Multicenter comparison of outcomes for clinical and pathologic T3a renal cell carcinoma.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 758-758
Author(s):  
Aaron Bradshaw ◽  
Fady Ghali ◽  
Nathan Miller ◽  
Cathrine Keiner ◽  
Raksha Dutt ◽  
...  

758 Background: The identification of venous thrombus in patients with renal cell carcinoma (RCC) is particularly challenging, with a substantial number upstaged to pathologic T3a following intervention. We compared survival outcomes between patients with initial cT3a status versus those upstaged to pT3a. Methods: This is a retrospective, multicenter analysis of patients with cT3a or pT3a RCC who underwent operative management. Primary outcome was recurrence-free survival (RFS). Secondary outcomes were overall survival (OS) and cancer-specific survival (CSS). Cox regression multivariable analysis (MVA) was utilized for primary outcome. Kaplan-Meier analyses (KMA) were conducted to describe RFS, OS, and CSS with log-rank test comparing clinical and upstaged pathologic T3a groups. Results: 770 patients were analyzed (cT3a 184, pT3a 586, median follow-up 28 months). Average pathologic tumor size was smaller in pT3a (7.2 cm vs 8.7 cm, p < 0.01), with no significant differences in clinical variables. A similar proportion underwent radical nephrectomy (vs. partial) (89.7% cT3a and 85.0% pT3a, p = 0.11) with no significant different in positive margin rate (3.8% cT3a, 4.8% pT3a, p = 0.23). However, a higher proportion of patients with cT3a disease were pathologically node positive (19.0% vs. 10.8%, p < 0.01) and demonstrated a higher rate of recurrence (cT3a 51.1% vs. pT3a 34.1%, p < 0.01) despite shorter mean follow-up (cT3a 33.0 vs. pT3a 50.7 mo, p < 0.01). MVA for RFS revealed cT3a staging (pT3a referent, HR 1.72, p < 0.01), positive margins (HR 2.85, p < 0.01), and clear cell histology (HR 1.68, p < 0.01) to be independently associated with higher recurrence rate, while partial nephrectomy (radical referent, HR 0.259, p < 0.01) was associated with a decreased rate. KMA revealed 5-year RFS of 34.4% and 60.6% for cT3a and pT3a respectively (p < 0.01). KMA for secondary outcomes revealed 5-year OS rates of 56.7% and 62.0% (p = 0.02) and 5-year CSS of 74.4% and 67.7% for cT3a and pT3a respectively (p = 0.01). Conclusions: Patients with cT3a RCC have poorer oncologic outcomes than those with upstaged pT3a RCC. Suspected venous involvement on pre-operative imaging may indicate more aggressive or advanced disease than that found during surgery.

2008 ◽  
Vol 2 (6) ◽  
pp. 610 ◽  
Author(s):  
Pierre I. Karakiewicz ◽  
Claudio Jeldres ◽  
Nazareno Suardi ◽  
George C. Hutterer ◽  
Paul Perrotte ◽  
...  

Objective: Based on combined data for 4880 patients, 2 previous studies reported that advanced age is a predictor of increased renal cell carcinoma–specific mortality (RCC-SM). We explored the effect of age in cubic spline analyses to identify the age groups with the most elevated risk for renal cell carcinoma (RCC).Methods: Our study included 3595 patients from 14 European centres who had partial or radical nephrectomies. We used the Kaplan–Meier method to compile life tables, and we performed Cox regression analyses to assess RCC-SM. Covariates included age at diagnosis, sex, TNM (tumour, node, metastasis) stage, tumour size, Fuhrman grade, symptom classification and histological subtype.Results: Age ranged from 10 to 89 (mean 63, median 67) years. The median duration of follow-up was 2.9 years. The median survival for the cohort was 13.4 years. Stage distribution was as follows: 1915 patients (53.3%) had stage I disease, 388 (10.8%) had stage II, 895 (24.9%) had stage III and 397 (11.0%) had stage IV disease. In multivariate analyses, we coded age at diagnosis as a cubic spline, and it achieved independent predictor status (p < 0.001). The risk of RCC-SM was lowest among patients younger than 50 years. We observed an increase in RCC-SM until the age of 50, at which point the level of risk reached a plateau. We observed a second increase among patients aged 75–89 years. We found similar patterns when we stratified patients according to the 2002 American Joint Committee on Cancer (AJCC) stages.Conclusion: The effect of age shows prognostic significance and indicates that follow-up and possibly secondary treatments might need to be adjusted according to the age of the patient.


2019 ◽  
Vol 37 (27_suppl) ◽  
pp. 63-63
Author(s):  
Paulo Gustavo Bergerot ◽  
Cristiane Decat Bergerot ◽  
Nazli Dizman ◽  
Nicholas Salgia ◽  
Joann Hsu ◽  
...  

63 Background: Comprehensive genomic profiling (CGP) has been used to guide treatment selection in metastatic renal cell carcinoma (mRCC). This study sought to determine if genomic alterations guided treatment and contributed to improved outcomes. Methods: From a single institution, patients (pts) diagnosed with mRCC who had CGP in the course of clinical care were identified. Pts were tested on a CLIAA-certified platform (FoundationOne; Cambridge, MA). Pts who died/initiated hospice within the 30 days after the test was performed or who were lost to follow-up were excluded. Duration of therapy (DOT) was measured as months between first and last day of therapy following CGP test. The Kaplan-Meier method was undertaken to estimate the association of CGP-directed therapy with overall survival (OS). Cox regression was also performed and adjusted for histologic subgroup. Results: A total of 64 patients underwent CGP between February 2014 and August 2018. From this group, 15 patients were excluded due to death/hospice within 30 d (n = 10) and lack of follow-up (n = 5). Median age at diagnosis was 60 years (range, 24-84), and 79% were male. Most patients (69%) were diagnosed with clear cell RCC. The median identified genomic alterations (GAs) was 3 (range, 0-7). The most common GAs were VHL (54%), PBRM1 (28%), TERT (21%), TP53 (15%), BAP1 (13%), and SETD2 (13%). Of the 49 patients included in this analysis, 47% had actionable mutations based on their CGP results. Of those, 13 patients received directed-therapy of whom 57% had stable disease, 28% had partial response, and 14% had progressive disease. The median time from CGP test to treatment was 1 month (range, 0-17). The median duration of directed-therapy was 12 months (range, 1-28) and of non-directed therapy was 4 months (range, 1-40) (P = 0.04). Directed-therapy was significantly associated with better OS (adjusted HR, 0.32 [95% CI, 0.13 to 0.82]; P = 0.018) compared to non-directed therapy. Conclusions: This study provides preliminary evidence to justify CGP-guided therapy in mRCC. Forthcoming studies should prospectively explore the use of CGP in treatment allocation for mRCC to validate these findings.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 350-350 ◽  
Author(s):  
Robert John Motzer ◽  
Timothy Eisen ◽  
Thomas E. Hutson ◽  
Cezary Szczylik ◽  
Mizue Krygowski ◽  
...  

350 Background: Tivozanib hydrochloride (tivozanib) is a potent, selective, tyrosine kinase inhibitor targeting all three vascular endothelial growth factor receptors, with a long half-life. Tivozanib has shown tolerability and superior progression-free survival and overall response rate versus sorafenib in a phase III trial (TIVO-1) in patients with advanced renal cell carcinoma. Final overall survival (OS) data (August 27, 2012) from TIVO-1 and its open-label, multicenter extension study are reported. Methods: A total of 517 patients were randomized 1:1 to tivozanib 1.5 mg/d (3 weeks on, 1 week off) or sorafenib 400 mg/d (twice a day, continuously) (J Clin Oncol2012;30[suppl]:Abstract 4501). In the extension study, patients who progressed (PD) on sorafenib based on investigator assessment were eligible to receive tivozanib, and patients with PD on tivozanib received subsequent treatment according to regional standards of care. Final OS analysis was planned to be conducted after all patients had died or were lost to follow-up, or when all patients in follow-up had been on study for at least 2 years, whichever occurred first. OS was compared using the stratified log-rank test. OS distribution was estimated using the Kaplan-Meier method. Hazard ratio (HR) was estimated using the Cox proportional hazard regression model. Results: At the time of final OS analysis (2 years after last patient was enrolled), 219 deaths had occurred (tivozanib, n=118 [45.4%]; sorafenib, n=101 [39.3%]) (stratified HR=1.245; 95% confidence interval [CI] 0.954–1.624; p=0.105), trending in favor of the sorafenib arm. Median OS (95% CI) was 28.8 months (22.5–NA) for tivozanib and 29.3 months (29.3–NA) for sorafenib. Of the 257 patients on sorafenib, 155 (60.3%) had started next-line tivozanib at the time of the analysis. Conclusions: There was no significant difference in OS between the two treatment arms. The high rate of utilization of second-line tivozanib in patients following PD on sorafenib may have affected the OS outcome. Clinical trial information: NCT01030783.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4578-4578
Author(s):  
Bimal Bhindi ◽  
Jeffrey Graham ◽  
Connor Wells ◽  
Frede Donskov ◽  
Felice Pasini ◽  
...  

4578 Background: While the CARMENA trial prompts more caution with upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC), 17% of patients in the sunitinib alone arm underwent deferred CN (dCN). Upfront systemic therapy has been proposed as a potential litmus test to identify patients suitable for CN, but data on outcomes are limited. We sought to characterize outcomes of dCN after upfront sunitinib relative to sunitinib alone. Methods: Patients with newly diagnosed mRCC receiving upfront sunitinib were identified from the International mRCC Database Consortium (IMDC) from 2006-2018. All CNs done after initial sunitinib were included, excluding CNs performed after sunitinib failure. The outcomes were overall survival (OS) and time to treatment failure (TTF). Kaplan Meier and multivariable Cox regression analyses were performed; dCN was analyzed as a time-varying covariate to account for immortal time bias. Results: The cohort included 708 patients of whom 53 (7.5%) underwent dCN at a median of 6.5 months (IQR 3.5,10.5) from diagnosis. Patients in the dCN group were more likely to have better Karnofsky performance status (KPS), intermediate IMDC risk, fewer metastatic sites, and response to upfront sunitinib (Table). There were 604 deaths during a median follow-up of 63 months. Median OS and TTF with dCN were 43.5 and 19.8 months vs. 9.4 and 4.3 months without, respectively. Upon multivariable analysis, dCN remained significantly associated with OS (HR 0.45, 95%CI 0.31-0.65; p < 0.001) but not TTF (HR 0.73, 95%CI 0.52-1.01; p = 0.056). Conclusions: Patients who received dCN were carefully selected and achieved long OS. With these benchmark outcomes, optimal selection criteria need to be identified and confirmation of the role of dCN in a clinical trial is warranted. [Table: see text]


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sung Han Kim ◽  
Boram Park ◽  
Eu Chang Hwang ◽  
Sung-Hoo Hong ◽  
Chang Wook Jeong ◽  
...  

AbstractThis retrospective, five-multicenter study was aimed to evaluate the prognostic impact of pathologic nodal positivity on recurrence-free (RFS), metastasis-free (MFS), overall (OS), and cancer-specific (CSS) survivals in patients with non-metastatic renal cell carcinoma (nmRCC) who underwent either radical or partial nephrectomy with/without LN dissection. A total of 4236 nmRCC patients was enrolled between 2000 and 2012, and followed up through the end of 2017. Survival measures were compared between 52 (1.2%) stage pT1-4N1 (LN+) patients and 4184 (98.8%) stage pT1-4N0 (LN−) patients using Kaplan–Meier analysis with the log-rank test and Cox regression analysis to determine the prognostic risk factors for each survival measure. During the median 43.8-month follow-up, 410 (9.7%) recurrences, 141 (3.3%) metastases, and 351 (8.3%) deaths, including 212 (5.0%) cancer-specific deaths, were reported. The risk factor analyses showed that predictive factors for RFS, CSS, and OS were similar, whereas those of MFS were not. After adjusting for significant clinical factors affecting survival outcomes considering the hazard ratios (HR) of each group, the LN+ group, even those with low pT stage, had similar to or worse survival outcomes than the pT3N0 (LN−) group in multivariable analysis and had significantly more relationship with RFS than MFS. All survival measures were significantly worse in pT1-2N1 patients (MFS/RFS/OS/CSS; HR 4.12/HR 3.19/HR 4.41/HR 7.22) than in pT3-4N0 patients (HR 3.08/HR 2.92/HR 2.09/HR 3.73). Therefore, LN+ had an impact on survival outcomes worse than pT3-4N0 and significantly affected local recurrence rather than distant metastasis compared to LN− in nmRCC after radical or partial nephrectomy.


2012 ◽  
Vol 79 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Umberto Capitanio ◽  
Rayan Matloob ◽  
Nazareno Suardi ◽  
Firas Abdollah ◽  
Fabio Castiglione ◽  
...  

Background Controversies exist regarding the effect of lymphadenectomy (LND) in renal cell carcinoma (RCC). We hypothesized that patients with locally advanced cancer invading beyond Gerota's fascia (pT4 Nany Many RCC) might benefit from an extended LND not only for staging but also for survival purposes. Materials and Methods Clinical and pathologic data were prospectively gathered in 1.847 patients treated at a single Academic Center, between 1987 and 2011. Only patients with pT4 RCC (TNM 2009, n=44, 2.4%) were included. Univariable (UVA) and multivariable (MVA) Cox regression analyses targeted the association between the number of lymph nodes removed and cancer specific mortality (CSM). Analyses were adjusted for age, Fuhrman grade, symptoms at presentation, metastases at diagnosis, ECOG performance status, tumor size, number of positive nodes, and presence of necrosis or sarcomatoid features. Results Mean number of nodes removed was 11.8 (median 8, range 1–37). Mean number of positive nodes was 4.8 (median 2, range 0–36). Cancer-specific survival rates at 1, 2 and 3 years of follow-up were 39.3%, 25.0% and 8.6%, respectively. When stratified for nodal status, cancer-specific survival rates at 1, 2 and 3 years of follow-up were 65.0, 36.1, and 9.0% vs. 13.3, 13.0, and 6.7%, for pN0 vs. pN+ cases, respectively (p=0.004). At MVA, after adjusting for all the possible confounders, the number of positive nodes resulted independently associated with CSM (HR 1.25, p=0.001). Interestingly, at MVA, the number of nodes removed achieved the independent predictor status, as well (HR 0.84, p=0.007) showing a protective effect on survival. The risk of dying increased of 16% every positive node found (p<0.001), and decreased of 8% every node removed (p=0.02) (Table II). Conclusions A more extended retroperitoneal lymphadenectomy at the time of nephrectomy statistically significantly decreased CSM in pT4 cases.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
J. Godlewski ◽  
J. Kiezun ◽  
B. E. Krazinski ◽  
Z. Kozielec ◽  
P. M. Wierzbicki ◽  
...  

The aim of the study was to determine by immunohistochemistry cellular localization and immunoreactivity levels of YAP1 and LATS1 proteins in paired sections of tumor and unchanged renal tissues of 54 clear cell renal cell carcinoma (ccRCC) patients. Associations between clinical-pathological and overall survival (OS; median follow-up was 40.6 months) data of patients and YAP1 and LATS1 immunoreactivity were analyzed by uni- and multivariate Cox regression model and log-rank test. YAP1 immunoreactivity was found in the nuclei of tumor cells in 64.8% of ccRCC patients, whereas only 24.1% of tumors revealed cytoplasmic YAP1 expression. LATS1 immunoexpression was observed only in the cytoplasm of tumor cells in 59.3% of patients. LATS1 immunoreactivity in cancer cells negatively correlated with the size of primary tumor. The overall YAP1 immunoreactivity did not correlate with clinical-pathological data of patients. However, the subgroup of ccRCC patients who presented with cytoplasmic YAP1 immunoexpression had significantly shorter OS (median = 26.8 months) than patients without cytoplasmic YAP1 expression (median undefined). Multivariate Cox analysis revealed that increased cytoplasmic YAP1 (HR = 4.53) and decreased LATS1 immunoreactivity levels (HR = 0.90) were associated with worse prognosis, being independent prognostic factors. These results suggest that YAP1 and LATS1 can be considered as new prognostic factors in ccRCC.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16564-e16564
Author(s):  
Justin Ferdinandus ◽  
Ines Maríc ◽  
Christopher Darr ◽  
Claudia Kesch ◽  
Thomas Hilser ◽  
...  

e16564 Background: Positron emission tomography with (18F)-fluorodeoxyglucose (FDG-PET) is not considered a standard of care (SOC) in renal cell carcinoma (RCC) because of its variability in metabolic activity. We investigated the rate of PET-positivity in our institutional cohort and tested whether PET-positivity had prognostic value in metastatic (m)RCC. Methods: Patients with FDG-PET imaging at any time during the course of disease were identified from medical records. PET-positivity was defined according to PERCIST criteria and a five-point rating scale analogue to Deauville Scoring was used to stratify PET-avidity. Tracer uptake of the hottest lesion was measured as SUVmax. Clinical parameters and PET-positivitywere correlated with overall survival (OS). Kaplan-Meier plots, log-rank analyses, kendall rank correlation, univariate and multivariable cox regression models were employed, where appropriate. Results: A totalof 90 patients was analyzed. The median age was 64.0 (34.0-83.0) and 56 (62.2%) patients had clear cell RCC. Metastatic disease was present in 64 (71.1%) and 22 (24.4%) patients received ongoing medical treatment. 72 (80.0%) patients had prior nephrectomy. PET-positivity occurred in 57 (63.3%) patients, with similar rates among metastatic (41/64; 64%) and non-metastatic patients (16/26; 62%). PET-positive patients had shorter median OS compared to PET-negative patients (38.5 months (CI95:24.5-NR) vs. not reached (CI95: 69.6-NR), P= 0.0013). A weak correlation was found between PET-Uptake and histologic grade (Kendall’s tau 0.22; P= 0.03). Prior nephrectomy, presence of primary lesions, presence of distant metastases, histologic grade and PET-positivity were significant predictors of OS in univariate regression. In multivariable analysis, only PET-positivity remained significant (HR 4.1 (CI95: 1.1-15.4), P= 0.04). Conclusions: RCC is a metabolically active cancer, which in the majority of patients is suitable for FDG-PET diagnostic procedures. PET-positivity was an independent prognostic factor for OS in RCC, indicating its putative clinical use. Further studies to define the role of FDG-PET imaging in RCC are ongoing.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 676-676
Author(s):  
Stephen Ryan ◽  
Ahmet Bindayi ◽  
Aaron Bloch ◽  
Ryan Nasseri ◽  
Zachary Hamilton ◽  
...  

676 Background: AUA guidelines recommend consideration of nephron sparing surgery in patients with comorbidities that are likely to impact renal function, such as diabetes mellitus (DM). We compared the impact of partial nephrectomy (PN) and radical nephrectomy (RN) on overall survival (OS) in patients with pre-existing DM and Stage I Renal Cell Carcinoma (RCC). Methods: Multicenter retrospective analysis of surgically treated Stage I RCC from 2005-16 with or without DM. Primary outcome was OS analyzed by DM+ or DM- and surgical approach (PN or RN) for AJCC Stage I. Logistic (OR) and Cox (HR) regression were utilized for OS. Results: 2173 patients were analyzed (1223 RN, 1819 PN, 555 DM+, 2487 DM-) with mean follow-up of 49.1 months. Increasing Age (OR 1.028, p = .009), RN (OR 2.446, p = .001), and most recent eGFR < 45 (OR 2.306 p = .002) remained significant on multivariate analysis for OS (Table 1). In the PN subgroup, DM+ or DM- was not associated with decreased OS (HR 1.48 p = 0.19). DM+ was associated with decreased OS in the RN subgroup (HR 1.97 p = 0.005). Conclusions: In Stage I RCC, DM and RN negatively impacted OS, while only RN remained significant on MVA. Subgroup analysis of PN showed that OS was similar in DM- and DM+ patients, but diagnosis of DM had a profound impact on OS in the RN group. This supports the guideline statements and offers evidence that urologists should prioritize nephron sparing surgery in patients with DM and Stage I Renal Cell Carcinoma.[Table: see text]


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Kihun Kim ◽  
Yeji Ko ◽  
Dai Sik Ko ◽  
Yun Hak Kim

Purpose. Owing to its worldwide spread, the coronavirus disease (COVID-19) epidemic was declared a pandemic by the World Health Organization on March 11, 2020. Angiotensin-converting enzyme 2 (ACE2) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys and plays an important role in molecular docking of the severe acute respiratory syndrome coronavirus 2. In this study, we aimed to analyze the difference in the survival rate according to ACE2 expressions in pan-cancer. Materials and Methods. We downloaded clinical and genomic data from The Cancer Genome Atlas. We used Kaplan-Meier with a log-rank test, and the Cox proportional hazards regression to analyze prognostic significance. Results. In the Kaplan-Meier curve, clear cell renal cell carcinoma (ccRCC), uveal melanoma, and prostate adenocarcinoma showed statistical significance. In the Cox regression, thyroid carcinoma and glioblastoma multiforme and ccRCC showed significant results. Only ccRCC had statistical significance, and high ACE2 expression is related to good prognosis. It is known that the ACE inhibitor, a primary antihypertensive agent, increases ACE2 expression. Conclusion. Based on these results, we believe that the ACE inhibitor will be important to increase the lifespan of ccRCC patients. This study is the first research to offer a recommendation on the use of anti-hypertensive drugs to ccRCC patients.


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