Cytoreductive Nephrectomy In Patients Research Articles

1659 A POPULATION-BASED ANALYSIS OF PERIOPERATIVE COMPLICATIONS AND MORTALITY ASSOCIATED WITH CYTOREDUCTIVE NEPHRECTOMY FOR METASTATIC RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Advanced1 Apr 20101659 A POPULATION-BASED ANALYSIS OF PERIOPERATIVE COMPLICATIONS AND MORTALITY ASSOCIATED WITH CYTOREDUCTIVE NEPHRECTOMY FOR METASTATIC RENAL CELL CARCINOMA Giovanni Lughezzani, Lars Budaus, Claudio Jeldres, Rodolphe Thuret, Daniel Liberman, Maxine Sun, Shahrokh F. Shariat, Hugues Widmer, Philippe Arjane, Wassim Kassouf, Markus Graefen, Francesco Montorsi, Paul Perrotte, and Pierre I. Karakiewicz Giovanni LughezzaniGiovanni Lughezzani Milano, Italy More articles by this author , Lars BudausLars Budaus Hamburg, Germany More articles by this author , Claudio JeldresClaudio Jeldres Montreal, Canada More articles by this author , Rodolphe ThuretRodolphe Thuret Montpellier, France More articles by this author , Daniel LibermanDaniel Liberman Montreal, Canada More articles by this author , Maxine SunMaxine Sun Montreal, Canada More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat Montreal, Canada More articles by this author , Hugues WidmerHugues Widmer Montreal, Canada More articles by this author , Philippe ArjanePhilippe Arjane Montreal, Canada More articles by this author , Wassim KassoufWassim Kassouf Montreal, Canada More articles by this author , Markus GraefenMarkus Graefen Hamburg, Germany More articles by this author , Francesco MontorsiFrancesco Montorsi Milano, Italy More articles by this author , Paul PerrottePaul Perrotte Montreal, Canada More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz Montreal, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1462AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cytoreductive nephrectomy (CNT) may improve survival of patients with metastatic RCC (mRCC). However, it may be associated with higher morbidity and mortality rates relative to nephrectomy in non-mRCC patients. We assessed the perioperative outcomes of CNT in patients with mRCC and compare these to the outcomes of individuals who underwent a nephrectomy for non-mRCC in a large population-based dataset METHODS Between 1988 and 2008, 1985 and 27037 patients underwent a nephrectomy for respectively mRCC and non-mRCC in the state of Florida. We examined patient characteristics, complications and perioperative mortality rates of patients with mRCC who underwent a CNT and we compared those with the characteristics and outcomes of individuals with non-mRCC. RESULTS Relative to non-mRCC individuals, a larger proportion of mRCC patients were males (67.9 vs. 61.6%; p<0.001) and represented emergency admissions (27.5 vs. 19.4%; p<0.001). Length of stay was statistically significantly longer in patients with mRCC relative to their non-mRCC counterparts (9.5 vs. 6.7 days; p<0.001). The overall complication rate was also higher in mRCC patients (29.6 vs. 22.8%; p<0.001). Specifically, the rates of accidental intraoperative lacerations (5.6 vs. 3.6%; p<0.001), postoperative cardiac complications (4.2 vs. 2.4%; p<0.001), vascular complications (2.5 vs. 0.8)%; p<0.001), respiratory complications (8.4 vs. 6.4%; p=0.001), hemorrhage (2.6 vs. 1.4%; p<0.001), and postoperative infections (2.0 vs. 1.4%; p=0.02) were higher in patients with mRCC. Perioperative in-hospital mortality rate was also higher in mRCC patients (3.0 vs. 1.2%; p<0.001). In multivariable logistic regression models, after adjusting for patient age, gender, race, insurance type, average annual surgical and hospital volume, mRCC was a statistically significant predictor of any complication type (OR: 2.7 [95%CI: 2.0-3.5]; p<0.001), and predicted higher perioperative mortality (OR: 1.4 [95%CI: 1.3-1.6]; p<0.001). CONCLUSIONS Nephrectomy in individuals with mRCC is associated with higher complication and perioperative mortality rates relative to nephrectomy performed in patients with non-mRCC. This information should be included in informed consent. Moreover, careful patient selection is critical to minimize morbidity and mortality after CNT. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e640-e641 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giovanni Lughezzani Milano, Italy More articles by this author Lars Budaus Hamburg, Germany More articles by this author Claudio Jeldres Montreal, Canada More articles by this author Rodolphe Thuret Montpellier, France More articles by this author Daniel Liberman Montreal, Canada More articles by this author Maxine Sun Montreal, Canada More articles by this author Shahrokh F. Shariat Montreal, Canada More articles by this author Hugues Widmer Montreal, Canada More articles by this author Philippe Arjane Montreal, Canada More articles by this author Wassim Kassouf Montreal, Canada More articles by this author Markus Graefen Hamburg, Germany More articles by this author Francesco Montorsi Milano, Italy More articles by this author Paul Perrotte Montreal, Canada More articles by this author Pierre I. Karakiewicz Montreal, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP-14.15: Cytoreductive Nephrectomy in Patients with Metastatic Renal Carcinoma: Reasons for Failure to Complete Protocol Based Treatment

MP-14.15: Cytoreductive Nephrectomy in Patients with Metastatic Renal Carcinoma: Reasons for Failure to Complete Protocol Based Treatment

Phase II Presurgical Feasibility Study of Bevacizumab in Untreated Patients With Metastatic Renal Cell Carcinoma

To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy. Patients with newly diagnosed, clear cell mRCC whose primary tumors were considered resectable were enrolled. In this single-arm, phase II trial, patients received bevacizumab plus erlotinib (first patients, n = 23) or bevacizumab alone (n = 27 patients) for 8 weeks followed by restaging. If patients demonstrated progressive disease and had declining performance statuses after 8 weeks, nephrectomy procedures were deferred. Postoperatively, patients continued on the study drug or drugs if disease stabilization or regression had occurred. Between March 2005 and March 2008, 52 patients were enrolled on study, and 50 were included in the analysis. By Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk, features. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI, 5.5 to 15.6 months). Median overall survival was 25.4 months (95% CI, 11.4 months to not estimable). Two perioperative deaths occurred; neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients and treatment delay for two others. Presurgical treatment with bevacizumab therapy yields clinical outcomes comparable to post-surgical treatment with antiangiogenic therapy in patients with mRCC, but it may result in wound-healing delays. Prospective, randomized trials to test the use of presurgical therapy as a method to select appropriate patients for cytoreductive nephrectomy are warranted.

Phase II presurgical study of bevacizumab plus erlotinib in untreated patients with metastatic renal cell carcinoma

5004 Background: The safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC) is not known. The current study was designed to answer these clinical questions, and to define predictive tissue biomarkers using nephrectomy specimens from patients on trial. Methods: Patients with newly diagnosed clear cell mRCC whose primary tumor was considered resectable were enrolled. In this single arm phase II trial, patients received bevacizumab plus erlotinib or bevacizumab alone for 8 weeks, followed by restaging. Primary endpoint was progression free survival (PFS). If patients demonstrated progressive disease and had a declining performance status after eight weeks, nephrectomy was deferred. Postoperatively, patients continued on study drug(s) if disease stabilization or regression had occurred. Reverse phase protein arrays (RPPAs) were generated from nephrectomy specimens. Results: Between March 2005 and March 2008, 52 patients were enrolled on the study, and 50 were included in the analysis. By the Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk features. Twenty-three patients received bevacizumab plus erlotinib, and 27 received bevacizumab alone. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI: 5.5, 15.6 months). Median overall survival was 25.4 months (95% CI 11.4, not estimable). Two perioperative deaths occurred, and neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients. RPPA analysis demonstrated a clear separation of better versus worse responding patients. Conclusions: Presurgical treatment with bevacizumab therapy is relatively safe and yields clinical outcomes comparable to post surgical treatment with antivascular therapy in patients with mRCC. Prospective randomized trials testing the use of presurgical therapy to select appropriate patients for cytoreductive nephrectomy are warranted. [Table: see text]

Cytoreductive nephrectomy for T4NxM1 renal cell carcinoma: The M.D. Anderson Cancer Center experience: Kassouf W, Sanchez-Ortiz R, Tamboli P, Jonasch E, Merchant MM, Spiess PE, Wood CG, Department of Urology, McGill University Health Center, Montreal, Quebec, Canada

Although cytoreductive nephrectomy may provide a survival benefit in metastatic renal cell carcinoma, patients with locally advanced lesions may be denied cytoreduction because of a perceived worse outcome and increased morbidity. We reviewed our experience with cytoreductive nephrectomy in patients with contiguous organ involvement (Stage T4NxM1) to evaluate the outcome and morbidity. From 1993 to 2004, 498 patients underwent cytoreductive nephrectomy for renal cell carcinoma. Of those, 23 patients had Stage T4NxM1 disease. The analyzed variables included surgical complications, palliation of symptoms, and survival. The median patient age was 55 years (range 35–73), with a median tumor size of 15 cm (range 7–30). The median overall and disease-specific survival was 6.8 months (range 1.4–25.7). The distribution of the histologic type was conventional in 16, papillary in 2, and unclassified in 5. Sarcomatoid features were present in 9 patients. In 2 patients, surgery was aborted because of unresectable disease. Three patients developed postoperative complications (one wound dehiscence, one pancreatic collection, and one seizure). The median length of stay was 7 days (range 5–19). Of the 7 patients with local symptoms, 5 experienced postoperative palliation. Most patients (79%) received postoperative systemic therapy after a median of 39 days (range 24–114). Five patients did not receive systemic therapy because of disease progression. The median disease-specific survival for the patients who received systemic therapy was 7.1 months (range 1.4–25.7), but only 2.5 months (range 0–5.2) for those who had not ( P = 0.003). Cytoreductive nephrectomy in Stage T4NxM1 renal cell carcinoma is feasible and provides significant palliation in symptomatic patients; however, the survival benefit is unclear. Our retrospective series has demonstrated that the prognosis in these patients is poor.

Cytoreductive Nephrectomy for T4NxM1 Renal Cell Carcinoma: The M.D. Anderson Cancer Center Experience

Although cytoreductive nephrectomy may provide a survival benefit in metastatic renal cell carcinoma, patients with locally advanced lesions may be denied cytoreduction because of a perceived worse outcome and increased morbidity. We reviewed our experience with cytoreductive nephrectomy in patients with contiguous organ involvement (Stage T4NxM1) to evaluate the outcome and morbidity. From 1993 to 2004, 498 patients underwent cytoreductive nephrectomy for renal cell carcinoma. Of those, 23 patients had Stage T4NxM1 disease. The analyzed variables included surgical complications, palliation of symptoms, and survival. The median patient age was 55 years (range 35 to 73), with a median tumor size of 15 cm (range 7 to 30). The median overall and disease-specific survival was 6.8 months (range 1.4 to 25.7). The distribution of the histologic type was conventional in 16, papillary in 2, and unclassified in 5. Sarcomatoid features were present in 9 patients. In 2 patients, surgery was aborted because of unresectable disease. Three patients developed postoperative complications (one wound dehiscence, one pancreatic collection, and one seizure). The median length of stay was 7 days (range 5 to 19). Of the 7 patients with local symptoms, 5 experienced postoperative palliation. Most patients (79%) received postoperative systemic therapy after a median of 39 days (range 24 to 114). Five patients did not receive systemic therapy because of disease progression. The median disease-specific survival for the patients who received systemic therapy was 7.1 months (range 1.4 to 25.7), but only 2.5 months (range 0 to 5.2) for those who had not (P = 0.003). Cytoreductive nephrectomy in Stage T4NxM1 renal cell carcinoma is feasible and provides significant palliation in symptomatic patients; however, the survival benefit is unclear. Our retrospective series has demonstrated that the prognosis in these patients is poor.

The Role of Nephron Sparing Surgery for Metastatic (pM1) Renal Cell Carcinoma

Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic renal cell carcinoma. We evaluated the role of nephron sparing surgery in these patients. We selected all patients with pM1 renal cell carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 renal cell carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry. We identified 16 patients who underwent nephron sparing surgery for pM1 renal cell carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 renal cell carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron sparing surgery for solitary kidney cases were more likely to have early (33% vs 10%, p = 0.009) or late (50% vs 19%, p = 0.018) complications compared with pM1 radical nephrectomy cases. There were no significant differences in early (p = 0.475) or late (p = 0.350) complications between pM1 nephron sparing surgery cases and 139 pM0 nephron sparing surgery cases. Cancer specific survival rates in pM1 nephron sparing surgery cases were comparable to pM1 radical nephrectomy cases. Although there were differences in early and late complications between the pM1 nephron sparing surgery and pM1 radical nephrectomy groups, there were no differences when compared with imperative pM0 nephron sparing surgery cases. This study demonstrates that nephron sparing surgery can achieve adequate cytoreductive therapy while preserving renal function, with postoperative complication rates similar to those of pM0 nephron sparing surgery cases.

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

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. 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. 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. 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.

Cytoreductive Nephrectomy in Patients With Metastatic Renal Cancer: A Combined Analysis

Metastatic renal cancer is associated with a poor prognosis. Recent advances in immunotherapy for this problem have rekindled interest in cytoreductive nephrectomy. We report a combined analysis of 2 prospective randomized trials that used an identical study protocol. A total of 331 patients were randomized to 2 identical protocols comparing cytoreductive nephrectomy plus interferon alpha-2b vs interferon alpha-2b alone in patients with metastatic renal cancer, in whom the primary tumor was present and believed to be resectable. The primary end point for each trial was overall survival with a secondary end point of the response rate. Patients were stratified at pre-randomization by performance status (0 or 1), site of metastases (lung only vs other) and disease measurability. All results were analyzed by intent to treat criteria. Assuming a median survival of 1 year for interferon only, the Southwest Oncology Group trial was designed to detect a 50% improvement in median survival duration and a 15% improvement in response rate with a power of 0.85. The European Organization for the Research and Treatment of Cancer accrued an additional 80 patients in that study. The combined analysis of these 2 trials yielded a median survival of 13.6 months for nephrectomy plus interferon vs 7.8 months for interferon alone. This difference represents a 31% decrease in the risk of death (p = 0.002). There was no evidence of a difference in the size of the treatment effect according to pre-randomization stratification factors. Cytoreductive nephrectomy appears to improve significantly overall survival in patients with metastatic renal cancer treated with interferon immunotherapy independent of patient performance status, the site of metastases and the presence of measurable disease. Although it is highly statistically significant, the overall survival advantage is only 5.8 months for the entire group. These data emphasize the need to determine if this survival advantage can be further improved using more aggressive immunotherapy or other novel agents in the setting of cytoreductive nephrectomy.

Renal Cell Carcinoma With Tumor Thrombus: Is Cytoreductive Nephrectomy For Advanced Disease Associated With An Increased Complication Rate?

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. 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. 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. 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.

Cytoreductive nephrectomy: is it a realistic option in patients with renal cancer?

To evaluate the role of cytoreductive nephrectomy (CRN) in improving survival in patients with renal cell cancer. The case-notes of 268 consecutive patients who presented to our specialized renal cancer clinic between 1998 and 2001 were reviewed. All patients with metastatic disease were assessed for CRN. If their primary tumour was considered operable, they were assessed further using the European Cooperative Oncology Group performance score; only patients with a performance score of 0 or 1 were considered for surgery. In all, 168 patients underwent nephrectomy with curative intent for M0 disease and 11 were treated conservatively. Ninety-four patients with M+ disease (mean age 65 years, range 38-80) were considered for CRN. Thirty-eight patients had an inoperable primary. Of the remaining 56 patients, 20 had a performance status of 0 or 1 and were offered CRN. Metastatic disease at presentation occurred in 34% of all patients referred; 40% patients had an inoperable primary and 38% had a performance score of > or =2. With an active policy of considering all patients for CRN, only 7% of those with renal cancer were suitable for this procedure. CRN is unlikely to have a significant effect on overall survival within a population of patients with renal cancer.

Laparoscopic cytoreductive nephrectomy as preparation for administration of systemic interleukin-2 in the treatment of metastatic renal cell carcinoma: a pilot study

Objectives. Cytoreductive nephrectomy is commonly performed in patients with metastatic renal cell carcinoma before systemic interleukin-2 (IL-2) therapy. Open nephrectomy is associated with prolonged recovery during which metastatic disease can progress. The feasibility of laparoscopic cytoreductive surgery in these patients with large renal tumors was examined. The role of tumor morcellation in reducing the recovery period and allowing earlier treatment with IL-2 was investigated. Methods. Patients with metastatic renal cancer underwent either open nephrectomy (group 1, n = 19) or laparoscopic cytoreductive nephrectomy (n = 11; 6 with tumor morcellation [group 2], 5 with removal of the tumor through a small incision [group 3]). The three groups were compared to evaluate relative recovery, suitability for treatment with IL-2, and laparoscopic port site seeding. Results. A group of 19 patients underwent open nephrectomy (group 1). Eleven patients with a median tumor volume of 377 cm 3 (median tumor diameter 9 cm) underwent laparoscopic cytoreductive nephrectomy. Six of these patients underwent tumor morcellation (group 2) and 5 underwent laparoscopic assisted nephrectomy (group 3). There was no difference in patient age, sex, sites of metastatic disease, ECOG status, size of renal tumor, or surgical complication rates among groups. Patients whose tumor was morcellated had reduced postoperative parenteral narcotic requirements and were discharged sooner than patients undergoing open cytoreductive nephrectomy. Time to treatment with IL-2 was shortest in the morcellation group (median time to treatment 37 days). No port site seeding was observed. Conclusions. Laparoscopic cytoreductive nephrectomy in patients with bulky renal disease is a safe procedure in selected patients. This pilot study demonstrated a significant association of laparoscopic tumor morcellation with less postoperative pain, faster time to discharge, and shorter time to treatment with IL-2. A randomized study is warranted to determine the role of laparoscopic cytoreductive nephrectomy with tumor morcellation.