Role Of Nephrectomy Research Articles

Patients with metastatic renal cell carcinoma who receive immune-targeted therapy may derive survival benefit from nephrectomy

BackgroundNephrectomy, whether in the era of cytokine therapy or targeted therapy, has an important role in the treatment of metastatic renal cell carcinoma. With the advent of immunotherapy, immunotherapy combined with targeted therapy has become the mainstream of systemic therapy, but the role of nephrectomy in metastatic renal cell carcinoma is unclear. In this study, we retrospectively analyzed the impact of nephrectomy on survival in patients with metastatic renal cell carcinoma who received immune-targeted therapy.MethodsPatients with metastatic renal cell carcinoma who received immune-targeted therapy at three centers between May 17, 2019 and August 1, 2022 were collected, who were divided into two groups based on whether nephrectomy was performed or not. Survival, response rate and adverse event were compared between the two groups. The primary end point was progression free survival, Subgroup analysis and univariate and multivariable prognostic analyses were also assessed.ResultsWith a median follow-up time of 29.3 months (95% CI 28.5–30.2), 165 patients were recruited and divided into two groups based on whether they underwent nephrectomy or not. There were 68 patients in the non-nephrectomy group, 97 in the nephrectomy group. Compared to patients treated with immune-targeted therapy, patients treated with immune-targeted therapy plus nephrectomy were able to achieve survival benefits, with a median PFS of 10.8 months (95% CI 8.3–13.3) and 14.4 months (95% CI 12.6–16.2), respectively, as well as an HR of 0.476 (95% CI 0.323–0.701, p = 0.0002). The 12-month and 18-month PFS rates were 30.9% versus 60.8% and 7.4% versus 25.8%, respectively. The objective response rate (ORR) was 52.9% and 60.8%, respectively, in the non-nephrectomy and nephrectomy groups (p = 0.313), and the disease control rate (DCR) was 75% and 83.5%, respectively (p = 0.179). The most common adverse events related to treatment were hypothyroidism, immune-related pneumonitis and rash. Multivariate analysis showed that primary tumor nephrectomy prior to immune-targeted therapy, clear cell renal carcinoma and oligo metastasis were independent prognostic factors.ConclusionsNephrectomy may provide PFS benefit with tolerable safety for patients with metastatic renal cell carcinoma who receive immune-targeted therapy. In multivariate analysis, nephrectomy, clear cell carcinoma, and oligo-organ metastasis were found to be favorable independent prognostic factors.

The prognostic role of nephrectomy in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with immunotherapy according to the novel prognostic Meet-URO score: Subanalysis of the Meet-URO 15 study.

4535 Background: Most of mRCC pts with favorable and intermediate prognosis, according to the IMDC classification, are offered a nephrectomy. However, in the immunotherapy era, the role of nephrectomy is still unclear. In the Meet-URO 15 study we reported the higher prognostic accuracy of the Meet-URO score compared to the IMDC score, by the addition of the neutrophil-to-lymphocyte ratio (NLR) and the presence of bone metastases to the IMDC score, identifying five categories with progressively worse prognosis. For this reason, we aimed to explore the prognostic impact of the previous nephrectomy (PN) on mRCC pts receiving immunotherapy and according to the Meet-URO score groups. Methods: The Meet-URO 15 study was a multicentric retrospective analysis on 571 pretreated mRCC pts receiving nivolumab. Univariable analysis of the correlation between PN and overall survival (OS) and multivariate analysis adjusted for IMDC score, therapy line, NLR and metastatic sites were performed. The interaction of PN with the Meet-URO prognostic groups was then evaluated. Results: 503/571 pts (88%) underwent PN. A reduced risk of death (HR = 0.44; 95% CI: 0.32-0.60; p< 0.001) and higher mOS and OS rate were observed in pts with PN than without (mOS: 36 vs 13 monhts; 1-year-OS 72% vs 52% and 2-year-OS 57% vs 24%, respectively). The reduced risk of death for pts who underwent PN was confirmed at the multivariate analysis (HR = 0.69; 95% CI: 0.49-0.97; p= 0.032). The percentage of pts receiving PN progressively reduced through the five Meet-URO prognostic groups (PN: group 1: 98%, group 2: 95%, group 3: 84%, group 4: 79%, group 5: 59%). No significant interaction was observed between the PN and Meet-URO score when all the five groups were considered ( p= 0.17). A significant interaction was observed when the Meet-URO groups 1,2 and 3 were taken together (HR = 0.40; 95% CI: 0.25-0.63; p< 0.001), highlighting the significant protective role of the PN on OS for these three groups. For the Meet-URO groups 4 and 5, the interaction was indeed not significant (HR = 0.81; 95% CI: 0.51-1.30; p= 0.39). Conclusions: PN has a favourable prognostic impact on pretreated mRCC pts receiving immunotherapy. This benefit may be limited to mRCC pts with more favorable diseases as belonging to Meet-URO prognostic groups 1, 2 and 3. Further analysis of the type of PN (i.e., radical vs cytoreductive) is ongoing and confirmatory prospective evaluations are warranted.

“PROBE”ing the Role of Cytoreductive Nephrectomy in Advanced Renal Cancer

The Southwest Oncology Group (SWOG)1931 trial, also known as PROBE (ClinicalTrials.gov Identifier: NCT04510597) is a phase III study evaluating the role of cytoreductive nephrectomy (CN) in metastatic renal cell cancer (RCC). Kidney cancer presenting with synchronous metastases has demonstrated shorter survival outcome compared to the patients relapsing with metastases after nephrectomy. Previously, CN has been associated with survival improvement when interferon-based systemic therapy was used. In the setting of antivascular therapy sunitinib, a prospective randomized clinical trial demonstrated no benefit of CN. Immune checkpoint-based combination therapy has now become the standard-of-care in the frontline setting for RCC. The role of nephrectomy or primary resection has not been evaluated in the setting of immune checkpoint-based systemic therapy. The sequence and optimal timing of nephrectomy is also not established. The PROBE study design attempts to answer the question whether CN has an impact on overall survival outcomes in RCC within the context of immune checkpoint-based combination regimens. The study requires starting with systemic therapy; any one of the FDA approved immunotherapy-based regimens at the time the study was activated are permitted. The disease status and response are evaluated at 9–12 weeks of therapy and then consented patients are randomized 1:1 to receive CN or to continue systemic therapy. The patients who have rapid disease progression are considered ineligible for randomization as they need a switch in systemic therapy. Both groups should continue systemic therapy as long as they are tolerating the treatment and continuing to derive clinical benefit. Quality-of-life, tumor genomic testing, microbiome, radiomics and circulating tumor DNA assessments as predictive biomarkers are planned as study correlatives. The study hypothesis is that CN will improve OS in synchronous metastatic RCC when surgery is performed after starting systemic immune checkpoint-based combination therapy. A potential mechanism leading to improved survival is the broader antigen spread and higher neoantigen load enabled by the primary tumor enhancing the efficacy of the immune therapy. CN after initial systemic therapy would help select the patient subset most likely to benefit and will potentially enable eradication of immune resistant clones within the primary tumor.

The role of nephrectomy in metastatic renal cell carcinoma in the immuno-oncology era.

Three first line, randomized phase III trials (Keynote 426, Checkmate 9ER and Checkmate 214) relied on predefined statistical criteria to validate the survival advantage of immuno-oncology (IO) based systemic treatment in metastatic renal cell carcinoma (mRCC) relative to Sunitinib. Within each of these three trials, a stratification according to prior nephrectomy was addressed in post-hoc progression free survival (PFS) and overall survival (OS) analyses.

Outcomes of Adults With Ewing Sarcoma Family of Tumors (ESFT) of the Kidney: A Single-Institution Experience.

Ewing sarcoma family of tumors (ESFT) of the kidney are exceedingly rare. Given the rarity of this neoplasm and the complexity associated with its management, information regarding treatment and outcome is warranted. We conducted a retrospective study of patients with ESFT of the kidney who were treated at MDACC between January 1, 2001 and January 1, 2011. Descriptive statistics were used. Thirteen patients were identified (median age, 33 y; male:female 11:2). Common presenting symptoms were back pain, flank pain, and hematuria. Six patients had metastatic disease at presentation. Initial diagnostic biopsy was performed in 6 patients. Immunohistochemistry showed strong positivity for CD99 (mic2) and cytogenetic analysis demonstrated evidence of EWSR1 fusion gene in 8 cases. Nine patients underwent nephrectomy. Frequently used chemotherapy regimens consisted of vincristine, doxorubicin, and ifosfamide. Median overall survival was 17.2 months. Three patients were alive at the time of analysis, at 2, 7, and 11 years from diagnosis (the latter without evidence of disease). Renal ESFT carry a guarded prognosis with limited response to therapy and short median overall survival. For patients with metastatic disease, diagnostic biopsy and sarcoma-based chemotherapy regimens are recommended as upfront therapeutic strategy. The role of nephrectomy in the metastatic setting is unclear. Future studies with novel therapies are needed.

878 - The Role of Nephrectomy in Metastatic Renal Cell Carcinoma - A Single Centre Analysis

ABSTRACT The approval of new therapeutic options has increased the survival of metastatic renal cell carcinoma (mRCC) patients (pts). These drugs were mostly studied in pts who underwent nephrectomy (Sx) prior to the diagnosis of metastatic disease (MD). Sx is also indicated for pts with MD who are suitable and have good performance status (PS). The aim of this work is to retrospectively analyse the benefit of Sx in the pts with mRCC referred to the Oncology Division at Santa Maria Hospital from 01/2006 to 10/2010. Two groups of pts were defined: pts who had Sx and pts who had no Sx. The first group was further divided into pts who had Sx whilst with non-MD (SxNMD) and pts who did it whilst with MD (SxMD). With significance set at p = 0.05 and the aid of IBM® SPSS® Statistics 20, statistical analysis was performed using descriptive statistics and Fisher's exact test. Overall survival (OS) - time from diagnosis of MD to death - was plotted using the Kaplan–Meier method and compared by log-rank test. The population had 44 pts: 72,7% (n = 32) male, 59,1% (n = 26) under 65 years old, 90,9% (n = 40) with Karnofsky PS (KPS) ≥80 and 59,1% (n = 26) with clear cell carcinoma. Half were diagnosed with non-MD (NMD) (n = 22) and progressed to MD in a mean of 45,9 months (m). Thirty-eight pts (86,4%) did medical therapy, of those 86,8% (n = 33) had favourable or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) criteria and 86,8% (n = 33) did target therapy. Thirty pts underwent Sx (68,2%) and 14 didn't (31,8%). There was no statistical difference between groups regarding gender, age, KPS, histology, MSKCC risk and medical therapy. The median OS was 14 and 27 m respectively for the no Sx group versus the Sx group (p = 0,027). In the pts who had Sx, 21 (70%) were part of the SxNMD group and 9 (30%) of the SxMD group. Except for Fuhrman grade (p = 0,022), there was no statistical difference between groups regarding gender, age, KPS, histology, MSKCC risk and medical therapy. The median OS for SxNMD had not been reached while the median OS for SxMD was 21 m (p = 0,682). In the population studied there was no difference in OS curves between the SxNMD group and the SxMD group. This suggests that Sx has a valuable role in pts diagnosed with MD in addition to medical therapy, namely target therapy. Disclosure All authors have declared no conflicts of interest.

The 7th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting

The 7th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting

Therapies and outcomes of non-renal cell carcinoma (non-RCC) neoplasms of the kidney: A single-institution experience.

431 Background: Non-RCC neoplasms of the kidney include neuroendocrine tumors (small cell carcinoma and carcinoid) and Primitive Neuroectodermal Tumors (PNET). Small cell carcinoma and renal carcinoids are small blue cell tumors that rarely occur as primary renal neoplasms. PNET, known as extraskeletal Ewing sarcoma, is characterized by t(11;22), the gold standard for diagnosis. It is a small round cell tumor derived from the neural crest and treated with chemotherapy; the role of nephrectomy is unclear. Methods: We reviewed records of patients seen at MDACC between 01/01/2001 and 01/01/2011 for PNET, small cell carcinomas, and carcinoid tumors of the kidney. Overall survival (OS) was determined from diagnosis to death. Results: 21 pts met inclusion criteria. Disease-specific data is shown in the table. Common treatments included: carboplatin/etoposide for small cell carcinomas; vincristine/doxorubicin/ifosfamide, vincristine/doxorubicin/cyclophosphamide, and doxorubicin/ifosfamide alternating with cisplatin/etoposide for PNET. Irinotecan was a common salvage agent in PNET. Most carcinoid tumors were treated with surgery alone. Two patients with small cell received whole brain radiation for brain metastases. Conclusions: Carcinoid tumors of the kidney had better outcomes compared to renal small cell carcinomas or PNET. Local carcinoid tumors of the kidney were generally managed with surgery alone. Renal small cell carcinomas and PNET were treated with systemic therapies. [Table: see text]

6 First and further lines of therapy in clear cell renal cell carcinoma

Until the development of novel targeted agents directed against angiogenesis and tumour growth, few treatment options have been available for the treatment of metastatic renal-cell carcinoma (mRCC).This review discusses current targeted therapies for mRCC and provides consensus statements regarding treatment algorithms.Medical literature was retrieved from PubMed up to April 2011. Additional relevant articles and abstract reviews were included from the bibliographies of the retrieved literature.Targeted treatment for mRCC can be categorized for the following patient groups: previously untreated patients, those refractory to immunotherapy, and those refractory to vascular endothelial growth factor (VEGF)–targeted therapy. Sunitinib and bevacizumab combined with interferon alpha are generally considered first-line treatment options in patients with favourable or intermediate prognoses. Temsirolimus is considered a first-line treatment option for poor-risk patients. Either sorafenib or sunitinib may be valid second-line treatments for patients who have failed prior cytokine-based therapies. For patients refractory to treatment with VEGF-targeted therapy, everolimus is now recommended. Pazopanib is a new treatment option in the first- and second-line setting (after cytokine failure). Sequential and combination approaches, and the roles of nephrectomy and tumour metastasectomy will also be discussed.Increasing clinical evidence is clarifying appropriate first- and second-line treatments with targeted agents for patients with mRCC. Based on phase 2 and 3 trials, a sequential approach is most promising, while combination therapy is still investigational. The role of nephrectomy in mRCC is being evaluated in ongoing phase 3 clinical trials.

Prognostic factors and survial of advanced renal cell carcinoma with predominant sarcomatoid histology.

400 Background: Sarcomatoid renal cell carcinoma (SRCC) is known to have aggressive clinical course and poor response to treatment. Very limited data of clinical feature, prognostic factor, and survival are available for advanced disease with predominant sarcomatoid histology. We evaluated clinical features, response to treatment, and prognostic factors for survival. Methods: Between 2001 and 2010, 30 patients with metastatic or recurrent RCC with predominant sarcomatoid histology (sarcomatoid component 30% or more for resected kidney or exclusive sarcomatoid carcinoma on needle biopsy) were treated at our institution. We reviewed these patients' records to identify clinical and pathologic features which could affect survival. The role of nephrectomy and systemic therapy on patient outcome was also investigated. Results: There were 20 male and 10 female patients with a median age of 58 years (range, 43–83). Twenty patients had initially metastatic disease and 16 patients (53%) had ECOG performance status (PS) of 0–1. The most frequent metastatic site was lung (57%) followed by bone (43%) and distant lymph nodes (23%). Fourteen (70%) out of 20 patients with initially metastatic disease underwent primary nephrectomy and six patients also underwent metastasectomy. The median % of sarcomatoid component was 80% (range, 30–100%). All patients (N=10) who received immunotherapy had progressive disease as their best response and only one out of 5 patients treated with sunitinib or everolimus had a partial response. With a median follow-up duration of 22 months, the median survival was 3.6 months (95% CI, 0∼7.5) with 6-month survival rate of 43%. Only ECOG PS had impact on survival (P<0.001: ECOG=0, 14.1 months; ECOG=1, 7.4 months; ECOG=2, 3.2 months, and ECOG=3, 1.64 months). Survivals for initially metastatic disease were not significantly different whether patients underwent nephrectomy or not (2.0 months vs. 3.4 months, HR=0.62, 95% CI, 0.16–2.44 after correcting for potential prognostic factors). Conclusions: Patients with SRCC have a fulminant clinical course and the majority of patients had disease progression irrespective of any treatment. Only performance status dose have impact on overall survival. No significant financial relationships to disclose.

Thérapies ciblées : traitements séquentiels et combinés

The treatment of metastatic kidney cancer has dramatically changed in the last three years, with demonstration of efficacy of sunitinib, sorafenib, temsirolimus, bevacizumab combined with interferon and more recently everolimus. Although the international guidelines have recently been reviewed, some major questions are still open. Particularly, the best order of administration of these targeted therapies should be considered, since sequential schedule becomes usual with the availability of these new agents. At the same time, the tolerability and efficacy of the combination of the targeted therapies are under investigation in clinical trials. We report recent studies, mainly presented during the ASCO 2007 and 2008 congress. Furthermore, other studies are ongoing to answer other important questions, to optimize the treatment of this disease, such as the role of nephrectomy in case of synchronous metastatic disease, or the efficacy of the targeted therapies in different histological subtype than clear cell carcinoma, or in neoadjuvant and adjuvant settings.

Avancées et synthèse des derniers congrès : ASCO-GU, EAU, AUA, ASCO concernant la prise en charge médicale du cancer du rein localement avancé ou métastatique

During the recent congress of urology and oncology key topics discussed were the evolution of survival data in metastatic kidney cancer which median is now around 40 months, persistent questions about the role of nephrectomy, including access to the systemic treatment of nephrectomized patients and tumor resectability induced by systemic therapies, the emergence of new prognostic models which are adapted to new therapeutic standards, and the emergence of promising new drugs including pazopanib. This article describes these advances.

Ausblick: Therapie des Nierenzellkarzinoms von morgen

Zielgerichtete Substanzen haben die Therapie des metastasierten Nierenzellkarzinoms (mRCC) grundlegend verÄndert. Sunitinib ist heute ein international empfohlener Referenzstandard in der First-line-Therapie; weitere Substanzen wie Temsirolimus, Everolimus, Bevacizumab (in Kombination mit Interferon-alpha) und Sorafenib gehÖren zum therapeutischen Armamentarium. Die Behandler verfÜgen damit Über mehr und bessere Behandlungsoptionen, und die Prognose fÜr mRCC-Patienten hat sich dadurch deutlich verbessert. Zahlreiche ForschungsaktivitÄten sind nun darauf ausgerichtet, den Nutzen dieser neuen Wirkstoffe zu optimieren bzw. diese auch in frÜheren Therapiesituationen zu prÜfen. Schwerpunkte der weiteren Entwicklung beim RCC sind die Optimierung der derzeitigen Therapieoptionen durch Entwicklung neuer zielgerichteter Therapien, die Suche nach idealen Kombinationspartnern aus der Gruppe der zielgerichteten Substanzen, aber auch anderer AnsÄtze: der adjuvante bzw. neoadjuvanter Einsatz sowie die optimale Reihenfolge von Targeted Therapies und Nephrektomie. Der folgende Beitrag gibt einen Überblick Über derzeit laufende Studien und vermittelt so einen Einblick in die Therapie des RCC von morgen.

The Accuracy of Multidetector Computerized Tomography for Evaluating Tumor Thrombus in Patients With Renal Cell Carcinoma

New advances in computerized tomography, including multidetector computerized tomography with 3-dimensional reformatting has recently called into question the absolute need for magnetic resonance imaging for evaluating renal cell carcinoma with suspected venous involvement. We assessed the accuracy of multidetector computerized tomography for predicting tumor thrombus and the level of venous involvement in patients with renal cell carcinoma. We retrospectively reviewed clinical and pathological features in 41 patients with renal cell carcinoma who underwent staging multidetector computerized tomography before surgery. Multidetector computerized tomography findings regarding the presence and level of tumor thrombus were compared to findings at surgery and at final pathological evaluation. All multidetector computerized tomography studies were read by a single radiologist (EKF) before surgery. When excluding patients with segmental venous involvement only, the concordance rate between multidetector computerized tomography and pathological findings was 84%. Multidetector computerized tomography accurately predicted the level of tumor thrombus in 26 of 27 patients (96%). Four cases of negative multidetector computerized tomography findings were up staged to renal vein involvement based on pathological findings. All 4 patients had early distal thrombi that did not change operative management. Multidetector computerized tomography with 3-dimensional mapping is an effective imaging modality for accurately characterizing the level of venous thrombus in patients with renal cell carcinoma. This modality effectively identified patients with clinically significant venous thrombus. Patients with renal cell carcinoma in whom multidetector computerized tomography fails to detect tumor thrombus are unlikely to have a tumor thrombus found at surgery that would change the surgical approach.

Nephrectomy After Transplant Failure: Current Practice and Outcomes

The role of transplant nephrectomy after transplant failure is uncertain. We report the use and consequences of transplant nephrectomy among 19 107 transplant failure patients between 1995 and 2003 in the United States. Among 3707 patients with early transplant failure (graft survival <12 m), nephrectomy was performed in 56%, and was associated with an increased risk of death (HR 1.13, 95% CI 1.01-1.26). In contrast, among 15,400 patients with late transplant failure (graft survival > or =12 m), nephrectomy was performed in 27%, and was associated with a decreased risk of death (HR 0.89, 95% CI 0.83-0.95). In early transplant failure patients, nephrectomy was associated with a lower risk of repeat transplant failure (HR 0.72, 95% CI 0.56-0.94), while among late transplant failure patients; nephrectomy was associated with a higher risk of repeat transplant failure (HR 1.20, 95% CI 1.02-1.41). Definitive conclusions are not possible from this observational study. The role of nephrectomy in the management of dialysis treated transplant failure patients, and the implications of nephrectomy for repeat transplantation should be further studied in prospective studies.

Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma: Is It Still Imperative in the Era of Targeted Therapy?

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 re-emerged 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.

Changing Concepts in the Surgical Management of Renal Cell Carcinoma

The foundations of the generally accepted principles underlying the surgical management of renal cell carcinoma (RCC) were best annunciated in 1969 by Robson in his classic description of the radical nephrectomy [J Urol 1969;101;297]. Since then, much has changed in our understanding of the basic biology and genetics of kidney cancer, advances in renal imaging and clinical staging have led to the increased detection of incidental, lower stage, organ-confined tumors more amendable to expanded surgical options, surgical techniques themselves have evolved, and surgical equipment technology has advanced to make possible new methods of managing renal tumors in situ . Thus, the management of both localized and metastatic RCC has changed dramatically in the last 20 years, predicated on these major advancements in renal imaging, surgical techniques, and the development of effective immunotherapies for advanced disease. In this review, the evolution in thinking regarding the tenets of the radical nephrectomy will be examined, including the necessity for removal of the entire kidney, the possibility of sparing the adrenal gland, when and how extensive a lymphadenectomy should be performed, the development of laparoscopic and percutaneous nephron-sparing surgery using ablative technologies, and the role of nephrectomy and metastasectomy in patients with metastatic RCC. Here, we review current concepts and outcomes on the surgical management of RCC to help elucidate some of these changes, from the evolution of open to laparoscopic to percutaneous, from radical to partial to ablative approaches.

Changing concepts in the surgical management of renal cell carcinoma.

The foundations of the generally accepted principles underlying the surgical management of renal cell carcinoma (RCC) were best annunciated in 1969 by Robson in his classic description of the radical nephrectomy [J Urol 1969;101;297]. Since then, much has changed in our understanding of the basic biology and genetics of kidney cancer, advances in renal imaging and clinical staging have led to the increased detection of incidental, lower stage, organ-confined tumors more amendable to expanded surgical options, surgical techniques themselves have evolved, and surgical equipment technology has advanced to make possible new methods of managing renal tumors in situ. Thus, the management of both localized and metastatic RCC has changed dramatically in the last 20 years, predicated on these major advancements in renal imaging, surgical techniques, and the development of effective immunotherapies for advanced disease. In this review, the evolution in thinking regarding the tenets of the radical nephrectomy will be examined, including the necessity for removal of the entire kidney, the possibility of sparing the adrenal gland, when and how extensive a lymphadenectomy should be performed, the development of laparoscopic and percutaneous nephron-sparing surgery using ablative technologies, and the role of nephrectomy and metastasectomy in patients with metastatic RCC. Here, we review current concepts and outcomes on the surgical management of RCC to help elucidate some of these changes, from the evolution of open to laparoscopic to percutaneous, from radical to partial to ablative approaches.

Renal Cell Carcinoma With Tumor Thrombus Extension: Biology, Role of Nephrectomy and Response to Immunotherapy

We outline the biology, prognosis and role of immunotherapy for renal cell carcinoma with gross venous tumor thrombus. 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. 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%). 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.

The role of nephrectomy in the acutely injured.

The high mortality in patients who undergo nephrectomy after trauma is not secondary to the nephrectomy itself but is the consequence of a more severe constellation of injuries associated with renal injuries that require operative intervention. A retrospective review of all patients identified using International Classification of Diseases, Ninth Revision codes as having sustained renal injuries over a 62-month period. Seventy-eight patients with renal injuries who underwent exploratory laparotomy were identified. All medical records were reviewed for patient management, definitive care, and outcome. Based on outcome, patients were assigned to either the survivor or nonsurvivor group. For patients who underwent nephrectomy, intraoperative core temperature changes, estimated blood loss, and operative time were also reviewed. Seventy-eight patients with renal injuries who underwent exploratory laparotomy were identified. Twenty-nine patients underwent laparotomy with conservative management of the renal injury, of whom 5 (17.2%) died. Twelve patients had renal injuries repaired and all survived. Thirty-seven patients underwent nephrectomy, of whom 16 (43.2%) died. Compared with nephrectomy survivors, nephrectomy nonsurvivors had a significantly lower initial systolic blood pressure, higher Injury Severity Score, higher incidence of extra-abdominal injuries, shorter operative duration, and higher estimated operative blood loss. The nephrectomy survivors' core temperature increased a mean of 0.5 degrees C in the operating room, while the nephrectomy nonsurvivors' core temperature cooled a mean of 0.8 degrees C. Patients who undergo trauma nephrectomy tend to be severely injured and hemodynamically unstable and warrant nephrectomy as part of the damage control paradigm. That a high percentage of patients die after nephrectomy for trauma demonstrates the severity of the overall constellation of injury and is not a consequence of the nephrectomy itself.