Predictor Of Cancer-specific Mortality Research Articles

Sarcomatoid Dedifferentiation as a Predictor of Cancer-Specific Mortality in Surgically Treated Localized Renal Cell Carcinoma

BackgroundIn contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint.MethodsWithin the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used.ResultsIn 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation, p < 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio [HR] 1.8, p < 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (p < 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (p < 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (p < 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM.ConclusionsIn contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM.

Collecting duct carcinoma: Epidemiology, clinical characteristics and survival

IntroductionCollecting duct carcinoma (CDC) is a rare renal malignancy. We relied on a large population-based cohort to address epidemiology, clinical characteristics, and treatment of CDC patients. We also tested survival in the overall cohort, as well as in stage-specific fashion. Materials and methodsWithin Surveillance, Epidemiology, and End Results (2004–2018) database, we identified 399 CDC patients. Based on Kaplan-Meier plots survival estimates, conditional survival rates were derived according to disease stage. Cox regression models tested for predictors of cancer specific mortality (CSM). ResultsOverall, 273 (68.4%) patients were male, 236 (59.2%) had T3-4 stages, 148 (37.1%) had lymph node invasion, and 156 (39.1%) had distant metastases at initial diagnosis. Nephrectomy alone was commonest in stage I-II (n = 91/99, 92%) and III (n = 94/116, 81%). Combination of both nephrectomy and systemic therapy was commonest in stage IV (n = 62/172, 36%). In the overall cohort, median cancer specific survival was 18 months. Provided a disease-free interval of 24 months, five-year Kaplan-Meier estimated survival at diagnosis increased from 74.2 to 91.0% in stage I–II, from 31.1 to 65.3% in stage III, and from 6.3 to 34.1% in stage IV. In multivariable Cox regression models addressing CSM, systemic therapy (Hazard Ratio [HR]: 0.47, P = 0.020), nephrectomy (HR: 0.37, P < 0.001) and combination of both (HR: 0.28, P < 0.001) exhibited a strong protective effect. ConclusionDespite its highly aggressive phenotype and dismal survival, CDC is sensitive to nephrectomy and/or systemic therapy. Moreover, even for advanced stage, a more favorable prognosis can be achieved in patients, who benefit of disease-free interval after diagnosis and initial treatment.

Prognostic Impact of Nutritional Status Assessed by the Controlling Nutritional Status (CONUT) Score in Patients with Surgically Treated Renal Cell Carcinoma

Purpose: The prognostic role of the controlling nutritional status (CONUT) score in renal cell carcinoma (RCC) has not been evaluated. The aim of the current study was to clarify the prognostic significance of the CONUT score in Korean patients with surgically treated RCC.Materials and methods: A database of 1,881 patients with surgically treated RCC from a multiinstitutional Korean collaboration between 1999 and 2015 was analyzed. The preoperative CONUT score was calculated from serum albumin, total cholesterol concentrations, and total lymphocyte count. Clinicopathological variables and survival rates were compared between the CONUT score groups.Results: A high CONUT score was associated with older age, lower body mass index, lower preoperative prognostic nutritional index, and presence of diabetes or hypertension (each P < 0.001). Regarding pathologic features, a high CONUT score was associated with aggressive tumor characteristics including large tumor size, advanced stage, high nuclear grade, lymphovascular invasion, and sarcomatous differentiation (each P < 0.001). Multivariate Cox regression analysis indicated that a high CONUT score (≥ 2) was an independent predictor of cancer-specific mortality (hazard ratio, 1.892; 95% CI: 1.118–3.201; P = 0.018).Conclusion: The CONUT score, an easily measurable immune-nutritional biomarker, may provide useful prognostic information in patients with surgically treated RCC.

Does perioperative chemotherapy improve survival in upper tract urothelial carcinoma? A population based analysis.

ObjectivesTo evaluate the utilization and outcomes of perioperative chemotherapy in non-metastatic UTUC patients over the past decade using a large national database.MethodsAll patients aged 18 and older diagnosed with non-metastatic UTUC between 2004 and 2013 were identified within the Surveillance, Epidemiology and End Results (SEER) database. Relevant clinical data was collected and predictors of cancer specific mortality (CSM) and other cause mortality (OCM) were analyzed.ResultsThe total cohort included 8,762 patients. Of these, 1,402 (16%) patients received chemotherapy, including only 35% of high-risk patients (>pT2 or N1). Treated patients had higher CSM (21.3% vs. 13.1%, p<0.001). Predictors of chemotherapy utilization included residence in Midwest states, tumor located in the ureter, higher stage and grade. Predictors of CSM included older age, residence in southern states, receipt of chemotherapy (HR = 1.151, 95% CI: 1.003-1.32, p=0.044), higher stage and grade. OCM was predicted by male gender, older age, ureteral tumor, and higher stage. A subset analysis of patients younger than 65 showed similar predictors, while an analysis of high risk patients demonstrated that chemotherapy receipt did not predict CSM or OCM.ConclusionsIn this large contemporary non-metastatic UTUC cohort, chemotherapy utilization was found to be quite infrequent, but increasing steadily. Perioperative chemotherapy had no effect on CSM in high-risk patients, while correlated to higher CSM in the younger patients.

High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma: A population-based analysis

// Thenappan Chandrasekar 1 , Zachary Klaassen 1 , Hanan Goldberg 1 , Rashid K. Sayyid 1 , Girish S. Kulkarni 1 and Neil E. Fleshner 1 1 Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, Ontario, Canada Correspondence to: Thenappan Chandrasekar, email: thenappan.chandrasekar@gmail.com Keywords: carcinoma, renal cell; neoplasm metastasis; drug therapy; survival; mortality Received: August 29, 2017 Accepted: February 26, 2018 Published: March 30, 2018 ABSTRACT Objective: To utilize a population-based approach to address the role of adjuvant TT in the management of RCC. Methods: Patients with RCC (2006-2013) in the SEER database were stratified by metastatic disease at the time of diagnosis (cM0/cM1). cM0 patients following surgical excision were stratified into low and high-risk (ASSURE and S-TRAC criteria). Multivariable analyses performed to identify predictors of TT receipt; Fine and Gray competing risks analyses used to identify predictors of cancer-specific mortality (CSM). Subset analyses included patients with clear cell histology and high-risk cM0. Survival analyses were used to evaluate overall survival (OS) and cancer-specific survival (CSS) for all cohorts, stratified on TT receipt. Results: 79,926 patients included (71,682 cM0, 8,244 cM1); median follow-up for the entire cohort was 40.1 months. Of 31,453 patients with histologic grade data, 18,328 and 13,125 were low- and high-risk cM0, respectively. TT utilization in cM1 patients peaked at 50.6% and was associated with reduced CSM (HR 0.73, p<0.01). In contrast, TT utilization (presumed salvage therapy) never exceeded 2.2% in the entire cM0 cohort and 3.5% in the high-risk cM0 cohort. On competing risks analysis, TT receipt was associated with increased CSM in all cohorts. Conclusion: When compared to the cM1 patients, TT receipt in cM0 patients does not provide any cancer-specific survival benefit, even in the small percentage of patients that eventually progress to metastatic disease. Competing risks mortality further limit any potential benefit in this population. Based on current evidence, adjuvant TT cannot be recommended for RCC patients.

MP58-10 PREOPERATIVE HEMOGLOBIN TO PLATELET RATIO AS A PREDICTOR OF SURVIVAL AFTER RADICAL CYSTECTOMY.

You have accessJournal of UrologyBladder Cancer: Invasive V1 Apr 2017MP58-10 PREOPERATIVE HEMOGLOBIN TO PLATELET RATIO AS A PREDICTOR OF SURVIVAL AFTER RADICAL CYSTECTOMY. Giovanni La Croce, Marco Moschini, Alessandro Nini, Dell'Oglio Paolo, Eugenio Ventimiglia, Ettore Di Trapani, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Andrea Gallina, and Renzo Colombo Giovanni La CroceGiovanni La Croce More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Alessandro NiniAlessandro Nini More articles by this author , Dell'Oglio PaoloDell'Oglio Paolo More articles by this author , Eugenio VentimigliaEugenio Ventimiglia More articles by this author , Ettore Di TrapaniEttore Di Trapani More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Andrea GallinaAndrea Gallina More articles by this author , and Renzo ColomboRenzo Colombo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1805AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The role of cancer-related inflammation pathways as proxy of aggressiveness is well known in several cancers. Preoperative anemia and thrombocytosis are known to be associated with aggressive disease features in bladder cancer (BCa). Accordingly, we hypothesized that a single variable including hemoglobin (HB) and platelet count (PLT) (HB to PLT ratio [HPR]) could consider the synergic effect of both factors. We aim to evaluate if HPR can represent a predictor of cancer specific mortality (CSM) or overall mortality (OM) in patients treated with radical cystectomy (RC) for BCa METHODS We evaluated 963 patients diagnosed with BCa and treated with RC between 1987 and 2015 at our institution. Routine laboratory measurements were performed preoperatively the day before surgery. Univariate and multivariable Cox proportional hazards regression analyses were used to predict CSM and OM. Covariates included age at surgery, gender, pathological T stage, pathological N stage, preoperative hydronephrosis, ASA score, surgical margins, lymph vascular invasion and neoadjuvant chemotherapy RESULTS Median age was 69 years (IQR 62-75 years). HB was measured as g/L while PLT was measured as 10^9 L-1. Preoperative median HPR was 0.55 (IQR 0.41-0.70 ). Overall, 304, 129 and 540 patients were recorded with lymph node metastases, positive surgical margins and pT3-4 stage, respectively. CSM was observed in 385 (39%) patients, whereas OM was observed in 148 patients (48%). Median follow-up was 58 months (IQR 15-84 ). Patients with a HPR lower than 0.55 had adverse pathological characteristics, such as high grade (P < 0.001), advanced T stage (P < 0.001) and lymph node invasion (P < 0.001). At univariate analysis HPR higher than 0.55 was associated with lower risk of CSM and OM (respectively HR 0.224 and 0.291; CI 0.131-0.381 and 0.291-0.468; all p <0.001). At multivariate analysis preoperative HPR was associated with lower risk to incur CSM and OM (respectively HR 0.134 and 0.162; CI 0.05-0.37 and 0.07-0.41; all p <0.001). Other predictors of CSM were N stage and positive margins while neoadjuvant chemotherapy was inversely associated to CSM. Other predictors of OM were ASA score, age at surgery and N stage while neoadjuvant chemotherapy was inversely linked to OM CONCLUSIONS Despite the well known role of anemia and thrombocytosis as predictors of survival in BCa, HPR (that include both factors) should be considered as a powerful prognostic marker, expression of inflammation and of the disease aggressiveness. However further investigations are needed to fully understand the impact of inflammation in BCa © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e776 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Giovanni La Croce More articles by this author Marco Moschini More articles by this author Alessandro Nini More articles by this author Dell'Oglio Paolo More articles by this author Eugenio Ventimiglia More articles by this author Ettore Di Trapani More articles by this author Andrea Salonia More articles by this author Alberto Briganti More articles by this author Francesco Montorsi More articles by this author Andrea Gallina More articles by this author Renzo Colombo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP70-15 INCREASING COMPLEXITY OF TUMOR THROMBI IN RENAL CELL CARCINOMA OVER 40 YEARS OF EXPERIENCE

INTRODUCTION AND OBJECTIVES: Our objective was to report determinants of oncologic outcome and temporal changes in presentation of patients treated with surgical intervention for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). METHODS: We identified 845 patients with RCC and VTT treated with nephrectomy and tumor thrombectomy from 1970-2009. Perioperative complications and mortality were assessed in early (1970-89), mid (1990-99), and late (2000-09) time periods. Following pathological re-review, clinicopathologic features and outcomes were compared. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method and Cox proportional multivariate modeling was used to determine factors prognostic of cancer specific mortality (CSM). Median follow-up was 7.9 years. RESULTS: There were 510 (60%), 91 (11%), 139 (16%), 57 (7%), and 48 (6%) patients with levels 0, I, II, III, and IV VTT, respectively. The proportion of level III-IV VTT increased between 1970-89 (5.5%), 1990-99 (14.6%), and 2000-09, (18.9%, p<0.001). In total, 717 patients died, of whom 550 died from RCC. Although 30-day Clavien IIIIV complications (overall n1⁄447, 5.6%) have increased over time (early: 4.6% to late: 8.7%, p 1⁄4 0.03), 30-day perioperative mortality (overall n 1⁄4 25, 3%) decreased from 4.6% (early) to 1.9% (late, p 1⁄4 0.04). Median CSS for patients with levels 0-IV VTT occurred at 4.9, 2.2, 2.4, 2.0, and 1.7 years (p<0.001). Patients with levels I-IV VTT had increased CSM compared to level 0 VTT (HR 1.59, p<0.001); however, no incremental risk in CSS was noted within levels I-IV (p1⁄40.81). Median CSS by pNM status occurred at 7.4, 1.9, 1.2, and 0.8 years in pNx/0M0, pN1M0, pNx/ 0M1, and pN1M1 disease (p<0.001). Independent predictors of CSM (table) include increasing tumor thrombus level (Level II e IV, HR 1.4 e 1.55, p < 0.05), surgery in 2000-09 (HR 0.5, p < 0.001), fat invasion (HR 1.5, p < 0.001), pN1 (HR 1.7, p < 0.001) or M1 disease (HR 2.7, p < 0.001), coagulative tumor necrosis (HR 1.7, p < 0.001), and sarcomatoid differentiation (HR 1.7, p 1⁄4 0.003). CONCLUSIONS: CSS is inferior in patients with IVC VTT compared to renal vein VTT alone and in those with simultaneous nodal and metastatic disease at presentation. Despite increasing rates of level III-IV VTT in recent years, perioperative mortality and cancer-specific mortality has declined. Multivariate Cox proportional hazards model evaluating predictors of cancer-specific mortality among patients with tumor thrombus treated with radical nephrectomy and tumor thrombectomy (n 1⁄4 845, treated 1970 2009).

Impact of perioperative blood transfusion on oncologic outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma.

358 Background: Patients treated for urothelial carcinoma of the urinary bladder treated with radical cystectomy and pelvic lymph node dissection have worse clinical outcomes if they receive perioperative blood transfusion. We evaluated the impact of perioperative blood transfusion on oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods: We conducted a single-center, retrospective review of 405 patients treated with RNU for UTUC. Clinicopathologic characteristics were recorded. Hospital charts were reviewed to determine if patients received perioperative blood transfusion. Characteristics were compared between groups based on transfusion status using Chi-square analyses. Survival was assessed using the Kaplan-Meier method. Cox regression analysis addressed cancer-specific mortality (CSM). Results: Median age was 71.4 years (IQR 63.7-76.5) and the majority of patients were male (64%). Median follow up was 43.4 months (IQR 16.7-86.6). CSM occurred in 26.2% of patients. Perioperative transfusion was associated with higher rates of invasive T stage (&gt;/=T2), (62% vs. 47%, p=0.019) and lymph node positive disease (23% vs. 10.3%, p=0.029). Three year disease-specific survival (DSS) was 80% for the entire cohort. DSS was significantly shorter (p=0.003) for patients receiving transfusion (66.3%, 95% CI 53.7%-76.3%) than those who did not (83.3%, 95% CI 78.3%-87.3%). Transfusion was an independent predictor of CSM on multivariable analysis including gender, grade, invasive T stage, nodal status, and transfusion (Table 1). Conclusions: Perioperative blood transfusion may be associated with adverse pathologic and oncologic outcomes in patients undergoing RNU for UTUC. [Table: see text]

Predictors of cancer-specific mortality

Predictors of cancer-specific mortality

Predictors of Cancer-specific Mortality After Disease Recurrence in Patients with Squamous Cell Carcinoma of the Penis

Disease recurrence occurs frequently after surgical treatment for squamous cell carcinoma of the penis (SCCp). We sought to determine prognostic factors that influence cancer-specific mortality (CSM) after disease recurrence in patients with SCCp. We performed a retrospective analysis of 314 patients who experienced disease recurrence after surgical treatment for SCCp between 1949 and 2012. Competing risk regression analysis addressed factors associated with CSM after SCCp recurrence. Median time from surgery to disease recurrence was 10.5 mo (interquartile range [IQR]: 5.9–21.3). Of the recurrences, 165 (53%), 118 (38%), and 31 (9.9%) were local, regional, or distant, respectively. Within a median follow-up of 4.5 yr (IQR: 2.0–6.5), 108 patients died of SCCp and 41 patients died of causes other than SCCp. Shorter time to disease recurrence was found to be significantly associated with a higher risk of CSM (p=0.0006). Lymph node metastasis at the time of initial treatment (subdistribution hazard ratio [SHR]: 1.96; 95% confidence interval [CI] 1.23– 3.11; p=0.005) and regional recurrence (SHR: 4.14; 95% CI, 2.16–7.93; p<0.0001) or distant recurrence (SHR: 5.75; 95% CI, 2.59–12.73; p<0.0001) were associated with increased risk of CSM after disease recurrence. Inclusion of time to recurrence into risk stratification may help patient counseling and treatment planning.

More Extensive Pelvic Lymph Node Dissection Improves Survival in Patients with Node-positive Prostate Cancer

BackgroundThe role of extended pelvic lymph node dissection (ePLND) in treating prostate cancer (PCa) patients with lymph node invasion (LNI) remains controversial. ObjectiveThe relationship between the number of removed lymph nodes (RLNs) and cancer-specific mortality (CSM) was tested in patients with LNI. Design, setting, and participantsWe examined data of 315 pN1 PCa patients treated with radical prostatectomy (RP) and anatomically ePLND between 2000 and 2012 at one tertiary care centre. All patients received adjuvant hormonal therapy with or without adjuvant radiotherapy (aRT). Outcome measurements and statistical analysisUnivariable and multivariable Cox regression analyses tested the relationship between RLN number and CSM rate, after adjusting to all available covariates. Survival estimates were based on the multivariable model; patients were stratified according to RLN number using points of maximum separation. Results and limitationsThe average number of RLNs was 20.8 (median: 19; interquartile range: 14–25). Mean and median follow-up were 63.1 and 54 mo, respectively. At 10-yr, the CSM-free survival rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients with 8, 17, 26, 36, and 45 RLNs, respectively. By multivariable analyses, the number of RLNs independently predicted lower CSM rate (hazard ratio [HR]: 0.93; p=0.02). Other predictors of CSM were Gleason score 8–10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRT treatment (HR: 0.26; all p ≤ 0.006). The study is limited by its retrospective nature. ConclusionsIn PCa patients with LNI, the removal of a higher number of LNs during RP was associated with improvement in cancer-specific survival rate. This implies that ePLND should be considered in all patients with a significant preoperative risk of harbouring LNI. Patient summaryWe found that removing more lymph nodes during prostate cancer surgery can significantly improve cancer-specific survival in patients with lymph node invasion.

Long-term oncological outcome in men with T3 prostate cancer: radical prostatectomy versus external-beam radiation therapy at a single institution

This study was designed to compare the long-term oncological outcome of patients with clinical T3 (cT3) prostate cancer (PCA) treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and to identify predictors of oncological outcomes. A total of 231 patients with cT3 PCA underwent either RP (n = 112) or EBRT (n = 119). Local progression-free (LPFS), distant metastasis-free (DMFS), cancer-specific (CSS), and overall survival curves were generated with the Kaplan-Meier method, and the differences in survival rates between the two groups were assessed with a log-rank test. Cox proportional stepwise multivariate analysis was used to assess the association of variables to the oncological outcomes. The median follow-up of the RP and EBRT groups was 93 and 85 months, respectively (p = 0.004).The 10-year LPFS, DMFS, and CSS rates were not statistically different between the two groups (90.2, 73.9, and 93.7 % in the RP group and 82.7, 88.2, and 85.1 % in the EBRT group; p = 0.25, 0.10, and 0.10, respectively). The Cox proportional multivariate analysis revealed that clinical T3b (cT3b) (p = 0.001) and a biopsy Gleason score of 7-10 (p = 0.043) were significant predictors of cancer-specific mortality and that cT3b was also a significant predictor of local progression and all-cause mortality. In cT3 PCA, both RP and EBRT provide an excellent long-term oncological outcome. cT3b was the strongest predictor of oncological outcome for the patients with locally advanced PCA who underwent the definitive therapy.

Comparison of post-operative intravesical recurrence and oncological outcomes after open versus laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma

To retrospectively evaluate intravesical recurrence and oncological outcomes after open or laparoscopic radical nephroureterectomy (RNU) for the upper urinary tract urothelial carcinoma (UUT-UC). This study comprised 122 patients diagnosed UUT-UC and subsequently nephroureterectomy was performed on. Several clinical and pathological parameters were emphasized for comparison of clinical outcomes. Among 122 patients with UUT-UC, 101 (82.8 %) and 21 (17.2 %) underwent open or laparoscopic radical nephroureterectomy (ONU or LNU), respectively. In univariable and multivariable Cox regression models, the surgical procedure exerted an impact neither on post-operative intravesical recurrence rate (p = 0.179 and 0.213, respectively) nor on cancer-specific mortality rate (p = 0.561 and 0.159, respectively). The 1-, 2- and 5-year cancer-specific survival (CSS) rates of patients undergoing ONU or LNU were 92.1 versus 95.2 %, 87.1 versus 90.5 %, 79.2 versus 85.7 %, respectively, and the Kaplan–Meier plot illustrated that patients from two groups enjoyed an equivalent survival rate (p = 0.559). Moreover, we added that previous history of bladder tumor and pre-operative hydronephrosis was associated with intravesical recurrence, whereas three prognostic factors, including pathological tumor stage, grade, and lymphovascular invasion, showed possibility to be predictors of cancer-specific mortality. There existed no significant difference of intravesical recurrence and CSS between patients after ONU and LNU. Conclusively, laparoscopic radical nephroureterectomy did not present superiority to open management for patients with UUT-UC.

Clinical and pathological nodal staging score for urothelial carcinoma of the bladder: an external validation

Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

813 Time to disease recurrence is a strong predictor of cancer-specific mortality in upper tract urothelial carcinoma

813 Time to disease recurrence is a strong predictor of cancer-specific mortality in upper tract urothelial carcinoma

A genomic classifier independently prognostic of prostate cancer death in a high-risk surgical cohort.

60 Background: Biomarkers may improve ascertainment of progression risk after radical prostatectomy (RP). We compared two validated post-RP classifiers: the Decipher genomic classifier (GC) and CAPRA-S (based on standard clinicopathologic parameters), to predict prostate cancer-specific mortality (CSM) in a contemporary cohort of RP patients. Methods: From a cohort of 1,010 RP patients treated from 2000-06, a case-cohort design was used to analyze a subset of 219 men with one or more high risk features and available paraffin-embedded tissue. Median follow-up was 6 years. The GC, derived from expression levels of 22 biomarkers and dichotomized to denote low- and high-risk, and CAPRA-S, calculated from preoperative PSA and pathologic grade and staging variables, scores were determined. The scores were evaluated individually and in combination using concordance index, decision curve, (DC), re-classification, and Cox analyses for prediction of CSM. Results: 212 men had full data available to calculate the CAPRA-S; 27 experienced CSM. The c-index for GC (0.78) and CAPRA-S (0.76) were similar, although GC showed improved calibration and higher net-benefit on DC analysis. In 103 patients with high-risk CAPRA-S scores (≥6), GC scores were likewise high-risk for 49, among whom 19 had CSM events. The other 54 men were reclassified as low-risk by GC; among these only 1 CSM event was observed. In multivariable Cox analysis both GC and CAPRA-S were independently prognostic of CSM, with hazard ratios of 1.62 (p&lt;0.001) and 1.22 (p=0.01), respectively for unit score increases. A combined model defined based on the Cox model as (0.20*CAPRA-S + 5.68*GC) was more accurate than either score alone (p&lt;0.001 by likelihood ratio test). DC analysis indicated greater net benefit for the combined model than for either score alone. Conclusions: In men treated with RP at high risk of recurrence based on clinical and pathologic variables, both GC and CAPRA-S were significant predictors of CSM. Notably, GC was able to 'down-risk' &gt;50% of men stratified to high risk based on CAPRA-S alone. Thus the GC provides independent prognostic information, and a model integrating GC and CAPRA-S may further improve the prediction of lethal prostate cancer.

Determinants of outcomes after resection of renal cell carcinoma with venous involvement

To determine the outcomes and to identify prognostic variables determining mortality and recurrence after surgery for renal cell cancer (RCC) with venous involvement. Retrospective evaluation of the medical records of 132 patients with RCC and tumor thrombi treated at Johns Hopkins Hospital (1997-2008) was done. Kaplan-Meier analysis was used to determine survivals. Uni- and multivariate Cox proportional analysis was done to identify predictors for recurrence, all-cause mortality (ACM) and cancer-specific mortality (CSM). Mean follow-up was 30.3 (0.03-159.5) months. Sixty-four (48.5%) patients had renal vein thrombus (Group 1), 55 (41.7%) had subdiaphragmatic inferior vena cava (IVC) tumor thrombus (Group 2), while 13 (9.8%) had involvement of IVC above diaphragm or atrial extension (Group 3). IVC thrombus was more common from the right-sided tumors. Patients with higher thrombus levels had more blood loss and complicated and longer hospital stay. Thrombus level was not found to be a predictor of recurrence, ACM and CSM. One- and three-year recurrence-free survivals for non-metastatic patients were 69 and 53%. Tumor size (p=0.015), grade (p=0.007) and venous wall invasion (p=0.027) were predictors for recurrence. Five-year overall survival was 48, 35 and 13% for 3 groups, respectively. Presence of distant metastasis (p=0.032), size (p=0.002), histology (p=0.020) and grade (p=0.013) were predictors of ACM. Five-year cancer-specific survival was 65, 43 and 36 for 3 groups, respectively. Tumor size (p=0.001) and distant metastasis at presentation (p=0.025) were the predictors of CSM. Tumor thrombus level does not predict recurrence or mortality in RCC with venous involvement. Survival is determined by inherent aggressiveness of the cancer manifested by tumor size, grade and distant metastasis at presentation.

The Prognostic Value of Erythrocyte Polyamine in the Post-Nephrectomy Stratification of Renal Cell Carcinoma Specific Mortality

The polyamines spermine and spermidine are ubiquitous polycationic structures which are essential for cell proliferation and differentiation. Circulating polyamines, spermine and spermidine, represent valuable prognostic markers in prostate cancer, acute leukemia and supratentorial malignant glioma. We tested whether spermine and spermidine could improve the prognostic ability of several established predictors of cancer specific mortality after partial or radical nephrectomy for renal cell carcinoma. Testing was performed on 399 patients with stages T(1-4), N(0-2), M(0-1) renal cell carcinoma who were treated with radical or partial nephrectomy at a single institution between 1990 and 2007. Univariable and multivariable Cox regression models tested the prognostic ability of spermine and spermidine levels in cancer specific mortality predictions. Covariates consisted of TNM stage, Fuhrman grade, tumor size and symptom classification. Harrell's concordance index (c-index) quantified accuracy and 200 bootstrap resamples were used to correct for overfit bias. The 5-year cancer specific mortality-free survival of patients with spermine levels 3 or less, 3.1 to 8, 8.1 to 13 and greater than 13 nmol/8x10(9) erythrocytes was 88.8%, 75.8%, 40.2% and 21.8%, respectively. Similarly the 5-year cancer specific mortality-free survival of patients with spermidine levels 12 or less, 12.1 to 15, 15.1 to 21 and greater than 21 nmol/8x10(9) erythrocytes was 79.0%, 56.6%, 53.2% and 27.4%, respectively. On multivariable analyses addressing cancer specific mortality after surgery spermine (p = 0.007) and spermidine (p = 0.04) achieved independent predictor status. Consideration of spermine and spermidine also improved the accuracy of established cancer specific mortality predictors by 2.2% (p <0.001). Spermine and spermidine may significantly improve the prognostic value of established cancer specific mortality predictors after partial or radical nephrectomy for all stages of renal cell carcinoma. Independent external validation of our findings is required.

Location of the Primary Tumor is Not an Independent Predictor of Cancer Specific Mortality in Patients With Upper Urinary Tract Urothelial Carcinoma

The prognostic significance of renal pelvis vs ureteral upper urinary tract urothelial carcinoma tumor location is controversial. We assessed the prognostic significance of upper urinary tract urothelial carcinoma tumor location in a large, population based data set. Our analyses relied on 2,824 patients treated with nephroureterectomy for upper urinary tract urothelial carcinoma within 9 SEER registries between 1988 and 2004. Univariable and multivariable models tested the effect of tumor location on cancer specific mortality rates. Covariates consisted of age, race, SEER registry, gender, type of surgery (nephroureterectomy with vs without bladder cuff removal), pT stage, pN stage, grade and year of surgery. Relative to ureteral tumors renal pelvis tumors were of higher stage (T3/T4 disease 38.4% vs 57.9%, p <0.001) and had a higher rate of lymph node metastases (6.0% vs 9.8%, p = 0.003) at nephroureterectomy. The respective 5-year cancer specific mortality-free survival estimates were 81.0% vs 75.5% (p = 0.007). However, after multivariable adjustment tumor location failed to reach independent predictor status of cancer specific mortality (p = 0.8). To our knowledge this is the largest cohort in which the impact of upper urinary tract urothelial carcinoma tumor location on cancer specific mortality was examined. At nephroureterectomy renal pelvis tumors had significantly more advanced T and N stages compared to ureteral tumors. However, after adjustment for stage, grade and other covariates tumor location did not independently predict cancer specific mortality. Thus, the biological behavior of renal pelvis vs ureteral tumors is the same after nephroureterectomy as long as stage, grade, and other patient and tumor characteristics are accounted for.