Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma.

PURPOSE: To describe survival in previously treated patients with metastatic renal cell carcinoma (RCC) who are candidates for clinical trials of new agents as second-line therapy. PATIENTS AND METHODS: The relationship between pretreatment clinical features and survival was studied in 251 patients with advanced RCC treated during 29 consecutive clinical trials between 1975 and 2002. Clinical features were first examined in univariate analyses, and then a stepwise modeling approach based on Cox regression was used to form a multivariate model. RESULTS: Median survival for the 251 patients was 10.2 months and differed according to year of treatment, with patients treated after 1990 showing longer survival. In this group, the median overall survival time was 12.7 months. Because the purpose of this analysis was to establish prognostic factors for present-day clinical trial design, prognostic factor analysis was performed on these patients. Pretreatment features associated with a shorter survival in the multivariate analysis were low Karnofsky performance status, low hemoglobin level, and high corrected serum calcium. These were used as risk factors to categorize patients into three different groups. The median time to death in patients with zero risk factors was 22 months. The median survival in patients with one of these prognostic factors was 11.9 months. Patients with two or three risk factors had a median survival of 5.4 months. CONCLUSION: Treatment with novel agents during a clinical trial is indicated for patients with metastatic RCC after progression to cytokine treatment. Three prognostic factors for predicting survival were used to categorize patients into risk groups. These risk categories can be used in clinical trial design and interpretation.     

Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma.

PURPOSE: To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma (RCC) treated with interferon-alfa as initial systemic therapy. The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy. PATIENTS AND METHODS: Four hundred sixty-three patients with advanced RCC administered interferon-alpha as first-line systemic therapy on six prospective clinical trials were the subjects of this retrospective analysis. Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model. RESULTS: The median overall survival time was 13 months. The median time to progression was 4.7 months. Five variables were used as risk factors for short survival: low Karnofsky performance status, high lactate dehydrogenase, low serum hemoglobin, high corrected serum calcium, and time from initial RCC diagnosis to start of interferon-alpha therapy of less than one year. Each patient was assigned to one of three risk groups: those with zero risk factors (favorable risk), those with one or two (intermediate risk), and those with three or more (poor risk). The median time to death of patients deemed favorable risk was 30 months. Median survival time in the intermediate-risk group was 14 months. In contrast, the poor-risk group had a median survival time of 5 months. CONCLUSION: Progression-free and overall survival with interferon-alpha treatment can be compared with new therapies in phase II and III clinical investigations. The prognostic model is suitable for risk stratification of phase III trials using interferon-alpha as the comparative treatment arm.     

Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy

BACKGROUND: Therapy targeted against the vascular endothelial growth factor (VEGF) pathway is a standard of care for patients with metastatic renal cell carcinoma (RCC). The identification of patients who are more likely to benefit from these agents is warranted. METHODS: In total, 120 patients with metastatic clear-cell RCC received bevacizumab, sorafenib, sunitinib, or axitinib on 1 of 9 prospective clinical trials at the Cleveland Clinic. Clinical features associated with outcome were identified by univariate analysis; then, a stepwise modeling approach based on Cox proportional hazards regression was used to identify independent prognostic factors and to form a model for progression-free survival (PFS). A bootstrap algorithm was used to provide internal validation. RESULTS: The overall median PFS was 13.8 months, and the objective response according to the Response Criteria in Solid Tumors was 34%. Multivariate analysis identified time from diagnosis to current treatment <2 years; baseline platelet and neutrophil counts >300 K/microL and >4.5 K/microL, respectively; baseline corrected serum calcium <8.5 mg/dL or >10 mg/dL; and initial Eastern Cooperative Oncology Group performance status >0 as independent, adverse prognostic factors (PF) for PFS. Three prognostic subgroups were formed based on the number of adverse prognostic factors present. The median PFS in patients with 0 or 1 adverse prognostic factor was 20.1 months compared with 13 months in patients with 2 adverse prognostic factors and 3.9 months in patients with >2 adverse prognostic factors. CONCLUSIONS: Five independent prognostic factors for predicting PFS were identified and were used to categorize patients with metastatic RCC who received VEGF-targeted therapies into 3 risk groups. These prognostic factors can be incorporated into patient care and clinical trials that use such novel, VEGF-targeted agents.     

Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma.

PURPOSE: To evaluate the relationship between treatment with cytokine therapy and survival, investigate the effect of nephrectomy on survival, and identify long-term survivors among a cohort of 670 patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: A total of 670 patients with advanced RCC treated on 24 clinical trials of systemic chemotherapy or cytokine therapy were the subjects of this retrospective analysis. Treatment was categorized as cytokine (containing interferon alfa and/or interleukin-2) in 396 patients (59%) and as chemotherapy (cytotoxic or hormonal therapy) in 274 (41%). Among the 670 patients, those with survival times of greater than 5 years were identified as long-term survivors. RESULTS: Patients treated with cytokine therapy had a longer survival time than did those treated with chemotherapy, regardless of the year of treatment or risk category based on pretreatment features. The median survival times for favorable-, intermediate-, and poor-risk patients were 27, 12, and 6 months for those treated with cytokines and 15, 7, and 3 months for those treated with chemotherapy, respectively. The magnitude of difference in median survival was greater in the favorable- and intermediate-risk groups. The median survival time was less than 6 months in the poor-risk group for both treatment programs. Median survival time was 14 months among patients with prior nephrectomy plus time from diagnosis to treatment greater than 1 year versus 8 months among those with time from diagnosis to treatment less than 1 year, regardless of pretreatment nephrectomy status. Thirty patients (4.5%) among the 670 patients were identified as long-term survivors; 12 were free of disease after nephrectomy and treatment with interferon alfa, interleukin-2, or surgical resection of metastasis. CONCLUSION: The low proportion of patients with advanced RCC who achieve long-term survival emphasizes the need for clinical investigation to identify more effective therapy.     

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.     

Clinical outcome and prognostic survival factors in patients with advanced renal cell carcinoma treated with very low-dose interleukin-2, interferon-α, and tegafur-uracil: a single-institution experience

BACKGROUND: The objective of the current study was to determine the efficacy and safety of very low-dose interleukin-2 (IL-2), interferon (IFN)-alpha, and tegafur-uracil for patients with unresectable renal cell carcinoma (RCC), metastatic RCC, or both. Clinical prognostic factors were also investigated. METHODS: Fifty consecutive patients underwent a 3-week treatment cycle of IL-2 (0.7 x 10(6) Japanese reference units [JRU])/person on days 1-3 weekly), IFN-alpha (3 x 10(6) international units/person, on days 1-5 weekly), and tegafururacil (300 mg/person daily). RESULTS: The median follow-up after treatment initiation was 11.3 months. A median of three (range, 1-20) treatment cycles was administered. Of 47 eligible patients, 4 had a treatment response (3 complete responses and 1 partial response; objective response rate, 8.5%). The median progression-free and overall survivals were 8.3 months (95% confidence interval [CI], 5.5-10.9 months) and 38.8 months (95% CI, 27.8-49.7 months), respectively. Only 8 patients had grade III/IV toxicities. Two parameters, i.e., the absence of a previous nephrectomy and a low hemoglobin level, were identified as independent factors predictive of poor survival. Patients with low or intermediate risk (presence of none or one of the two prognostic factors) had a durable median survival exceeding 30 months. High-risk patients with both risk factors had rapid disease progression despite treatment. CONCLUSION: While the effectiveness of this immunochemotherapy resulted in a limited antitumor response, low-and intermediate-risk patients with metastatic RCC seemed likely to have a survival benefit. Patient selection is essential to enhance treatment efficiency and avoid useless treatment for high-risk patients.     

A new prognostic classification for overall survival in Asian patients with previously untreated metastatic renal cell carcinoma

The aims of the present study were to: (i) develop a clinically useful prognostic classification in Asian patients with metastatic renal cell carcinoma (RCC) by combining metastatic features with several pretreatment parameters; and (ii) evaluate the validity of this prognostic classification. Baseline characteristics and outcomes were collected for 361 patients who underwent interferon‐α‐based therapy between 1995 and 2005. Relationships between overall survival (OS) and potential prognostic factors were assessed using Cox's proportional hazard model. The predictive performance of the model was evaluated using bootstrap resampling procedures and by using an independent dataset obtained from randomly selected institutions. The predictive accuracy was measured using the concordance index (c‐index). Four factors were identified as independent prognostic factors: time from initial diagnosis to treatment, anemia, elevated lactate dehydrogenase (LDH), and poor prognostic metastatic group (liver only, bone only, or multiple organ metastases). Each patient was assigned to one of three risk groups: favorable risk (none or one factor; n = 120), in which median OS was 51 months; intermediate risk (two factors; n = 101), in which median OS was 21 months; and poor risk (three or four factors; n = 102), in which median OS was 10 months. The c‐index was 0.72 in the original dataset and 0.72 in 500 random bootstrap samples. In the independent dataset for external validation, the c‐index was 0.73. Thus, the new prognostic classification is easily applicable for Asian patients with previously untreated metastatic RCC and should be incorporated into patient care, as well as clinical trials performed in Asia.     

Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma.

PURPOSE: To validate the Motzer et al prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma (RCC) and to identify additional independent prognostic factors. PATIENTS AND METHODS: Data were collected on 353 previously untreated metastatic RCC patients enrolled onto clinical trials between 1987 and 2002. RESULTS: Four of the five prognostic factors identified by Motzer were independent predictors of survival. In addition, prior radiotherapy and presence of hepatic, lung, and retroperitoneal nodal metastases were found to be independent prognostic factors. Using the number of metastatic sites as surrogate for individual sites (none or one v two or three sites), Motzer's definitions of risk groups were expanded to accommodate these two additional prognostic factors. Using this expanded criteria, favorable risk is defined as zero or one poor prognostic factor, intermediate risk is two poor prognostic factors, and poor risk is more than two poor prognostic factors. According to Motzer's definitions, 19% of patients were favorable risk, 70% were intermediate risk, and 11% were poor risk; median overall survival times for these groups were 28.6, 14.6, and 4.5 months, respectively (P < .0001). Using the expanded criteria, 37% of patients were favorable risk, 35% were intermediate risk, and 28% were poor risk; median overall survival times of these groups were 26.0, 14.4, and 7.3 months, respectively (P < .0001). CONCLUSION: These data validate the model described by Motzer et al. Additional independent prognostic factors identified were prior radiotherapy and sites of metastasis. Incorporation of these additional prognostic factors into the Motzer et al model can help better define favorable risk, intermediate risk, and poor risk patients.     

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma

BACKGROUND: Lenalidomide (LEN) is a structural and functional analogue of thalidomide that has demonstrated enhanced immunomodulatory properties and a more favorable toxicity profile. A Phase II, open-label study of LEN in patients with metastatic renal cell carcinoma (RCC) was conducted to determine its safety and clinical activity. METHODS: Patients with metastatic RCC received LEN orally at a dose of 25 mg daily for the first 21 days of a 28-day cycle. The primary endpoint was the objective response rate. Time to treatment failure, safety, and survival were secondary endpoints. RESULTS: In total, 28 patients participated in the trial and were included in the current analysis. Three of 28 patients (11%) demonstrated partial responses and continued to be progression-free for >15 months. Eleven patients (39%) had stable disease that lasted >3 months, including 8 patients who had tumor shrinkage. In total, 6 patients (21%) remained on the trial, and 5 additional patients continued to be followed for survival. The median follow-up for those 11 patients was 13.5 months (range, 8.3-17.0 months). The median survival had not been reached at the time of the current report. Serious adverse events included fatigue (11%), skin toxicity (11%), and neutropenia (36%). CONCLUSIONS: LEN demonstrated an antitumor effect in metastatic RCC, as evidenced by durable partial responses. LEN toxicities were manageable. Further studies will be required to assess the overall activity of LEN in patients with metastatic RCC.     

Feasibility of prolonged use of interferon-alpha in metastatic kidney carcinoma: a phase II study

BACKGROUND: Interferon-alpha has proven effective in the treatment of metastatic renal cell carcinoma. However, the optimal schedule has not yet been determined. The authors have studied the efficacy and toxicity of prolonged use interferon-alpha2a (IFN-alpha) in metastatic renal cell carcinoma (RCC). Interferon-alpha was administered intermittently for outpatients. METHODS: Seventy-five patients with metastatic RCC without prior biochemotherapy were treated. During the first month, the IFN-alpha dose was increased from 4.5 to 18 million units (MU) 3 times a week to define the individual maximal tolerated dose for each patient. The treatment was continued at the maximal tolerated dose with a 1-week pause each month until either progression or intolerable toxicity was observed or up to 2 years. RESULTS: The overall response rate (5 complete response [CRs] and 8 partial responses [PRs]) was 17% (95% confidence interval, 10-28%). Stable disease was observed in 32 patients (43%). Three late objective responses (4%) occurred after 12 months treatment. The median progression free time of all patients was 12.3 months, and median survival time was 19.3 months. The median duration of response in CR/PR patients was 16 months. In multivariate analysis independent prognostic factors were poor performance status (P = 0.004), presence of bone metastases (P = 0.001), and time to metastases less than 24 months (P = 0.003), which predicted poor survival. Six patients (8%) discontinued the treatment because of fatigue, elevation of liver enzymes, or cardiac arrhythmias. No life-threatening side effects were observed. CONCLUSIONS: Prolonged and intermittently administered IFN-alpha2a three times per week in 3 weekly cycles in metastatic RCC is a feasible and effective therapy. A prolonged treatment duration of more than 12 months for stable and responding patients is beneficial and may improve the outcome of patients with RCC.     

Treatment outcome for metastatic papillary renal cell carcinoma patients

BACKGROUND: Most clinical trial reports in metastatic renal cell carcinoma (RCC) do not distinguish between histologic subtypes, making it difficult to assess specific treatment efficacy. The current retrospective study sought to define clinical features and outcome data for metastatic papillary RCC. METHODS: Clinical features, treatment outcome, and survival were evaluated in 38 patients with metastatic papillary RCC who underwent clinical evaluation at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1985 and 2005. Twenty-three of 513 individuals were identified from a clinical trial database, 14 of 1895 from a surgery database, and 1 of 357 from a pathology database. A literature review of systemic therapy in metastatic papillary RCC was performed. RESULTS: Among the 38 patients, 30 had been treated at MSKCC with various systemic therapies, including cytokines. Twelve therapies resulted in stable disease, 30 in initial progression of disease, and 1 in an unknown response. One patient had a partial response to sunitinib, a novel multitargeted tyrosine kinase inhibitor. The median overall survival time for the entire study group was 8 months (95% confidence interval, 5-12). A literature review on treatment of metastatic papillary RCC produced 4 reports, confirming a lack of efficacy for systemic therapy. CONCLUSIONS: A resistance to systemic therapy characterizes patients with metastatic papillary RCC. Further understanding of the genetics and molecular biology and subtypes involved may provide the basis for more effective agents. Treatment with targeted therapies or other experimental agents is warranted.     

Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma.

PURPOSE: To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics. RESULTS: CCI-779 produced an objective response rate of 7% (one complete response and seven partial responses) and minor responses in 26% of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779-related adverse events of all grades were maculopapular rash (76%), mucositis (70%), asthenia (50%), and nausea (43%). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar. CONCLUSION: In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested.     

Metastatic renal carcinoma long-term survivors treated with s.c. interferon-alpha and s.c. interleukin-2

AIM: The aim of this retrospective analysis was to identify common features of long-term survivors among 218 advanced renal cell carcinoma patients sequentially entered on subcutaneous-recombinant-cytokine- based therapies between 1988 and 1993. PATIENTS AND METHODS: All patients were treated with subcutaneous (s.c.) interferon-alpha2a (IFN-alpha2a) and s.c. interleukin-2 (IL-2) alone (n = 98 pts) or in combination with intravenous (i.v.) 5-fluorouracil (5-FU) (Atzpodien regimen; n = 120 pts); those patients who survived more than 10 years were classified as long-term survivors. RESULTS: Thirteen patients (6.3%) were identified as long-term survivors with a median follow-up of 141 months (range, 122-174 months). According to a validated model of known clinical predictors, the long-term survivor group consisted of 6 low-risk, 5 intermediate-risk, and 2 high-risk patients, respectively. Within their clinical course, 9 longterm survivors achieved a complete response with a median duration of 141 months (range, 91-161 months), 1 patient yielded a partial remission, and 3 patients achieved stable disease. Maximum response was observed between 2 and 40 months after treatment initiation (median, 4 months), while treatment time to maximum response ranged from 2 to 14 months (median, 4 months). There was no correlation between treatment time and maximum response. Overall, long-term survivors underwent treatment for 4 and up to 80 months (median, 8 months). CONCLUSION: Our data suggest that long-term survival of metastatic renal carcinoma patients beyond 10 years is independent of known clinical risk factors and treatment time. However, long-term survival of cytokine-treated, advanced renal cell carcinoma (RCC) patients remains a rare event and, thus, emphasizes the need for further investigations toward more effective therapies.     

Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology.

PURPOSE: To define outcome data for patients with metastatic renal cell carcinoma (RCC) with histology other than clear-cell type, including collecting duct (or medullary carcinoma), papillary, chromophobe, and unclassified histologies. PATIENTS AND METHODS: Sixty-four patients with metastatic non-clear-cell RCC histology were the subjects of this retrospective review. Included in the analysis were 22 (8%) of 286 patients from a clinical trials database, 19 of 1,166 patients from a surgery database, and 23 of 357 patients from a pathology database. RESULTS: The prevalent histology was collecting duct, present in 26 (41%) patients. The number of patients with chromophobe and papillary histologies was 12 (19%) and 18 (28%), respectively. Eight (12%) of the patients had tumors that could not be classified for specific tumor histology. Among the 43 patients treated with 86 systemic therapies, including 37 cytokine therapies, two patients (5%) were observed to have a partial response. The median overall survival time was 9.4 months (95% confidence interval, 8 to 14 months). The survival was longer for patients with chromophobe tumors compared with collecting duct or papillary histology, and this group included four patients with survival of greater than 3 years. CONCLUSION: RCC consists of a heterogeneous group of tumors including clear-cell, papillary, chromophobe, collecting duct, and unclassified cell types. Non-clear-cell histologies constitute less than 10% of patients in general populations of patients with advanced RCC treated on clinical trials. Metastatic non-clear-cell RCC is characterized by a resistance to systemic therapy and poor survival, with the survival for patients with chromophobe tumors longer than that for patients with metastatic collecting duct or papillary RCC. Treatment with novel agents on clinical trials is warranted.     

Characteristics of metastasis as a prognostic factor for immunotherapy in metastatic renal cell carcinoma

AIMS AND BACKGROUND: This study aimed to evaluate the significance of characteristics of metastasis as prognostic factors in metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: A total of 148 patients who had received immunotherapy were included in the study. Patients were categorized in various ways according to the characteristics of metastasis, including a synchronous metastasis group (n = 77) vs a metachronous metastasis group (n = 71), and a solitary metastasis group (n = 93) vs a multiple metastases group (n = 55). RESULTS: In the synchronous and metachronous metastasis groups, median progression-free survival was 4.3 months (95% confidence interval [CI] 2.9-5.7) and 11.1 months (95% CI 6.7-15.5), respectively (P = 0.004). Median overall survival was 17.1 months (95% CI 9.5-24.7) and 54.8 months (95% Cl 38.371.3) in the two groups (P = 0.019). In the solitary and multiple metastasis groups, median progression-free survival was 11.0 months (95% CI 6.6-15.5) and 3.9 months (95% CI 2.6-5.2), respectively (P <0.001). Median overall survival was 55.2 months (95% CI 50.7-59.7) and 15.6 months (95% CI 10.9-20.3) in the two groups (P <0.001). Multivariate Cox proportional hazards model analysis using the clinical variables showed that T stage (P = 0.026), number of metastatic sites (P = 0.009) and time to metastasis (P = 0.019) were independent predictors of progression-free survival. Using the same variables, only the number of metastatic sites was an independent prognostic predictor of overall survival (P = 0.014). CONCLUSIONS: Our findings suggest that the time to metastasis and the number of metastases are important prognostic factors in metastatic RCC.     

Overall survival of first‐line axitinib in metastatic renal cell carcinoma: Japanese subgroup analysis from phase II study

Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression‐free survival of 27.6 months in treatment‐naïve Japanese patients with metastatic renal cell carcinoma (RCC). This analysis evaluated overall survival (OS) and safety in 44 Japanese patients and compared the results with 169 non‐Japanese patients. In addition, baseline characteristics for predictive factors that may influence OS in first‐line metastatic RCC were explored in all patients using a Cox proportional hazard model. With median follow‐up of 33 months, fewer than half (16 of 44) of the Japanese patients had died and median OS was not reached (95% confidence interval [CI], 38.8 months–not estimable), whereas 107 of 169 (63%) non‐Japanese patients had died and median OS was 33.9 months (95% CI, 28.9–42.7). Estimated 1‐year, 2‐year and 3‐year survival probability (95% CI) was 86.4% (76.2–96.5), 75.0% (62.2–87.8) and 68.2% (54.4–81.9), respectively, in Japanese patients, and was higher than that in non‐Japanese patients (75.1% [68.4–81.8], 62.1% [54.5–69.7] and 47.2% [39.3–55.1], respectively). The updated safety analysis did not reveal any new adverse events of concern among Japanese or non‐Japanese patients. The multivariate analysis identified that lower baseline Eastern Cooperative Oncology Group performance status, lower baseline tumor burden, and longer time from histopathological diagnosis to treatment were significant positive predictors of OS. The current analysis confirmed the clinical activity of axitinib in treatment‐naïve Japanese patients with metastatic RCC, with an acceptable toxicity profile.     

Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy.

PURPOSE: Metastatic renal cell carcinoma (RCC) has a poor prognosis and an unpredictable course. To date, there are no molecular markers which can reliably predict RCC outcome. We investigated whether a novel kidney cancer marker, carbonic anhydrase IX (CAIX), is associated with progression and survival. EXPERIMENTAL DESIGN: Immunohistochemical analysis using a CAIX monoclonal antibody was performed on tissue microarrays constructed from paraffin-embedded specimens from patients (N = 321) treated by nephrectomy for clear cell RCC. CAIX staining was correlated with response to treatment, clinical factors, pathologic features, and survival. RESULTS: CAIX staining was present in 94% of clear cell RCCs. Survival tree analysis determined that a cutoff of 85% CAIX staining provided the most accurate prediction of survival. Low CAIX (相似文献   

Prognostic factors associated with long-term survival in previously untreated metastatic renal cell carcinoma.

PURPOSE: To identify prognostic factors (PF) for long-term survival in metastatic renal cell carcinoma (RCC) patients. METHODS: We retrospectively reviewed a metastatic RCC database at the Cleveland Clinic Foundation consisting of 358 previously untreated patients who were enrolled in institutional review board-approved clinical trials of immunotherapy and/or chemotherapy at our institution from 1987 to 2002. In order to identify patient characteristics associated with long-term survival, we compared 226 'short-term' survivors [defined as overall survival (OS) <2 years] with 31 'long-term' survivors (OS >or=5 years). RESULTS: Using logistic regression models, four adverse PF were identified as independent predictors of long-term survival: hemoglobin less than the lower limit of normal, greater than two metastatic sites, involved kidney (left), and Eastern Cooperative Oncology Group (ECOG) performance status (PS). Using the number of poor prognostic features present, three distinct risk groups could be identified. Patients with 0 or 1 adverse prognostic feature present had an observed likelihood of long-term survival of 32% (21/66) compared with 9% (8/91) for patients with two adverse features present and only 1% (1/93) for patients with more than two adverse features. CONCLUSIONS: Independent predictors of long-term survival in previously untreated metastatic RCC include baseline hemoglobin level, number of involved sites, involved kidney, and ECOG PS. Incorporation of these factors into a simple prognostic scoring system enables three distinct groups of patients to be identified.     

Renal cell carcinoma with retroperitoneal lymph nodes. Impact on survival and benefits of immunotherapy

BACKGROUND: The current study was performed to determine the impact of the presence of retroperitoneal lymphadenopathy on the survival and response to immunotherapy of patients with metastatic renal cell carcinoma (RCC). METHODS: A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical, and pathologic data from 1087 patients. Patients with RCC who did not present with metastatic disease, who did not undergo nephrectomy as part of their cancer treatment, and those in whom either the lymph node (N) or metastatic (M) status was unknown, were excluded. A total of 322 M1 patients who met these criteria and who underwent nephrectomy for unilateral RCC formed the principal study population. RESULTS: Two hundred thirty-six patients presented with N0M1 disease and 86 patients presented with N+M1 disease. In M1 patients, the presence of positive regional lymph nodes was associated with larger sized, higher grade, locally advanced primary tumors that were more commonly associated with sarcomatoid features. N0M1 patients were more likely to achieve an objective response to systemic immunotherapy compared with N+M1 patients (P = 0.01). N+M1 patients overall had worse short-term and long-term survival compared with N0M1 patients, with a median survival of 10.5 months compared with 20.4 months, respectively. The median survival of N0M1 patients was improved to 28 months in those who received adjunctive immunotherapy (P = 0.0008), whereas the median survival of patients with N+M1 disease was the same in those treated with and those treated without adjunctive immunotherapy (P = 0.18). CONCLUSIONS: Even in the modern era of systemic immunotherapy, the presence of regional lymphadenopathy exerts a detrimental effect on the survival of patients with metastatic RCC. Lymph node status is a strong predictor of the failure to achieve either an objective immunotherapy response or an improvement in survival when immunotherapy is given as an adjunctive treatment after cytoreductive nephrectomy. However, in multivariate analysis, including both clinical and pathologic variables, lymph node status was found to have less of an impact on survival than primary tumor stage and grade and patient performance status.     

Stage migration and increasing proportion of favorable‐prognosis metastatic renal cell carcinoma patients

BACKGROUND:

The Memorial Sloan‐Kettering Cancer Center risk model classifies patients with metastatic renal cell carcinoma (RCC) by 5 pretreatment features as favorable, intermediate, and poor risk. The number of Memorial Sloan‐Kettering Cancer Center patients in each risk group was examined by year of treatment to analyze stage migration.

METHODS:

The distribution of risk groups was examined retrospectively in 789 Memorial Sloan‐Kettering Cancer Center patients with metastatic RCC treated in a first‐line therapy clinical trial from 1975 to 2007. Date of treatment onset was divided into 6 cohorts between 1975 and 2007 (1975‐1980, 1981‐1985, 1986‐1990, 1991‐1995, 1996‐2001, and 2001‐2007).

RESULTS:

The median age of the first‐line metastatic RCC clinical trial patients was 59 years (range, 20‐82 years). Most patients received cytokine therapy (55%), 37% received chemotherapy/other, and 8% received vascular endothelial growth factor‐targeted therapies. Overall survival increased with each consecutive cohort year group (P < .001). Median survival was 0.43 years (95% confidence interval [CI], 0.27‐0.68) in the 1973‐1980 cohort and 1.5 years in the 2001‐2007 cohort (95% CI, 1.15‐2.11). Memorial Sloan‐Kettering Cancer Center risk‐group distribution shifted between 1975 and 2007 (P < .0001). The poor‐risk group proportion became smaller (from 44% in 1975‐1980 to 13% in 2001‐2007), whereas the favorable‐risk group increased (from 0% in 1975‐1980 to 49% in 2001‐2007). The intermediate‐risk group remained stable at 50%. After adjusting for type of therapy, the shifts continue to be significant (P < .0001).

CONCLUSIONS:

The risk‐group distribution for metastatic RCC patients in clinical trials shifted from 1975 to 2007. These shifts have direct implications for data analysis, interpretation of metastatic RCC trends, and drug development. Cancer 2010. © 2010 American Cancer Society.