The role of metastasectomy in patients with renal cell carcinoma with sarcomatoid dedifferentiation: A matched controlled analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 565-565
Author(s):  
Arun Z. Thomas ◽  
Mehrad Adibi ◽  
Rebecca Slack ◽  
Leonardo Daniel Borregales ◽  
Megan M. Merrill ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survival Benefit ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Surgical Patients ◽  
Ecog Performance Status ◽  
Risk Of Death ◽  
Increased Risk

565 Background: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive tumor generally associated with a poor clinical course. Management of metastatic sRCC remains a therapeutic challenge with no standard treatment strategies. Our objective was to evaluate whether metastasectomy has any survival benefit in patients with synchronous or asynchronous metastatic sRCC treated with radical nephrectomy (RN). Methods: From an institutional database of 273 patients with sRCC treated with nephrectomy, we matched 80 patients with synchronous and asynchronous metastasis for age, ECOG performance status, histology and nodal status. Matched pairs were then retained only if patients who did not undergo metastasectomy were comparably alive at the time of metastasectomy in matched surgical patients to reduce the bias in survival outcomes. Overall survival (OS) from nephrectomy was studied using univariable and multivariable proportional hazards regression. Results: Median OS was 8.3 months (95%CI 6.5-10.5 months) and 18.5 months (95%CI 11.5-42.9 months) for patients with synchronous and asynchronous metastases, respectively. OS for patients undergoing metastasectomy for synchronous metastasis was comparable to non-surgical patients (8.4 and 8.0 months, respectively, p=0.35). Similarly, within the asynchronous cohort, median OS was 36.2 months (95%CI 7.6-Not Reached) in the metastasectomy group and 13.7 months (95%CI 8.8-41.6) in the non-metastasectomy group (p=0.29). On multivariable analysis, positive lymph node (LN) at nephrectomy was associated with increased risk of death in both synchronous and asynchronous patients groups; (HR=2.1 [95%CI 1.1-4.0] p=0.03) and (HR=3.3 [95%CI 1.2-9.2] p=0.02), respectively. Conclusions: Metastasectomy in patients with synchronous or asynchronous metastases after nephrectomy does not appear to confer significant survival benefit in patients with sRCC, particularly in patients with pathological LN positive disease at nephrectomy.

Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma

2021 ◽  
pp. 107815522110055
Author(s):  
Ruggero Lasala ◽  
Fiorenzo Santoleri ◽  
Alessia Romagnoli ◽  
Felice Musicco ◽  
Paolo Abrate ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Performance Status ◽  
Relevant Literature ◽  
Real Life ◽  
Ecog Performance Status ◽  
Target Therapies ◽  
Baseline Characteristics

Introduction Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. Materials and Methods Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. Results We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS. Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.

First-line phase II trial of sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma unsuitable for cytokine treatment

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15640-15640 ◽  
Author(s):  
P. Maroto-Rey ◽  
J. Bellmunt ◽  
J. M. Trigo ◽  
V. Guillem ◽  
J. A. López-Martín ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Antiangiogenic Agents ◽  
First Line ◽  
Ecog Performance Status ◽  
Cytokine Treatment

15640 Background: Sorafenib (BAY 43–9006) is a serine/threonine and receptor tyrosine kinase inhibitor that prevents tumor cell proliferation and angiogenesis. The objective of this open-label, phase II trial was to determine median progression-free survival (PFS) following sorafenib therapy in patients with renal cell carcinoma (RCC) unsuitable for cytokine treatment. Methods: Eligible patients had cytologically or histologically confirmed clear cell RCC; Eastern Cooperative Oncology Group (ECOG) Performance Status 0–1; adequate renal, liver and medullar function; no active central nervous system metastases; had received no previous treatment with antiangiogenic agents; and had at least one evaluable lesion. Sorafenib was given as first-line treatment in patients unsuitable for cytokine therapy, defined as being intolerant to or ineligible for immunotherapy. Treatment consisted of oral sorafenib 400mg twice daily continuously until disease progression or unacceptable toxicity. The primary endpoint was PFS; secondary endpoints were response rate according to Response Evaluation Criteria in Solid Tumors, tolerability and overall survival. Results: Twenty-six patients were enrolled between March and July 2006 (median age: 68.5 years [48–82]; male/female: 17/9, ECOG Performance Status 0: 11 patients; prior nephrectomy: 19 patients). The main metastatic locations were lung and bone, 14 patients had = 2 metastatic lesions, and 2 patients had abnormal lactate dehydrogenase levels. As of 31 December 2006, with a median follow-up of 6.4 months, the median PFS had not been reached. In 19 patients evaluable for response, the overall clinical benefit rate was 68.4% (1 complete response; 1 partial response; 11 stable disease). Six patients experienced serious adverse events, only one of which was related to treatment. Conclusions: Sorafenib first-line therapy is a tolerable alternative for patients unsuitable for cytokine treatment. Final PFS data will be available in June 2007. No significant financial relationships to disclose.

The impact of rhabdoid differentiation on prognosis in patients with grade 4 renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 494-494
Author(s):  
Ben Yiming Zhang ◽  
John C. Cheville ◽  
Robert Houston Thompson ◽  
Stephen A. Boorjian ◽  
Christine M. Lohse ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Risk Of Death ◽  
Pathologic Features ◽  
Increased Risk ◽  
Grade 3 ◽  
Rhabdoid Differentiation ◽  
The Impact ◽  
Sarcomatoid Differentiation

494 Background: Renal cell carcinoma (RCC) with rhabdoid differentiation is thought to portend a poor prognosis, similar to RCC with sarcomatoid differentiation. Both rhabdoid and sarcomatoid differentiation are classified as grade 4 RCC based on the most recent International Society of Urological Pathology (ISUP) grading system. We sought to determine the prognostic value of rhabdoid differentiation in comparison to RCC with sarcomatoid differentiation, grade 4 RCC without rhabdoid or sarcomatoid differentiation, and grade 3 RCC. Methods: Using the Mayo Clinic Nephrectomy Registry, we identified 406 patients with ISUP grade 4 RCC and 1,758 patients with grade 3 RCC. A urologic pathologist reviewed all specimens to determine the presence of both rhabdoid and sarcomatoid differentiation. Associations of clinical and pathologic features with death from RCC were evaluated using Cox models. Results: Among the 406 grade 4 RCC tumors, 111 (27%) had rhabdoid differentiation and 189 (47%) had sarcomatoid differentiation, although only 28 (7%) demonstrated both rhabdoid and sarcomatoid differentiation. In multivariable analysis of grade 4 RCC tumors, the presence of rhabdoid differentiation was not associated with death from RCC (HR 0.95, p=0.75); in contrast, sarcomatoid differentiation was significantly associated with death from RCC (HR 1.63, p<0.001). Patients with RCC with rhabdoid differentiation were significantly more likely to die of RCC than patients with grade 3 RCC (HR 2.45, p<0.001) and grade 3 RCC with necrosis (HR 1.62; p<0.001). Conclusions: This study confirms that RCC with rhabdoid differentiation is appropriately classified as grade 4. However, unlike sarcomatoid differentiation, the presence of rhabdoid differentiation in grade 4 RCC is not associated with an increased risk of death from RCC. Therefore, rhabdoid and sarcomatoid differentiation should not be grouped together when assessing risk in a patient with grade 4 RCC.

scholarly journals Influence of Tumor Thrombus on Occurrence of Distant Venous Thromboembolism and Survival in Patients With Renal Cell Carcinoma After Surgery

2019 ◽  
Vol 25 ◽  
pp. 107602961882328 ◽  
Author(s):  
Hyunkyung Park ◽  
Chang Wook Jeong ◽  
Hyeongdong Yuk ◽  
Ja Hyeon Ku ◽  
Hyeon Hoe Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Cell Carcinoma ◽  
Venous Thromboembolism ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Thrombus ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Increased Risk ◽  
The Impact

Tumor thrombus is a unique characteristic of renal cell carcinoma (RCC). However, only a few studies have reported its clinical influence on the occurrence of venous thromboembolism (VTE). This study aimed to clarify the influence of tumor thrombus and other risk factors for VTE and to elucidate the impact of tumor thrombus on survival outcomes. We retrospectively reviewed data from patients with RCC who underwent radical or partial nephrectomy from September 1999 to August 2015 at Seoul National University Hospital. A total of 2762 patients were enrolled. The 1- and 5-year cumulative incidences of VTE were 0.5% ± 0.1% and 1.5% ± 0.3%, respectively. During a median follow-up of 39.0 months (95% confidence interval [CI], 37.1-41.0 months), deep vein thrombosis occurred in 13 patients and pulmonary embolism in 15 patients. Patients with tumor thrombus (diagnosed by surgical pathology findings) had a significantly higher incidence of VTE than those without thrombus (odds radio 8.160, 95% CI, 1.480-45.004). Older age (≥60 years) and higher preoperative C-reactive protein (>0.5 mg/dL) were also significant risk factors for VTE. Additionally, tumor thrombus was independently associated with worse progression-free survival (PFS) but not with overall survival (OS) in multivariable analysis (hazard ratio [HR] 1.916, 95% CI, 1.295-2.834 for PFS; HR 1.164, 95% CI, 0.755-1.793 for OS). In conclusion, the incidence of VTE was relatively low in patients who underwent surgery for RCC. Nevertheless, patients with tumor thrombus had an increased risk of VTE and should be closely monitored for VTE.

Association of topoisomerase II expression and cancer-specific death in patients with surgically resected clear cell renal cell carcinoma.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
Faithlore Patrice Gardner ◽  
Richard Wayne Joseph ◽  
Daniel Serie ◽  
Tracy W. Hilton ◽  
Mansi Parasramka ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Risk Of Death ◽  
Pathologic Features ◽  
Increased Risk ◽  
Risk Of Cancer

446 Background: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. Methods: We identified 947 patients who underwent nephrectomy to treat clinically localized ccRCC between January 16, 1990, and September 27, 2006. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features, we employed Kruskal-Wallis tests and for associations with cancer-specific survival, we generated Cox proportional hazard regression models. Results: HigherTOP2a expression is associated with later stage, higher grade and higher Mayo SSIGN score (all p < 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend < 0.0001). Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.31 95% CI 1.64-3.25; p < 0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ~95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.09 95% CI 1.29-7.40; p = 0.01). Conclusions: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.

The role of cytoreductive nephrectomy in elderly patients with metastatic renal cell carcinoma in an era of targeted therapy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 499-499
Author(s):  
Dipesh Uprety ◽  
Amir Bista ◽  
Yazhini Vallatharasu ◽  
David E. Marinier
Keyword(s):  
Renal Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Survival Benefit ◽  
Performance Status ◽  
Cytoreductive Nephrectomy ◽  
Significant Survival

499 Background: The role of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) has not been clearly understood after the approval of new targeted therapies, particularly in an elderly population. We therefore conducted this study to evaluate survival difference (CN vs. no CN) among elderly patients with mRCC in targeted era. To limit the heterogeneity in use of targeted agents we define targeted era as February 2006 to December 2011, as sunitinib got FDA approval for use in RCC in January 2006. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER-18) database to identify elderly (≥ 65 years) patients with mRCC, as first primary malignancy, who were diagnosed between February 2006 and 2011. Kaplan-Meier curve and log rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between patients receiving CN and not receiving CN. Cox proportional hazard model was used for multivariate analysis. Results: Out of 3,365 patients, 1088 (32.3%) received CN. There was a significant survival benefit for those who received CN vs. those who did not (Median OS: 22 months vs. 5 months, p< 0.001; Median CSS: 25 months vs. 6 months, p<0.001). After adjusting for age, sex, race, T-stage, N-stage, histology types, and year of diagnosis, patient receiving CN had significantly better 3-year OS and 3-year CSS compared to patients not receiving CN with HR of 0.37, 95% CI of 0.34 to 0.41; p<0.001 and HR of 0.37, 95% CI of 0.34 to 0.42, p <0.001 respectively. Among patients who received CN, younger age at diagnosis, other races (other than Caucasian and African American), and N0 stage were found to be independent factors predicting better survival. Conclusions: SEER database lacks individual patient’s information. One may argue that the non-surgical group may have larger proportion of patients with poor performance status. Despite this limitation, our study showed that CN has significant survival benefit and should be a serious consideration in elderly patients if they have good performance status.

Conditional immune adverse event rate in urothelial and renal cell carcinoma patients treated with immune checkpoint inhibitors.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 481-481
Author(s):  
Pier Vitale Nuzzo ◽  
Gregory Russell Pond ◽  
Sarah Abou Alaiwi ◽  
Amin Nassar ◽  
Ronan Flippot ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multivariable Analysis ◽  
Adverse Event Rate ◽  
Risk Of Death ◽  
Over Time

481 Background: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). While the incidence and prevalence of irAEs have been well characterized in the literature, much less is known about the cumulative incidence (CI) rate of irAEs. We sought to evaluate the CI of irAEs in metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC) patients (pts) treated with ICIs. Methods: We identified a cohort of mUC and mRCC pts who received ICIs at DFCI. irAEs were classified using CTCAE v.5.0 guidelines. The CI rate was a defined measure that accounted for elapsed time since treatment initiation and estimated the risk of irAE development conditioned on time elapsed without experiencing an irAE, accounting for the competing risk of death. Incidence and CI of irAEs at each monthly landmark time was calculated. Prognostic factors of irAE were assessed using the Fine and Gray method. Results: A total of 470 pts was treated with ICIs between July 2013 and October 2018 [mUC: 199 (42.3%); mRCC: 271 (57.7%)]. 341 (72.6%) pts received ICI monotherapy, 86 (18.3%) received ICIs in combination with targeted therapies, and 43 (9.2%) received a combination of two ICIs. Overall, 186 pts (39.5%) experienced any irAE at any time point. Common irAEs included hypothyroidism (n=42 [22.6%]), skin (n=36 [19.4%]), colitis (n=35 [18.8%]), transaminitis (n=32 [17.2%]), and pneumonitis (n=14 [7.5%]). The risk of developing an irAE over time was as follows: 33.5% if no irAE within the 1st month(mo), 27.3% if no irAE in 3mo, 18.8% if no irAE in 6mo, and 16.4% if no irAE by 12mo. No difference was observed in CI based on type of cancer (mUC vs mRCC) or agent (PD1 vs. PD-L1). Multivariable analysis showed that ICI combined with ICI or other agents vs. ICI monotherapy (p<0.001), firstline therapy (p=0.013) and PD-1 vs. PD-L1 inhibitors (p=0.008) were statistically correlated with the development of irAEs. Conclusions: This study quantitates the incidence of developing irAEs with ICI conditioned on time elapsed without irAE development. Although the incidence of irAEs decreased over time on therapy, irAEs require continuous vigilant monitoring because of the long tail in its incidence.

ECOG performance status 0 or 1 and symptom classification do not improve the ability to predict renal cell carcinoma-specific survival

2007 ◽  
Vol 43 (6) ◽  
pp. 1023-1029 ◽  
Author(s):  
Pierre I. Karakiewicz ◽  
Quoc-Dien Trinh ◽  
Alexandre de la Taille ◽  
Claude C. Abbou ◽  
Laurent Salomon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Ecog Performance Status
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