcome algorithm based on 1997 T stage, Fuhrman grade and performance score is validated using an international database. MATERIALS AND METHODS: A total of 1,060 patients from Nijmegen, the Netherlands (NN), MD Anderson (MDA) and University of California, Los Angeles (UCLA) who had localized renal cell carcinoma were evaluated for outcome prediction using a clinical outcome algorithm previously shown to stratify patients into low, intermediate and high risk groups. Validation was performed by comparing the 3 risk groups separately within the 3 centers as well as by comparing hazard ratios and concordance indices among the 3 centers. RESULTS: Estimated disease specific survival rates at 5 years for the low risk groups were 94% (NN), 92% (MDA) and 93% (UCLA). The 5-year disease specific survival rates for the intermediate risk groups were 65% (NN), 73% (MDA) and 78% (UCLA), while the rates for the high risk groups were 40% (NN), 30% (MDA) and 48% (UCLA). The concordance indices for each of the databases were 79% (NN), 86% (MDA) and 84% (UCLA). CONCLUSIONS: A clinical algorithm that uses only 3 prognostic variables (1997 T stage, Fuhrman grade and performance status) to stratify patients with localized renal cell carcinoma into 3 risk groups has been shown to be applicable to external databases. This algorithm may be useful for patient counseling, surveillance and identification of high risk patients for enrollment in clinical trials.

Paraneoplastic signs and symptoms of renal cell carcinoma: implications for prognosis.

PURPOSE: Renal cell carcinoma (RCC) can present with a wide range of signs and symptoms. To our knowledge we report the first study to describe the frequency of paraneoplastic findings in a modern RCC series and assess the prognostic significance of each finding. MATERIALS AND METHODS: Using the kidney cancer database at our institution 1,046 patients undergoing nephrectomy for RCC between 1989 and 2001 were assessed. The prognostic significance of symptoms present at diagnosis and findings on preoperative laboratory evaluation were examined in a univariate analysis as well as on multivariate analysis controlling for TNM stage, Fuhrman grade and Eastern Cooperative Oncology Group performance status (ECOG-PS). RESULTS: Mean followup to date of death or last contact for all patients was 40.3 months. Median time to death was 19.3 months. Most paraneoplastic signs and symptoms correlated with poor survival, although on multivariate analysis hypoalbuminemia, weight loss, anorexia and malaise predicted shorter survival. The frequency of each of these findings was 19.9%, 22.9%, 10.6% and 19.1%, respectively. Cachexia, defined as the presence of at least 1 of these findings, was noted in 35.3% of patients. Cachexia did not predict a higher recurrence rate in patients with localized disease and only malaise correlated with a decreased likelihood of responding to immunotherapy. CONCLUSIONS: Cachexia, defined as hypoalbuminemia, weight loss, anorexia or malaise, predicts worse survival after controlling for well established indicators of prognosis (TNM stage, Fuhrman grade and ECOG-PS). Consideration should be given to expanding the ECOG-PS to include measures for cachexia when applied to patients with RCC.