Renal Cell Carcinoma Recurrence After Nephrectomy for Localized Disease: Predicting Survival From Time of Recurrence

2006 ◽  
Vol 24 (19) ◽  
pp. 3101-3106 ◽  
Author(s):  
Scott E. Eggener ◽  
Ofer Yossepowitch ◽  
Joseph A. Pettus ◽  
Mark E. Snyder ◽  
Robert J. Motzer ◽  
...  

Purpose Prognostic factors for patients with metastatic renal cell carcinoma (RCC) are well established. However, the risk profile is unknown for patients with recurrent RCC after a nephrectomy for localized disease. Patients and Methods From January 1989 to July 2005, we identified patients with localized RCC treated by nephrectomy who subsequently developed recurrent disease. We applied a validated prognostic scoring system previously developed for patients with metastatic RCC. Each patient was given a total risk score of 0 to 5, with one point for each of five prognostic variables (recurrence < 12 months after nephrectomy, serum calcium > 10 mg/dL, hemoglobin < lower limit of normal, lactate dehydrogenase > 1.5× upper limit of normal, and Karnofsky performance status < 80%). Patients were categorized into low- (score = 0), intermediate- (score = 1 to 2), and high-risk subgroups (score = 3 to 5). Results Our final cohort included 118 patients, with a median survival time of 21 months from the time of recurrence. Median follow-up time for survivors was 27 months. Overall survival was strongly associated with risk group category (P < .0001). Low-risk, intermediate-risk, and high-risk criteria were fulfilled in 34%, 50%, and 16% of patients, respectively. Median survival time for low-risk, intermediate-risk, and high-risk patients was 76, 25, and 6 months, respectively. Two-year overall survival rates for low-risk, intermediate-risk, and high-risk patients were 88% (95% CI, 77% to 99%), 51% (95% CI, 37% to 65%), and 11% (95% CI, 0% to 24%), respectively. Conclusion At disease recurrence after nephrectomy for localized disease, a scoring system based on objective clinical and laboratory data provides meaningful risk stratification for both patient counseling and clinical trial entry.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 753-753
Author(s):  
Margaret Frances Meagher ◽  
Ricardo Autorino ◽  
Maximilian Kriegmair ◽  
Maria Carmen Mir ◽  
Jose Rubio ◽  
...  

753 Background: The role of metastasectomy has been in flux as treatment paradigms for management of metastatic renal cell carcinoma (mRCC) have shifted. We examined outcomes of surgical metastasectomy stratified in the setting of different mRCC risk groups. Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. The cohort was subdivided by Motzer RCC criteria (low, intermediate, and high risk), and impact of metastasectomy was analyzed via multivariable analysis (MVA) and Kaplan Meier analyses (KMA). Primary outcome was progression free survival (PFS) and secondary outcome was overall survival (OS). Results: 438 patients (46 low risk, 262 intermediate risk, 140 high risk) with median follow-up 16 months were analyzed. Metastasectomy was performed in 18 (39%), 63 (24%), and 32 (23%) of low, intermediate and high risk groups (p=0.04). Risk groups differed significantly with respect to ECOG performance status (p<0.001), metastases at diagnosis (low 1.72, intermediate 3.49, high 6.45, p<0.001), hemoglobin (p<0.001) and LDH (p<0.001). MVA for PFS revealed age (OR=1.03, p=0.05), BMI (OR=1.05, p=0.01), and higher risk category [vs. low (referent) intermediate OR=7.4, p<0.001, high OR=3.4, p=0.01] to be independent risk factors. MVA for OS revealed age (OR=1.03, p=0.02), BMI (OR=1.06, p=0.01), and higher risk category [low (referent) vs. intermediate OR=2.8, p=0.03, high OR=2.3, p=0.01] to be independent risk factors. KMA for PFS demonstrated that metastasectomy was associated with longer PFS in intermediate (24.0 vs. 6.7 months, p=0.01) but not high risk (4.2 vs. 4.0 months, p=0.58) and low risk (p=0.51) groups. KMA for OS demonstrated that metastasectomy was associated with longer median OS in the intermediate (56.9 vs. 29.3 months, p=0.01) and high risk (18.2 vs. 10.5, p=0.01), but not low risk (p=0.21) groups. Conclusions: Receipt of metastasectomy was associated with improved PFS in intermediate risk and improved OS in intermediate and high risk mRCC patients. These findings challenge prevailing assumptions about utility of metastasectomy. Further investigation is requisite to refine criteria for employment.


BMC Medicine ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Tobias Klatte ◽  
Kevin M. Gallagher ◽  
Luca Afferi ◽  
Alessandro Volpe ◽  
Nils Kroeger ◽  
...  

Abstract Background The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery. Methods We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1–4, N0–1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups. Results We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups. Conclusions We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1015-1015 ◽  
Author(s):  
Ash A Alizadeh ◽  
James S. McClellan ◽  
Jason R. Gotlib ◽  
Steven Coutre ◽  
Ravindra Majeti ◽  
...  

Abstract Abstract 1015 Poster Board I-37 Background: Early mortality, mostly from hemorrhagic complications, occurs in less than 10% of patients currently treated in clinical trials for acute promyelocytic leukemia (APL). However, data about the proportion of patients developing such complications prior to clinical trial enrollment are scarce in the literature (Sanz M, et al Blood 2009). Approximately 5% of newly diagnosed patients with APL have been reported not to be eligible for participation in clinical trials due to very poor clinical condition, and their outcome has never been reported. However, enrollment on clinical trials may be difficult in specific clinical situations, such as after hours/weekend admissions and/or emergent requirement for therapy. This study reports the incidence, time of occurrence and clinical features of APL patients with a focus on early mortality. Methods: 150 consecutive APL patients treated at Stanford University between 8/1986 and 7/2009 were identified. Thirteen patients were excluded for lack of appropriate clinical information. Clinical features of patients with APL were analyzed for factors that might be relate to prognosis, including age, gender, white blood cell count, platelet count, fibrinogen, PTT, and INR. Continuous variables were compared with the t-test and categorical variables by Fisher's exact test or X-square statistic. The Kaplan–Meier method was applied to assess overall survival time. Results: Of the 137 patients included in this analysis, the median age at diagnosis was 45 (1-93) years and 78 (57%) were females. Using the PETHEMA criteria, there were 37, 46 and 20 patients with high-, intermediate- and low-risk disease (34 patients could not be classified based on partial/missing data). With a median follow-up time of 748 (0-6,235) days for the entire cohort, 52 (38%) have died. 19 (14%) and 11 (8%) of these patients died within 7 and 3 days of presentation, respectively. Patients with high-risk features had a 13% and 24% chance of dying with 3 and 7 days of presentation, respectively, with significantly inferior outcomes (p=0.045) when compared to those with intermediate-risk patients (6% and 13%) and low-risk disease (5% and 5%). Patients with unknown risk category faired similarly to low-risk patients. The most common cause of early mortality in these 19 patients was intracranial hemorrhage (n=11). Patients with early death (ED) (either <=3 or <=7 days) tended to be older than APL patients with non-early deaths (>7d), or APL patients alive as of their last follow-up (median age 54 years vs. 50 years vs. 39 years), and were more likely to have higher risk disease, though coagulopathy appeared not significantly different amongst the groups. Median fibrinogen, PTT and INR for each individual group are presented on Table 1. The 3-year overall survival (% +/- SE) of the low, intermediate, and high risk patients was 90+/-7, 74+/-7, and 64+/-8, respectively, though early mortality (death within 7 days) was a major determinant of this stratification (p=0.045). Conclusions: Risk of early death in APL patients appears to be higher than previously reported in clinical trials, where trial registration may exclude patients requiring urgent therapeutic interventions. In this cohort, 25% and 13% patients with high- and intermediate-risk APL died within 7 days of presentation, respectively. Risk group stratification was very predictive of risk of early death. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3128-3128
Author(s):  
Jin S. Im ◽  
Rima M Saliba ◽  
Susan C Abraham ◽  
Asif Rashid ◽  
William Ross ◽  
...  

Abstract Lower Gastrointestinal Graft versus Host Disease (GI GVHD) is a major cause for GVHD related non-relapsed mortality (NRM). High dose corticosteroid is the initial therapy for suspected lower GI GVHD, and additional therapy is often required for steroid refractory cases. The identification of high-risk patients is critical as timely intensification of treatment through early institution of second line therapy improves outcomes. To develop a reliable lower GI GVHD risk scoring system, Gastrointestinal Acuity Score (GAS), we evaluated 210 consecutive patients who underwent endoscopic biopsy for suspected lower GI GVHD within 6 months from the transplant from 2009 to 2012 at M.D. Anderson Cancer Center. We first identified 5 significant prognostic factors that accounted for the increased NRM in lower GI GVHD using univariate analysis: histologic grade, clinical stage, age, multi-organ GVHD, and donor type (Table 1). Gender, donor cell type, conditioning regimen (myeloablative vs non-myeloablative), time of diagnosis, disease status did not significantly influence NRM. Next, we performed multivariate Classification and Regression Tree (CART) analysis that utilizes sequential binary decision nodes to categorize 197 patients into subgroups according to their risk profile and outcome (Figure 1). The decision tree identified 7 subgroups starting with the presence of multi-organ GVHD as the first major decision node. This was followed by clinical stage 3/4, Age > 40 years, histology grade 3/4, and histology grade 1. We then consolidated subgroups with comparable risk profiles into low, intermediate, and high NRM risk groups (Figure 1). The 3 NRM risk groups correlated with day 28 response, the need for second line therapy and overall survival (Figure 2). The complete response rates at day 28 from the initiation of steroid therapy were significantly lower in the high (15%, p<0.001) and intermediate (43%, p=0.003) risk group compared to the low-risk group (70%). Accordingly, the high-risk patients were 4.3 (p < 0.001) and 1.6 (p=0.02) folds more likely to need second line therapy compared to low and intermediate risk patients, respectively. The intermediate risk patients were 2.7 (p=0.02) folds more likely to need second line therapy compared to the low risk group. In addition, the high-risk group was associated with the highest NRM (HR 5.4, p<0.001), followed by the intermediate risk (HR 3.8, p<0.001) compared to the low risk group. This translated into worse overall survival at 1 year for the high-risk patients. Lastly, there was a trend towards a lower chronic GVHD rate in the low risk group (25%, HR=0.6, p 0.06) compared to the high and intermediate risk groups (37%). In conclusion, we developed a novel risk scoring system, Gastrointestinal Acuity Score (GAS), incorporating histologic grades and clinical factors through multivariate CART analysis, and demonstrated that GAS predicts both early outcomes (day 28 CR rate and need for second line therapy) and late outcomes (NRM and overall survival) in patients with lower GI GVHD. Once prospectively validated in a larger cohort of lower GI GVHD patients, it will be of great use for clinicians with limited access to GVHD biomarker analysis in making treatment decisions as our new risk scoring system utilizes readily available variables. Figure 1. Univariate Analysis of risk factors for NRM at 1 year in Lower GI GVHD Figure 1. Univariate Analysis of risk factors for NRM at 1 year in Lower GI GVHD Figure 2. CART Analysis: Decision Tree for Risk Assessment Figure 2. CART Analysis: Decision Tree for Risk Assessment Figure 3. Need for second line therapy, NRM and OS Figure 3. Need for second line therapy, NRM and OS Disclosures Alousi: Therakos, Inc: Research Funding.


2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 361-361
Author(s):  
V. A. Master ◽  
O. Kucuk ◽  
W. Harris ◽  
B. Cross ◽  
A. Abbasi ◽  
...  

361 Background: Systemic inflammation has been associated with increased tumor grade and disease progression in renal cell carcinoma (RCC). Erythrocyte sedimentation rate (ESR) reflects systemic inflammation in other disease states. However, the relationship between ESR and survival remains unclear in localized RCC following potentially curative nephrectomy. We hypothesized that preoperative ESR would be a prognostic indicator of overall survival in localized RCC following radical nephrectomy. Methods: 167 patients undergoing nephrectomy for localized RCC had ESR measured preoperatively. Receiver operating characteristics (ROC) curves were constructed and used to determine the area under the curve (AUC) and relative sensitivity and specificity of preoperative ESR in predicting overall survival. From this curve, cut-offs for low risk (0.0-20.0 mm/hr), intermediate risk (20.1-50.0 mm/hr), and high risk (> 50.0 mm/hr) groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based risk groups on overall survival. Finally, univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results: 55.2%, 27.0% and 17.8% were in the low, intermediate, and high risk groups, respectively. Median (95% CI) survivals for these groups were 44.1 (42.6-45.5), 35.5 (32.3-38.8), and 32.1 (25.5-38.6) months, respectively. After controlling for patient age, race, gender, Charlson Comorbidity Index, T-Stage, Fuhrman Nuclear grade, and tumor size, intermediate risk and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735-27.649) and 18.5-fold (HR: 18.531, 95% CI: 2.117-162.228) increased risk of overall mortality, respectively. Conclusions: Preoperative ESR values represent a robust categorical predictor of overall survival following nephrectomy in localized renal cell carcinoma in this cohort. Clinicians may consider including ESR measurements in counseling patients before nephrectomy, as well as managing patients according to their ESR-based risk category. No significant financial relationships to disclose.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Chetan Jeurkar ◽  
Benjamin E Leiby ◽  
Joshua Banks ◽  
Margaret Kasner ◽  
Gina Keiffer ◽  
...  

Introduction The hypomethylating agents (HMA) decitabine (dec) and azacytidine (aza) are used in acute myeloid leukemia (AML) for induction therapy in patients with either newly diagnosed or relapsed disease and who are above the age of 60 or for those who would not tolerate intensive induction chemotherapy. As a result, HMA have been widely used at our institution, on both inpatient (IP) and outpatient (OP) services. The decision to administer IP-HMA vs OP-HMA is complex, but IP-HMA is recommended at our institution for neutropenic infections, debility, or risk of tumor lysis. The prognostic significance of this decision, if any, has not been widely explored. We hypothesized that because patients who receive their first cycle of HMA as an IP were at higher risk for complications, they would have a worse 100-day survival than their OP counterparts. Methods This was a retrospective observational study of patients treated at Thomas Jefferson University Hospital from January 2016-January 2020. Inclusion criteria were patients who had a diagnosis of AML, were above the age of 18 when treated, were treated with an HMA during the course of their disease, and were treated at our institution where electronic medical records (EMR) were complete and readily accessible. Exclusion criteria were patients who had died as a direct result of their hematopoietic stem cell transplant (HSCT) and whose records were incomplete or who had been treated at an outside institution. Logistic regression models were used to analyze data. Survival was calculated from day one of the first cycle of HMA received. Results A total of 68 patients were evaluated. Twenty-nine patients received IP-HMA while 39 received OP-HMA. Mean overall survival from HMA initiation was 252 days (95% CI 164-340) in the IP-HMA group and 430 days (95% CI 269-591) in the OP-HMA group. Mean 100-day survival in the IP-HMA group was 78 days (95% CI 65-91) and 93 days (95% CI 87-99) in the OP-HMA group. The average age at HMA initiation in the IP group was 69 (95% CI 64-74) and was 66 (95% CI 62-70) in the OP group. Average Charlson co-morbidity index was 5.5 (95% CI 5.0-6.0) in the IP group and 5.6 (95% CI 5.0-6.2) in the OP group. In the IP group, there were 1 low risk, 7 intermediate risk, and 21 high risk patients according to the European LeukemiaNet (ELN) risk stratification scale. In the OP group, there were 3 low risk, 8 intermediate risk, and 28 high risk patients. Nineteen of the 29 patients in the IP group and 11 of the 39 patients in the OP group received venetoclax in addition to an HMA as part of their therapy. Using a logistic regression model, location of HMA induction was found to have a significant effect on 100-day survival with IP induction being associated with worse survival (odds ratio=3.94; p=0.028) (see figure 1). Co-variates for this model included age at HMA initiation as this was the only confounder found in Wilcoxon rank sum testing to be significant. Other confounders which were tested but not included in logistic regression due to non-significance included race, gender, ELN risk, and Charlson co-morbidity indices. Discussion In this retrospective study, we found that IP-HMA induction was associated with a worse 100 day and overall survival than its OP counterpart. Though we found that co-morbidity indices and ELN risk scores were similar between the two groups, we postulate the reason the IP group had a significantly worse 100 day survival was that being admitted for neutropenic fever, risk of tumor lysis, etc. inherently put them at higher risk for complications like septic shock and hypoxic respiratory failure. Additionally, we found that patients who received HMA as an IP were far more likely to die shortly after their induction, within 100 days and often within 20 days. This would indicate they were potentially poor candidates for chemotherapy and that a palliative approach may have been more appropriate.. This study describes the survival differences seen in patients receiving IP-HMA versus OP-HMA. Knowledge of these results could spawn a more palliative approach for future patients requiring IP-HMA induction. Figure Disclosures Kasner: Otsuka Pharmaceutical: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Palmisiano:AbbVie: Research Funding; Genentech: Research Funding.


2021 ◽  
Vol 11 ◽  
Author(s):  
Fabio Serpenti ◽  
Francesca Lorentino ◽  
Sarah Marktel ◽  
Raffaella Milani ◽  
Carlo Messina ◽  
...  

IntroductionAllogeneic stem cell transplantation survivors are at a relevant risk of developing chronic GvHD (cGvHD), which importantly affects quality of life and increases morbidity and mortality. Early identification of patients at risk of cGvHD-related morbidity could represent a relevant tool to tailor preventive strategies. The aim of this study was to evaluate the prognostic power of immune reconstitution (IR) at cGvHD onset through an IR-based score.MethodsWe analyzed data from 411 adult patients consecutively transplanted between January 2011 and December 2016 at our Institution: 151 patients developed cGvHD (median follow-up 4 years). A first set of 111 consecutive patients with cGvHD entered the test cohort while an additional consecutive 40 patients represented the validation cohort. A Cox multivariate model for OS (overall survival) in patients with cGvHD of any severity allowed the identification of six variables independently predicting OS and TRM (transplant-related mortality). A formula for a prognostic risk index using the β coefficients derived from the model was designed. Each patient was assigned a score defining three groups of risk (low, intermediate, and high).ResultsOur multivariate model defined the variables independently predicting OS at cGvHD onset: CD4+ &gt;233 cells/mm3, NK &lt;115 cells/mm3, IgA &lt;0.43g/L, IgM &lt;0.45g/L, Karnofsky PS &lt;80%, platelets &lt;100x103/mm3. Low-risk patients were defined as having a score ≤3.09, intermediate-risk patients &gt;3.09 and ≤6.9, and high-risk patients &gt;6.9. By ROC analysis, we identified a cut-off of 6.310 for both TRM and overall mortality.In the training cohort, the 6-year OS and TRM from cGvHD occurrence were 85% (95% CI, 70-92) and 13% (95% CI, 5-25) for low-risk, 64% (95% CI, 44-89) and 30% (95% CI, 15-47) for intermediate-risk, 26% (95% CI, 10-47), and 42% (95% CI, 19-63) for high-risk patients (OS p&lt;0.0001; TRM p = 0.015).The validation cohort confirmed the model with a 6-year OS and TRM of 83% (95% CI, 48-96) and 8% (95% CI, 1-32) for low-risk, 78% (95% CI, 37-94) and 11% (95% CI, 1-41) for intermediate-risk, 37% (95% CI, 17-58), and 63% (95% CI, 36-81) for high-risk patients (OS p = 0.0075; TRM p = 0.0009).ConclusionsIR score at diagnosis of cGvHD predicts GvHD severity and overall survival. IR score may contribute to the risk stratification of patients. If confirmed in a larger and multicenter-based study, IR score could be adopted to identify patients at high risk and modulate cGvHD treatments accordingly in the context of clinical trial.


2004 ◽  
Vol 171 (4S) ◽  
pp. 263-263
Author(s):  
Nathalie Rioux-Leclercq ◽  
Florence Jouan ◽  
Pascale Bellaud ◽  
Jacques-Philippe Moulinoux ◽  
Karim Bensalah ◽  
...  

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