Is Cytoreductive Nephrectomy Still a Standard of Care in Metastatic Renal Cell Carcinoma? (original) (raw)
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Clinical Cancer Research, 2007
In the era before cytokine therapy, controversy existed about the need for cytoreductive nephrectomy in treating patients with metastatic renal cell carcinoma. In 1978, Dekernion showed that nephrectomy alone had no effect on survival. During this period, removal of the malignant kidney was confined to palliative therapy in some settings of metastatic RCC, such as pain related to the kidney mass, intractable hematuria, erythrocytosis, uncontrolled hypertension, or poorly controlled hypercalcemia.When interleukin-2 was approved by the Food and Drug Administration in 1992, the role of nephrectomy was reexamined. After a decade of controversy, two randomized controlled studies established that cytoreductive surgery has a role in properly selected patients and offers a survival advantage when done before cytokine therapy. Unfortunately, the mechanisms underlying this benefit remain poorly understood. Immunotherapy may work best when there is a small volume of cancer present, and removing a large primary tumor may prevent the seeding of additional metastases. Data have also suggested that primary tumors were capable of producing immunosuppressive compounds that might decrease the efficacy of immunotherapy. Another hypothesis suggested that removing the kidney altered the acid/base status of the patient to such an extent that the growth of the tumor was hindered. With the emergence in 2006 of two targeted agents for advanced renal cell carcinoma, the role of cytoreductive nephrectomy has reemerged as a source of controversy. Although evidence-based medical practice suggests a role for nephrectomy before the use of targeted agents, the arguments for and against this practice will be weighed.
International Journal of Urology, 2014
In the era before cytokine therapy, controversy existed about the need for cytoreductive nephrectomy in treating patients with metastatic renal cell carcinoma. In 1978, Dekernion showed that nephrectomy alone had no effect on survival. During this period, removal of the malignant kidney was confined to palliative therapy in some settings of metastatic RCC, such as pain related to the kidney mass, intractable hematuria, erythrocytosis, uncontrolled hypertension, or poorly controlled hypercalcemia.When interleukin-2 was approved by the Food and Drug Administration in 1992, the role of nephrectomy was reexamined. After a decade of controversy, two randomized controlled studies established that cytoreductive surgery has a role in properly selected patients and offers a survival advantage when done before cytokine therapy. Unfortunately, the mechanisms underlying this benefit remain poorly understood. Immunotherapy may work best when there is a small volume of cancer present, and removing a large primary tumor may prevent the seeding of additional metastases. Data have also suggested that primary tumors were capable of producing immunosuppressive compounds that might decrease the efficacy of immunotherapy. Another hypothesis suggested that removing the kidney altered the acid/base status of the patient to such an extent that the growth of the tumor was hindered. With the emergence in 2006 of two targeted agents for advanced renal cell carcinoma, the role of cytoreductive nephrectomy has reemerged as a source of controversy. Although evidence-based medical practice suggests a role for nephrectomy before the use of targeted agents, the arguments for and against this practice will be weighed.
Urologia internationalis, 2012
To describe for surgeons contemplating performing cytoreductive nephrectomy (CRN) on patients after neoadjuvant sunitinib compared to a benchmark of open radical nephrectomy, describing technical difficulties, safety and feasibility. We compared measurable surgical parameters and perioperative complications in 22 patients with metastatic renal cell carcinoma (mRCC) undergoing CRN after neoadjuvant sunitinib, with 28 patients who underwent open radical nephrectomy for non-metastatic disease (nmRCC). Median blood loss (320 vs. 775 ml), median operative time (128 vs. 195 min) and median length of stay (5 vs. 7 days) were greater in the mRCC group. Surgery after sunitinib was technically challenging due to fibrosis, loss of the tissue planes that usually facilitate radical nephrectomy and abnormal blood vessel formation. Side effects of sunitinib resulted in predictable complications. CRN after treatment with sunitinib is safe and feasible in our hands, although the surgery is more time...
Medical Science
Introduction: Renal cell carcinoma presents with metastatic disease in approximately 30% of cases. Since the introduction of targeted therapies, they have demonstrated impressive gains in overall survival, progression-free survival and response rates over the previously utilized immunotherapies in cases with mRCC. The rates of cytoreductive nephrectomy have declined since the introduction of targeted therapy. We report our experience with cytoreductive nephrectomy plus targeted therapy. Materials & Methods: We retrospectively collected the hospital inpatient and outpatient records of mRCC who had undergone cytoreductive nephrectomy trailed by targeted treatment. Data included demographic, clinical, imaging and laboratory data and those that were found to have prognostic value. Measured outcomes included OS. Results: 78 patients (61 males and 17 females) 60.17± 8.76 years was mean age who underwent cytoreductive nephrectomy for mRCC of clear cell type. 43 (55.1%) patients had comorbidity. 78 patients had huge renal masses (mean 10.167±2.756 cms) on CT imaging. All patients were introduced on target therapy four to eight weeks after surgery. The mean overall survival of the patients was 27.98±1.47 months. Conclusions: Presently the important role of cytoreductive nephrectomy is not well defined in the ear of targeted therapy. However, in our study patient with good performance statuses do better than patients with existing health risks.
JAMA Oncology, 2018
patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown. OBJECTIVE To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied. INTERVENTIONS Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy. MAIN OUTCOMES AND MEASURES Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points. RESULTS The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%). CONCLUSIONS AND RELEVANCE Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01099423.
Cancers, 2020
The role of cytoreductive nephrectomy (CN) in treatment of locally advanced or metastatic renal cell carcinoma (mRCC) in the era of targeted therapies (TT) is still not clearly defined. The study population consisted of 730 patients with synchronous mRCC. The RenIS (Renal carcinoma Information System) registry was used as the data source. The CN/TT cohort included patients having CN within 3 months from the mRCC diagnosis and subsequently being treated with TT, while the TT cohort included patients receiving TT upfront. Median progression-free survival from the first intervention was 6.7 months in the TT arm and 9.3 months in the CN/TT patients (p < 0.001). Median overall survival was 14.2 and 27.2 months, respectively (p < 0.001). Liver metastasis, high-grade tumor, absence of CN, non-clear cell histology, and MSKCC (Memorial Sloan-Kettering Cancer Center) poor prognosis status were associated with adverse treatment outcomes. According to the results of this retrospective stu...
Journal of Translational Medicine
Background Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era. Methods We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups. Results Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32–0.60, p < 0.001) with a longer median overall survival (OS) (35.9 months vs 12.1 months), 1-year OS of 71.6% vs 50.5% and 2-years OS of 56.5% vs 22.0% compared to those who did not. No significant interaction between nephrectomy and the overall five Meet-URO score risk groups was...
Current Urology, 2015
Renal cell carcinoma • Laparoscopic nephrectomy • Cytoreductive nephrectomy • Targeted therapy • Metastatic renal cell carcinoma We present a 55-year-old male, with good performance status who was diagnosed with a case of metastatic renal cell carcinoma following a pathologic femur fracture. Despite good performance status, multifocal metastases and poor-prognostic features portended a grim prognosis with predicted overall survival of less than nine months. On initial presentation, he was excluded from cytoreductive nephrectomy based on brain metastasis and interleukin-2 was not pursued as the primary tumor was to be left in situ. The patient was reconsidered for cytoreductive nephrectomy after sustained response to fifth line targeted therapies with shrinkage of tumor burden. The post-operative course was uneventful and the patient was discharged home on postoperative day one. Temsirolimus was resumed one week after surgery and the patient reported returning to his normal activities at the two week follow-up visit. We highlight important clinical features of metastatic renal cell carcinoma,