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

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.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 343-343
Author(s):  
B. Shuch ◽  
G. Bratslavsky ◽  
J. H. Shih ◽  
D. Finley ◽  
B. Castor ◽  
...  

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.


2018 ◽  
Vol 18 (5) ◽  
pp. 468-479 ◽  
Author(s):  
Carla Cavaliere ◽  
Carmine D`Aniello ◽  
Chiara Della Pepa ◽  
Salvatore Pisconti ◽  
Massimiliano Berretta ◽  
...  

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.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 520-520
Author(s):  
Ilya Tsimafeyeu ◽  
Natalia N. Petenko ◽  
Anton Snegovoy ◽  
Sergey Varlamov ◽  
Lev V. Demidov

520 Background: Targeted therapy has improved clinical outcomes in metastatic renal cell carcinoma (mRCC). However, patients with unfavorable performance status are often under-represented in clinical trials of mRCC. Methods: Patients with mRCC (clear or non-clear cell) and ECOG PS >2 were included in retrospective study.Primary objective of this study was to evaluate the overall duration of targeted therapy (ODT). ODT was defined as time from initiation of first-line therapy until the end of last-line therapy. Results: 79 patients with ECOG PS >2 (median age, 60 [48-70]; male, 73%; clear-cell RCC, 95%; MSKCC intermediate/poor risk, 97%/3%) were treated with sunitinib (77%), sorafenib (23%), everolimus (20%), bevacizumab + IFN (15%), pazopanib (4%), temsirolimus (2.5%) of which 55 (70%) received only first-line therapy, 24 (30%) received 2 lines, and 9 (11%) received 3 lines of therapy. The median ODT was 9.8 months (95% CI 6–13.6). The median time to progression of patients that received 1, 2 or 3 lines was 7.1, 5.9, and 6.3 months, respectively. One patient showed complete response and 2 patients had partial responses during first-line therapy, 2 patients had partial responses during second-line therapy, and 1 patient had partial response after 2 months of third-line therapy. Among the patients who discontinued treatment, disease progression was the most common reason for discontinuation. There was no unexpected serious toxicity. Conclusions: mRCC patients with unfavorable performance status could be treated with targeted therapy during 9.8 months.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16048-e16048
Author(s):  
Bradley Curtis Carthon ◽  
Manal Tabba ◽  
Wayne Harris ◽  
Omer Kucuk ◽  
Viraj A. Master ◽  
...  

e16048 Background: The PD-1/PD-L1 pathway plays an important role in tumor growth and tolerance among renal cancer cells. Renal cell carcinoma (RCC) consists of several different histological subtypes, including clear cell and non-clear cell varieties. Papillary RCC is the most common non-clear cell type and accounts for almost 13% of RCC cases. Our center has a large volume of papillary RCC patients treated by nephrectomy or with systemic therapy. This retrospective study examines pathological criteria, outcomes, and PD-1/PD-L1 expression in a defined cohort. Methods: Institutional review board (IRB) approval was obtained to access and retrospectively review clinical and pathological data of patients that presented with papillary RCC and had a partial or radial nephrectomy during a 1 year duration at our institution. We collected data on survival, systemic treatments, and pathological staging. Tumor samples from the patients were also stained and analyzed for PD-1 and PD-L1 expression. Results: 31 patients were identified with papillary histology after nephrectomy. 45% (14/31) of the patients underwent a radial nephrectomy while 55% (17/31) underwent a partial nephrectomy. Of these 31 patients, 23 had tumor slides available for staining and review. 65% (15/23) of the tumor samples were type 1 papillary RCC, and 35% (8/23) were type 2. PD-L1 was expressed in 13% (3/23) of the cases and PD-1 was expressed in 52% (12/23) of the cases. 71% of the patients were pT1 and 84% of the patients were alive at 5 years. Only 1/31 patients required use of systemic therapy. 74% (17/23) of patients were African American. Conclusions: Patients undergoing nephrectomy for papillary RCC at our institution commonly had small primary tumors with excellent survival. 46% of the tumors expressed PD-1, whereas only 12% expressed PD-L1. Trials that study the inhibition of the PD-1/ PD-L1 pathway may be helpful in strategies for treating both localized and metastatic papillary RCC. Further genomic and pathological examination of additional samples is currently underway.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Makoto Toguchi ◽  
Toshio Takagi ◽  
Yuko Ogawa ◽  
Satoru Morita ◽  
Kazuhiko Yoshida ◽  
...  

AbstractTo investigate the detection of peritumoral pseudocapsule (PC) using multi-detector row computed tomography (MDCT) for tumors resected by robot-assisted laparoscopic partial nephrectomy (RAPN) for T1 renal cell carcinoma (RCC). Study participants included 206 patients with clinical T1 RCC who underwent RAPN between October 2017 and February 2018. Two radiologists who were blinded to the pathological findings evaluated the computed tomography (CT) images. Radiological diagnosis of a PC was defined by a combination of observations, including a low-attenuation rim between the tumor and renal cortex in the cortico-medullary phase and a high-attenuation rim at the edge of the tumor in the nephrogenic or excretory phase. A PC was detected on CT in 156/206 tumors (76%) and identified by pathology in 182/206 (88%) tumors including 153/166 (92%) clear cell RCC, 13/14 (93%) papillary RCC, and 7/16 (44%) chromophobe RCC. In the whole cohort, CT findings showed a sensitivity of 81.3% (148/182), specificity of 66.7% (16/24), and positive predictive value of 94.9% (148/156). When the data were stratified according to pathological subtypes, MDCT was observed to have a sensitivity of 86.9% (133/153) and specificity of 61.5% (8/13) in clear cell RCC, sensitivity of 38.5% (5/13) and specificity of 100% (1/1) in papillary RCC, and sensitivity of 44.4% (4/7) and specificity of 66.7% (6/9) in chromophobe RCC. A low or high-attenuation rim around the tumor in the cortico-medullary or nephrographic-to-excretory phase indicates a PC of RCC, though the accuracy is not satisfactory even with 64- or 320-detector MDCT.


2019 ◽  
Vol 143 (9) ◽  
pp. 1154-1158 ◽  
Author(s):  
Jianping Zhao ◽  
Eduardo Eyzaguirre

Clear cell papillary renal cell carcinoma (ccpRCC) is a recently recognized entity and represents the fourth most common variant of renal cell carcinoma (RCC). It has unique morphologic and immunohistochemical features and demonstrates an indolent clinical behavior. Microscopically, it may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC with clear cell changes. A high index of suspicion is required to keep ccpRCC in the differential diagnosis of RCCs with features of clear cell and/or papillary architecture. In equivocal cases, immunohistochemistry is generally sufficient to substantiate the diagnosis of ccpRCC. In this review, we discuss the clinical, gross, and histopathologic features, immunohistochemical and genetic profiling, and prognosis of ccpRCC.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14646-14646 ◽  
Author(s):  
E. M. Posadas ◽  
S. Undevia ◽  
A. D. Colevas ◽  
E. Manchen ◽  
E. E. Vokes ◽  
...  

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.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Francisco Emilio Vera-Badillo ◽  
Arnoud Templeton ◽  
Alberto Ocana ◽  
Paulo deGouveia ◽  
Priya Aneja ◽  
...  

425 Background: Clinical data supporting the efficacy of systemic therapy in non-clear cell renal cell carcinoma (non-ccRCC) are limited and based on retrospective analyses, expanded access programs and single arm phase II trials. Therefore the optimal treatment for this subgroup remains uncertain. Methods: A systematic review of electronic databases was conducted to identify publications evaluating the outcomes of patients with non-ccRCC (excluding those with sarcomatoid tumors) treated with different systemic approaches (immunotherapy, chemotherapy, targeted agents, small molecules). The primary endpoint was response rate and secondary endpoints were median progression free (PFS) and overall survival (OS). Where possible, data were pooled in a meta-analysis using the Mantel-Haenszel random-effect modeling. For studies comprising of unselected patients, outcomes of those with non-ccRCC were compared with clear cell renal cell carcinoma (ccRCC). Results: Forty-nine studies comprising 7,799 patients were included: 471 patients were enrolled on studies conducted exclusively in non-ccRCC and 7,328 patients on studies of unselected renal cell carcinoma. Among these, 903 (12%) had non-ccRCC and 6,425 (88%) had ccRCC. For non-ccRCC, overall response rate, median PFS and median OS were 9%, 7.9 and 13.4 months, respectively. By comparison, the overall response rate for ccRCC was 15% (Risk Ratio for response [RR] 0.67, 95% CI 0.52-0.86, p=0.002). This association was independent of type of treatment administered. Among the different novel agents (bevacizumab, lenalidomide, linefanib, sorafenib, sunitinib, pazopanib, everolimus and temsirolimus), sunitinib was significantly less efficacious in non-ccRCC than ccRCC (RR 0.56, 95% CI 0.42-0.72), but there was no significant difference in response rates for sorafenib (RR 0.64, 95% CI 0.31-1.35) or other agents (RR 1.10, 95% CI 0.50-2.44), However, confidence intervals were wide. Results of further analyses will be presented at the meeting. Conclusions: Patients with non-ccRCC have lower response rates than those with ccRCC, but the absolute difference between them is modest. Further study of targeted therapy in non-ccRCC is warranted.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 583-583
Author(s):  
Aline Fusco Fares ◽  
Isabela Cunha ◽  
Daniel Vilarim Araujo ◽  
Leonardo de Azevedo Boente ◽  
Daniel Garcia ◽  
...  

583 Background: In mRCC, there are no prospectively validated biomarkers to guide the treatment and therapy decision is based on prognostic scores and histology. STAT-3 and Wnt/b-cateninare cell proliferation pathways and have already been related to prognostic in renal cell carcinoma. Objective: to evaluate the role of STAT-3 and b-catenin expression as prognostic biomarkers in clear cell mRCC. Methods: 684 medical records of renal cell carcinoma patients treated at AC Camargo Cancer Center from 2007 to 2015 were reviewed. 86 out of 684 patients fulfilled the study criteria: metastatic clear cell carcinoma, no sarcomatoid features, previous systemic therapy, previous nephrectomy and available tumor specimens from metastatic site. Pathological samples were arranged in a TMA. The number of positive stainings cells for each antibody in each core was categorized as low positive or negative versus highly positive expression. Results: We had available tissue blocks from 47 tumors. 32/45 patients (71,1%) had highly positive membrane b-catenin and none of the patients was positive for nuclear b-catenin. 27 /45 (60%) were categorized as low positive or negative STAT-3. There was no statistically significant association between STAT-3 and b-catenin expression with clinical prognostic criteria (MSKCC and Heng criteria). In the multivariate analysis, KPS < 80% (p = 0.02; HR: 2.7), time from nephrectomy to metastasis < 1 year (p = 0.04; HR: 2.1), no hypothyroidism (p = 0.05; HR: 2.4) and MSKCC criteria (p = 0.02; HR: 2.5) were confirmed as negative prognostic factors. Associative analysis showed that none of the patients with negative membrane b-catenin had response to systemic therapy (p=0.02). OS was 35.5 months (IC 22.2-48.8) and PFS was 12.5 months (IC 10.0-14.0). Conclusions: in our cohort, STAT-3 and B-catenin expression are not associated with the prognostic criteria (MSKCC and Heng). The loss of B-catenin expression is associated to a worse response rate to antiangiogenic therapy in metastatic clear cell renal cancer. [Table: see text]


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