Impact of pathologic tumor characteristics in patients with sarcomatoid renal cell carcinoma.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 343-343
Author(s):  
B. Shuch ◽  
G. Bratslavsky ◽  
J. H. Shih ◽  
D. Finley ◽  
B. Castor ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Performance Status ◽  
Poor Performance ◽  
Response To Therapy ◽  
Poor Performance Status ◽  
Tumor Characteristics ◽  
Sarcomatoid Renal Cell Carcinoma

343 Background: Patients with sarcomatoid renal cell carcinoma (sRCC) are known to have a poor prognosis and response to therapy. We sought to determine the influence of pathologic tumor characteristics on outcome in order to aid clinical management. Methods: A single center database was reviewed from 1989-2009 to identify all patients with sRCC. Clinical and staging variables were collected and pathologic information including histology, necrosis, percentage of sarcomatoid features (PSF), and microvascular invasion (MVI) was recorded. Influence of clinicopathologic variables on outcome was assessed. Results: A total of 104 patients had confirmed sRCC. The median size of tumors was 9.5 cm (range 2.5-30), 65% of patients had areas of clear cell RCC, and 69.2% had metastatic disease at presentation. The PSF did not influence tumor size, stage, necrosis, MVI, nodes, or metastasis. A total of 85 patients (81.7%) died during the follow-up period with a median survival of 5.9 months. In the overall cohort poor performance status, metastatic disease, and MVI were independent predictors of poor survival. Increased PSF was associated with worse outcome, but it failed to reach significance on multivariate analysis. In a subset analysis of those with non-metastatic disease, MVI and non-clear histology influenced prognosis, but only PSF was the only predictor of outcome. Conclusions: The PSF has limited influence on pathologic characteristics. However, increased PSF amounts may impact survival, especially in those with non-metastatic disease. The presence of MVI is an independent predictor of poor outcome while carcinoma grade and subtype have limited impact on survival. When counseling patients or designing clinical trials for these patients, PSF and MVI, not carcinoma grade or subtype should be considered. No significant financial relationships to disclose.

Current and Emerging Treatments for Metastatic Renal Cell Carcinoma

2018 ◽  
Vol 18 (5) ◽  
pp. 468-479 ◽  
Author(s):  
Carla Cavaliere ◽  
Carmine D`Aniello ◽  
Chiara Della Pepa ◽  
Salvatore Pisconti ◽  
Massimiliano Berretta ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Special Focus ◽  
Systemic Treatments

In the last decades, the treatment of mRCC, metastatic Renal Cell Carcinoma, has become more and more complex due to the approval of a great number of effective systemic treatments that have significantly improved the prognosis of patients suffering from such disease. An additional knowledge of the genetic aberrations and the molecular pathways alterations that underlie RCC, has promoted the development of several novel agents, known as target therapies (TTs). Even though TTs are not curative and all patients eventually progress, an adequate sequencing of these drugs can provide a significant benefit in terms of PFS, Progression Free Survival, and hopefully OS, Overall Survival. To date, there are few data about the optimal sequential use of the TTs hence, in clinical practice, the therapeutic strategy is chosen on the basis of the safety profile of the drug, patients medical history and the pivotal trial results, though such studies often exclude patients with poor performance status and/or severe comorbidities that we routinely see in our clinics. This review aims to provide an overview of the systemic therapies for mRCC both in the newly diagnosed patients and in the subsequent lines of treatment, with a special focus on the last advances about TTs and immunotherapy.

Metastatic papillary renal cell carcinoma: A retrospective study from two large academic centers in Sweden.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 535-535
Author(s):  
Maria Stenman ◽  
Andreas Demetrios Nearchou ◽  
Per Sandström ◽  
Magnus Lindskog ◽  
Ulrika Harmenberg
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Clear Cell ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Papillary Rcc ◽  
Ecog Ps

535 Background: Non-clear cell renal cell carcinoma (nccRCC) constitute about 10-15% of all metastatic renal cell carcinoma (mRCC) and typically include papillary, chromophobe and collecting duct histologies. Despite differences in clinical behavior between subtypes they are often grouped as one due to small patient numbers. Hence, there is a lack of knowledge on type-specific prognosis and treatment options. Methods: Patients diagnosed with metastatic nncRRC (56 out of 526 patients; 10.8%) during the years 2005-2013 were retrospectively identified using data from medical records at two large academic centers in Sweden. The characteristics and outcome of those with papillary subtype (n = 44; 79% of nccRCC) was analyzed. Results: Metastatic papillary RCC patients were more often male (82%), had a median age of 69 years and 48% had M1 disease. 9% were type I, 41% type II, 4% mixed and 41% papillary NOS. 89% had a nephrectomy and 56% received at least one line of systemic therapy. The median overall survival (OS) of all papillary patients was 10.1 months. Factors associated with OS included performance status (PS; OS 25.8 months for ECOG PS 0-1 patients vs OS 3.1 months for ECOG PS > 1 patients, p = 0.00002), and systemic therapy (OS 23.4 months vs 3.8 months for patients not treated systemically, p = 0.002). Systemic therapies (ST) included VEGF targeting agents (88%), mTOR inhibitors (50%), or interferon (21%) for all lines. The most common first line ST was VEGF targeting agents (75%). 42% received one line, 33% two lines, and 25% three or more lines of ST. Characteristics of patients treated with ST included lower age at diagnosis, higher proportion of M1 disease and better PS. The reasons for not giving systemic treatment were primarily poor performance status or comorbidities. ECOG PS > 1 (p = 0.04) and poor MSKCC risk group (p = 0.02) were predictive of OS among patients treated with ST. Conclusions: Patients with metastatic papillary RCC and good performance status (ECOG PS 0-1) seem to benefit from systemic therapy using drugs primarily evaluated for clear cell RCC. However, patients not eligible for systemic therapy due to poor performance status or other reasons have a dismal prognosis.

A phase II study of ixabepilone (BMS 247550) in metastatic renal cell carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14646-14646 ◽  
Author(s):  
E. M. Posadas ◽  
S. Undevia ◽  
A. D. Colevas ◽  
E. Manchen ◽  
E. E. Vokes ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Ii Study ◽  
Performance Status ◽  
Response To Therapy ◽  
Synthetic Analog ◽  
Minor Response

14646 Introduction Ixabepilone (BMS) is a semi-synthetic analog of Epothilone B that functions as a microtubule stabilizer and has anti-cancer effects in several cancers including renal cell carcinoma (RCC) (Zhuang, ASCO 2004). The initial phase II study in RCC utilized a difficult and unconventional dosing schedule (6 mg/m2 IV days 1–5 every 21 days). Hence, this phase II study in RCC was designed to verify previous observations and to test the safety, feasibility, and activity of administering BMS once every 3 weeks- a schedule used in other malignancies. Methods Treatment consists of BMS 40 mg/m2 IV on day 1 every 3 weeks. Eligibility included metastatic RCC with clear or non-clear cell histology, no limits on the number of previous treatments, performance status 0–2, and normal organ function. The primary endpoint is the overall response rate by RECIST criteria on radiologic evaluation conducted every 9 weeks. Accrual to the full planned 41 patients (pts) will proceed provided that 2 or more responses are observed in the first 21 pts. Results Ten pts have enrolled (4 clear cell) with 1 declining participation prior to receiving any treatment. Eight pts have completed at least 3 cycles. Grade 3–4 toxicities include lymphopenia-2, diarrhea-2, alopecia-1, and infection-1. Grade 1–2 toxicities seen in more than 50% of pts include alopecia, neuropathy, nausea, fatigue, anemia, and lymphopenia. We have observed 1 unconfirmed partial response of short duration and 1 pt exhibited stable disease with a minor response but discontinued treatment due to excessive neurotoxicity. Three pts continue on treatment. Conclusions Toxicity at 40 mg/m2 IV on day 1 every 3 weeks is higher than previously reported with the daily x 5 schedule. While lymphopenia, diarrhea, neuropathy, and fatigue are all expected adverse events, the rates of toxicity across all grades is higher than previous reports. VHL mutation analysis is planned and will be correlated with response to therapy. Accrual and pt follow up continue. No significant financial relationships to disclose.

Von Hippel-Lindau gene mutation status is associated with a dichotomous response in primary and metastatic tumors in patients receiving bevacizumab and erlotinib for metastatic renal cell carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15522-15522
Author(s):  
D. Tsavachidou ◽  
N. M. Tannir ◽  
C. G. Wood ◽  
P. Corn ◽  
K. Do ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Mutation ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Renal Cell ◽  
Response To Therapy ◽  
Gene Inactivation ◽  
Vhl Gene ◽  
Von Hippel Lindau

15522 Background: A single arm phase II study is underway evaluating the safety and clinical benefit of presurgical bevacizumab and erlotinib in the management of patients with untreated conventional renal cell carcinoma (RCC). It is not known how the presence or absence of von Hippel Lindau (VHL) mutations affect the response to therapy in the primary or metastatic site, and whether VHL mutational status is predictive for either. Methods: Patients enrolled had conventional RCC, measurable metastatic disease, a primary tumor in place, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. A total of 35 patients were enrolled as of January 8, 2007. Patients were treated with bevacizumab for 4 cycles and erlotinib for 8 weeks, and underwent cytoreductive nephrectomy at week 10 (4 weeks after the last dose of bevacizumab). A VHL gene mutation and methylation analysis was completed on nephrectomy specimens from the first 18 evaluable patients. Patients were grouped according to the presence or absence of functional VHL gene inactivation (mutation and/or methylation). Two-sample T-test and Fisher’s exact test were performed. Results: Ten patients (55%) demonstrated either VHL mutation or methylation ( table 1 ). Patients with no VHL gene inactivation demonstrated more robust primary tumor shrinkage, but did not demonstrate partial responses (PRs). Table 1 . Conclusions: These findings, although preliminary, suggest a dichotomous response in the primary and metastatic disease sites according to VHL functional status. Ongoing evaluation of new treatment strategies using antivascular/targeted agents in RCC may benefit from molecular stratification. [Table: see text] No significant financial relationships to disclose.

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

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 400-400
Author(s):  
I. Park ◽  
J. Lee ◽  
J. Ahn ◽  
D. Lee ◽  
C. Song ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Clinical Course ◽  
Performance Status ◽  
Sarcomatoid Carcinoma ◽  
Response To Treatment ◽  
Pathologic Features

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.

Risk Group Assessment and Clinical Outcome Algorithm to Predict the Natural History of Patients With Surgically Resected Renal Cell Carcinoma

2002 ◽  
Vol 20 (23) ◽  
pp. 4559-4566 ◽  
Author(s):  
Amnon Zisman ◽  
Allan J. Pantuck ◽  
Jeffery Wieder ◽  
Debby H. Chao ◽  
Fredrick Dorey ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Risk Group ◽  
Response To Therapy ◽  
Low Risk ◽  
Disease Specific Survival ◽  
Free Survival ◽  
Disease Specific

PURPOSE: To create a comprehensive algorithm that can predict postoperative renal cell carcinoma (RCC) patient outcomes and response to therapy. PATIENTS AND METHODS: A prospective cohort study was performed with outcome assessment on the basis of chart review of 814 patients who underwent nephrectomy between 1989 and 2000. At diagnosis, M1 or N1/N2M0 metastatic disease (M) was present in 346 patients (43%), whereas 468 patients had no metastatic disease (NM) (N0M0). On the basis of UCLA Integrated Staging System category and the presence of metastases, patients were divided into low-risk (LR), intermediate-risk (IR), and high-risk (HR) groups. Decision boxes integrating tumor-node-metastasis staging, tumor grade, and performance status were compiled for determining a patient’s risk group. RESULTS: NM-LR patients had 91% disease-specific survival at 5 years, lower recurrence rate, and better disease-free survival compared with NM-IR and HR patients. Disease progressed in 50% of NM-HR patients. Disease-specific survival of NM-HR patients who received immunotherapy (IMT) for recurrent disease was similar to that of M-LR patients treated with cytoreductive nephrectomy and adjuvant IMT. Time from recurrence to death for NM-HR patients was inferior to that for M-LR patients. After IMT, approximately 25% of M-LR and 12% of M-IR patients had long-term progression-free survival. M-HR patients did poorly despite IMT. CONCLUSION: Stratifying RCC patients into high-, intermediate-, and low-risk subgroups provides a clinically useful system for predicting outcome and provides a unique tool for risk assignment and outcome analysis. Subclassifying RCC into well-defined risk groups should allow better patient counseling and identification of both NM-HR subgroups that need adjuvant treatment and nonresponders who need alternative therapies.

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.

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