Are tumor-associated micro-angiogenesis and lymphangiogenesis considered as the novel prognostic factors for patients with Xp11.2 translocation renal cell carcinoma?

Abstract Background Tumor micro-angiogenesis and lymphangiogenesis are effective prognostic predictors in many solid malignancies. However, its role on Xp11.2 translocation RCC has not been fully elucidated. Herein, we purposed to explore the correlation between quantitative parameters of tumor-related micro-angiogenesis or lymphangiogenesis and the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 translocation RCC). Methods Tissue samples were obtained from 34 Xp11.2 translocation RCC and 77 clear cell renal cell carcinoma (ccRCC) between January 2007 and December 2018. Micro-angiogenesis was detected using CD34 antibody and quantified with microvessel density (MVD) and microvessel area (MVA), while the lymphangiogenesis in RCC was immunostained with D2–40 antibody and assessed using lymphatic vessel density (LVD) and lymphatic vessel area (LVA). The Kaplan-Meier method of survival analysis was used to estimate prognosis, and both univariate and multivariate analysis was performing using the Cox proportional hazards. Results The MVD and MVA of Xp11.2 translocation RCC in two detected areas (intratumoral and peritumoral area) were not significantly different from that of ccRCC (all P > 0.05). Notably, D2–40-positive lymphatic vessels of Xp11.2 translocation RCC were highly detected in the peritumoral area compared to the intratumoral area. Interestingly, the peritumoral LVD and LVA of Xp11.2 translocation RCC were higher than that of ccRCC (all P < 0.05). Furthermore, both intratumoral MVD or MVA and peritumoral LVD or LVA were significantly associated with pT stage, pN stage, cM stage, AJCC stage, and WHO/ISUP grade (all P < 0.05). Univariate analysis of Cancer-specific survival (CSS) revealed that CSS was substantially longer in patients with low intratumoral MVD or MVA than in patients with high intratumoral MVD or MVA (P = 0.005 and P = 0.001, respectively). Lastly, the Cox proportional hazards model in CSS demonstrated that both intratumoral MVD or MVA and peritumoral LVD or LVA were not independent prognostic parameters (all P > 0.05). Conclusions This study outlines that Xp11.2 translocation RCC is a highly vascularized solid RCC, characterized by rich lymph vessels in the peritumoral area. Quantitative parameters of micro-angiogenesis and lymphangiogenesis could not be considered as novel prognostic factors for patients with xp11.2 translocation RCC.

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The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma

Therapeutic Advances in Urology ◽

10.1177/1756287217732660 ◽

2017 ◽

Vol 10 (1) ◽

pp. 3-10 ◽

Cited By ~ 1

Author(s):

Reza Mehrazin ◽

Essel Dulaimi ◽

Robert G. Uzzo ◽

Karthik Devarjan ◽

Jianming Pei ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Cytogenetic Analysis ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Renal Tumors ◽

Rank Test

Background: The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. Results: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method ( n = 11) or CMA ( n = 7). Gain of 8q was associated with higher T stage ( p < 0.001), grade ( p < 0.001), nodal involvement ( p = 0.005), and distant metastasis ( p < 0.001). No association between gain of 8q and age ( p = 0.23), sex ( p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83–18.34, p < 0.001] and 3.31-fold (95% CI, 1.56–7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto-oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.

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Alpha-1 blocker use increased risk of subsequent renal cell carcinoma: A nationwide population-based study in Taiwan

PLoS ONE ◽

10.1371/journal.pone.0242429 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242429

Author(s):

Shian-Ying Sung ◽

Trang Thi Huynh Le ◽

Jin- Hua Chen ◽

Teng-Fu Hsieh ◽

Chia-Ling Hsieh

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Research Database ◽

Antihypertensive Medications ◽

Increased Risk ◽

Underlying Mechanisms

Elevated Renal cell carcinoma (RCC) risk has been associated with the use of several antihypertensive medications but has not yet been elucidated in the populations prescribed alpha-1 blockers that are commonly used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS-BPH). The aim of the present study was to investigate the association between alpha-1 blocker use and the risk of developing RCC using a nationwide population-based database in Taiwan. Patients who were treated with alpha-1 blockers for at least 28 days were identified through the Taiwan National Health Insurance Research Database from 2000 to 2010. The unexposed participants were matched with the exposed cases according to age, sex, and index year at a ratio of 3:1. Cox proportional hazards regression, stratified by sex and comorbidities and adjusted for age, was performed to estimate hazard ratios (HRs) for the risk of subsequent RCC. Among 2,232,092 subjects, patients who received alpha-1 blocker treatment had a higher risk of RCC than the unexposed group. Taking into account hypertension and BPH, the adjusted HR was significantly higher in male alpha-1 blocker users who had no BPH and either the presence (HR: 1.63, 95% confidence interval [CI] = 1.22–2.18) or absence (HR: 2.31, 95% CI = 1.40–3.81) of hypertension than in men not receiving these drugs. Taken together, male alpha-1 blocker users who had no comorbidity of BPH exhibited an increased risk for developing RCC independent of hypertension. Further study is warranted to elucidate the underlying mechanisms of this association.

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Association of hypothyroidism with improved outcomes in first-line treatment of renal cell carcinoma with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.466 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 466-466 ◽

Cited By ~ 2

Author(s):

Flavio Augusto Ismael Pinto ◽

Augusto Akikubo Rodrigues Pereira ◽

Maria Nirvana Formiga ◽

Marcello Ferretti Fanelli ◽

Ludmilla T. D. Chinen ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Prognostic Factors ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitor ◽

Univariate Analysis ◽

Intermediate Risk ◽

Line Treatment ◽

First Line ◽

First Line Treatment

466 Background: Sunitinib, a multitarget tyrosine-kinase inhibitor, has become a standard of care for first-line low and intermediate risk metastatic renal cell carcinoma (mRCC). Sunitinib-induced hypothyroidism and hypertension have been correlated with better outcomes in those patients. Methods: Fifty patients with mRCC, treated in the first-line with sunitinib, were retrospective analyzed at one brazilian institution, for overall survival (OS), progression free survival (PFS), overall response rate (ORR) and toxicity. We evaluated clinical and laboratory parameters, such as hypothyroidism (TSH level > 5,5 mIU/L) and hypertension, to identify prognostic factors. Results: The median age of patients was 58 years (range: 37-73 years), 82% were male, 54% were ECOG 0 or 1, and 76% were classified in low or intermediate risk. Nefrectomy was performed in 96% of cases. Lung and bone were the most common sites of metastases. The incidence of hypothyroidism and hypertension during treatment were 40% and 34%, respectively. ORR for the entire population was 40% and it was statistically superior in patients that developed hypothyroidism during treatment (90% vs. 20%; p<0,0001). Median survival and PFS were 21.7 months (10.65-17.70 months, 95% CI) and 14.2 months (15.77-27.58 months, 95% CI), respectively. In univariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001), hypothyroidism (p<00001) and hypertension (p=0,001) were associated with OS. In multivariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001) and hypothyroidism (p<00001) were independent prognostic factors for OS. The most common severe adverse events (G3-4) were asthenia (14%), diarrhoea (6%), neutropenia (14%), thrombocytopenia (10%), hand-foot syndrome (6%) and hypertension (8%). Conclusions: Efficacy in survival and toxicity profile of sunitinib in first-line treatment of mRCC in patients out of clinical trials were comparable to prior studies. Hypothyroidism, MSKCC criteria and ECOG were independent prognostic factors for survival.

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Risk factors for dementia onset in older adults with metastatic renal cell carcinoma

Innovation in Aging ◽

10.1093/geroni/igab046.2608 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 701-702

Author(s):

Samuel Miller ◽

Lauren Wilson ◽

Melissa Greiner ◽

Jessica Pritchard ◽

Tian Zhang ◽

...

Keyword(s):

Older Adults ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression ◽

The Impact

Abstract Renal dysfunction is a driver of dementia. It is also associated with renal cell carcinoma, possibly the result of the tumor itself or from cancer treatment. This study evaluates metastatic renal cell carcinoma (mRCC) as a risk factor for developing mild cognitive impairment or dementia (MCI/D) as well as the impact of RCC-directed therapies on the development of MCI/D. We identified all patients diagnosed with mRCC in SEER-Medicare from 2007-2015. The main outcome was incident MCI/D within one year of mRCC diagnosis or cohort entry. Exclusion criteria included age <65 at mRCC diagnosis and diagnosis of MCI/D within preceding year of mRCC diagnosis. Patients with mRCC (n=2,533) were matched to non-cancer controls (n=7,027) on age, sex, race, comorbidities and year. Cox proportional hazards regression showed that having mRCC (HR 8.52, 95% MCI/D 6.49-11.18, p<0.001) and being older (HR 1.05 for 1-year age increase, 95% MCI/D 1.03-1.07, p<0.001) were predictive of developing MCI/D. A second Cox proportional hazards regression of only patients with mRCC revealed that neither those initiating treatment with oral anticancer agents (OAAs) nor those who underwent nephrectomy were more likely to develop MCI/D. Black patients had a higher risk of dementia compared to white patients (HR 1.92, 95% MCI/D 1.02-3.59, p=0.047). In conclusion, patients with mRCC were more likely to develop MCI/D than those without mRCC. The medical and surgical therapies evaluated were not associated with increased incidence of MCI/D. The increased incidence of MCI/D in older adults with mRCC may be the result of the pathology itself.

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Prognostic biomarker exploration for patients with metastatic renal cell carcinoma receiving VEGFR TKI.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.491 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 491-491

Author(s):

Inkeun Park ◽

Yong Mee Cho ◽

Jae-Lyun Lee ◽

Jin-Hee Ahn ◽

Dae Ho Lee ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Prognostic Factors ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Risk Group ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Coagulative Necrosis ◽

Prognostic Importance

491 Background: To verify the prognostic importance of selected tumor tissue biomarkers in metastatic renal cell carcinoma (mRCC) patients (pts), we performed immunohistochemical (IHC) staining in tumor sample and statistical analyses. Methods: The clinicopathological features, treatment, and outcome of mRCC pts treated with vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) between July 2006 and March 2011 at our center were reviewed. IHC staining for FGF base, FGFR1, 2, 3, and 4, HGF, PTEN, CAIX, pS6, HIF-1a, HIF-2a, IL-8, mTOR was done, and each specimen was scored based on the staining intensity and the percentage of positive cells. We performed univariate and multivariable analyses to verify prognostic factors for overall survival (OS). Results: We found 123 pts who met inclusion criteria. Most pts had clear cell carcinoma (107 pts, 87.0%). Fuhrman’s nuclear grade (NG) was 2 in 21 (17.1%), 3 in 49 (39.8%), and 4 in 52 (42.3%), respectively. Sarcomatoid change and coagulative necrosis were found in 51 pts and 58 pts. Using Heng’s criteria, 20 pts (16.3%), 87 (70.7%), and 16 (13.0%) belonged to favorable, intermediate, and poor risk group, respectively. First-line VEGFR TKIs prescribed were sunitinib (97 pts, 78.9%), sorafenib (23 pts, 18.7%), and pazopanib (3 pts, 2.4%). In univariate analysis, CAIX (less than 47.5% vs 47.5% or more, p=0.001), mTOR (20% or less vs more than 20%, p=0.0032), Heng risk group (good vs intermediate vs poor, p<0.001), sarcomatoid change (40% or less vs more than 40%, p<0.001), coagulative necrosis (20% or less vs more than 20%, p<0.001), Furhman NG (2 vs 3 vs 4, p=0.037) were statistically significant. In multivariable analysis, CAIX, Heng risk group, sarcomatoid change, and hyaline necrosis were identified as independent prognostic factors (Table). Conclusions: All investigated biomarkers but CAIX did not show prognostic importance for mRCC pts receiving VEGFR TKI. [Table: see text]

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Self-reported quality of life as a predictor of survival in renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.595 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 595-595

Author(s):

Ridwan Alam ◽

Hiten Patel ◽

Phillip M. Pierorazio

Keyword(s):

Quality Of Life ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Competing Risks ◽

Renal Cell ◽

Proportional Hazards ◽

Predictive Accuracy ◽

Cox Proportional Hazards ◽

Group 1

595 Background: Quality of life (QOL) in cancer patients has gained increasing attention and may provide prognostic value above and beyond traditional demographic and disease parameters. We evaluate the utility of self-reported QOL to predict mortality in patients with renal cell carcinoma (RCC). Methods: The Medicare Health Outcomes Survey was linked to SEER data to identify patients who completed a QOL questionnaire after the diagnosis of RCC from 1998-2014. Mental component summary (MCS) and physical component summary (PCS) scores were classified as high (≥50) or low ( < 50) based on a population mean score of 50 points. Patients were classified into four groups: 1) high MCS, high PCS; 2) high MCS, low PCS; 3) low MCS, high PCS; and 4) low MCS, low PCS. Multivariable Cox proportional hazards regression evaluated associations between QOL and all-cause mortality (ACM). The Harrell’s concordance statistic (C-index) estimated predictive accuracy. Fine and Gray competing risks models adjusted for stage, demographics, and comorbidities evaluated RCC-specific and non-RCC-specific mortality. Results: A total of 1494 patients with a median age of 73.4 years (IQR 68.8-79.3) at survey completion were included. Median follow-up was 5.6 years (IQR 4.0-8.3). There were 747 deaths, of which 139 were due to RCC. Models showed that each additional MCS and PCS point reduced the hazard of ACM by 1.3% (95% CI 0.981-0.993, P< 0.001) and 2.2% (95% CI 0.972-0.985, P< 0.001), respectively. The C-index was 72.1%. In the competing risks model, the subdistribution hazard ratio (SHR) of RCC mortality in Groups 2, 3, and 4 were 2.71 (95% CI 1.18-6.22, P= 0.02), 4.55 (95% CI 1.57-13.18, P= 0.005), and 3.11 (95% CI 1.35-7.16, P= 0.008), respectively, compared to Group 1. The SHR for non-RCC mortality were 1.50 (95% CI 1.16-1.94, P= 0.002), 1.03 (95% CI 0.59-1.78, P= 0.9), and 1.83 (95% CI 1.41-2.38, P< 0.001), respectively, relative to Group 1. Conclusions: Self-reported QOL metrics can be used to predict ACM in RCC patients with good accuracy; lower PCS and MCS scores led to higher rates of ACM, even after accounting for differences in disease, demographics, and comorbidity. Furthermore, non-RCC mortality was associated more with low physical health rather than low mental health.

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Management of Comorbidities in Diabetics With Renal Cell Carcinoma

Journal of Pharmacy Practice ◽

10.1177/0897190013501698 ◽

2013 ◽

Vol 27 (1) ◽

pp. 31-39 ◽

Cited By ~ 2

Author(s):

Jonathan L. Rabey ◽

Jingjing Yin ◽

Tammy M. Kublas ◽

Terry Mashtare ◽

Alice C. Ceacareanu

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Proportional Hazards ◽

Progression Free Survival ◽

Clinical History ◽

Cox Proportional Hazards ◽

Rank Test ◽

Cholesterol Lowering ◽

Treatment Groups

Objectives: This study evaluated whether particular diabetes mellitus (DM), hyperlipidemia, or hypertension pharmacotherapy was associated with improved renal cell carcinoma (RCC) outcomes in diabetics with emergent RCC. Methods: All DM cases newly diagnosed with RCC at Roswell Park Cancer Institute (January 01, 2003-December 31, 2010) were included (n = 95). Baseline demographic information, clinical history, and cancer outcomes were documented after chart review. Fisher’s test was used for the analysis of categorical outcomes across different treatment groups. Univariate and multivariate analyses for the comparisons of the overall survival and progression-free survival across treatment groups were assessed using Kaplan-Meier log-rank test and Cox proportional hazards models. Results: We found that DM pharmacotherapy users, which may represent a more advanced disease as compared to those controlled by diet alone, displayed significantly greater mortality ( P = .01). Additionally, we found that cholesterol-lowering pharmacotherapy use was associated with decreased RCC mortality (hazard ratio = 0.54, P = .06). Individuals receiving combined hypertension regimens had a lower chance to present with baseline metastasis; however, hypertension pharmacotherapy use added no survival benefit. Conclusion: Reinforcing guidelines compliance for hyperlipidemia management in patients with DM may provide a considerable cancer benefit if diagnosed with RCC. Studies evaluating the need for cholesterol-lowering pharmacotherapy in guidelines-noncompliant DM cases upon RCC diagnosis are currently needed.

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Delaying surgery for clinical T1b-T2bN0M0 renal cell carcinoma: Oncologic implications in the COVID-19 era and beyond.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.283 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 283-283

Author(s):

Arnav Srivastava ◽

Hiren V. Patel ◽

Sinae Kim ◽

Brian Shinder ◽

Joshua Sterling ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Proportional Hazards ◽

Clinical Stage ◽

Cox Proportional Hazards ◽

Renal Masses ◽

Logistic Regression Models ◽

Kaplan Meier ◽

Cox Proportional Hazards Models

283 Background: During COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined, RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival (OS). Methods: We retrospectively abstracted cT1b-cT2bN0M0 RCC patients from the National Cancer Database (NCDB), stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within <1 month, 1-3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed OS. Results: 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (OR=0.90; 95%CI: 0.77–1.05, p = 0.170), cT2a (OR=0.90; 95%CI: 0.69–1.19, p=0.454), or cT2b (OR=0.96; 95%CI:0.62–1.51, p=0.873) masses (Table). In all clinical stage strata, non-clear cell RCCs were significantly less likely to be upstaged (p<0.001). A sensitivity analysis, performed for delays of <1, 1-3, 3-6, and >6 months, also showed no increase in upstaging risk. Conclusions: Delaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered. [Table: see text]

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Entry Bias: Order of Patient Entry Influences Outcome in Trials of Allogeneic Transplant for Renal Cell Carcinoma.

Blood ◽

10.1182/blood.v104.11.269.269 ◽

2004 ◽

Vol 104 (11) ◽

pp. 269-269

Author(s):

Andrew S. Artz ◽

Masha Kocherginsky ◽

Koen Van Besien

Keyword(s):

Renal Cell Carcinoma ◽

Prognostic Factors ◽

Cell Carcinoma ◽

Patient Selection ◽

Renal Cell ◽

Surrogate Marker ◽

Cox Proportional Hazards ◽

Patient Specific ◽

Prognostic Information ◽

Probability Of Response

Abstract Early trials evaluating nonmyeloablative allogeneic hematopoietic transplant (NST) for metastatic renal cell carcinoma (RCC) have reported widely discordant results. We performed a meta-analysis of the published literature to identify prognostic factors for NST. However, known RCC prognostic factors are not often detailed in these studies, hindering the identification of patient differences among studies. We explored the order of patient entry as a surrogate marker for patient selection, hypothesizing that patient selection, rather than treatment differences, accounted for early promising results. Patient specific data and adequate follow-up were available for 76 patients from six studies. The rank of patient entry on each individual trial was recorded as well as ≥ grade 2 acute graft-versus-host disease (aGVHD), recipient age, recipient sex, response (partial plus complete), and survival. Multivariable analyses for response and survival were modeled using logistic and cox proportional hazards regression, respectively. The mean overall response rate was 22/76 (29%), with responses across individual studies significantly varying from 0% to 57% P =.009 by Chi-square). Median Kaplan-Meier survival was 263 days. Neither age nor sex was significantly ( associated with response or survival. Acute GVHD occurred in 42% of individuals and correlated with response (OR=9.9, P =0.012) but not survival (HR=1.53, P=0.28). When adjusting by study, later patient entry rank reduced the probability of response (OR=0.30, P =0.007) and survival (HR=1.89, P =0.006). Alternatively, being among the first five patients enrolled in a given study relative to subsequent patients, increased the probability of response (OR=6.69, 95% CI 1.95–39.1, P=0.005), even when adjusting for aGVHD, and afforded a survival benefit (HR= 0.45, 95% CI 0.022 −0.92, P=0.028). The prognostic strength of patient entry rank strongly suggests “entry bias” in patient selection. This bias potentially accounts for the large variation in outcome among studies and for the promising results in early studies. Entry bias analysis offers a novel method to assess early phase trials for selection bias, when detailed individual prognostic information is lacking. Further study is warranted to determine to what extent, if any, entry bias occurs in other clinical trial settings. Figure Figure

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A nomogram predicting disease-specific survival after nephrectomy for papillary renal cell carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5091 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5091-5091

Author(s):

T. Klatte ◽

M. Remzi ◽

J. W. Said ◽

A. Haitel ◽

F. F. Kabbinavar ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Proportional Hazards ◽

Papillary Renal Cell Carcinoma ◽

Cox Proportional Hazards ◽

Microvascular Invasion ◽

Disease Specific Survival ◽

Collecting System ◽

Disease Specific

5091 Background: Whereas multiple nomograms have been developed to assess outcomes of patients with clear cell renal cell carcinoma, a model to assess prognosis of papillary renal cell carcinoma (PRCC) has not yet been developed. After data collection and slide review of a large cohort of patients, the aim of this study was to develop and to internally validate a nomogram for prediction of disease-specific survival for PRCC. Methods: Out of 2,687 patients who underwent surgery for a renal tumor between 1989 and 2008 at two institutions, 258 (10%) were found to have PRCC. H&E slides were reviewed by one uro-pathologist at each institution for papillary sub-type, tumor grade, microvascular invasion, sarcomatoid features, collecting system invasion and presence and extent of tumor necrosis. A nomogram was constructed as a graphical representation of significant variables of disease-specific survival in multivariate Cox proportional hazards regression analysis. The discrimination and calibration of the nomogram were assessed, both utilizing bootstrapping to obtain relatively unbiased estimates. Results: After a median follow-up of 35 months, 49 PRCC-related deaths (19%) had occurred. In univariate analysis, incidental detection, T, N, M stage, grade, microvascular invasion, collecting system invasion, papillary sub-type, sarcomatoid features, and necrosis were all associated with prognosis. Multivariate Cox proportional hazards analysis, however, identified incidental detection, T stage, M stage, microvascular invasion, and necrosis, but not papillary sub-type as independent prognostic factors of disease-specific survival. These variables formed the basis of the nomogram that predicted 5-year disease-specific survival probability. The nomogram predicted well, with a bootstrapped corrected concordance index of 0.93, and showed good calibration. Conclusions: A highly accurate tool utilizing basic clinical and pathological information for predicting disease-specific survival was developed specifically for PRCC. This tool should be helpful for identification of the subset of PRCC patients with aggressive clinical behavior, and may contribute to the ability to individualize postoperative surveillance and therapy. No significant financial relationships to disclose.

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