Renal cell carcinoma with tumor thrombus: is cytoreductive nephrectomy for advanced disease associated with an increased complication rate?

PURPOSE: We examined whether cytoreductive nephrectomy in patients with venous tumor thrombus and metastatic disease is associated with more complications than in those with thrombus without metastatic disease. MATERIALS AND METHODS: Between 1989 and 2000, 74 patients with renal vein extension, 87 with inferior vena caval extension and 491 without tumor thrombus underwent nephrectomy at our institution. Metastatic and nonmetastatic renal vein extension in 51 and 23 cases, inferior vena caval extension in 54 and 33, and nontumor thrombus in 171 and 320, respectively, were compared for symptoms at presentation, surgical data, mortality and complications. RESULTS: For nonmetastatic and metastatic inferior vena caval extension presenting symptoms, hospital stay, surgical time and the number of patients undergoing thoraco-abdominal incision, lymph node dissection, venacavotomy alone for thrombus and adrenal sparing surgery were similar. Five patients with thrombus died intraoperatively or postoperatively, including 3.1% with and 0.8% without thrombus (p = 0.03), while 3 had metastatic (2.3%) and 2 (2.6%) had nonmetastatic disease. The rate of postoperative complications was higher in thrombus cases overall but there was no difference in nonmetastatic and metastatic disease with thrombus. On multivariate analysis inferior vena caval thrombus (odds ratio 10.5), adjacent organ resection due to locally advanced tumor (odds ratio 6), partial nephrectomy (odds ratio 3.8), regional lymph node involvement (odds ratio 1.7) and lower preoperative hemoglobin (odds ratio 1.6) were independent variables predicting bleeding requiring transfusion. Inferior vena caval thrombus (odds ratio 1.7) and adjacent organ resection (odds ratio 2) were also associated with nonhemorrhagic complications. Systemic metastasis was not an independent risk factor in either analysis. CONCLUSIONS: To our knowledge there are no published data comparing surgical complications in patients with metastatic and nonmetastatic renal cell carcinoma who have gross tumor thrombus. Cytoreductive surgery in patients with thrombus and metastasis is not associated with an increase in the extent of surgery, morbidity or mortality compared with their counterparts with nonmetastatic disease.     

术前影像诊断肾癌的肾脏良性病变发生率及预测因素分析

目的:研究在中国患者中术前影像学诊断肾癌行肾脏部分切除手术或根治性肾切除手术的肾脏良性占位病变发生率,并分析其预测因素。方法:回顾性分析从2003年1月～2010年9月共1 531例术前影像学诊断为肾癌并行肾脏部分切除手术或根治性肾切除手术患者的临床资料,多因素回归分析术后病理检查证实为良性患者的临床病理资料。结果:在1 531例患者中,共有81例(5.3%)为良性,其中包括错构瘤52例(3.4%),嗜酸细胞腺瘤12例(0.8%),复杂性囊肿6例(0.3%),其他类型11例(0.7%)。单因素分析显示女性、肿瘤最大径较小、年龄较小、囊性占位病变为临床表现者,病理检查证实为良性的可能性大。多因素回归分析显示,女性(OR,3.13;95%CI,1.95～5.04;P<0.001)、肿瘤最大径较小(OR,0.75;95%CI,0.66～0.85;P<0.001)、年龄较小(OR,0.94;95%CI,0.92～0.96;P<0.001)是良性占位病变的独立预测因素,而囊性占位病变不是显著性预测因素。结论:在中国患者中,术前影像学检查诊断为肾癌术后病理检查证实为良性病变的发生率为5.3%,较国外同类研究明显偏低。良性占位病变中最常见的类型为错构瘤,而欧美同类研究中为嗜酸细胞腺瘤。女性、年龄较小、肿瘤最大径较小是良性占位病变的独立预测因素。     

Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy

PURPOSE: We compared outcomes between patients treated with nephron sparing surgery (NSS) without imperative indications for renal preservation and radical nephrectomy (RN) for 4 to 7 cm renal cell carcinoma (RCC). MATERIALS AND METHODS: We identified 91 patients treated with NSS and 841 patients treated with RN for 4 to 7 cm RCC between 1970 and 2000. Cancer specific, distant metastases-free and recurrence-free survivals were estimated using the Kaplan-Meier method. RESULTS: Cancer specific survival rates at 5 years for patients treated with NSS and RN for 4 to 7 cm RCC were 98% and 86%, respectively. On univariate analysis patients treated with RN for 4 to 7 cm RCC were more likely to die of RCC compared to patients treated with NSS. However, after adjusting for features associated with death from RCC including stage, grade, histological tumor necrosis and histological subtype, this difference was no longer statistically significant (risk ratio 1.60, 95% CI 0.50-5.12, p = 0.430). Distant metastases-free survival rates at 5 years for patients treated with NSS and RN were 94% and 83%, respectively. On univariate analysis patients treated with RN were more likely to have tumors that metastasized compared to patients treated with NSS, although this difference was no longer significant after adjusting for the features listed previously (risk ratio 1.76, 95% CI 0.64-4.83, p = 0.273). Recurrence-free survival rates at 5 years for patients treated with NSS and RN were 94% and 98%, respectively. On univariate analysis patients treated with RN were less likely to have recurrence compared to patients treated with NSS (risk ratio 0.32, 95% CI 0.12-0.85, p = 0.022). CONCLUSIONS: There were no statistically significant differences in cancer specific survival and distant metastases-free survival between patients treated with NSS and RN for 4 to 7 cm RCC after adjusting for important pathological features. NSS for 4 to 7 cm RCC results in excellent outcome in appropriately selected patients.     

Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma

PURPOSE: The accuracy of the pT3a primary tumor classification for renal cell carcinoma has been questioned recently. We investigated the association of perinephric and renal sinus fat invasion with death from renal cell carcinoma independent of tumor size. MATERIALS AND METHODS: We identified 2,165 patients treated with open radical nephrectomy or nephron sparing surgery for clinically localized, sporadic pT1a, pT1b, pT2 or pT3a renal cell carcinoma between 1970 and 2002. Patients with pT3a disease were then subdivided into 3 groups according to tumor size to match the size definitions for the pT1a, pT1b and pT2 tumor classifications. RESULTS: There were 834 patients with pT1a RCC, 674 with pT1b, 494 with pT2 and 163 with pT3a RCC. At last followup 317 patients died of RCC at a median of 3.8 years following surgery. The median followup among the 1,087 patients still alive at last followup was 7.8 years (range 0 to 34). The risk ratios (95% CI) for the association between fat invasion and death from RCC among patients with tumors 4 cm or smaller, 4 to 7 cm and more than 7 cm were 6.15 (1.84-20.50, p = 0.003), 4.12 (2.50-6.78, p <0.001) and 2.13 (1.53-2.97, p <0.001), respectively. These associations remained statistically significant in a multivariate analysis that included nuclear grade and histological coagulative tumor necrosis. CONCLUSIONS: Peripheral perinephric and renal sinus fat invasion was associated with death from RCC independent of tumor size. Our data contradict reports suggesting that pT3a tumors should be reclassified according to tumor size only.     

Surgical strategy for treating renal cell carcinoma with thrombus extending into the inferior vena cava

OBJECTIVE: A surgical strategy for treating malignant renal tumors with thrombus extending into the inferior vena cava (IVC) was assessed. METHODS: We retrospectively reviewed the records for all patients with renal cell carcinoma (RCC; n=30) or Wilms tumor (n=1) with tumor thrombus extending into the IVC who underwent surgical intervention at our institution between January 1980 and December 2001. Tumors were classified preoperatively according to the cephalad extension of thrombus, and intraoperative procedures were selected on the basis of degree of extension. Patients with RCC underwent radical nephrectomy and removal of thrombus with (n=11) or without (n=19) IVC resection. Partial normothermic cardiopulmonary bypass without cardiac arrest was used in 4 patients. The Pringle maneuver was performed in 8 patients. Infrarenal abdominal aortic cross-clamping was used in 8 patients to maintain systemic blood pressure. IVC cross-clamping and the Pringle maneuver were performed in 5 patients with suprahepatic thrombus extension. Temporary placement of a filter in the IVC or plication of the IVC above the hepatic vein was performed before hepatic mobilization, to decrease the risk for pulmonary embolism. RESULTS: One patient died intraoperatively of pulmonary embolism. Postoperative complications occurred in 11 patients; all resolved with conservative therapy. The postoperative duration of survival in patients with RCC was 37 +/- 44 months (range, 4-180 months); the 5-year survival rate was 42%. CONCLUSION: Aortic cross-clamping during IVC occlusion prevented hypotension and maintained hemodynamic stability that has required bypass in other series. This surgical treatment with the less extensive approach could result in long-term survival of patients with RCC in whom tumor thrombus extends into the IVC. We recommend that radical nephrectomy and tumor thrombectomy, with or without caval resection, be performed in these patients, with less invasive additional maneuvers.     

pT2 classification for renal cell carcinoma. Can its accuracy be improved?

PURPOSE: The 2002 tumor classification for renal cell carcinoma (RCC) classifies pT2 tumors as more than 7 cm in greatest dimension, limited to the kidney. In this study we determined whether a size cutoff point exists within pT2 tumors and whether such subclassification would further improve the accuracy of the current tumor classification. MATERIALS AND METHODS: We studied 544 patients with unilateral, sporadic pT2 RCC treated with radical nephrectomy or nephron sparing surgery between 1970 and 2000. The association of tumor size with death from RCC was examined using martingale residuals from a Cox proportional hazards regression model to determine the optimal size cutoff point. RESULTS: There were 204 deaths from RCC a median of 3.8 years following nephrectomy. Univariately tumor size was significantly associated with death from RCC (risk ratio 1.08, 95% CI 1.04 to 1.13, p <0.001). A scatterplot of tumor size vs expected risk of death per patient suggested that a cutoff point between 9 and 10 cm was appropriate. When adjusted for regional lymph node involvement and distant metastases, the 10 cm cutoff point performed better than the 9 cm point (risk ratio 1.42, 95% CI 1.07 to 1.90, p = 0.017 vs 1.22, 95% 0.86 to 1.72, p = 0.268). Therefore, we propose using a 10 cm cutoff point to subclassify patients into pT2a and pT2b. CONCLUSIONS: Our data suggest that the prognostic accuracy of the 2002 pT2 tumor classification can be further improved by subclassifying patients with tumors greater than 7 and less than 10 cm into a pT2a category, and those with tumors 10 cm or greater into a pT2b category.     

pT1 substaging in renal cell carcinoma: validation of the 2002 TNM staging modification of malignant renal epithelial tumors

PURPOSE: Tumor size has been used as one of the criteria to stratify renal cell carcinoma (RCC) into different pathological stages (pT). The recent 2002 UICC/TNM classification of malignant epithelial renal tumors is modified to substratify pT1 RCC into pT1a (less than 4.0 cm) and pT1b (greater than 4.0 but less than 7.0 cm). In this study we ascertained if this stage modification has prognostic relevance. MATERIALS AND METHODS: A total of 259 consecutive radical nephrectomy specimens of organ confined RCC from 1970 to 1997 at 1 institution, including 153 of conventional RCC (CRCC), 71 of papillary RCC, 28 of chromophobe RCC, 1 of collecting duct carcinoma and 6 of RCC not otherwise specified, with a mean clinical followup of 7.5 years (median 6.4) were included in the study. RESULTS: There were 115 pT1a (44.4%), 95 pT1b (36.7%) and 49 pT2 tumors (18.9%). Disease recurrences (DR) and disease specific death occurred in 2 (1.7%) and 0 cases (0%) of pT1a, 7 (7.3%) and 5 (5.3%) of pT1b, and 16 (32.6%) and 12 (24.5%) of pT2. DR for pT1b was higher compared with pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p = 0.106). If only CRCCs were analyzed, DR in the pT1b group was statistically higher compared with pT1a (RR 8.54, p = 0.047). Disease specific survival in pT1a could not be evaluated because no deaths occurred in this subgroup. DR and disease specific survival were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p = 0.001 and 5.49, p = 0.001) and for the CRCC subtype (RR 5.50, p = 0.001 and 5.18, p = 0.005, respectively). Using size as a continuous variable the logarithmic change in tumor size was a significant predictor of DR (RR 8.82, p = 0.001). All statistical analyses were adjusted for age and sex. CONCLUSIONS: Substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modification for malignant renal epithelial malignancies. The substratification of pT1 is particularly useful in tumors with CRCC histology.     

Obesity is associated with a higher risk of clear‐cell renal cell carcinoma than with other histologies

Study Type – Prognosis (cohort)
Level of Evidence 2a

OBJECTIVE

To investigate the association between body mass index (BMI) and histology of renal cell carcinoma (RCC) in a contemporary cohort, as obesity is increasingly prevalent in the USA and might be contributing to the increasing incidence of RCC, but little is known about the relationship of obesity with the different histological subtypes of RCC.

PATIENTS AND METHODS

From January 2000 to December 2007 we identified 1640 patients with renal cortical tumours undergoing surgical extirpation at our institution, and who had their BMI recorded. Multivariable logistic regression models were used to test the association of BMI with RCC histology.

RESULTS

The median (interquartile range) BMI was 28 (25–32) kg/m² and 38% of patients were classified as obese (BMI >30 kg/m²). After adjusting for tumour size, age, gender, American Society of Anesthesiologists score, estimated glomerular filtration rate, hypertension, diabetes mellitus and smoking, the BMI was significantly associated with clear‐cell histology; the odds ratios were 1.04 for each unit of BMI (95% confidence interval, CI, 1.02–1.06; P < 0.001) and 1.48 when comparing obese vs non‐obese patients (95% CI 1.19–1.84; P < 0.001). In the subgroup of patients with RCC (excluding benign renal cortical tumours), BMI was still an independent predictor of clear‐cell histology (odds ratio 1.04, 95% CI 1.02–1.06, P = 0.001).

CONCLUSIONS

These results suggest that BMI is an independent predictor of clear‐cell histology in patients with a renal cortical tumour. While the aetiology of this phenomenon requires further study, these findings might have implications in determining a patient’s risk of harbouring a clear‐cell RCC and in subsequent treatment recommendations.     

Histotype predicts the rate of lymph node invasion at nephrectomy in patients with nonmetastatic renal cell carcinoma

BackgroundLymph node invasion (LNI) at nephrectomy is one of the most important predictors of mortality in patients with nonmetastatic renal cell carcinoma (RCC). We analyzed the effect of histology on lymph node metastases at nephrectomy and its effect on survival in a contemporary cohort of patients with nonmetastatic RCC.MethodsWithin the Surveillance, Epidemiology, and End Results database (2004-2015), we identified 100,060 patients with clear-cell, papillary, chromophobe, sarcomatoid, and collecting duct RCC, who underwent nephrectomy with or without lymph node dissection for nonmetastatic RCC. Logistic regression models, cumulative incidence plots, and competing-risks regression models were performed.ResultsOverall, 10,590 patients underwent lymph node dissection for nonmetastatic RCC. Of these, LNI was recorded in 52 (7.0%), 615 (8.7%), 282 (13.9%), 316 (25.1%), 129 (38.3%), 45 (71.4%) patients with chromophobe, clear-cell, nonotherwise specified RCC, papillary, sarcomatoid, and collecting duct RCC histological subtypes, respectively. In logistic regression models, relative to clear-cell, papillary Odds ratio (OR 3.9), sarcomatoid (OR 6.3), collecting duct (OR 14.6) but not chromophobe RCC (OR 0.9; P = 0.5) independently predicted LNI at surgery. Moreover, in competing-risks regression models, LNI increased the risk of CSM 1.8-fold for sarcomatoid, 3.6-fold for clear-cell, 4.1-fold for papillary, and 6.7-fold for chromophobe histological subtype.ConclusionsHistology is an independent predictor of increased risk of LNI at nephrectomy. Moreover, the effect of pathological nodal stage on survival differs according to different histology.     

Metachronous renal tumours after surgical management of oncocytoma

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Oncocytoma is a benign renal tumour that cannot be differentiated from renal cell carcinoma radiographically. Follow‐up after surgery for oncocytoma is highly variable and the natural history of surgically treated renal oncocytoma is poorly defined. We sought to assess the risk of metachronous renal tumours in a cohort of patients treated surgically for renal oncocytoma. We report a large cohort of oncocytoma patients following surgical management. This study defines the risk of metachronous renal tumours after surgical treatment of renal oncocytoma. Our findings suggest that patients with metachronous renal tumours after treatment of renal oncocytoma may have a smaller risk of renal cell carcinoma compared with patients presenting with a primary renal mass. Our findings did not support concern for increased risk of renal cell carcinoma following surgical treatment of primary renal oncocytoma.

OBJECTIVE

? To assess the risk of metachronous renal cell carcinoma (RCC) and benign renal tumours after surgical treatment of primary renal oncocytoma.

PATIENTS AND METHODS

? Patients treated for primary renal oncocytoma between 1970 and 2007 were identified. Tumours were reviewed by a urological pathologist and patients were followed for subsequent renal tumours.

RESULTS

? Of 424 patients with a median follow up of 7.1 year, 17 (4.0%) patients were diagnosed with a metachronous renal tumour at a median of 3.0 years (range 0.3–16 years). Of the 17 metachronous tumours, eight were oncocytoma, four were RCC and five were not resected or biopsied. ? Eleven metachronous tumours occurred after solitary unilateral oncocytoma, five occurred after multifocal unilateral oncocytoma, and one occurred after multifocal bilateral oncocytoma. ? Estimated 10‐year tumour‐free and RCC tumour‐free survival was 94.8% and 98.7%, respectively. Patients with primary multifocal oncocytoma were at higher risk of metachronous tumour (hazard ratio 4.0; P = 0.007). Initial oncocytoma size (hazard ratio 1.1; P = 0.11) was not highly associated with risk of tumour recurrence.

CONCLUSIONS

? To our knowledge, we report the largest cohort of oncocytoma after surgical management. Metachronous renal neoplasm in a patient with previous oncocytoma is more likely to be benign compared with patients who present with a renal tumour for the first time. Multifocal primary oncocytoma is associated with metachronous renal tumours. ? Overall, the risk of metachronous RCC in a patient with an oncocytoma is similar to that of the general population, which does not support the use of routine cross‐sectioning imaging surveillance.     

Associations with contralateral recurrence following nephrectomy for renal cell carcinoma using a cohort of 2,352 patients

PURPOSE: We determined the incidence of and factors associated with the development of renal cell carcinoma (RCC) in the contralateral kidney after nephrectomy for localized RCC. MATERIALS AND METHODS: Between 1970 and 2000, 2,352 patients with sporadic, localized unilateral RCC and a normal contralateral kidney underwent nephrectomy for RCC. Cancer specific survival rates were estimated using the Kaplan-Meier method. Univariate Cox proportional hazards models were used to determine associations with outcome. RESULTS: Of the 2,352 patients studied 28 (1.2%) had RCC in the contralateral kidney, including 20 with clear cell and 8 with papillary RCC. Mean time from primary surgery to contralateral recurrence was 5.2 years (median 4.8, range 0 to 18) for clear cell RCC compared with 5.6 years (median 1.3, range 0 to 21) for papillary cell RCC. Positive surgical margins (risk ratio 14.23, p = 0.010) and multifocality (risk ratio 5.74, p = 0.019) were significantly associated with contralateral recurrence following nephrectomy for clear cell RCC, while nuclear grade (risk ratio for grades 3/4 vs 1/2, 4.78, p = 0.040) was significantly associated with contralateral recurrence following nephrectomy for papillary RCC. In patients with clear cell RCC estimated cancer specific survival rates 1, 3, and 5 years following contralateral recurrence were 93.8%, 80.2% and 72.9%, respectively. CONCLUSIONS: In patients with localized RCC and a normal contralateral kidney who underwent nephrectomy for RCC positive surgical margins and multifocality were significant predictors of contralateral recurrence for clear cell RCC, while nuclear grade was a significant predictor of contralateral recurrence for papillary RCC.     

Extranodal extension in regional lymph nodes is associated with outcome in patients with renal cell carcinoma

PURPOSE: The 2002 American Joint Committee on Cancer pN classification for renal cell carcinoma is based on the number of positive regional lymph nodes. We examined the associations of pathological features of lymph node metastases with patient outcome to improve the prognostic accuracy of the current classification. MATERIALS AND METHODS: We studied the records of 2,076 patients treated with radical nephrectomy for unilateral, sporadic pM0 renal cell carcinoma between 1970 and 2000. There were 34 patients with metastasis in a single regional lymph node (pN1) and 35 with metastases in more than 1 lymph node (pN2). Pathological features of lymph node metastases, including the number and percent of positive lymph nodes, total number of lymph nodes removed, grade, necrosis, extranodal extension, and largest dimension and surface area of metastases were determined by 2 urological pathologists (HHD and JCC). RESULTS: There was no statistically significant association between the pN classification and death from renal cell carcinoma (pN2 vs pN1 RR 1.05, 95% CI 0.62 to 1.79, p = 0.846). However, patients with extranodal extension were twice as likely to die of renal cell carcinoma than patients in whom metastases did not extend outside of the lymph node capsule (RR 2.02, 95% CI 1.18 to 3.45, p = 0.010). The 5-year cancer specific survival rate was 18% and 35% in patients with and without extranodal extension, respectively. CONCLUSIONS: We believe that a pN classification based on the presence or absence of lymph node metastases with a notation regarding the presence or absence of extranodal extension represents a significant improvement in the prognostic accuracy of the current pN classification.     

Renal cell carcinoma and end stage renal disease

PURPOSE: Patients with ESRD secondary to acquired renal cystic disease have been reported to have a higher incidence of RCC than the general population. We examined the clinical and pathological significance of incidental renal masses in patients with ESRD. MATERIALS AND METHODS: From January 1994 to July 2000, 852 consecutive patients with ESRD who were being considered for renal transplantation at University of Mississippi Medical Center were evaluated with renal ultrasound as part of assessment for possible kidney transplantation. Those patients with ultrasound suspicious for a malignant renal lesion were further evaluated with CT of the abdomen with and without intravenous contrast medium. Any patient with CT findings suspicious for RCC was recommended to undergo radical nephrectomy before kidney transplantation. RESULTS: A total of 19 patients had CT criteria for a possible malignant renal lesion. Seven patients had Bosniak class 3 renal cysts and 12 patients had solid, enhancing renal masses. Of the patients 17 underwent radical nephrectomy. On pathological examination 14 patients had RCC with a 1.64% prevalence in the population screened. Mean Fuhrman nuclear grade in our patients was 2.45. CONCLUSIONS: RCC in patients with ESRD are of clinical significance, considering the size, grade, histology and pathological stage of these tumors. The higher prevalence of clinically significant RCC in patients with ESRD as well as the risk of cancer progression while patients are on immunosuppressive medications justifies screening for RCC in patients with ESRD who are awaiting renal transplantation.     

Resection of the abdominal inferior vena cava for complicated renal cell carcinoma with tumour thrombus

OBJECTIVE: To describe our experience of excising the inferior vena cava (IVC) without a graft; en bloc resection of a renal cell carcinoma (RCC) with the renal vein and vena cava tumour thrombus and a segment of the entire abdominal IVC is technically feasible, but traditionally, after resection, attempts are made to restore continuity with the use of synthetic or homologous venous grafts. PATIENTS AND METHODS: Between May 1997 and September 2004, 60 patients (mean age 62 years) underwent surgical resection of a renal tumour with a thrombus extending into the IVC. To resect the entire evident tumour, excision of the affected portion of the IVC was required in three patients (5%); the IVC was not reconstructed. RESULTS: The three patients were aged 38, 39 and 74 years; the mean operative duration was 5.88 h, the mean (range) estimated blood loss was 833 (500-1000) mL, the mean number of blood units transfused was 3.3 (0-7) units, and the mean follow-up was 24 months. The course after surgery was uneventful; specifically, none of the patients had a venous thrombosis or a pulmonary embolus. CONCLUSIONS: RCC has a propensity to invade the renal vein and IVC. Occasionally the thrombus invades the wall of the IVC and complete removal requires excision of a circumferential portion of the IVC; this can be done safely without a graft.     

Renal oncocytoma: a clinicopathological analysis of 45 consecutive cases

OBJECTIVE: To evaluate the clinical behaviour and pathology of renal oncocytoma in a well-defined population over a 30-year period. PATIENTS AND METHODS: In a retrospective population-based study we assessed relevant clinical and pathological factors in 45 patients (31 men and 14 women) diagnosed with renal oncocytoma in Iceland between 1971 and 2000. Clinical presentation, pathology, survival and causes of death were evaluated. RESULTS: The age-standardized incidence was 0.3 per 100,000 per year for both men and women, the incidence of oncocytomas being 5.5% of renal cell carcinomas (RCCs) diagnosed during the same period in Iceland. Fourteen patients were diagnosed at autopsy for an unrelated disease. Of 31 living patients (mean age 70.5 years), seven were diagnosed incidentally (23%), and the others had presented with haematuria (32%), abdominal pain (29%), and weight loss (10%). All the patients had a radical nephrectomy, except for one with bilateral oncocytoma who had a partial nephrectomy. The mean (range) tumour size was 5.7 (0.9-12) cm. Eighteen patients (58%) were diagnosed at Tumour-Node-Metastasis stage I, 10 at stage II (32%) and three at stage III (10%), all of those at stage III having renal capsular penetration or tumour invasion into perirenal fat tissue (T3aN0M0). No patients were diagnosed with lymph node or distant metastasis. Two cases of coexisting RCC were detected. After a median follow-up of 8.3 years there were no recurrences or deaths from oncocytoma (100% disease-specific survival). The overall 5-year survival was 63%, with most patients dying from cardiovascular diseases or nonrenal cancers. CONCLUSIONS: In most cases renal oncocytoma behaves like a benign tumour; the long-term prognosis is excellent. Thus, in the present patients, radical nephrectomy could be regarded as an over-treatment and nephron-sparing surgery as more appropriate, especially in patients with small tumours. However, both coexisting RCC and perirenal fat invasion, a hallmark of malignant behaviour, might indicate that more radical surgery is warranted in some of these patients.     

Renal cell carcinoma with inferior vena caval extention: impact of tumour extent on surgical outcome

OBJECTIVE

To evaluate our experience with surgical resection of renal cell carcinoma (RCC) with inferior vena cava (IVC) involvement and examine the relationship between prognosis and tumour extent.

PATIENTS AND METHODS

A retrospective review of nephrectomy performed between 1985 and 2005 identified 50 patients presenting with tumour thrombus extension into the IVC. Clinical characteristics and outcome were evaluated.

RESULTS

Of the 50 patients evaluated, 7, 26, 10 and 7 presented with level I, II, III and IV thrombus, respectively. Major postoperative complications occurred in 16% of patients. Local or distant failure occurred in 25 (64%) patients. The mean time to recurrence was 10 months. Only supra‐diaphragmatic extension of the tumour thrombus was predictive of disease recurrence.

CONCLUSION

Locally advanced RCC with IVC thrombus remains associated with significant local and distant failure rate. The level of thrombus extension is significantly associated with disease recurrence. Effective adjuvant therapy is needed to improve outcome in this patient population.     

Metastatic potential of a renal mass according to original tumour size at presentation

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE ? To determine the metastatic potential of renal masses based on original tumour size. MATERIALS AND METHODS ? We identified 2651 patients who had undergone surgical resection for a unilateral, sporadic renal tumour between 1990 and 2006. ? Associations of tumour size with synchronous metastasis at presentation [M1 renal cell carcinoma (RCC)] and development of metastases, death from RCC, and death from any cause after surgery were evaluated using logistic and Cox proportional hazards regression. RESULTS ? Of the 2651 patients studied, 182 (6.9%) presented with M1 RCC. Tumour size was significantly greater in patients with M1 RCC than in patients with M0 RCC (a median size of 10 vs 4.5 cm; P < 0.001). Only 1 of the 629 patients (0.2%) with a tumour <3 cm had M1 RCC and that tumour was 2.5 cm. The risk of M1 RCC increased from 1.1% for patients with tumours 3–3.9 cm to 16.5% for patients with tumours ≥7 cm. ? Of the 2124 patients with M0 RCC, 430 developed distant metastases at a median (range) of 1.4 (0.1–16.2) years after surgery. Only 9 of the 498 patients (1.8%) with a tumour <3 cm developed distant metastases after surgery. ? Each 1‐cm increase in tumour size increased the risk of death from RCC by 20%[hazard ratio (HR) 1.20; 95% confidence interval (CI) 1.18–1.22; P < 0.001] and death from any cause by 10% (HR 1.10; 95% CI 1.09–1.12; P < 0.001). ? For the 1346 patients who were still alive at last follow‐up, the median (range) duration of follow‐up was 6.9 (0.1–19.7) years. CONCLUSIONS ? Tumour size is significantly associated with metastases in patients with renal masses. ? Patients with tumours <3 cm have a low risk of synchronous metastatic disease.     

Endoluminal occlusion of the inferior vena cava in renal cell carcinoma with retro- or suprahepatic caval thrombus

OBJECTIVE: To evaluate endoluminal occlusion of the inferior vena cava (IVC) during surgical treatment of renal cell carcinoma (RCC) with either retrohepatic (level II) or suprahepatic (level III) caval tumour thrombus. PATIENTS AND METHODS: From January 2000 to February 2005, 31 patients with renal vein/IVC involvement (T3b/c) of 278 who had a radical nephrectomy, were selected for review. Of these 31, 13 consecutive patients with RCC presenting a thrombus level II or III were prospectively treated with endoluminal occlusion of the free IVC cranial to the thrombus, to avoid dissection of the suprahepatic IVC or the subdiaphragmatic IVC. The occlusion balloon was positioned using transoesophageal echocardiography (TEE) control through a cavotomy at the ostium of the renal vein. Thrombectomy and radical nephrectomy were then performed. The operative duration, peri-operative bleeding, and complications during and after surgery were assessed. Overall patient survival time, disease-free survival and development of metastasis were calculated. RESULTS: Caval thrombectomy was successful in all patients. The IVC needed to be replaced with an expanded polytetrafluoroethylene graft in three patients and a patch closure after lateral cavectomy was used in four. There was no case of air embolism. One case of asymptomatic tumour migration was detected during the procedure by TEE. The mean (sd) and median (range) operative duration was 170 (29) and 170 (120-210) min, and the mean number of units of packed red cells transfused during hospitalization was 5 (5) and 3 (0-16). There was no peri-operative mortality. The complications were one splenectomy and one early thrombosis of the IVC. The mean (range) follow-up was 22.1 (2-50) months. Distant metastases occurred in seven patients; there was no local or IVC tumour recurrence. Four patients died from metastatic progression and six are alive with no progression. CONCLUSION: Endoluminal occlusion of the IVC with TEE monitoring for level II and III thrombus avoided a suprahepatic or subdiaphragmatic approach to the IVC. This technique caused no major complications and was very reliable, due to TEE monitoring. Segmental resection and reconstruction of the IVC could also be used for adherent thrombi.     

Three-dimensional tumour volume and cancer-specific survival for patients undergoing nephrectomy to treat pT1 clear-cell renal cell carcinoma

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The positive association of tumour size (largest tumour dimension on pathology review) and risk of RCC progression and survival following nephrectomy is well documented. Moreover, several clinicopathological scoring systems (i.e. nomograms and algorithms) have been developed to predict outcomes for surgically treated RCC patients and each of these includes tumour size as an independent predictor of RCC outcome. There is still the question of whether information on three‐dimensional tumour volume (cm³) can provide additional prognostic information, particularly among patients with small pT1 tumours where the range of tumour size is more limited. Our study demonstrates that increasing tumour volume is associated with a greater risk of RCC‐specific death in patients with pT1 ccRCC, with a more pronounced association in pT1a tumours specifically. In addition, we observed evidence that tumour volume may provide more accurate prognostic information than tumour size alone in pT1a patients. Tumour volume may add prognostic information specifically in pT1a RCC.

OBJECTIVE

• ? To address whether information on three‐dimensional tumour volume can provide additional prognostic information for patients with small, localized renal cell carcinoma (RCC) superior to tumour size alone.

PATIENTS AND METHODS

• ? We identified 955 patients treated with radical nephrectomy or nephron‐sparing surgery for unilateral, sporadic, pT1, pN0/NX, M0, non‐cystic clear‐cell RCC (ccRCC) between 1980 and 2004, including 515 pT1a patients and 440 pT1b patients.
• ? We estimated tumour volume using three tumour dimensions recorded on pathological analysis and the equation for the volume of an ellipsoid [π/6 (length × width × height)]. For tumour size alone, we used the maximum tumour diameter recorded on pathological analysis.
• ? Univariate and multivariable associations with RCC‐specific death were evaluated using Cox proportional hazards regression models summarized with hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS

• ? Among pT1a patients, the risk of RCC death associated with having a tumour volume above the median (HR = 4.55; 95% CI, 1.30–15.83; P= 0.018) was markedly higher than having a tumour size above the median (HR = 2.55; 95% CI 0.83–7.85; P= 0.10).
• ? Comparison of concordance (c) index values further supported the idea that additional prognostic information was provided by tumour volume (c= 0.659) compared with tumour size (c= 0.600) for pT1a patients.
• ? Among pT1b patients, we noted that associations of tumour volume and tumour size with RCC‐specific death were similar.
• ? Multivariable adjustment did not alter our findings.

CONCLUSIONS

• ? Tumour volume could provide valuable prognostic information for patients with pT1a ccRCC but not pT1b ccRCC.
• ? Future investigations are needed to confirm this finding, explore other RCC subtypes and evaluate accuracy of tumour volume determination on radiographic imaging for potential patient management before surgery.

     

Renal cell carcinoma with tumor thrombus extension: biology,role of nephrectomy and response to immunotherapy

PURPOSE: We outline the biology, prognosis and role of immunotherapy for renal cell carcinoma with gross venous tumor thrombus. MATERIALS AND METHODS: A total of 207 patients with unilateral renal cell carcinoma and tumor thrombus into the renal vein (107) and inferior vena cava (100) who underwent nephrectomy and thrombectomy were compared with 607 without tumor thrombus. RESULTS: At diagnosis 77 patients (37%) had N0M0 disease and 130 (63%) had lymph node (N+) or distant (M1) metastases. Compared with nontumor thrombus cases tumor thrombus was associated with more advanced stage, N+ (26% versus 12%), M1 (54% versus 31%) disease, higher grade and Eastern Cooperative Oncology Group performance status. In N0M0 cases with inferior vena caval tumor thrombus capsular penetration, collecting system invasion and extension into the hepatic vein were more important prognostic variables then the level of inferior vena caval thrombus. In patients with confined N0M0 tumors mean 2 and 5-year survival +/- SD was 83% +/- 8.8% and 72% +/- 10.7% in those with inferior vena caval tumor thrombus, and 90% +/- 9.4% and 68% +/- 16.1% in those with renal vein tumor thrombus, similar to the 93.4% +/- 1.7% and 81 +/- 3.1% rates, respectively, in those without thrombus who had no recurrence within 6 months after nephrectomy. Of patients with M1 disease in whom cytoreductive surgery was done those with and without thrombus showed a similar response to immunotherapy. When there was inferior vena caval and renal vein thrombus, mean 2-year survival was higher after nephrectomy and immunotherapy than after nephrectomy alone (41% +/- 9% and 52% +/- 7% versus 32% +/- 13% and 45% +/- 7%), immunotherapy alone (0% and 13% +/- 12%, respectively) and no treatment (0%). CONCLUSIONS: Renal cell carcinoma with tumor thrombus is associated with worse characteristics. Local tumor extension has greater prognostic importance than the level of inferior vena caval tumor thrombus. Survival is fair in patients with truly confined N0M0 disease and thrombus. The combination of surgery and immunotherapy has a role in thrombus cases. Our data provide the rationale for a prospective study of adjuvant immunotherapy after surgery in N0M0 cases with extensive tumor thrombus.