Metastasectomy For Renal Cell Carcinoma Research Articles

Randomized, Double-Blind Phase III Study of Pazopanib Versus Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease After Metastasectomy: ECOG-ACRIN E2810.

Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy. Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate. From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; Pone-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo (Ptwo-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period. Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.

Morbidity and mortality of metastasectomy for renal cell carcinoma: is centralization of care the way forward?

Morbidity and mortality of metastasectomy for renal cell carcinoma: is centralization of care the way forward?

International Multi-institutional Characterization of the Perioperative Morbidity of Metastasectomy for Renal Cell Carcinoma

BackgroundSurgical resection of metastatic renal cell carcinoma (mRCC) has been associated with better cancer-specific survival; however, high-quality data on its perioperative morbidity are lacking. Existing population-based data are severely limited by reliance on billing claims to identify outcomes, which may overestimate events owing to a lack of code specificity. ObjectiveTo study 30-d complications after metastasectomy for mRCC. Design, setting, and participantsThe study involved a retrospective cohort of patients who underwent metastasectomy for mRCC between 2005 and 2020 at two high-volume centers. Outcome measurements and statistical analysisWe used generalized estimating equations for a binary response to evaluate associations of features with 30-d complications classified according to Clavien-Dindo grade. Results and limitationsA total of 740 metastasectomies in 522 patients were identified, including 543 performed in the Mayo Clinic and 197 in UZ Leuven. Among the 740 metastasectomies, 193 (26%, 95% confidence interval [CI] 23–29%) had a 30-d complication and 62 (8%, 95% CI 7–11%) had a major (Clavien-Dindo III–V) complication, including eight (1%) perioperative deaths. Age, body mass index, American Society of Anesthesiologists score, metastasectomy concurrent with nephrectomy, multiple sites of metastasis, pancreatic resection, and metastasis size were significantly associated with postoperative complications (all p < 0.05). Age, multiple sites of metastasis, and pancreatic resection were significantly associated with major (Clavien-Dindo III–V) complications (all p < 0.05). Limitations include the retrospective design and surgical selection bias. ConclusionsIn this multi-institutional series, fewer than 10% of metastasectomies for mRCC resulted in a major complication within 30 d of surgery, which is considerably lower than previously observed in population-based data. Favorable perioperative outcomes can be achieved with metastasectomy at high-volume centers in well-selected patients. Patient summaryIn this study we found that fewer than 10% of patients who underwent surgical removal of one or more sites of metastatic kidney cancer experienced a major complication within 30 days of surgery.

Metastasectomy in renal cell carcinoma: where are we now?

Metastatic RCC has a variable natural history. Treatment choice depends on disease and patient factors, but most importantly disease burden and site of metastasis. This article highlights key variables to consider when contemplating metastasectomy for RCC and provide a narrative review on the evidence for metastasectomy in these patients. Tumour subtype is associated with differing patterns of recurrence. Patients with single or few metastatic sites have better outcomes, and those with greater time interval from initial nephrectomy. Local recurrence is particularly amenable to minimally invasive surgical resection and is oncologically sound. Very well selected cases of liver or brain metastases may benefit from metastectomy, although lung and endocrine metastases have more favourable outcomes. Although site and burden of disease is important, the key determinate of outcome in metastasectomy depends mostly on the ability to achieve a complete resection. Adjuvant treatment is not currently advocated. Metastasectomy should be generally reserved for cases where complete resection is achievable, unless the goal of treatment is to palliate symptoms. This field warrants ongoing research, particularly as systemic therapy and minimally invasive surgical techniques evolve. Elucidating tumour biology to inform patient selection will be important in future research.

Benefit of Metastasectomy in Renal Cell Carcinoma: A Propensity Score Analysis.

To quantify the magnitude of benefit of metastasectomy as compared to medical treatment alone in patients with metastatic renal cell carcinoma (mRCC). We therefore conducted a propensity score analysis of overall survival (OS) in 106 mRCC patients with metachronous metastasis, of whom 36 (34%) were treated with metastasectomy, and 70 (66%) with medical therapy alone. The most frequent metastasectomy procedures were lung resections (n=13) and craniotomies (n=6). Median time-to-progression after metastasectomy was 0.7 years (25th-75th percentile: 0.3-2.7). After a median follow-up of 6.2 years and 63 deaths, 5-year OS estimates were 41% and 22% in the metastasectomy and medical therapy group, respectively (log-rank P=.00007; Hazard ratio (HR)=0.38, 95%CI: 0.21-0.68). Patients undergoing metastasectomy had a significantly higher prevalence of favorable prognostic factors, such as fewer bilateral lung metastases and longer disease-free intervals between nephrectomy and metastasis diagnosis. After propensity score weighting for these differences and adjusting for immortal time bias, the favorable association between metastasectomy and OS became much weaker (HR=0.62, 95%CI: 0.39-1.00, P=.050). Propensity-score-weighted 5-year OS estimates were 24% and 20% in the metastasectomy and medical therapy group, respectively (log-rank P=.001). In exploratory analyses, the benefit of metastasectomy was confined to patients who achieved complete resection of all known metastases. Within the limitations of an observational study, these findings support the concept of metastasectomy being associated with an OS benefit in mRCC patients. Metastasectomies not achieving complete resection of all known lesions are likely without OS benefit.

Prognostic impact of complete metastasectomy in metastatic renal cell carcinoma in the era of immuno-oncology-based combination therapies

PurposeComplete metastasectomy of renal cell carcinoma (RCC) is receding into the past due to the progress of immuno-oncology-based combinations (IO) in systemic therapy. The prognostic impact of curative intended complete metastasectomy vs. immediate IO-based therapy or tyrosine kinase inhibition (TKI) on progression-free survival (PFS) and cancer-specific survival (CSS) was investigated in the first-line setting.Methods205 patients with synchronous or metachronous metastasis received complete metastasectomy (n = 80) or systemic therapy (n = 125, TKI: 87, TKI–IO: 13, IO–IO: 25) as first-line therapy. The prognostic impact of these therapies was assessed using Cox regression and Kaplan–Meier analyses.ResultsFirst-line complete metastasectomy significantly improved CSS compared to both TKI monotherapy (6.1 vs. 2.6 years, HR 0.45, p < 0.001) and IO-based combination therapy (IO–IO/TKI–IO, 6.1 vs. 3.5 years, HR 0.28, p = 0.007). Repetitive complete metastasectomy without ever receiving systemic therapy vs. systemic therapy in first-line significantly prolonged CSS (11.3 vs. 3.1 years, HR 0.34, p = 0.002). First-line complete metastasectomy and subsequent systemic therapy at tumor progression was associated with a significant CSS benefit vs. systemic therapy (5.8 vs. 3.1 years, HR 0.53, p = 0.003), also compared to IO-based combinations (5.8 vs. 3.5 years, HR 0.30, p = 0.017). Median PFS was improved by IO-based therapy compared to TKI monotherapy in the first-line setting (HR 0.61, p = 0.05), with maximal benefit of the TKI–IO combination vs. TKI monotherapy (HR 0.27, p = 0.01), as well as compared to PFS of complete metastasectomy (HR 0.34, p = 0.035).ConclusionDespite the progress of IO-based combination therapies in first line, complete metastasectomy remains an integral part of the multimodality treatment of metastatic RCC.

A0373 - Perioperative morbidity of surgical metastasectomy for renal cell carcinoma: An international multicenter study

A0373 - Perioperative morbidity of surgical metastasectomy for renal cell carcinoma: An international multicenter study

The Value of Metastasectomy in Renal Cell Carcinoma in 2021

The Value of Metastasectomy in Renal Cell Carcinoma in 2021

Clinical outcomes and prognostic factors following spinal metastasectomy of renal cell carcinoma

Clinical outcomes and prognostic factors following spinal metastasectomy of renal cell carcinoma

Pulmonary metastasectomy in renal cell carcinoma: Predictive and prognostic elements from paired histopathological analysis of primary tumors and respective metastases

Objective:To identify histopathological and immunophenotypical features with potential predictive or prognostic value in patients undergoing pulmonary metastasectomy from renal cell carcinoma (RCC).Methods:We retrospectively collected all consecutive patients undergoing pulmonary metastasectomy from RCC after prior nephrectomy. Paired samples of primary tumors and corresponding pulmonary metastases were analyzed, revising histopathological features and testing C-MET, mTOR, and PD-L1 by immunohistochemistry.Results:A total of 25 patients were included. Median overall survival (mOS) from metastasectomy was 5.5 years (95% CI = 1.9–9.1). The laterality of metastases had a significant predictive value, with median relapse-free survival (mRFS) from metastasectomy not reached (NR) at mean follow-up (FU) of 60.8 months for left lung involvement, mRFS of 52.9 months (95% CI = 0–145.5) for the right lung and 6.4 months (95% CI = 1.7–11) for bilateral metastases ( p = 0.028). Primary RCC with positive expression of mTOR had higher mOS after metastasectomy than negative cases ( p &lt; 0.001), NR at mean FU of 4.3 years versus mOS of 2 years (95% CI = 0.7–3.3), respectively. PD-L1 positivity on intra-tumor (TILs) and peri-tumor (RILs) infiltrating lymphocytes of metastases was related to higher OS, NR versus 2 years (95% CI = 1.2–2.7, p = 0.003), and NR versus 1.4 years (95% CI = 0.2–2.6, p = 0.012), respectively. The shorter was the surgical interval, the more probably the metastases had high c-MET expression (&gt;70%) ( p = 0.007) and PD-L1 expression &gt;10% on TILs ( p = 0.024).Conclusions:mTOR positivity on primary RCC could be a favorable prognostic factor to select patients for pulmonary metastasectomy. The positive impact of PD-L1 expression on immune cells is opposite to the well-known negative prognostic value of PD-L1 on tumor cells in RCC.

Pulmonary metastasectomy in renal cell carcinoma: a mainstay of multidisciplinary treatment

Renal cell carcinoma (RCC) remains a public health issue and seems to be increasing. A significant proportion of RCC patients will develop pulmonary metastasis at some point in their evolution. In this review, we aimed to update the surgical management of pulmonary metastases as well as systemic therapy, including targeted therapies, according to recent data in the literature. We retrospectively reviewed studies evaluating the benefit of pulmonary metastasectomy in RCC patients and evaluating the place of different chemotherapies, targeted therapies and immunotherapies through November 1, 2019. Several retrospective studies have shown the benefit of pulmonary metastasectomy in metastatic RCC (mRCC), most in a situation with only pulmonary metastases. According to the prognostic criteria of the IMDC risk model, the patient is classified into a prognostic group to identify the best systemic treatment. With the development of targeted therapies, the modalities are multiple and may involve tyrosine kinase inhibitors/checkpoint inhibitors and soon vaccine therapy or CAR-T cells. At the local level, in patients who cannot benefit from surgery, stereotactic radiotherapy or radiofrequency has a place to be considered. Although there is a lack of a randomized study, pulmonary metastasectomy appears to be feasible and effective. The place and modalities of systemic therapies in the era of targeted therapies remain to be more clearly defined.

Prognostic impact of metastasectomy in renal cell carcinoma in the postcytokine therapy era

ObjectivesTo explore the real-world data regarding survival following metastasectomy (MS) for renal cell carcinoma (RCC) in the postcytokine therapy era. Patients and MethodsPatients diagnosed with metastatic renal cell carcinoma (mRCC) between January 2008 and December 2018 at our institutions were retrospectively evaluated. The patients were classified into three groups according to their MS status: (1) complete MS (cMS), (2) incomplete MS (icMS), and (3) without MS (nonMS). Factors for overall survival (OS) after diagnosis were analyzed. ResultsOverall, 314 patients were evaluated. During the follow-up period (median: 25.3 months), a total of 98 patients (31.2%) underwent at least one MS. The cMS group (n = 45, 14.3%) had a significantly longer OS (median: not reached [N.R.]) than the icMS (n = 53, 16.9%) (81.5 months, P= 0.0042) and nonMS groups (28.1 months, P< 0.0001). The icMS group had a significantly longer OS than the nonMS group did (P= 0.0010). Multivariate analysis showed that the MS status was an independent factor for OS (cMS vs. nonMS: P= 0.0004; icMS vs. nonMS: P= 0.0176), together with histopathological type, International Metastatic Renal Cell Carcinoma Database Consortium risk, liver metastasis status, and prior nephrectomy status (all, P< 0.05). In addition, the OS was comparable throughout the eras of systemic therapy (early molecular-targeted therapy, late molecular-targeted therapy, and immune checkpoint inhibitor eras) in the MS group (median: 121.9 vs. N.R. vs. N.R. months, P= 0.948). ConclusionsMS, especially cMS improved survival in selected patients with mRCC in the postcytokine therapy era. In addition, MS still plays a significant role in the current systemic therapy.

Factors Affecting Long-Term Survival Following Pulmonary Metastasectomy of Renal Cell Carcinoma.

Role of pulmonary metastasectomy of renal cell carcinoma (RCC) is significant considering its contribution to survival rates. The aim of this study is to present the prognostic factors affecting the surgical outcomes and long-term survival. Forty-eight patients who had undergone pulmonary metastasectomy of RCC between 2000 and 2018 were analyzed in terms of gender, age, subtypes and pathological T stages of RCC, side and size of pulmonary metastases, disease-free interval (DFI) and type of lung resections in order to reveal the prognostic factors from the stand point of selecting suitable patients for lung metastasectomy. Overall survival was 56.2 ±21.7 months. Survival time was less than 3 years for 7 (14.6%) , between 3 and 5 years for 11 (22.9%) and more than 5 years for 30 (62.5%) patients. Young age, female gender, unilateral pulmonary lesions, longer DFI, lung metastases limited in number and volume were statistically significant for better survival rates (P <.05) whereas subtypes and pathological stage of the primary tumor or the type of pulmonary metastasectomy did not act on the outcomes (P >.05). The most distinctive factor affecting the surgical outcomes is the complete resection of lung metastases rather than the extent of the surgery. This study clearly states that patients aged under 50 years with unilateral lung metastases counting less than 3 and measuring smaller than 4 cm3 and also DFI lasting longer than 32 months benefit from pulmonary metastasectomy of RCC.

Extended hepatic metastasectomy for renal cell carcinoma\u2014new aspects in times of targeted therapy: a single-center experience over three decades

PurposeDespite the introduction of novel targeted therapies on patients with renal cell carcinoma, syn- and metachronous metastases (including hepatic lesions) are observed frequently and significantly influence patient survival. With introduction of targeted therapies as an effective alternative to surgery, therapeutical strategies in stage IV disease must be reevaluated.MethodsThis is a retrospective analysis of 40 patients undergoing hepatic resection of histologically confirmed RCC metastases at our institution between April 1993 and April 2017.ResultsThe interval between nephrectomy for renal cell carcinoma and hepatic metastasectomy was 44.0 months (3.3–278.5). Liver resections of different extents were performed, including multivisceral resections. The median follow-up was 37.8 months (0.5–286.5). Tumor recurrence after resection of hepatic metastases occurred in 19 patients resulting in a median disease-free survival of 16.2 months (0.7–265.1) and a median overall survival of 37.8 months (0.5–286.5). Multivariable analysis identified multivisceral resection as an independent risk factor for disease-free and overall survival (p = 0.043 and p = 0.001, respectively). A longer interval between nephrectomy and hepatic metastasectomy was identified as an independent significant protective factor for overall survival (p < 0.001). Patients undergoing metastasectomy after introduction of sunitinib in Europe in 2006 (n = 15) showed a significantly longer overall survival (45.2 (9.1–111.0) versus 27.5 (0.5–286.52) months in the preceding era; p = 0.038).ConclusionHepatic metastasectomy, including major and extended resections, on patients with metastasized renal cell carcinoma can be performed safely and may facilitate long-term survival. Due to significant morbidity and increased mortality, multivisceral resections must be weighed against other options, such as targeted therapy.

P113 - Clinical outcome after radical metastasectomy in renal cell carcinoma: Results from a randomized phase 2 study

P113 - Clinical outcome after radical metastasectomy in renal cell carcinoma: Results from a randomized phase 2 study

Complete metastasectomy in renal cell carcinoma: a propensity-score matched by the International Metastatic RCC Database Consortium prognostic model.

IntroductionWe evaluated overall survival (OS) benefit of complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) using a propensity score-matched (PSM) analysis to balance groups by age, gender and by the International Metastatic RCC Database Consortium prognostic model (IMDC).MethodsWe included patients (pts) treated at the AC Camargo Cancer Center between 2007 and 2016. Pairs were matched by age, gender and IMDC. Kaplan–Meier survival estimates and Cox proportional hazard models were used to evaluate OS on CM and no-CM group.ResultsWe found 116 pts with clear cell mRCC. After PSM, the number was reduced to 74 (37 CM, 37 no-CM). The median OS for CM and no-CM was 98.3 months and 40.5 months, respectively (hazard ratio 0.24 95%CI 0.11–0.53 p < 0.001). The OS benefit of CM was confirmed on favourable and intermediate IMDC but was absent on poor IMDC. The CM group received less systemic therapy than the no-CM group. Ten pts in the CM group still have no evidence of disease (NED).ConclusionAfter matching for age, gender and IMDC, we found CM impacts on OS and also diminishes the need for systemic treatment. Survival benefit was confirmed for favourable/intermediate IMDC but not for the poor IMDC prognostic model. Further studies correlating IMDC and metastasectomy are needed to guide clinical decision-making.

Complete Surgical Metastasectomy of Renal Cell Carcinoma in the Post-Cytokine Era.

Data supporting complete metastasectomy of metastatic renal cell carcinoma were derived primarily from the era of cytokine therapy. Whether complete metastasectomy remains beneficial in patients who receive more recently approved systemic therapies has not been well studied. The objective of this study was to examine survival outcomes among patients treated with complete metastasectomy in the era of targeted therapy and checkpoint blockade availability. We queried our institutional nephrectomy registry and identified 586 patients who underwent partial or radical nephrectomy of unilateral, sporadic renal cell carcinoma with a first occurrence of metastasis between 2006 and 2017. Of these patients 158 were treated with complete metastasectomy. Associations of complete metastasectomy with cancer specific and overall survival were assessed using Cox proportional hazards models. Median followup after the diagnosis of metastasis was 3.9 years, during which 403 patients died, including 345 of renal cell carcinoma. Of the patients treated with complete metastasectomy 147 (93%) did not receive any systemic treatment of the index metastatic lesion(s). Two-year cancer specific survival was significantly greater in patients with vs without complete metastasectomy (84% vs 54%, p <0.001). After adjusting for age, gender, and the timing, number and location of metastases complete metastasectomy was associated with a significantly reduced likelihood of death from renal cell carcinoma (HR 0.47, 95% CI 0.34-0.65, p <0.001). Complete surgical resection of metastases of renal cell carcinoma was associated with improved cancer specific survival in the post-cytokine era. It may be considered in appropriate patients after a process of shared decision making.

Outcomes and prognostic factors associated with pulmonary metastasectomy for renal cell carcinoma

Outcomes and prognostic factors associated with pulmonary metastasectomy for renal cell carcinoma

Complications After Metastasectomy for Renal Cell Carcinoma—A Population-based Assessment

Metastasectomy has long been considered a valid treatment option for patients with oligometastatic renal cell carcinoma (oligo-mRCC). However, the literature on complications in this setting is scarce. Our objective was to describe in-hospital complications after metastasectomy in a contemporary cohort of patients with mRCC. Using the National Inpatient Sample database (2000–2011), 45 279 mRCC patients were identified. Of those, 1102 underwent metastasectomies. The metastatic sites were the lungs, bone, liver, lymph nodes, adrenal glands, and brain in, respectively, 52%, 29%, 19%, 14%, 11%, and 3.4% of patients. The overall complication rate was 45.7%. Major complications (Clavien III–V) constituted 27.5%. Resections of hepatic lesions were significantly associated with higher odds of overall complications compared with any other site (odds ratio 2.59, 95% confidence interval 1.84–3.62, p<0.001). While metastasectomy remains a potential treatment option in RCC with oligometastatic disease, the associated complication rates are non-negligible; therefore, careful patient selection is warranted. Patient summaryWe studied outcomes of patients with metastatic kidney cancer treated with metastasectomy. While metastasectomy is a treatment option for metastatic renal cell carcinoma, complications are not insignificant and our results may guide preoperative counseling.

Spinal metastasectomy of renal cell carcinoma: A 16-year single center experience with a minimum 3-year follow-up.

Metastasectomy of spinal lesions from renal cell carcinoma (RCC) is a promising strategy. However, its clinical outcome after spinal metastasectomy is unknown owing to the difficulty of curative surgical resection. This is the first study to examine the survival rates of patients who underwent metastasectomy of solitary spinal metastases from RCC. A retrospective cohort study of 36 consecutive patients with RCC who underwent nephrectomy and complete removal of solitary spinal lesions between 1995 and 2010 at our institution. Cancer-specific survival (CSS) time from the spinal metastasectomy to death or last follow-up was the main endpoint. Potential factors associated with survival were evaluated with Kaplan-Meier analysis and the long-rank test. For all patients, the estimated median CSS time was 130 months. The 3, 5, and 10-year CSS rates were 77.8%, 69.1%, and 58.0%, respectively, for all patients, and 72.7%, 54.5%, and 27.3%, respectively, for patients with lung metastases at the time of surgery. Only the presence of liver metastases was significantly associated with short-term survival after spinal metastasectomy. Liver metastases were associated with short-term survival, although lung metastases were not. For selected patients, curative resection of solitary spinal metastases can potentially prolong survival. J. Surg. Oncol. 2016;113:587-592. © 2016 Wiley Periodicals, Inc.