External validation of extranodal extension and lymph node density as predictors of survival in node-positive bladder cancer after radical cystectomy.

BACKGROUND: Prognostic factors in pathologic node-positive patients after radical cystectomy are debated. Extranodal extension (ENE) and lymph node density (LND) are strong predictors of survival. The aim of this study was to assess factors predictive of survival and to evaluate the prognostic significance of the tumor, node, metastasis staging system (TNM) nodal classification in a retrospective cohort of node-positive bladder cancers after radical cystectomy. METHODS: We retrospectively reviewed the data of 75 patients with node-positive bladder cancer after radical cystectomy. Node pathological examination was performed by two experienced uropathologists. Cox regression analysis was performed to identify factors predictive of progression. RESULTS: The median number of removed lymph node was 18 (range 3-49). The median number of positive lymph nodes was 3 (range 1-35). Overall progression-free and cancer-specific survival were 5 and 12 %. In multivariate analysis, ENE, LND with a 20 % cutoff, and adjuvant chemotherapy were independent predictors of progression-free survival (p = 0.007, 0.006, <0.0001). Neither the 2002 nor the 2009 TNM nodal classification was associated with recurrence. CONCLUSIONS: ENE and LND are strong predictors of clinical outcome in patients with node-positive bladder cancer treated by cystectomy. The actual TNM classification could probably be improved using these criteria, allowing better prognostic classification of node-positive bladder cancer after radical cystectomy.

Impact of body mass index on perioperative morbidity, oncological, and functional outcomes after extraperitoneal laparoscopic radical prostatectomy.

OBJECTIVE: To evaluate the impact of obesity on the outcomes of laparoscopic radical prostatectomy. METHODS AND MATERIALS: In a prospective urologic cancer database, 765 patients underwent extraperitoneal laparoscopic radical prostatectomy for localized prostate cancer. The patients were categorized into 3 groups of body mass index (kg/m(2)): <25.0 (n = 276, 30%, "normal weight"), 25.0 to 30.0 (n = 365, 48%, "overweight") and >30.0 (n = 124, 16%, "obese"). We assessed the perioperative, oncological, and functional outcomes in this cohort of patients. Preoperative and postoperative evaluation of continence and erectile function were performed using validated questionnaires. RESULTS: Mean operative time was significantly longer in obese patients (P < .001) and blood loss was also more important (P < .01). The obese patients had the highest likelihood of having aggressive tumors: nonorgan confined prostate cancer (49%, P = .002) and Gleason score ≥ 7 (80%, P = .005). The obese group had the higher positive surgical margins rate (overall: 27%, P = .012; pT2: 20%, P = .02). With a mean follow-up of 38 months, obesity was not an independent predictive factor of biochemical recurrence. At the 12-month follow-up, 85%, 74%, and 72% of normal, overweight, and obese men, respectively, were continent (no pad) (P = .04). At the 12-month follow-up, 57%, 58%, and 40% of normal, overweight, and obese men, respectively, reported an erection sufficient for intercourse (P = .01). CONCLUSION: Laparoscopic radical prostatectomy is a safe and effective procedure in obese men with midterm cancer control. However, obese patients are at higher risk of aggressive disease. Recovery of continence and potency in these patients are significantly lower compared to nonobese men.

Transforming growth factor ß-receptor II protein expression in benign prostatic hyperplasia is associated with prostate volume and inflammation.

OBJECTIVE: To assess transforming growth factor ß-receptor II (TGFBRII) protein expression in benign prostatic hyperplasia (BPH) using immunohistochemistry analysis, and to compare the analysis with phenotypic properties. METHODS: TGFBRII protein expression was profiled using three clinical outcome tissue microarrays (TMAs), sampled from 231 patients who underwent surgery for BPH. Using these TMAs, five inflammatory cell markers were also assessed, including CD3, CD4, CD8, CD20, and CD163. The surgical procedure was open prostatectomy in 95 patients and transurethral resection of the prostate in 136 patients. RESULTS: TGFBRII protein expression was found in BPH epithelium cells for both basal and secretory cells, as well as in fibromuscular stromal cells. TGFBRII staining was also strong in most of the lymphocytes infiltrating the prostate. TGFBRII stromal staining was found to be significantly associated with prostate volume (P = 0.04), whereas TGFBRII epithelial staining was found to be significantly associated with 5-α-reductase-inhibitor medical therapy received by patients before surgery (P = 0.004). Both stromal and epithelial TGFBRII staining were found to be associated with CD4 T-lymphocyte infiltrate, independently of prostate volume (P < 0.001 and P = 0.002). CONCLUSIONS: TGFBRII protein expression in BPH is associated with prostate gland volume and with CD4 T-lymphocyte prostatitis. TGFBRII might be a promising therapeutic target to prevent prostate enlargement or even to decrease prostate volume.

Occupational exposure to polycyclic aromatic hydrocarbons influenced neither the frequency nor the spectrum of FGFR3 mutations in bladder urothelial carcinoma.

Occupational exposure to polycyclic aromatic hydrocarbons (PAH) is associated with an increased risk of urothelial carcinoma (UC). FGFR3 is found mutated in about 70% of Ta tumors, which represent the major group at diagnosis. The influence of PAH on FGFR3 mutations and whether it is related to the emergence or shaping of these mutations is not yet known. We investigated the influence of occupational PAH on the frequency and spectrum of FGFR3 mutations. We included on 170 primary urothelial tumors from five hospitals from France. Patients (median age, 64 yr) were interviewed to gather data on occupational exposure to PAH, revealing 104 non- and possibly PAH exposed patients, 66 probably and definitely exposed patients. Tumors were classified as follows: 75 pTa, 52 pT1, and 43 > or =pT2. Tumor grades were as follows: 6 low malignant potential neoplasms (LMPN) and 41 low-grade and 123 high-grade carcinomas. The SnaPshot method was used to screen for the following FGFR3 mutations: R248C, S249C, G372C, Y375C, A393E, K652E, K652Q, K652M, and K652T. Occupational PAH exposure was not associated with a particular stage or grade of tumors. Thirty-nine percent of the tumors harbored FGFR3 mutations. After adjustment for smoking, occupational exposure to PAH did not influence the frequency [OR, 1.10; 95% CI, 0.78-1.52], or spectrum of FGFR3 mutations. Occupational exposure to PAH influenced neither the frequency nor the spectrum of FGFR3 mutations and there was no direct relationship between these mutations and this occupational hazard.

External validation of the updated partin tables in a cohort of French and Italian men.

PURPOSE: To test the discrimination and calibration properties of the newly developed 2007 Partin Tables in two European cohorts with localized prostate cancer. METHODS: Data on clinical and pathologic characteristics were obtained for 1,064 men treated with radical prostatectomy at the Creteil University Health Center in France (n = 839) and at the Milan University Vita-Salute in Italy (n = 225). Overall discrimination was assessed with receiver operating characteristic curve analysis, which quantified the accuracy of stage predictions for each center. Calibration plots graphically explored the relationship between predicted and observed rates of extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node invasion (LNI). RESULTS: The rates of ECE, SVI, and LNI were 28%, 14%, and 2% in the Creteil cohort vs. 11%, 5%, and 5% in the Milan cohort. In the Creteil cohort, the accuracy of ECE, SVI, and LNI prediction was 61%, 71%, and 82% vs. 66%, 92% and 75% for the Milan cohort. Important departures were recorded between Partin Tables' predicted and observed rates of ECE, SVI, and LNI within both cohorts. CONCLUSIONS: The 2007 Partin Tables demonstrated worse performance in European men than they originally did in North American men. This indicates that predictive models need to be externally validated before their implementation into clinical practice.

BPH gene expression profile associated to prostate gland volume.

The aim of the current study was to analyze gene expression profiles in benign prostatic hyperplasia and to compare them with phenotypic properties. Thirty-seven specimens of benign prostatic hyperplasia were obtained from symptomatic patients undergoing surgery. RNA was extracted and hybridized to Affymetrix Chips containing 54,000 gene expression probes. Gene expression profiles were analyzed using cluster, TreeView, and significance analysis of microarrays softwares. In an initial unsupervised analysis, our 37 samples clustered hierarchically in 2 groups of 18 and 19 samples, respectively. Five clinical parameters were statistically different between the 2 groups: in group 1 compared with group 2, patients had larger prostate glands, had higher prostate specific antigen levels, were more likely to be treated by alpha blockers, to be operated by prostatectomy, and to have major irritative symptoms. The sole independent parameter associated with this dichotome clustering, however, was the prostate gland volume. Therefore, the role of prostate volume was explored in a supervised analysis. Gene expression of prostate glands <60 mL and >60 mL were compared using significance analysis of microarrays and 227 genes were found differentially expressed between the 2 groups (>2 change and false discovery rate of <5%). Several specific pathways including growth factors genes, cell cycle genes, apoptose genes, inflammation genes, and androgen regulated genes, displayed major differences between small and large prostate glands.

Prognostic variables to predict cancer-related death in incidental renal tumours.

OBJECTIVE: To identify, in a large multicentre series of incidental renal tumours, the key factors that could predict cancer-related deaths, as such tumours have a better outcome than symptomatic tumours and selected patients are increasingly being included in watchful-waiting protocols. PATIENTS AND METHODS: Data from 3912 patients were extracted from three international kidney-cancer databases. Age, gender, Eastern Cooperative Oncology Group (ECOG) performance status (PS), Tumour-Node-Metastasis (TNM) stage, tumour size, Fuhrman grade, and final pathology were recorded. Benign tumours and malignant lesions with incomplete information were excluded from final analysis. RESULTS: The mean (SD) age of the patients was 60.6 (12.2) years and the mean tumour size 5.5 (3.5) cm. Most tumours were malignant (90.2%) and of low stage (T1-T2, 71.7%) and low grade (G1-G2, 72.4%). There were nodal and distant metastases in 5.7% and 13% of the patients. In all, 525 (14.4%) patients died from cancer; in this group, tumours were >4 cm in 88.2% and had nodal or distant metastases in 20.2% and 49.3%, respectively. Multivariable analysis showed that tumour size >4 cm, ECOG PS >or=1, TNM stage and Fuhrman grade were independent predictors of cancer-related death. CONCLUSION: A significant proportion of incidental renal tumours can lead to the death of the patient. Standard prognostic variables for renal cell carcinoma appear to remain valid for this subset of patients. A watchful-waiting strategy should not be recommended if the tumour diameter is >4 cm, if biopsy confirms high-grade tumours, or if there is an impaired ECOG PS, or computed tomography findings suggest the presence of advanced T stage.

ECOG performance status 0 or 1 and symptom classification do not improve the ability to predict renal cell carcinoma-specific survival.

OBJECTIVES: We tested and compared the improvement in prognostic ability related to the consideration of either ECOG performance status (ECOGPS) and/or symptom classification (S-CLASS) in renal cell carcinoma specific mortality (RCC-SM) predictions. METHODS: Univariate and multivariate Cox regression analyses targeted RCC-SM in 2570 RCC patients treated with either partial or radical nephrectomy. The increment in predictive accuracy related to the addition of either ECOGPS, S-CLASS or both was quantified using Harrell's concordance index. RESULTS: Follow-up ranged from 0.1 to 23 years (median 3.2) and 610 patients (23.7%) died of RCC. In multivariable analyses, ECOGPS and S-CLASS represented independent predictors of RCC-SM. The addition of ECOGPS to established RCC-SM predictors increased the predictive accuracy by 0.3% (p=0.8) versus 0.6% (p=0.5) for S-CLASS versus 0.6% (p=0.5) for both. CONCLUSIONS: Neither ECOGPS nor S-CLASS improves the ability to predict RCC-SM. Therefore, these variables may be safely omitted when RCC-SM risk is quantified.

Collecting duct renal cell carcinoma: a matched analysis of 41 cases.

OBJECTIVES: Collecting duct renal cell carcinoma (CDRCC) is a rare but reportedly aggressive histologic subtype. We assessed the stage and histologic features of patients with CDRCC and compared cancer-specific mortality in CDRCC and matched patients with clear-cell renal cell carcinoma (CRCC). METHODS: Forty-one (0.6%) patients with CDRCC and 5246 CRCC patients were identified within a cohort of 6608 patients treated with either radical or partial nephrectomy for renal cancer. Within the 5246 CRCC cases, 105 were matched with CDRCC cases for grade, tumour size, and T, N, and M stages. Kaplan-Meier and life table analyses addressed RCC-specific survival. RESULTS: Of all CDRCC patients, 76% had pT3 disease at nephrectomy versus 37% for those with CRCC. The predominant Fuhrman grades were III (56%) and IV (22%) in CDRCC versus II (42%) and III (28%) for CRCC. Moreover, 49% of CDRCC patients were pN1-2 versus 8% for CRCC. Of CDRCC patients 19% had distant metastases at nephrectomy versus 14% for CRCC. Finally, 73% of CDRCC patients had either local or systemic symptoms versus 56% for CRCC. After matching, the RCC-specific mortality of CDRCC patients was no different from that for CRCC patients (RR=1.1; p=0.8). One- and 5-yr CDRCC-specific survival rates were 86% and 48%, respectively, versus 86% and 57% for matched CRCC controls. CONCLUSIONS: CDRCC patients present with more advanced stage and with more aggressive disease compared with CRCC patients. After nephrectomy, when CDRCC cases were matched with CRCC, the same cause-specific survival was seen.

Use of haemostatic agents and glues during laparoscopic partial nephrectomy: a multi-institutional survey from the United States and Europe of 1347 cases.

OBJECTIVES: Laparoscopic partial nephrectomy (LPN) is a technically challenging procedure for the management of renal tumours. Major complications of LPN include bleeding and urine leakage. Haemostatic agents (HAs) and/or glues may reduce haemorrhage and urine leakage. We sought to examine the current practice patterns for urologists performing LPN with regard to HA use and its relationship with bleeding and urine leakage. MATERIALS AND METHODS: A survey was sent via e-mail to urologists currently performing LPN in centres in the United States and Europe. We queried the indications for HA/glue usage, type of HAs/glues used, and whether concomitant suturing/bolstering was performed. In addition, the total number of LPNs performed, laparoscopic tools used to resect the tumour, tumour size, and tumour position were queried. RESULTS: Surveys suitable for analysis were received from 18 centres (n=1347 cases). HAs and/or glues were used in 1042 (77.4%) cases. Mean tumour size was 2.8cm, with 79% of the tumours being defined as exophytic and 21% deep. The HAs and glues used included gelatin matrix thrombin (FloSeal), fibrin gel (Tisseel), bovine serum albumin (BioGlue), cyanoacrylate glue (Glubran), oxidized regenerated cellulose (Surgicel), or combinations of these. Sixteen centres performed concomitant suturing/bolstering. The overall postoperative bleeding requiring transfusion and urine leakage rates were 2.7% and 1.9%, respectively. CONCLUSIONS: The use of HAs and/or glues is routine in most centres performing LPN. The overall haemorrhage and urine leakage rates are low following LPN. More studies are needed to assess the potential role of HAs and/or glues in LPN.

[Comparison of open and laparoscopic partial nephrectomy: a French multicentre experience]. / Comparaison de la néphrectomie partielle par voie laparoscopique et par voie ouverte: une expérience multicentrique française.

OBJECTIVES: To compare open (OPN) and laparoscopic (LPN) partial nephrectomy (PN) techniques in the light of a French multicentre series. MATERIAL AND METHODS: Data corresponding to 741 PN (91 laparoscopic and 650 open procedures) were compared in terms of the indications, tumour diameter, operative data, complication rates and length of hospital stay. RESULTS: Tumours were smaller in the LPN group (2.7 vs 3.4 cm, p = 0.001). There were fewer malignant tumours (71.1% vs 80% p = 0.05) and fewer NP by necessity (20.9% vs 31.4%. p = 0.04) in the LPN group than in the OPN group. There were fewer hilar tumours in the LPN group than in the OPN group (LPN: 4% vs OPN: 14.8%, p = 0.03). Pedicle clamping was performed less frequently in the LPN group (33% vs 50.2%, p = 0.002) but for a significantly longer mean duration (35 minutes vs 19 minutes, p = 0.0001). The mean operating time was longer in the LPN group (163 vs 150 minutes, p = 0.02). The surgical complication rate (17.6% vs 14.3%), transfusion rate (6.6% vs 10.5%) and mean blood loss (363 vs 434 ml) were not significantly different between the 2 groups. There were significantly more urinary fistulas (12.1% vs 2.5%, p < 0.001) and medical complications (24.2% vs 14%, p = 0.01) in the laparoscopy group, but, in the longer-term, urinarvfistula rates were comparable in the 2 groups. The length of hospital stay was shorter for LPN (9.1 vs 11.2 days, p = 0.009). CONCLUSION: This comparative series, reflecting initial experience, shows that laparoscopic partial nephrectomy achieves similar operative and perioperative results to those of open partial nephrectomy. However, the indications for laparoscopic partial nephrectomy remain selective, as the pedicle clamping time and medical complication rates are higher with laparoscopic surgery. Experience and technical progress in laparoscopic partial nephrectomy should make the operative technique comparable to that of open surgery.

Morbidity and clinical outcome of nephron-sparing surgery in relation to tumour size and indication.

OBJECTIVE: To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication. METHODS: The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancer-specific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using chi(2) (Fischer exact test) and Student t tests, respectively. RESULTS: A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4+/-2.1cm. In 730 elective procedures mean operative time (p=0.002), mean blood loss (p=0.01), the need for blood transfusion (p=0.001), and urinary fistula rate (p=0.01) were significantly increased for tumours >4 cm. However, these differences did not result in significantly increased medical (p=0.4), surgical complication rates (p=0.6), or length of hospital stay (p=0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumours < or =4 cm and >4 cm. CONCLUSION: Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours >4 cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity.

Regional copy number-independent deregulation of transcription in cancer.

Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.

Gefitinib inhibits the growth and invasion of urothelial carcinoma cell lines in which Akt and MAPK activation is dependent on constitutive epidermal growth factor receptor activation.

PURPOSE: Abnormally high levels of epidermal growth factor receptor (EGFR) protein are associated with advanced tumor stage/grade. The objective of this study was to evaluate the effects of the specific EGFR tyrosine kinase inhibitor gefitinib on activation of the Akt and mitogen-activated protein kinase (MAPK) pathways in human urothelial cell carcinoma (UCC) cell lines and to identify potential markers of gefitinib responsiveness in biopsy samples of UCC. EXPERIMENTAL DESIGN: Changes in markers of UCC growth and invasion after exposure to gefitinib were studied in six human UCC cell lines expressing various levels of EGFR. The findings were related to activation of Akt and MAPK. We studied the influence of gefitinib on intraepithelial expansion of the responsive 1207 cell line. EGFR, Akt, and MAPK activation was studied by Western blot analysis of a panel of 57 human UCC. RESULTS: Gefitinib had a growth-inhibitory and anti-invasive effect in two of six UCC cell lines (i.e., 647V and 1207). Gefitinib was also able to block the expansion of 1207 at the expense of normal urothelial cells. These effects did not depend on the level of expression of EGFR but they were associated with the down-regulation of MAPK and Akt activity; in 1207 cells, gefitinib activity was associated with p27 up-regulation and p21 and matrix metalloproteinase-9 down-regulation. Similarly, the Akt and MAPK pathways were found to be strongly phosphorylated in association with EGFR activation in a subset of human UCC specimens. CONCLUSIONS: Activation of EGFR, Akt, and MAPK defines a subset of UCC which might provide information for the identification of gefitinib responders.

Characterization of ZAG protein expression in prostate cancer using a semi-automated microscope system.

OBJECTIVE: Zinc-alpha-2-glycoprotein 1 (ZAG) is a 41-kD secreted protein that is known to stimulate lipid degradation in adipocytes. The aim of this study was to determine how ZAG protein expression is associated with prostate cancer (PCa). MATERIALS AND METHODS: An immunohistochemistry analysis was performed on a 227 PCa tissue microarray cases. ZAG protein expression was assessed using a semi-automated cellular image analysis system. RESULTS: ZAG expression was associated with tumor stage (pT2 > pT3 > metastasis cases, P < 0.001), and was inversely associated with Gleason score on pathology (P = 0.01). ZAG intensity was predictive of biochemical recurrence (P = 0.002). On multivariate analysis including pT2 patients, the predictive factors of biochemical recurrence were ZAG expression (P = 0.016), Gleason score (P = 0.011), and surgical margin status (P = 0.047). CONCLUSIONS: This study characterized ZAG protein expression in PCa using a semi-automated system. ZAG expression level found to have an independent prognostic value for pT2 patients.

Protocadherin-PC promotes androgen-independent prostate cancer cell growth.

BACKGROUND: Protocadherin-PC (PCDH-PC) expression is upregulated in apoptosis-resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we assess the role of PCDH-PC in CaP cells and its mRNA expression in human prostate tissues. METHODS: LNCaP cells transfected with PCDH-PC were tested for their ability to grow in vitro and in vivo in androgen-deprived conditions. PCDH-PC mRNA expression was evaluated by semi-quantitative RT-PCR and by in situ hybridization. RESULTS: PCDH-PC expression induced Wnt signaling in CaP cells and permitted androgen-independent growth of hormone-sensitive CaP cells. Expression of PCDH-PC-homologous transcripts was low and restricted to some epithelial cells in normal tissue and to CaP cells in tumors. However, hormone-resistant CaP cells expressed significantly higher levels of PCDH-PC-related mRNA. CONCLUSIONS: Our findings suggest a novel mechanism for the progression of CaP involving expression of PCDH-PC. This novel protocadherin induces Wnt signaling, promotes malignant behavior and hormone-resistance of CaP cells.

Proposal for revision of the TNM classification system for renal cell carcinoma.

BACKGROUND: The current study defined an optimal tumor size breakpoint to stratify localized renal cell carcinoma (RCC) into groups with significantly different cancer-related outcomes and proposed a revision of the TNM classification system. METHODS: The authors analyzed the data from 1138 patients who had undergone partial or radical nephrectomy for localized RCC at 7 European urologic centers. The optimal pathologic size breakpoint was calculated using the martingale residuals from a Cox proportional hazards regression model. RESULTS: The mean follow-up time was 87 months. The scatterplot of tumor size versus expected risk of death per patient suggested that an interval of 5-6 cm was appropriate. A total of 720 (63.3%) and 418 (36.7%) patients had tumors measuring < or = 5.5-cm and tumors measuring > 5.5-cm, respectively. Significant cancer-specific survival differences between the two groups of patients were reported in the series by all the centers participating in the study. On univariate analysis, the other variables found to be associated with cancer-specific survival were the patient's age, symptomatic tumor presentation, and the Fuhrman nuclear grade. On multivariate analysis, the pathologic stage of the primary tumor defined according to the 5.5-cm breakpoint was found to be an independent predictor of cancer-specific survival, as well as age, mode of presentation, and nuclear grade. According to the multivariate analysis, the authors clustered patients into 3 groups with statistically significant outcome differences: 1) patients with < or = 5.5-cm incidentally detected RCC; 2) patients with < or = 5.5-cm symptomatic RCC; and 3) patients with > 5.5-cm RCC. This cancer-related outcome stratification was valid regardless of the patient's age. CONCLUSIONS: The 5.5-cm breakpoint was found to be the optimal tumor size breakpoint with which to stratify patients with organ-confined RCC. The study supported the upgrade of the TNM classification system according to this breakpoint.

Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study.

BACKGROUND: The objective of the current study was to compare, in a large multicenter study, the discriminating accuracy of four prognostic models developed to predict the survival of patients undergoing nephrectomy for nonmetastatic renal cell carcinoma (RCC). METHODS: A total of 2404 records of patients from 6 European centers were retrospectively reviewed. For each patient, prognostic scores were calculated according to four models: the Kattan model, the University of California at Los Angeles integrated staging system (UISS) model, the Yaycioglu model, and the Cindolo model. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Discriminating ability was assessed by the Harrell c-index for censored data. The primary end point was overall survival (OS), and the secondary end points were cancer-specific survival (CSS) and disease recurrence-free survival (RFS). RESULTS: At last follow-up, 541 subjects had died of any causes, with a 5-year OS rate of 80%. The 5-year CSS and RFS rates were 85% and 78%, respectively. All models discriminated well (P < 0.0001). The c-indexes for OS were 0.706 for the Kattan nomogram, 0.683 for the UISS model, and 0.589 and 0.615 for the Yaycioglu and Cindolo models, respectively. The Kattan nomogram was found to improve discrimination substantially in the UISS intermediate-risk patients. CONCLUSIONS: The current study appears to better define the general applicability of prognostic models for predicting survival in patients with nonmetastatic RCC treated with nephrectomy. The results suggest that postoperative models discriminate substantially better than preoperative ones. The Kattan model was consistently found to be the most accurate, although the UISS model was only slightly less well performing. The Kattan model can be useful in the UISS intermediate-risk patients.

Multiinstitutional European validation of the 2002 TNM staging system in conventional and papillary localized renal cell carcinoma.

BACKGROUND: The current study validated the 2002 edition of the TNM staging system in a multicenter, multinational European series of localized renal cell carcinoma (RCC). METHODS: The authors analyzed the clinical data of 2217 patients who had undergone radical or partial nephrectomy for localized RCC in 7 urologic centers. RESULTS: In the current study, 1065 patients (48%) were classified as having pT1a disease, 771 (34.8%) were classified as having pT1b disease, and 381 (17.2%) were classified as having pT2 disease. Tumor histotype was conventional RCC in 1886 patients (85%), papillary in 182 (8.2%) patients, chromophobe in 64 (2.9%) patients, and unclassified in 85 (3.8%) patients. The mean follow-up time was 65.36 +/- 52.09 months. The 5 and 10-year disease-specific survival probabilities were 95.3% and 91.4% in patients with pT1a disease, 91.4% and 83.4% in patients with pT1b disease, and 81.6% and 75.2% in patients with pT2 disease (log-rank test P value = 0.0000). The disease-specific survival rates of patients with pT1a RCC were significantly higher than those recorded in patients with pT1b and pT2 RCC. Similarly, the disease-specific survival probabilities of patients with pT1b RCC were significantly better than those of patients with pT2 RCC. Analyzing the seven series individually, the 2002 TNM staging system provided appropriate stratification for only one series. The 2002 TNM staging system allowed significant stratification of the cancer-related outcomes in the subgroup of patients with conventional RCC but not in those with papillary carcinomas. CONCLUSIONS: The application of the 2002 TNM staging system in the current multicenter series enabled the authors to demonstrate optimal stratification of patients with localized RCC. Stratifying by tumor histotype, the data coming from the whole group analysis were reconfirmed for clear cell RCC only.

Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.