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Zattoni, Fabio (2018) The Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor for Patients with Urothelial Carcinoma of the Bladder Following Radical Cystectomy. [Ph.D. thesis]

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Abstract (italian or english)

Introduction: Pre-treatment neutrophil-to-lymphocyte ratio (NLR) has been associated with adverse pathology or survival in a variety of malignancies, including urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Whether the prognostic value of NLR is retained, or even increased, when measured postoperatively remains not well studied. In this study, we evaluated the association of preoperative and postoperative NLR with oncological outcomes following RC.
Methods: 132 consecutive patients with UCB treated with open RC were analyzed. NLR was analyzed both as a continuous variable and as a categorical variable using a cut-off of 2.7 based on previous studies. NLR was recorded as followed: before surgery (within 15 days prior to RC, [NLR1]), postoperatively (within 2 days [NLR2], between 7 and 15 days after RC before discharge [NLR3], few days before the evidence of recurrence or last available follow up [NLR4]. ∆NLR was calculated as the difference between NLR2 and NLR1 (NLR∆1) and between NLR 2 and NLR3 (NLR∆2). Tumour stage, lymphovascular invasion (LVI) and lymph node involvement were collected. Cancer-specific mortality (CSM), all-cause mortality (ACM) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariate logistic regression and Cox proportional hazard models were used to analyze the association of NLR with extravesical disease, LVI, lymph node involvement, recurrence of disease and mortality.
Results: During a follow up of 15.9 months, 45 (34.1%) patients had a recurrence of UBC, 60 (45.4%) patients died, 38 (28.8%) of UCB and 22 (16.7%) of other cause. 64 (48.5%) have no evidence of disease at follow-up. When assessed by multivariable analysis NLR1 remained independently associated with a significantly increased risk of extravescical disease (pT 3-4) [OR: 1.4, p<0.01] and Lymphovascular invasion [OR: 1.40, p<0.01]. NLR4 was independently associated with a significantly increased risk of CSM [HR=1.14, p=0.013]. In a postoperative
model, NLR3 was found to be an independent predictor of ACM [HR=1.11, 95%, p=0.01]. NLR1 was associated with a significantly increased risk of recurrence in the univariable preoperative model [HR=1.9, p=0.05] while in the postoperative model, NLR4 remained independently associated with a significantly increased risk of recurrence [HR 1.13, p=0.03].
Conclusions: In patients with UCB treated with RC, NLR is associated with more advanced tumour stage, LVI, lymph node metastasis and higher CSM. Furthermore, the variation of NLR after surgery might play a role to predict higher ACM and RFS.

Abstract (a different language)

Introduzione: Per diversi tumori solidi, il rapporto neutrofili-linfociti (NLR) è stato valutato come predittore di aggressività tumorale e di prognosi avversa. Tra i vari tumori è stato valutato anche il carcinoma uroteliale della vescica (UCB) tuttavia rimane poco studiato se il valore prognostico di NLR rimane valido quando misurato dopo l'intervento. In questo studio abbiamo valutato l'associazione tra NLR preoperatorio e postoperatorio con esiti oncologici e di sopravvivenza dopo cistectomia radicale (RC).
Metodi: sono stati analizzati 132 pazienti consecutivi con UCB trattati con RC. L'NLR è stato analizzato sia come variabile continua che come variabile categoriale utilizzando un valore soglia di 2,7 basato su studi precedenti. L'NLR è stata registrata come segue: prima dell'intervento (entro 15 giorni prima di RC, [NLR1]), postoperatorio (entro 2 giorni [NLR2], tra 7 e 15 giorni dopo RC prima della dimissione [NLR3], pochi giorni prima dell'evidenza di recidiva/ ultimo follow-up disponibile [NLR4]. ΔNLR è stato calcolato come differenza tra NLR2 e NLR1 (NLRΔ1) e tra NLR 2 e NLR3 (NLRΔ2).
Mortalità cancro specifica (CSM), mortalità globale (ACM) e sopravvivenza libera da recidiva (RFS) sono state stimate utilizzando il metodo di Kaplan-Meier e confrontate con il log-rank test. Sono stati utilizzati modelli uni e multivariati per analizzare l'associazione tra NLR e malattia extravescicale, invasione linfovascolare, coinvolgimento linfonodale, recidiva di malattia e mortalità.
Risultati: durante un follow-up di 15,9 mesi, 45 (34,1%) pazienti hanno avuto una recidiva di UBC, 60 (45,4%) pazienti sono morti, 38 (28,8%) di UCB e 22 (16,7%) di altra causa. 64 (48,5%) non hanno evidenza di malattia al follow-up. Quando valutato mediante analisi multivariata NLR1 è rimasto indipendentemente associato ad un rischio significativamente aumentato di malattia extravescicale (pT 3-4) [OR: 1,4, p <0,01] e invasione linfovascolare [OR: 1,40, p <0,01]. NLR4 è stato associato indipendentemente con un rischio significativamente aumentato di CSM [HR = 1,14, p = 0,013]. In un modello postoperatorio, NLR3 è risultato essere un predittore indipendente di ACM [HR = 1,11, 95%, p = 0,01]. NLR1 era associato ad un aumentato rischio di recidiva nel modello preoperatorio univariato [HR = 1,9, p = 0,05] mentre nel modello postoperatorio, NLR4 è rimasto indipendentemente associato ad un rischio significativamente aumentato di recidiva [HR 1,13, p = 0,03].
Conclusioni: Nei pazienti con UCB trattati con RC, NLR è associato ad uno stadio tumorale più avanzato, invasione linfovascolare, metastasi linfonodali e CSM superiore. Inoltre, la variazione di NLR dopo l'intervento chirurgico potrebbe avere un ruolo nella previsione di ACM e RFS.

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EPrint type:Ph.D. thesis
Tutor:Novara, Giacomo
Ph.D. course:Ciclo 31 > Corsi 31 > ONCOLOGIA CLINICA E SPERIMENTALE E IMMUNOLOGIA
Data di deposito della tesi:27 November 2018
Anno di Pubblicazione:30 September 2018
Key Words:neutrophil-to-lymphocyte ratio;bladder cancer;radical cystectomy;survival
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/24 Urologia
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche
Codice ID:11405
Depositato il:05 Nov 2019 17:19
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