Accuratezza prognostica dei principali sistemi predittivi integratinei pazienti con carcinoma renale parenchimale non a cellulechiare

Scopo del lavoro Obiettivi del lavoro sono stati: 1. valutare l\u2019accuratezza prognostica del Stage, SIze, Grade and Necrosis (SSIGN) score nei pazienti con RCC non a cellule chiare; 2. comparare la predittivit\ue0 dei 3 principali sistemi integrati (UCLA Integrated Staging System [UISS], SSIGN score e nomogramma di Karakiewicz) in questa popolazione di pazienti. Materiali e metodi Sono stati analizzati retrospettivamente i dati relativi a 5.463 neoplasie renali parenchimali sottoposte a trattamento chirurgico per RCC in 16 centri accademici di urologia nel periodo compreso tra gennaio 1995 e dicembre 2007. Per il presente studio sono stati estratti dal database tutti i casi in cui erano disponibili le seguenti informazioni: performance status ECOG; sintomi d\u2019esordio della neoplasia; stadio patologico del tumore primitivo; coinvolgimento linfonodale; presenza di metastasi a distanza; grading nucleare sec. Fuhrman; dimensioni patologiche del tumore primitivo; necrosi coagulativa; follow-up. Inoltre l\u2019analisi \ue8 stata limitata ai soli casi con RCC non a cellule chiare. Per ciascun caso \ue8 stato assegnato il relativo gruppo di rischio in accordo con l\u2019UISS, il relativo score in accordo con l\u2019SSIGN e la relativa probabilit\ue0 di decesso per malattia in accordo con il nomogramma di Karakiewicz. La regressione di Cox \ue8 stata utilizzata per l\u2019analisi univariata e multivariata dei dati. Il log-rank test \ue8 stato utilizzato per il confronto tra le curve di sopravvivenza. L\u2019accuratezza prognostica dei diversi modelli \ue8 stata calcolata a 12, 36 e 60 mesi dall\u2019intervento utilizzando il concordance index. La differenza statistica tra i differenti modelli \ue8 stata calcolata utilizzando il metodo di DeLong. Risultati 379 pazienti presentavano le caratteristiche necessarie per essere inclusi nello studio. Sia l\u2019UISS (p<0,0001) sia l\u2019SSIGN score (p<0,0001) sia il nomogramma di Karakiewicz (p<0,0001) sono risultati in grado di predire la sopravvivenza causa-specifica dei pazienti. Il concordance index dell\u2019UISS \ue8 risultato 90,2 a 12 mesi, 91,3 a 36 mesi e 91,9 a 60 mesi dall\u2019intervento chirurgico. Il concordance index dell\u2019SSIGN score \ue8 risultato 92,1 a 12 mesi, 89,9 a 36 mesi e 80,6 a 60 mesi dall\u2019intervento. Il concordance index del nomogramma di Karakiewicz \ue8 risultato pari a 95 a 12 mesi, 94,3 a 36 mesi e 93,6 a 60 mesi. Il nomogramma presenta un\u2019accuratezza prognostica lievemente maggiore rispetto al sistema UISS a 12 (p=0,04) e 36 (p<0,03) mesi. Nessuna differenza \ue8 stata osservata a 60 mesi (p=0,3). Viceversa, presenta un\u2019accuratezza prognostica maggiore dell\u2019algoritmo SSIGN a 12 (p=0,03), 36 (p=0,01) e 60 mesi (p<0,001). L\u2019SSIGN si \ue8 dimostrato meno accurato dell\u2019UISS a 60 mesi (p<0,001). Conclusioni Il nomogramma di Karakiewicz ed il sistema UISS devono essere considerati come i migliori sistemi integrati in grado di predire la prognosi delle neoplasie non a cellule chiare

Evidence-based Sex-related Outcomes After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: Results of Large Multicenter Study

OBJECTIVES To assess the sex differences in the clinical and pathologic characteristics of upper tract urothelial carcinoma (UTUC) and to determine the effect on prognosis after radical nephroure-terectomy (RNU) in a large multicenter series. METHODS The records of 1363 patients who had undergone RNU were reviewed from the UTUC Collaboration database. The median follow-up was 47 months (range 0-250). The pathologic slides were re-evaluated by genitourinary pathologists unaware of the original findings from the slides and the clinical Outcomes. The endpoints were freedom from tumor recurrence and disease-specific survival. RESULTS The male-to-female ratio was 2.1:1. The women were older than the men at diagnosis (70 +/- 11 vs 68 +/- 11 years; P <.001). No significant sex-related differences were found in the presence of symptoms at presentation (P = .70), pathologic stage (P = .98), tumor grade (P = .28), tumor architecture (P = .27), presence of lymphovascular invasion (P = .42), presence of concomitant carcinoma in situ (P = .08), or the presence of lymph node metastases (P = .24). Recurrence developed in 379 patients (28%), and 313 patients (23%) died of their disease. Sex was not associated with disease recurrence (P = .07) or disease-specific survival (P = .13). An adjustment for the effects of the pathologic features did not change the lack of association of sex with the clinical outcomes. CONCLUSIONS To our knowledge, this is the largest series analyzing the effect of sex on the outcomes after RNU. No difference was found in the clinicopathologic features or prognosis between women and men treated with RNU for UTUC. The results of this large, international series show that RNU provides durable local control and disease-specific survival for both men and women with UTUC. UROLOGY 73: 142-146, 2009. (C) 2009 Published by Elsevier Inc

Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients

To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive. The study included 1363 patients with UTUC and treated with radical NU at 12 centres worldwide. All slides were re-reviewed according to strict criteria by genitourinary pathologists who were unaware of the findings of the original pathology slides and clinical outcomes. Gross tumour architecture was categorized as sessile vs papillary. Papillary growth was identified in 983 patients (72.2%) and sessile growth in 380 (27.8%). The sessile growth pattern was associated with higher tumour grade, more advanced stage, lymphovascular invasion, and metastasis to lymph nodes (all P < 0.001). In multivariable Cox regression analyses that adjusted for the effects of pathological stage, grade and lymph node status, tumour architecture (sessile or papillary) was an independent predictor of cancer recurrence (hazard ratio 1.5, P = 0.002) and cancer-specific mortality (1.6, P = 0.001). Adding tumour architecture increased the predictive accuracy of a model that comprised pathological stage, grade and lymph node status for predicting cancer recurrence and cancer-specific death by a minimal but statistically significant margin (gain in predictive accuracy 1% and 0.5%, both P < 0.001). The tumour architecture of UTUC is associated with established features of biologically aggressive disease, and more importantly, with prognosis after radical NU. Including tumour architecture in predictive models for disease progression should be considered, aiming to identify patients who might benefit from early systemic therapeutic intervention

Assessment of the Minimum Number of Lymph Nodes Needed to Detect Lymph Node Invasion at Radical Nephroureterectomy in Patients With Upper Tract Urothelial Cancer

OBJECTIVES To determine whether a minimum number of lymph nodes (LNs) exist to detect lymph node invasion (LNI) in patients undergoing radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. METHODS The study included 551 consecutive patients, from 13 centers worldwide, who underwent RNU and lymphadenectomy (LND) between 1992 and 2006. LND was performed at the discretion of the surgeon. All pathological slides were re-reviewed by uropathologists according to strict criteria. Receiver-operating characteristic curve coordinates were used to determine the probability of diagnosing LNI according to the total number of nodes removed. Additionally, the relationship between the number of nodes removed and the rate of positive LNs was tested in univariate and multivariate logistic regression models. RESULTS Median patient age was 68 years (range: 27-97). Of 551 patients, 140 (25.4%) had positive lymph nodes. Median number of lymph nodes removed was 5 (mean 6.7, range 1-41). The Receiver-operating characteristic coordinates plot indicated that the removal of 13 nodes yielded a 90% probability to detect >= 1 positive LNs. The removal of 8 nodes resulted in a 75% probability of finding >= 1 positive nodes. Removal of > 8 LNs (P = .03; odds ratio 1.49) was independently associated with LN1 after adjusting for pathological stage and grade. CONCLUSIONS Our data indicate that 8 LNs need to be removed at radical nephroureterectomy to achieve a 75% probability of finding >= 1 positive nodes. Further improvement of the specificity of LND will require the removal of more lymph nodes. UROLOGY 74: 1070-1077, 2009. (C) 2009 Elsevier Inc