Christopher J. Weight

Nephrectomy Induced Chronic Renal Insufficiency is Associated With Increased Risk of Cardiovascular Death and Death From Any Cause in Patients With Localized cT1b Renal Masses

PURPOSE Radical nephrectomy has traditionally been preferred to partial nephrectomy in patients with localized renal cell cancer because of its simplicity and established cancer control. Recent data suggest that these patients have significant competing risks of death, some of which may be increased by chronic renal insufficiency. Therefore, we compared overall survival, cancer specific survival and cardiac specific survival in patients undergoing partial or radical nephrectomy for cT1b tumors. MATERIALS AND METHODS From 1999 to 2006, 1,004 patients with renal masses between 4 and 7 cm underwent extirpative surgery, partial nephrectomy (524) or radical nephrectomy (480). We generated a propensity model based on preoperative patient characteristics, and then modeled survival with the additional variables of pathological stage and new baseline renal function. RESULTS On multivariate analysis cancer specific survival was equivalent for patients treated with partial nephrectomy or radical nephrectomy. Those patients undergoing radical nephrectomy lost significantly more renal function than those undergoing partial nephrectomy. The average excess loss of renal function observed with radical nephrectomy was associated with a 25% (95% CI 3-73) increased risk of cardiac death and 17% (95% CI 12-27) increased risk of death from any cause on multivariate analysis. CONCLUSIONS Partial nephrectomy offers cancer specific survival equivalent to that of radical nephrectomy and is technically feasible in at least 50% of patients with cT1b tumors. Preservation of renal function was significantly better in patients treated with partial nephrectomy. Postoperative renal insufficiency was a significant independent predictor of overall and cardiovascular specific survival, and efforts should be made to limit the renal function loss associated with surgery for localized renal masses.

Factors Predicting Renal Functional Outcome After Partial Nephrectomy

PURPOSE Compared to radical nephrectomy, partial nephrectomy better preserves renal parenchyma and function. Although several clinical factors may impact renal function after partial nephrectomy including preoperative function, age, gender and comorbidities, the contributions of tumor and surgical factors have not been well studied. We evaluate independent factors predicting functional outcomes after partial nephrectomy. MATERIALS AND METHODS Preoperative and all postoperative serum creatinine values for 1,169 patients undergoing partial nephrectomy were used to estimate glomerular filtration rate. Postoperative nadir glomerular filtration rate and ultimate glomerular filtration rate were analyzed using multiple pertinent covariates. RESULTS Median preoperative, postoperative nadir and ultimate glomerular filtration rates were 77, 57 and 71 ml per minute per 1.73 m(2), respectively. Increasing age, gender, lower preoperative glomerular filtration rate, solitary kidney, tumor size, ischemia time and longer time to nadir glomerular filtration rate significantly predicted postoperative nadir glomerular filtration rate and ultimate glomerular filtration rate. Acute loss of renal function predicted lower ultimate glomerular filtration rate. In the entire cohort, in patients with normal preoperative renal function, and in those with baseline stage 3 and those with stage 4 chronic kidney disease the incidence of postoperative acute kidney injury after partial nephrectomy was 3.6%, 0.8%, 6.2% and 34%, and the incidence of chronic end stage renal disease after partial nephrectomy was 2.5%, 0.1%, 3.7% and 36%, respectively. CONCLUSIONS Lower preoperative glomerular filtration rate, solitary kidney, older age, gender, tumor size and longer ischemic interval all predicted lower glomerular filtration rate after partial nephrectomy. Therefore, duration of renal ischemia is the strongest modifiable surgical risk factor for decreased renal function after partial nephrectomy, and efforts to limit ischemic time and injury should be pursued in open and laparoscopic partial nephrectomy.

Independent Validation of the 2010 American Joint Committee on Cancer TNM Classification for Renal Cell Carcinoma: Results From a Large, Single Institution Cohort

PURPOSE In 2010 the American Joint Committee on Cancer updated the renal cell carcinoma TNM classification. Without independent validation of the new classification its predictive ability for cancer specific survival and generalizability remains unknown. In this setting we determined the predictive ability of the 2010 TNM classification compared to that of the 2002 classification. MATERIALS AND METHODS Using the nephrectomy registry at our institution we retrospectively reviewed the records of 3,996 patients with unilateral or bilateral synchronous renal cell carcinoma treated with radical nephrectomy or nephron sparing surgery between 1970 and 2006. Cancer specific survival was estimated using the Kaplan-Meier method and predictive ability was evaluated using the concordance index. RESULTS There were 1,165 deaths (29.1%) from renal cell carcinoma a median of 1.9 years after surgery compared to a median followup of 7.4 years for survivors. The estimated 10-year cancer specific survival rate was 96%, 80%, 66%, 55%, 36%, 26%, 25% and 12% for patients with 2010 primary tumor classifications of pT1a, pT1b, pT2a, pT2b, pT3a, pT3b, pT3c and pT4, respectively (p <0.001). The multivariate concordance index for the 2002 and 2010 TNM classifications was 0.848 and 0.850, respectively. CONCLUSIONS The new 2010 classification remains a robust predictor of cancer specific survival compared to the 2002 classification by dividing pT2 lesions into pT2a and pT2b, reclassifying ipsilateral adrenal involvement as pT4, reclassifying renal vein involvement as pT3a and simplifying nodal involvement as pN0 vs pN1. However, the 2010 TNM classification showed only modest improvement in predictive ability compared to the 2002 classification.

Comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: A systematic review and meta-analysis

PURPOSE The relative effectiveness of partial vs radical nephrectomy remains unclear in light of the recent phase 3 European Organization for the Research and Treatment of Cancer trial. We performed a systematic review and meta-analysis of partial vs radical nephrectomy for localized renal tumors, considering all cause and cancer specific mortality, and severe chronic kidney disease. MATERIALS AND METHODS Cochrane Central Register of Controlled Trials, MEDLINE®, EMBASE®, Scopus and Web of Science® were searched for sporadic renal tumors that were surgically treated with partial or radical nephrectomy. Generic inverse variance with fixed effects models were used to determine the pooled HR for each outcome. RESULTS Data from 21, 21 and 9 studies were pooled for all cause and cancer specific mortality, and severe chronic kidney disease, respectively. Overall 31,729 (77%) and 9,281 patients (23%) underwent radical and partial nephrectomy, respectively. According to pooled estimates partial nephrectomy correlated with a 19% risk reduction in all cause mortality (HR 0.81, p < 0.0001), a 29% risk reduction in cancer specific mortality (HR 0.71, p = 0.0002) and a 61% risk reduction in severe chronic kidney disease (HR 0.39, p < 0.0001). However, the pooled estimate of cancer specific mortality for partial nephrectomy was limited by the lack of robustness in consistent findings on sensitivity and subgroup analyses. CONCLUSIONS Our findings suggest that partial nephrectomy confers a survival advantage and a lower risk of severe chronic kidney disease after surgery for localized renal tumors. However, the results should be evaluated in the context of the low quality of the existing evidence and the significant heterogeneity across studies. Future research should use higher quality evidence to clearly demonstrate that partial nephrectomy confers superior survival and renal function.

Correlation of Radiographic Imaging and Histopathology Following Cryoablation and Radio Frequency Ablation for Renal Tumors

PURPOSE Followup after radio frequency ablation and cryotherapy for small renal lesions lacks pathological analysis. The definition of successful tumor ablation has been the absence of contrast enhancement on posttreatment magnetic resonance imaging or computerized tomography. We hypothesized that adding post-ablation kidney biopsy would help confirm treatment success. MATERIALS AND METHODS From April 2002 to March 2006 a total of 109 renal lesions in 88 patients were ablated with percutaneous radio frequency ablation and from September 1997 to January 2006 a total of 192 lesions in 176 patients were treated with laparoscopic cryoablation. Patients were followed with radiographic imaging and post-ablation biopsy at 6 months. RESULTS Radiographic success at 6 months was 85% (62 cases) and 90% (125) for radio frequency ablation and cryoablation, respectively. At 6 months 134 lesions (45%) were biopsied and success in the radio frequency ablation cohort decreased to 64.8% (24 cases), while cryoablation success remained high at 93.8% (91). Six of 13 patients (46.2%) with a 6-month positive biopsy after radio frequency ablation demonstrated no enhancement on posttreatment magnetic resonance imaging or computerized tomography. In patients treated with cryoablation all positive biopsies revealed posttreatment enhancement on imaging just before biopsy. CONCLUSIONS We observed a poor correlation between radiographic imaging and pathological analysis. We recommend post-radio frequency ablation followup biopsy due to the significant risk of residual renal cell cancer without radiographic evidence, although to our knowledge the clinical significance of these viable cells remains to be determined. In contrast, radiographic images of renal lesions treated with cryotherapy appeared to correlate adequately with corresponding histopathological findings in our series.

Active treatment of localized renal tumors may not impact overall survival in patients aged 75 years or older

Although nephrectomy cures most localized renal cancers, this oncologic benefit may be outweighed by the renal functional costs of such an approach. In this study, the authors examined overall survival in 537 patients who had localized renal tumors ≤7 cm detected at age ≥75 years to investigate whether surgical intervention improved survival compared with active surveillance.

Partial nephrectomy is associated with improved overall survival compared to radical nephrectomy in patients with unanticipated benign renal tumours.

BACKGROUND Partial nephrectomy (PN) has been associated with improved overall survival (OS) in select cohorts with localised renal masses when compared to radical nephrectomy (RN). The driving forces behind these differences have been difficult to elucidate given the heterogeneity of previously compared cohorts. OBJECTIVE Compare OS in a subset of patients with unanticipated benign renal masses to minimise the confounding effect of cancer. DESIGN, SETTING, AND PARTICIPANTS We retrospectively evaluated 2608 consecutive clinical T1 enhancing renal masses that were treated with extirpative surgery at our institution between 1999 and 2006. Of these, 499 tumours (19%) were found to be benign on final pathology. Preoperative data and renal functional data were used to generate a propensity model that was then plugged into a multivariate model of survival. Median follow-up for the entire cohort was 50 mo (interquartile range [IQR]: 32-73). INTERVENTION All patients underwent PN or RN. MEASUREMENTS We measured OS and cardiac-specific survival. RESULTS AND LIMITATIONS Five-year OS estimates for the PN (n=388) and RN (n=111) cohorts were 95% (95% confidence interval [CI], 93-98) versus 83% (95% CI, 74-90), respectively (P<0.0001). On multivariate analysis, controlling for both comorbidity and age, RN was associated with a 2.5-fold increased risk of death compared to PN (hazard ratio [HR]: 2.5; 95% CI, 1.3-5.1). Postoperative estimated glomerular filtration rate (eGFR) was also an independent predictor of OS and cardiac-specific survival (HR: 0.97; 95% CI, 0.95-0.99 and HR: 0.96; 95% CI, 0.93-0.99, respectively). The retrospective nature of this analysis limits the strength of the conclusions. CONCLUSIONS PN was associated with better OS when compared to RN in patients with unanticipated benign tumours. This observed survival advantage appears partly to be the result of better preservation of eGFR, but other kidney functions or unmeasured factors may also play a role. These data indicate that PN should be aggressively pursued in any patient where PN is technically feasible.

Laparoscopic Radical Versus Partial Nephrectomy for Tumors >4 cm: Intermediate-term Oncologic and Functional Outcomes

OBJECTIVES To compare the oncologic and functional outcomes of laparoscopic radical nephrectomy (LRN) and laparoscopic partial nephrectomy (LPN) for clinical Stage T1b-T3 renal cell carcinoma >4 cm in size. METHODS This retrospective analysis compared patients undergoing LRN (n = 75) or LPN (n = 35) at a tertiary referral center from April 2001 to December 2005 for Stage T1b-T3N0M0 renal cell carcinoma. The endpoints included radiologically verified systemic and local recurrence, cancer-specific mortality, overall mortality, and chronic kidney disease as determined from the calculated glomerular filtration rate and Kidney Foundation Dialysis Outcomes Quality Initiative diagnostic criteria. RESULTS The LRN group had larger tumors (5.3 vs 4.9 cm; P = .03), more T3a tumors (33% vs 9%; P = .006), and more clear cell pathologic features (85% vs 66%; P = .03). No surgical margins in either group were positive. The median follow-up was 57 months (range 27-79) for the LRN group and 44 months (range 27-85) for the LPN group (P = .1). The overall mortality (11% vs 11%), cancer-specific mortality (3% vs 3%), and recurrence (3% vs 6%) rates (P = .4) were equivalent. The postoperative decrease in the estimated glomerular filtration rate was less in the LPN group than in the LRN group at 13 and 24 mL/min, respectively (P = .03). Postoperatively, 2-stage increases in the chronic kidney disease stage occurred in 12% vs 0% of patients in the LRN and LPN groups, respectively (P < .001). CONCLUSIONS Our intermediate-term data have indicated that in appropriate patients with Stage T1b-T3 tumors >4 cm, LPN provides equivalent oncologic efficacy and superior renal functional outcomes compared with LRN. Future studies are required to confirm these trends.

Elective Partial Nephrectomy in Patients With Clinical T1b Renal Tumors Is Associated With Improved Overall Survival

OBJECTIVES Elective partial nephrectomy (PN) in patients with cT1b renal tumors is relatively unstudied. Most surgeons currently only perform radical nephrectomy (RN) in this population. Patients with localized kidney cancer may die from disease, but the risk of a non-cancerrelated death is significant and may be worsened by nephrectomy-induced chronic kidney disease (CKD). PN may offer the perfect combination of cancer control and preservation of renal function; therefore we compared overall and cancer-specific survival in patients treated for cT1b renal masses. METHODS From 1999 to 1906, 510 patients with renal tumors >4-7 cm, a glomerular filtration rate (GFR) >60, and a normal contralateral kidney underwent extirpative surgery (PN, n = 212 or RN, n = 298) at our institution. As the patients were not randomized, we generated a propensity model based on preoperative patient characteristics to control for selection bias. RESULTS Cancer-specific survival was similar between cohorts when compared by pathologic stage and grade. On multivariate analysis, RN was associated with postoperative CKD (odds ratio 3.4, 95% confidence interval [CI] 2.1-5.6). Survival analysis demonstrated that when controlling for the propensity score, PN was associated with better overall survival (hazard ratio 0.30, 95% CI = .13-.71). CONCLUSIONS Where technically feasible, PN offers cancer control equivalent to that of RN. Elective PN was associated with a significantly better overall survival in this cohort, even when controlling for age, tumor size, pathologic stage, and burden of comorbid diseases. The improvement in overall survival appears to be attributable in part to prevention of postoperative CKD.

Contemporary Trends in Nephrectomy for Renal Cell Carcinoma in the United States: Results From a Population Based Cohort

PURPOSE Despite benefits in functional renal outcome and the similar oncological efficacy of partial nephrectomy for renal cell carcinoma, previous studies show marked underuse of partial nephrectomy. We describe national trends in partial and radical nephrectomy using a contemporary, population based cohort. MATERIALS AND METHODS Using the 2003 to 2008 Nationwide Inpatient Sample we identified 188,702 patients treated with partial or radical nephrectomy for renal cell carcinoma at a total of 1,755 hospitals. Multivariate logistic regression was used to assess the independent associations of patient and hospital characteristics with partial nephrectomy. Post-estimations from multivariate logistic regression were done to ascertain the annual predicted probability of partial nephrectomy by hospital feature. RESULTS Overall 149,636 (79.3%) and 39,066 patients (20.7%) underwent radical and partial nephrectomy for renal cell carcinoma, respectively. Partial nephrectomy use increased each year from 16.8% in 2003 to 25.1% in 2008 (p for trend <0.001). On multivariate analysis patients were more likely to undergo partial nephrectomy at teaching (OR 1.31, p <0.001) and urban (OR 1.13, p = 0.05) hospitals compared to nonteaching and rural hospitals, respectively. Each quartile of higher nephrectomy annual volume was associated with higher odds of partial nephrectomy compared to the lowest quartile (OR 1.21, p <0.001). Although annual predicted partial nephrectomy use increased across all hospitals, differences in annual partial nephrectomy use by teaching status, site (urban vs rural) and case volume persisted with time. CONCLUSIONS Although the use of partial nephrectomy for renal cell carcinoma is increasing nationally across all hospitals, academic and urban hospitals as well as those with higher nephrectomy volume continue to show higher partial nephrectomy use for renal cell carcinoma.