Cytoreductive nephrectomy for metastatic renal cell carcinoma with nonclear cell histology

PURPOSE: To our knowledge the benefit of cytoreductive surgery for patients with metastatic renal cell carcinoma with nonclear cell histology is unknown. In this retrospective study we report our experience with cytoreductive nephrectomy for nonclear cell metastatic renal cell carcinoma at M. D. Anderson Cancer Center. We compared the outcomes with those in patients with clear cell metastatic renal cell carcinoma. MATERIALS AND METHODS: From 1991 to 2006, 606 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy and they formed the basis of this report. Of these patients 92 had nonclear cell metastatic renal cell carcinoma. The remaining 514 patients had clear cell metastatic renal cell carcinoma and they formed a comparative group. Multivariate Cox regression analysis was performed to evaluate the relationship between clinical variables and histology (clear cell vs nonclear cell) on disease specific survival. RESULTS: Compared with patients with clear cell histology those with nonclear cell metastatic renal cell carcinoma were younger (p = 0.0001), and more likely to have nodal metastases (p <0.0001) and sarcomatoid features (23% vs 13%, p = 0.026). On multivariate analysis median disease specific survival in patients with nonclear cell histology was significantly worse than that in patients with clear cell metastatic renal cell carcinoma (9.7 vs 20.3 months, p = 0.0003) even after adjusting for T stage, grade, performance status, age and sarcomatoid features. Sarcomatoid features were a predictor of poor outcome in cases of clear and nonclear cell histology, although even in the absence of sarcomatoid features nonclear cell histology was associated with worse disease specific survival (p = 0.017). Interestingly although there was a significantly higher incidence of positive nodes in patients with nonclear histology (p <0.0001), this phenotype was not associated with a worse disease specific survival, as it was in those with clear cell histology (p = 0.0001). In fact, patients with node negative disease with nonclear cell histology had the worst prognosis overall in the entire group. CONCLUSIONS: Patients with nonclear cell metastatic renal cell carcinoma were younger and had a higher incidence of nodal metastases, a higher incidence of sarcomatoid features and a worse prognosis than those with clear cell histology who underwent cytoreductive surgery.     

Results of radical nephrectomy for renal cell carcinoma. Report 1. Analysis according to the TNM staging system of the general rule for clinical and pathological studies on renal cell carcinoma

One hundred and six patients with renal cell carcinoma were treated with radical nephrectomy at our Department between 1970 to December, 1985. A retrospective analysis was performed with TNM staging system of The General Rule for Clinical and Pathological Studies on Renal Cell Carcinoma, which was established by the Japanese Urological Association in 1983. The 5-year survival rate according to pathological T-stage was 100% for 2 patients in pT1, 67.5% for 58 patients in pT2, 49.5% for 42 patients in pT3, 0% for 4 patients in pT4. Two patients in stage of pT1 had no venous involvement, lymph node metastasis, or distant metastasis. Twenty two patients had positive venous involvement (21%), 4 (7%) in stage of pT2, 16 (38%) in pT3, 2 (50%) in pT4. Twelve patients had positive lymph nodes (11%), 0 (0%) in stage of pT2, 10 (24%) in pT3, 2 (50%) in pT4. Twenty five patients, (24%) had distant metastasis at the time of nephrectomy, 8 (14%) in stage of pT2, 15 (38%) in pT3, 2 (50%) in pT4. The 5-year survival of 22 patients with venous involvement, 12 patients with lymph nodes metastasis, 25 patients with distant metastasis were 47%, 30%, 39% respectively. No significant difference of 5-year survival between 69% of 48 patients in T1 & 2VoNoMo (Robson-I) and 76% of 12 patients in T3VoNoMo (Robson-II) were considered to need the establishment of new classification for early stage of renal cell carcinoma. TNM staging system was thought to be better than Robson's Classification for analyzing the unique biological potential of renal cell carcinoma.     

索拉非尼治疗具有肉瘤样分化的转移性肾癌的疗效观察

目的 分析索拉非尼治疗具有肉瘤样分化的转移性肾癌的疗效.方法 已行肾脏原发肿瘤切除的转移性肾细胞癌患者14例,病理证实原发肿瘤中含有肉瘤样分化成分.平均年龄61(45～77)岁.肾透明细胞癌伴肉瘤样分化8例,乳头状癌伴肉瘤样分化2例,单纯肉瘤样癌4例,肾原发病灶中肉瘤样成分比例为20%～100%.肿瘤转移部位分别为肺、淋巴结、肾上腺、肝或骨.采用索拉非尼400 mg或600 mg,2次/d治疗.采用Kendall相关检验和Pearson相关检验分别检测肉瘤样成分比例与治疗客观反应及中位无疾病进展时间(PFS)的相关性.中位治疗时间8(3～19)个月.结果 部分缓解(PR)2例,其转移病灶均位于腹膜后及纵隔淋巴结,肉瘤样成分比例分别为100%和20%;疾病稳定(SD)7例,转移部位包括肺、淋巴结、肾上腺、骨和肝;疾病进展(PD)5例,总疾病控制率为64%.随访至2009年7月,出现PD 9例,PFS 6(0～19)个月.肉瘤样成分比例与治疗的客观反应及PFS均无相关性(P=0.247,P=0.554).结论 索拉非尼常规剂量治疗具有肉瘤样分化的转移性肾细胞癌有一定疗效,但客观有效率及PFS与肉瘤样成分的比例无明显相关性.     

A protocol for performing extended lymph node dissection using primary tumor pathological features for patients treated with radical nephrectomy for clear cell renal cell carcinoma

PURPOSE: We determined the primary pathological features of clear cell renal cell carcinoma that are predictive of positive regional lymph nodes at radical nephrectomy (RN) and developed a protocol for the selective use of extended lymph node dissection. MATERIALS AND METHODS: We studied 1,652 patients who underwent RN for unilateral pM0 sporadic clear cell renal cell carcinoma between 1970 and 2000. A multivariate logistic regression model was used to determine the pathological features of the primary tumor that were associated with positive regional lymph nodes at RN. RESULTS: There were 887 (54%) patients with no positive nodes (pN0), 57 (3%) with 1 positive node (pN1), 11 (1%) with 2 or more positive nodes (pN2) and 697 (42%) who did not have any lymph nodes dissected (pNx). Nuclear grade 3 or 4 (p <0.001), presence of a sarcomatoid component (p <0.001), tumor size 10 cm or greater (p = 0.005), tumor stage pT3 or pT4 (p = 0.017) and histological tumor necrosis (p = 0.051) were significantly associated with positive regional lymph nodes in a multivariate setting. These features can be used to identify candidates for extended lymph node dissection at the time of RN. For example, only 6 (0.6%) of the 1,031 patients with 0 or 1 of these features had positive lymph nodes at RN compared with 62 (10%) of the 621 patients with at least 2 of these features. CONCLUSIONS: The primary tumor pathological features of nuclear grade, sarcomatoid component, tumor size, stage and presence of tumor necrosis can be used to predict patients at the greatest risk for regional lymph node involvement at RN.     

Stage pT1 conventional (clear cell) renal cell carcinmoa: pathological features associated with cancer specific survival.

PURPOSE: The features predictive of aggressive behavior in stage pT1 conventional (clear cell) renal cell carcinoma are not completely known. We evaluated pathological features in a large series of stage pT1 conventional renal cell carcinoma cases and examined the association of these features with cancer specific survival. MATERIALS AND METHODS: Patients with solitary stage pT1 conventional renal cell carcinoma who underwent radical nephrectomy between 1970 and 1997 were eligible for study. For each of the 46 patients who died of renal cell carcinoma we selected a stratified random sample of at least 3 year matched controls who were still alive or dead of other causes. The study included 277 patients. We evaluated patient age at nephrectomy, sex, tumor size, Fuhrman grade, necrosis and sarcomatoid component. Univariate and multivariate Cox proportional hazards models were fit to assess the features associated with cancer specific survival. RESULTS: Multivariate modeling revealed that tumor size, Fuhrman grade and necrosis were jointly significantly associated with cancer specific survival. Of the 4.5, 5 and 6 cm. tumor size cutoffs examined on univariate analysis a cutoff of 5 cm. or greater was most predictive of cancer specific survival. CONCLUSIONS: In stage pT1 conventional renal cell carcinoma Fuhrman grade, tumor necrosis and tumor size together were jointly significantly associated with cancer specific survival. Specifically of the tumor size cutoffs analyzed the 5 cm. cutoff was most predictive of cancer specific survival.     

Prognostic impact of tumor size on pT2 renal cell carcinoma: an international multicenter experience

PURPOSE: The current tumor classification for renal cell carcinoma classifies pT2 tumors as larger than 7 cm in greatest dimension and limited to the kidney. We examined the current pT2 tumor classification of renal cell carcinoma and determined whether a tumor size cutoff exists that would improve prognostic accuracy. MATERIALS AND METHODS: We studied 706 patients with pT2 renal cell carcinoma treated with surgical extirpation at 9 international academic centers. Data collected from each patient included age at diagnosis, gender, 2002 TNM (tumor, node, metastasis) stage, tumor size, nuclear grade, performance status, histological subtype and disease specific survival. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median followup was 52 months. Univariate Cox regression analysis showed a significant association of tumor size with disease specific survival (HR 1.11, p<0.001). An ideal tumor size cutoff of 11 cm was identified, which led to the stratification of 2 groups with respect to disease specific survival (p<0.0001) with 5 and 10-year survival rates of 73% and 65% for pT2 11 cm or less, and 57% and 49% for pT2 larger than 11 cm, respectively. The incidence of metastases was significantly greater in the larger than 11 cm group, while Eastern Cooperative Oncology Group performance status, Fuhrman grade and histological subtype were similar. Multivariate Cox regression analysis retained tumor size as an independent prognostic factor and as the strongest prognostic factor for patients with pT2N0M0 disease. CONCLUSIONS: Our data suggest that the current pT2 classification can be improved by subclassification into pT2a and pT2b based on a tumor size cutoff of 11 cm. Patients in the proposed pT2bN0M0 group are at higher risk for death from renal cell carcinoma and should be considered for adjuvant therapies. External validation is warranted before suggesting change to the TNM classification.     

肾癌的病理类型与预后的关系

目的探讨肾癌的病理类型与预后的关系。方法对315例肾癌患者根据病情选择相应的手术治疗和病理分型,并进行病例随访。以Kaplan-Meier法计算生存率。Cox回归模型对预后影响因子进行分析。结果其中透明细胞癌202例(71.9%),颗粒细胞癌51例(18.1%),混合性腺癌15例(5.3%),乳头状腺癌7例(2.5%),集合管癌4例(1.4%),肉瘤样肾癌2例(0.7%)。Cox回归模型多因素分析显示病理类型可能是一个独立的影响预后的因子。透明细胞癌、颗粒细胞癌和混合性腺癌患者的3年、5年生存率差别无统计学意义。7例乳头状腺癌仅1例死亡。4例集合管癌和2例肉瘤样癌均已死亡,两者平均存活时间分别为6.3和5.5月。结论肾癌的病理分型对预后有一定的预测价值;乳头状腺癌预后优于其他类型肾癌;集合管癌和肉瘤样癌预后较差。     

Surgical management of renal cell carcinoma with vena cava-right atrium thrombus

Historically the presence of a thrombus in vena cava was associated with worse prognosis in patients with renal cell carcinoma, and the effective of surgery limited. However a extensive tumor thrombi can be present without evidence of lymph node and distant metastasis, an aggressive surgical approach with curative intent is justified. We retrospectively reviewed 25 patients with renal cell carcinoma and thrombus in vena cava and they underwent radical nephrectomy and thrombectomy. The IRM allowed to know the level of the thrombus into vena cava in all patients: 56% level I, 8% level II, 26% level III. There were 14 pT3b, 8 pT3c, 3 pT4, and 48% N+. The rate of complications was 36% and there were 4 perioperative death (16%). Patients without lymph node and no distant metastasis had a mean survival of 64% 46%, 37% to 2, 3, 4 years respectively. Patients with lymph node invasive an distant metastasis the prognosis was poor. We no noted correlation between level thrombus and prognosis.     

Renal cell carcinoma invading the urinary collecting system: implications for staging

PURPOSE: Current TNM staging of renal cell carcinoma is based on the tumor propensity for local extension (T), nodal involvement (N) and metastatic spread (M). Locally advanced renal cell carcinoma may involve the perirenal fat, adrenal glands, renal vein, vena cava and/or urinary collecting system. The existing TNM classification does not reflect the ability of renal cell carcinoma to invade the urothelium. We evaluated the incidence and characteristics as well as overall and cancer specific survival of renal cell carcinoma invading the urinary collecting system. METHODS AND MATERIALS: We reviewed pathological findings in 504 kidneys from 475 patients with renal cell carcinoma who presented to our institution in a 3-year period. Urothelial involvement required evidence of gross or histological invasion of the renal calices, infundibulum, pelvis or ureter. Demographic and survival data were obtained from medical records and an institutional cancer registry for tumors invading the urothelium. Stage specific survival data were then compared with tumors not involving the urinary collecting system. RESULTS: Definitive urothelial involvement by the primary tumor was interpretable in 426 of 504 kidneys. Invasion of the collecting system was identified in 61 of 426 cases (14%). Mean diameter of the invading lesions was 10.2 cm. (range 3 to 26). The majority of cases showed clear cell and sarcomatoid histology. Invasion by a papillary lesion was rare. Involvement of the collecting system was most common at the renal poles. Of 61 lesions invading the collecting system 48 (79%) were stage pT3 or greater, while only 13 (21%) were pathologically localized stage pT2 or less. Vascular invasion was identified in 38 renal cell carcinoma cases (62%) with urothelial involvement. A total of 16 cases (26%) were associated with vena caval thrombus. Invading tumors were high Fuhrman grade III or IV in 43 cases (70%). Overall disease specific survival was poor with a median of 19 months. In patients with localized stage pT1 or pT2N0M0 disease and urothelial invasion median disease specific survival was 46 months. CONCLUSIONS: Renal cell carcinoma lesions involving the renal collecting system are characteristically large, high grade and high stage. Clear cell carcinoma most commonly invades, while invasion by papillary tumors is rare. Overall the prognosis for high stage lesions with urothelial involvement is poor and does not appear significantly different from the reported disease specific survival of patients with high stage lesions without urothelial invasion. Localized tumors 4 cm. or less, which are amenable to elective nephron sparing surgery, rarely invade the urothelium. However, when a low stage pT2 or less renal lesion involves the urinary space, survival appears worse than equivalently staged renal cell carcinoma without invasion. Including urothelial invasion into current TNM staging systems for renal cell carcinoma is unlikely to provide significant additional prognostic or therapeutic information.     

Impact of clinicopathological parameters in patients treated for renal cell carcinoma

PURPOSE: We determined the impact of clinical and pathological factors in the outcome of patients with renal cell carcinoma treated surgically. MATERIALS AND METHODS: We retrospectively reviewed the records of 230 consecutive patients after radical or partial nephrectomy. We analyzed clinical (incidental or symptomatic disease) and pathological (tumor size, histological type, Fuhrman nuclear grade, microvascular invasion and lymph node involvement) parameters. Disease-free and cancer specific survival curves were individualized for each parameter and on multivariate analysis. RESULTS: Median postoperative followup was 34.3 months, median time to recurrence was 22 months and mean overall survival was 130 months. A total of 40 patients (17.3%) presented with local and/or metastatic recurrence and 32 (13.9%) died of the disease. Five-year disease-free and cancer specific survival rates on univariate analysis were 56.7% and 64% for symptomatic tumors, 76.6% and 68% for clear cell carcinoma, 26.9% and 39% for sarcomatoid tumors, 34.7% and 47.5% for high grade tumors, 26.7% and 39.7% for microvascular invasion, 37.5% and 49.1% for tumors larger than 7 cm, and 11% and 32% for lymph node involvement, respectively. On univariate analysis patients with lymph node involvement and microvascular invasion had a poor prognosis. Multivariate analysis showed that the single independent prognostic factor was microvascular invasion. CONCLUSIONS: This study points out different clinical and pathological prognostic factors of survival in patients treated for renal cell carcinoma. Microvascular invasion was the only independent prognostic factor on multivariate analysis.     

The influence of pNx/pN0 grouping in a multivariate setting for outcome modeling in patients with clear cell renal cell carcinoma

PURPOSE: Lymphadenectomy, especially extended lymphadenectomy, is not commonly performed in patients undergoing a radical nephrectomy for clear cell renal cell carcinoma. Surgeons may sample suspicious regional lymph nodes, but the lymph node status of many patients with renal cell carcinoma remains unknown, termed stage pNx. Outcome models based on large institutional reviews have been criticized for grouping stages pNx and pN0 cases because of concern that the pNx category may include unrecognized stages pN1/pN2 disease. We evaluated cancer specific survival differences in patients with clear cell renal cell carcinoma and a lymph node stage of pNx, pN0 or pN1/pN2. MATERIALS AND METHODS: We searched the registry at our institution for patients who underwent radical nephrectomy for clear cell histology renal cell carcinoma between 1970 and 1998. Those with distant metastases at surgery were excluded from study. Clinical features obtained from the medical record included age at surgery, history of tobacco use, hypertension and symptomatic disease at presentation. A single urological pathologist reviewed all tumor specimens for nuclear grade, tumor necrosis, surgical margin status, 1997 tumor stage and lymph node status. These features were compared in patients with stages pNx and pN0 tumors. Cox proportional hazards models were used to compare cancer specific survival in univariate fashion, and after adjusting for tumor stage and grade. RESULTS: The study cohort consisted of 1,535 patients with sporadic, unilateral clear cell renal cell carcinoma who underwent radical nephrectomy. There were 600 patients (39%) with stage pNx, 870 (57%) with stage pN0 and 65 (4%) with stages pN1/pN2 tumors. At an average of 4.2 years after surgery 414 patients died of renal cell carcinoma. On univariate analysis patients with stage pN0 tumors were significantly more likely to die of renal cell carcinoma than those with stage pNx tumors (risk ratio 1.40, 95% confidence interval 1.12 to 1.75, p = 0.003). However, after adjusting for tumor stage and nuclear grade the difference in outcome for stages pNx and pN0 tumors was not statistically significant (risk ratio 1.07 95% confidence interval 0.85 to 1.34, p = 0.583). Patients with stage pNx disease were significantly less likely to be symptomatic at presentation (p = 0.002), have tumors that were less than 5 cm. (p <0.001) and of lower stage (p <0.001) and grade (p = 0.005), and to have tumors with necrosis (p = 0.024) than patients with stage pN0 disease. CONCLUSIONS: Combining stages pNx and pN0 cases to create outcome prediction models after radical nephrectomy for clear cell renal cell carcinoma is appropriate in a multivariate setting that includes tumor stage and grade. Clinical features available preoperatively and during surgery can help guide the decision to perform limited lymph node sampling. When the tumor is 5 cm. or greater, shows pathological necrosis or is advanced grade 3 or 4, lymph node sampling adds little prognostic information.     

Treatment and prognosis of T 4 renal cell carcinoma]

BACKGROUND: We studied the cases with T 4 renal cell carcinoma (RCC) to characterize the factors associated with prolonged survival and to clarify the indication of extended nephrectomy. MATERIALS AND METHODS: The study population consisted of 53 patients (44 male and 9 female) with pT 4 RCC treated at the Yokohama City University Hospital and its affiliated hospitals from 1965 to 1994. Survival rates were analyzed with respect to clinicopathological factors (patient age, sex, symptom, tumor growing type, tumor size, histological grade, cell type, structural type, lymph node metastasis, vein invasion, distant metastasis and extended nephrectomy). RESULTS: One-year, 2-years, and 3-years survival rates of the cases with T 4 RCC were 30.4%, 16.4%, and 9.4% respectively. In univariate analysis, improved survival were correlated with no extra-urinary symptom (Logrank: p = 0.0048, Wilcoxon: p = 0.0423), no lymphnode metastasis (Logrank: p = 0.1045, Wilcoxon: p = 0.0199), no distant metastases (Logrank: p = 0.0007, Wilcoxon: p = 0.0006), and enforcement of extended nephrectomy (Logrank: p = 0.0018, Wilcoxon: p = 0.0008). In 28 cases with extended nephrectomy, improved survival was correlated with no extra-urinary symptom, no abdominal wall invasion and no distant metastases. In 5 cases with more than 3 year survival after extended nephrectomy, 4 cases were found to have no distant metastases at the time of operation. Non-operative therapy including interferon for 20 cases without extended nephrectomy were almost ineffective. CONCLUSIONS: These results indicate that if curative excision for T 4 RCC cases without distant metastases could be done, some patients might be appropriate candidates for extended nephrectomy.     

Results of curative or non-curative nephrectomy for renal cell carcinoma invading adjacent organs]

We reviewed 12 patients who had undergone curative or non-curative nephrectomy for renal cell carcinoma invading adjacent organs (stage T4). 83 patients with renal cell carcinoma confined within the perirenal fascia (T1-T3) who had undergone nephrectomy served as controls. Of the 12 patients with T4 tumor 6 had undergone simultaneous excision of involved adjacent organs (hemicolectomy in 4, resection of the tail of pancreas in 5, splenectomy in 2). At operation 6 patients with T4 tumor had distant metastasis, 3 had fixed lymph node metastases, and 4 had tumor extension into the main renal vein or vena cava. Although T4 tumor had distant or fixed lymph node metastasis more frequently than T1-T3 tumors, the incidence of gross tumor thrombus showed no such difference between T3 and T4 tumors. Postoperative follow-up of patients with T4 tumor showed that local recurrence developed within 9 months in 3 of 5 patients who had undergone curative excision, new distant metastasis developed within 6 months in 5 patients, 1 patient died of acute renal failure in the early convalescence, 10 patients died of the disease within 12 months and 1 died of the disease in 31 months. Pathological examination showed that T4 tumors tended to be classified as grade 3, to extend in an infiltrating fashion and to have a sarcomatoid structure. Patients who had a tumor where these three histological features were dominant died to tumor within 3 months after nephrectomy. These results indicate that curative excision of T4 renal cell carcinoma is not only difficult, but frequently associated with early local recurrence and new distant metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal cell carcinoma with retroperitoneal lymph nodes: role of lymph node dissection

PURPOSE: We better defined the benefits and morbidity of lymph node dissection in patients with localized renal cell carcinoma using the experience of patients treated at our institution. MATERIALS AND METHODS: A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical and pathological data in 1,087 patients with renal cell carcinoma treated at our institution. Patients with renal cell carcinoma who did not undergo nephrectomy as part of cancer treatment, those with bilateral disease and those for whom nodal status was unknown were not included in this study. A total of 900 patients meeting these criteria who underwent nephrectomy for unilateral renal cell carcinoma at our medical center form the principal study population. RESULTS: Positive lymph nodes were associated with larger, higher grade, locally advanced primary tumors that were more commonly associated with sarcomatoid features. Positive nodes were 3 to 4 times more common in patients with metastatic disease and the majority of these patients could be identified preoperatively. The survival of patients with regional lymph node involvement only was identical to that of patients with distant metastatic disease only. Patients with regional nodes and distant metastases had significantly inferior survival to those with either condition alone. In node negative cases lymph node dissection can be performed with no additional morbidity but it confers no survival advantage. In node positive cases lymph node dissection can also be performed safely but it is associated with improved survival and a trend toward an improved response to immunotherapy. CONCLUSIONS: Regional lymph node dissection is unnecessary in patients with clinically negative lymph nodes since it offers extremely limited staging information and no benefit in terms of decreasing disease recurrence or improving survival. In patients with positive lymph nodes lymph node dissection is associated with improved survival when it is performed in carefully selected patients undergoing cytoreductive nephrectomy and postoperative immunotherapy. When lymph nodes are present, they should be resected when technically feasible.     

A new staging system for locally advanced (pT3-4) renal cell carcinoma: a multicenter European study including 2,000 patients

PURPOSE: We provide an adequate prognostic stratification for locally advanced renal cell carcinoma and propose a new TNM classification. MATERIALS AND METHODS: We analyzed clinical and pathological data on a large series of patients undergoing radical nephrectomy for pT3-4 renal cell carcinoma at 12 European centers. Cancer specific survivals were estimated using the Kaplan-Meier method. The log rank test was used for comparing survival curves and for univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis. RESULTS: The analysis included 1,969 patients. Median survivor followup was 49 months. Five-year cancer specific survival was 60% for pT3a, 46.2% for pT3b, 10% for pT3c and 12% for pT4 tumors (p <0.0001). According to median survival we identified 3 prognostic groups, including 1--patients with renal vein thrombosis (117 months), fat invasion (98 months) or infradiaphragmatic vena caval thrombosis (67 months), 2--patients with adrenal invasion alone (24 months), renal vein thrombosis plus fat invasion (24 months) or infradiaphragmatic vena cava plus fat invasion (24 months) and 3--patients with renal or infradiaphragmatic caval thrombosis plus adrenal involvement (11 months), supradiaphragmatic vena caval thrombosis (12 months) or Gerota's fascia invasion (12 months). Five-year cancer specific survival rates in groups 1 to 3 were 61%, 35% and 12.9%, respectively (p <0.0001). On multivariate analysis the proposed classification had an independent prognostic value. CONCLUSIONS: Our results suggest the necessity of reclassifying locally advanced renal cell carcinoma according to the 3 described prognostic categories.     

Laparoscopic radical nephrectomy for renal cell carcinoma: the standard of care already?

PURPOSE OF REVIEW: Laparoscopic radical nephrectomy has been developed and applied for patients with renal cell carcinoma since 1992. The number of patients undergoing laparoscopic radical nephrectomy has increased explosively worldwide in recent years, and laparoscopy is now extended to patients with advanced disease. It is very important to clarify the present status of laparoscopic radical nephrectomy among the treatment modalities for patients with renal cell carcinoma. RECENT FINDINGS: Laparoscopic radical nephrectomy has a minimally invasive nature as well as comparable long-term cancer control in patients with pT1-3a renal cell carcinoma to open surgery. It is technically applicable for N1-2 disease and T3b disease if the tumor thrombus is within the renal vein. Also, it is feasible as a cytoreductive surgery for patients with M1 disease. SUMMARY: Laparoscopic radical nephrectomy is a standard treatment modality for T1-3a renal cell carcinoma patients. It is also available for treating patients with N1-2 disease, and for patients with M1 disease as a cytoreductive surgery.     

An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage,size, grade and necrosis: the SSIGN score

PURPOSE: Currently outcome prediction in renal cell carcinoma is largely based on pathological stage and tumor grade. We developed an outcome prediction model for patients treated with radical nephrectomy for clear cell renal cell carcinoma, which was based on all available clinical and pathological features significantly associated with death from renal cell carcinoma. MATERIALS AND METHODS: We identified 1,801 adult patients with unilateral clear cell renal cell carcinoma treated with radical nephrectomy between 1970 and 1998. Clinical features examined included age, sex, smoking history, and signs and symptoms at presentation. Pathological features examined included 1997 TNM stage, tumor size, nuclear grade, histological tumor necrosis, sarcomatoid component, cystic architecture, multifocality and surgical margin status. Cancer specific survival was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to test associations between features studied and outcome. The selection of features included in the multivariate model was validated using bootstrap methodology. RESULTS: Mean followup was 9.7 years (range 0.1 to 31). Estimated cancer specific survival rates at 1, 3, 5, 7 and 10 years were 86.6%, 74.0%, 68.7%, 63.8% and 60.0%, respectively. Several features were multivariately associated with death from clear cell renal cell carcinoma, including 1997 TNM stage (p <0.001), tumor size 5 cm. or greater (p <0.001), nuclear grade (p <0.001) and histological tumor necrosis (p <0.001). CONCLUSIONS: In patients with clear cell renal cell carcinoma 1997 TNM stage, tumor size, nuclear grade and histological tumor necrosis were significantly associated with cancer specific survival. We present a scoring system based on these features that can be used to predict outcome.     

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy

PURPOSE: We compared and evaluated clinical outcomes in patients with pathological superficial (pT2a) and deep (pT2b) invasion of bladder muscle with transitional cell carcinoma following radical cystectomy and urinary diversion. MATERIALS AND METHODS: From 1971 to 2001, 311 of 1,359 patients (23%), including 244 males (78%) and 67 females, were found to have pathological muscle invasive (pT2) bladder cancer following radical cystectomy. Of this group 147 patients (47%) had pT2a (superficial) and 164 (53%) had pT2b (deep) muscle invasive tumors. Overall 242 patients had no evidence of lymph node metastasis, including 127 with pT2a (86%) and 115 with pT2b (70%). A total of 69 patients (22%) had lymph node involvement, including 20 with pT2a (14%) and 49 with pT2b (30%). At a median followup of 14.3 years (range 0 to 30.1) clinical outcomes were determined, including recurrence-free and overall survival, and local vs distant recurrence. RESULTS: In the 311 patients with pT2 tumors 10-year recurrence-free and overall survival rates were 72% and 47%, respectively. There was a significantly higher risk of node positive disease with pT2b vs pT2a tumors (30% vs 14%, p <0.001). No significant difference was observed in 10-year recurrence-free survival in patients with pT2a node negative vs pT2b node negative tumors (84% vs 72%, p = 0.091). When comparing pT2a node positive vs pT2b node positive tumors, no significant difference was observed in 10-year recurrence-free survival (50% vs 48%, p = 0.84). Recurrence-free survival was significantly higher in patients with pT2 lymph node negative tumors than in those with pT2 lymph node positive tumors (79% vs 49%, p <0.001). Furthermore, these differences remained significant when stratified by pT2a and pT2b node negative vs positive disease. Local pelvic recurrence developed in 10 of 311 patients (3%) with pT2 disease, while 69 (22%) had distant metastatic disease. In patients with recurrence the local or distant recurrence site was not associated with tumor stage (pT2a vs pT2b p = 0.24) or lymph node status (node negative vs positive p = 0.37). CONCLUSIONS: In muscle invasive (pT2) bladder cancer treated with radical cystectomy there is a higher risk of lymph node positive disease in deep muscle (pT2b) vs superficial (pT2a) invasion. However, no apparent difference was observed in recurrence-free survival between pT2a (superficial) vs pT2b (deep) muscle invasive tumors when controlling for lymph node status. Recurrence-free survival is significantly improved in patients with pT2 lymph node negative tumors compared to survival in those with pT2 lymph node positive tumors. Patients with muscle invasive (pT2), lymph node negative tumors have excellent clinical outcomes following cystectomy, while those with muscle invasive (pT2), lymph node positive tumors have higher recurrence rates and should be considered for adjuvant treatment protocols.     

Lymph node dissection at the time of radical nephrectomy for high-risk clear cell renal cell carcinoma: indications and recommendations for surgical templates

Background

Observational studies suggest a proportion of patients with lymph node metastases will benefit from lymph node dissection (LND) at the time of nephrectomy for clear cell renal cell carcinoma (RCC).

Objective

Our aim was to report the performance of five previously identified high-risk pathologic features assessed by intraoperative examination on prediction of lymph node metastases and propose a template for LND based on locations of lymph node involvement.

Design, setting, and participants

The study included a historical cohort of consecutive patients from a single institution who received LND in conjunction with nephrectomy for high-risk clear cell RCC between 2002 and 2006.

Interventions

All patients underwent nephrectomy and LND.

Measurements

Patients were considered high risk for nodal metastasis if two or more of the following features were identified during intraoperative pathologic assessment of the primary tumor: nuclear grade 3 or 4, sarcomatoid component, tumor size ≥10 cm, tumor stage pT3 or pT4, or coagulative tumor necrosis. Based on these features, LND was performed at the time of nephrectomy, and the numbers and sites of regional lymph node metastasis were recorded for each patient.

Results and limitations

Of the 169 high-risk patients, 64 (38%) had lymph node metastases. All patients with nodal metastases had nodal involvement within the primary lymphatic sites of each kidney prior to involvement of the nodes overlying the contralateral great vessel. A limitation of the study is the lack of a standardized LND performed throughout the study period.

Conclusions

Pathologic features of renal tumors are associated with the risk of regional lymph node metastases and lymph node metastases that appear to progress though the primary lymphatic drainage of each kidney. Based on these findings we recommend that when performing LND the lymph nodes from the ipsilateral great vessel and the interaortocaval region be removed from the crus of the diaphragm to the common iliac artery.     

Low clinical stage renal cell carcinoma: relevance of microvascular tumor invasion as a prognostic parameter

PURPOSE: Renal cell carcinoma is a tumor with unpredictable behavior and defining reliable prognostic factors would be extremely valuable in the clinical setting. Tumor stage, nuclear grade and tumor cell type are the main prognostic clinical parameters available. In this study we evaluated the role of microvascular involvement in the primary lesion for predicting tumor behavior in patients with low stage clinical disease. MATERIALS AND METHODS: A total of 95 patients with clinically localized renal cell carcinoma (stages T1-T2 Nx M0) underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 45 months. The impact of microvascular tumor invasion on disease progression and its correlation with known pathological outcomes (tumor size, nuclear grade and cell type) were studied. RESULTS: Microvascular tumor invasion was observed in 24 patients (25%), of whom 50% had disease recurrence. Of the 71 patients without microvascular invasion only 4 (6%) showed tumor recurrence. When microvascular invasion was correlated with other histological parameters, a significant statistical association was noted with tumor diameter, perirenal fat invasion, macroscopic extension to the renal vein, nuclear grade, lymph node metastasis and sarcomatous elements in the tumor. Multivariate analysis showed that microvascular invasion and the involvement of regional lymph nodes were independent predictors of disease recurrence. Concerning cancer specific survival, microvascular invasion and perirenal fat infiltration were the only factors related to death. CONCLUSIONS: Microvascular invasion is an independent and relevant clinical prognostic parameter for low clinical stage renal cell carcinoma.