New Paradigms for Cytoreductive Nephrectomy (original) (raw)
Related papers
British Journal of Medical and Surgical Urology, 2011
Objective: We report a tertiary referral centre's experience of cytoreductive nephrectomy (CN) combined with immunotherapy as part of multimodality treatment for metastatic renal cell cancer (mRCC) over a period of 8 years. Patients and methods: Patients who underwent CN as part of multimodality treatment for mRCC were identified from our nephrectomy database. Demographic characteristics, oncological outcome, reasons for failure to start or to complete immunotherapy, pathological findings and a comparison between open and laparoscopic CN were evaluated. Results: Forty patients underwent CN for mRCC preceding immunotherapy. 26 (65%) failed to receive immunotherapy. This was most commonly due to poor performance status postoperatively (12/26, 46%). 14 patients (35%) received immunotherapy following surgery and 9 (23%) patients completed treatment. Laparoscopic CN was associated with a significantly lower blood loss, shorter hospital stay and lower rate of transfusion than the open approach. Conclusion: Patients are at significant risk of failure to proceed to adjuvant immunotherapy following CN for mRCC, most commonly due to poor performance status postoperatively. Laparoscopic CN is shown to be safe and effective in well-selected patients. As new targeted treatments for mRCC emerge and their * Corresponding author. Present address: C. Martenstein et al. use in combination with CN is evaluated, a detailed and multidisciplinary approach to selection of these patients will continue to be crucial.
Immunotherapy for metastatic renal cell carcinoma
The Cochrane library, 2017
Background Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both. Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients. In November 2015, nivolumab, a checkpoint inhibitor directed against programmed death-1 (PD-1), was approved as the first specific immunotherapeutic agent as second-line therapy in previously treated mRCC patients. Objectives To assess the effects of immunotherapies either alone or in combination with standard targeted therapies for the treatment of metastatic renal cell carcinoma and their efficacy to maximize patient benefit. Search methods We searched the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science and registers of ongoing clinical trials in November 2016 without language restrictions. We scanned reference lists and contacted experts in the field to obtain further information. Selection criteria We included randomized controlled trials (RCTs) and quasi-RCTs with or without blinding involving people with mRCC.
Is Cytoreductive Nephrectomy Still a Standard of Care in Metastatic Renal Cell Carcinoma?
Journal of Kidney Cancer and VHL
Cytoreductive nephrectomy has been an integral part of management in metastatic renal cell carcinoma for patients with good performance status, based on the benefit shown by prospective trials in the interferon era and retrospective trials in the targeted therapies era. Clinical Trial to Assess the Importance of Nephrectomy (CARMENA), the first prospective phase III trial comparing a targeted agent alone (sunitinib) versus nephrectomy plus sunitinib, has been recently published, showing non-inferiority for the nephrectomy-sparing arm. In this article, we discuss the impact of nephrectomy including its immune-mediated effects, surgical morbidity and mortality, and the clinical data supporting the indications of nephrectomy in order to analyze the CARMENA trial in context, with the aim to identify optimal strategies for different patient populations in the metastatic setting.
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.
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.
Immunotherapy of metastatic kidney cancer
International Journal of Cancer, 2001
122 MRCC patients were treated by monthly intralymphatic injections (containing a mean of 573 IL-2 U and 26 ؋ 10 6 LAK cells) and i.m. administration of IFN and TF; 71 patients also received a 3-day cycle of monthly IL-2 inhalations with a mean of 998 daily U. MRCC cases not treated by immunotherapy (n ؍ 89) represent our historical controls. Adverse clinical side effects related to treatment were negligible. CR (n ؍ 11) and PR (n ؍ 13) were noticed in 24/122 patients. Of 24 responding patients, 17 resumed progression, whereas 7 remain in remission 11-69 months later. The overall median survival of treated patients (28 months) was 3.5-fold higher than the median survival of historical controls (7.5 months), and a Kaplan-Meier curve showed 25% survival 11 years after the beginning of immunotherapy. Apparently, the addition of IL-2 by inhalation improved survival. The present immunotherapy protocol appears to be efficacious, safe, devoid of adverse side effects, far less costly than others and able to offer a good quality of life to MRCC patients; if confirmed in a multicenter trial, it could set the basis for developing lowdose immunomodulatory treatments.
Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review
BioMed Research International, 2015
Localized renal cell carcinoma (RCC) is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR) inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate...