The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma

PLOS ONE, Dec 2019

Purpose This study investigated the prognostic role of histopathological variants in patients with advanced urothelial carcinoma (UC) who were treated with systemic chemotherapy. Materials and Methods We conducted a retrospective analysis of patients with unresectable and/or metastatic UC who underwent systemic chemotherapy between January 1997 and December 2013 in Kaohsiung Chang Gung Memorial Hospital. Histopathological types were categorized as pure UC (PUC) and variants of UC (VUC). The overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier analyses and Cox proportional regression models. Results A total of 206 patients were enrolled; 53 of the patients (25.7%) had histopathological variants. The most common variant was squamous differentiation (68%). Compared with patients with PUC, patients with VUC significantly exhibited upper urinary tract origin (75% vs 52%, P = .008), chronic renal insufficiency (40% vs 23%, P = .03), and carboplatin-based chemotherapy (28% vs 10%, P = .003). According to univariate analysis, the median OS for PUC patients was significantly higher than that for VUC patients (15.9 vs 11.3 months, P = .007). The median PFS for patients who received first-line chemotherapy was 6.1 and 3.8 months for PUC patients and VUC patients, respectively (P = .004). Multivariate analysis revealed that VUC (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.16–2.40, P = .006), an age ≤ 60 years (HR 0.70, 95% CI 0.49–0.99, P = .045) and presence of visceral metastasis (HR 1.54, 95% CI 1.11–2.13, P = .009) were independent factors facilitating OS prediction. Conclusions The presence of histopathological variants indicates poor survival outcomes in patients with metastatic UC. Accordingly, VUC should be integrated into and considered an independent factor in a predictive model of survival.

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The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma

June The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma Meng-Che Hsieh 0 1 Ming-Tse Sung 0 1 Po-Hui Chiang 0 1 Cheng-Hua Huang 0 1 Yeh Tang 0 1 Yu- Li Su 0 1 0 Editor: Li-Mei Chen, University of Central Florida, UNITED STATES 1 1 Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung, Taiwan , 2 Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, 3 Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, 4 Division of Hematology-Oncology, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung , Taiwan This study investigated the prognostic role of histopathological variants in patients with advanced urothelial carcinoma (UC) who were treated with systemic chemotherapy. Materials and Methods We conducted a retrospective analysis of patients with unresectable and/or metastatic UC who underwent systemic chemotherapy between January 1997 and December 2013 in Kaohsiung Chang Gung Memorial Hospital. Histopathological types were categorized as pure UC (PUC) and variants of UC (VUC). The overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier analyses and Cox proportional regression models. - A total of 206 patients were enrolled; 53 of the patients (25.7%) had histopathological variants. The most common variant was squamous differentiation (68%). Compared with patients with PUC, patients with VUC significantly exhibited upper urinary tract origin (75% vs 52%, P = .008), chronic renal insufficiency (40% vs 23%, P = .03), and carboplatin-based chemotherapy (28% vs 10%, P = .003). According to univariate analysis, the median OS for PUC patients was significantly higher than that for VUC patients (15.9 vs 11.3 months, P = .007). The median PFS for patients who received first-line chemotherapy was 6.1 and 3.8 months for PUC patients and VUC patients, respectively (P = .004). Multivariate analysis revealed that VUC (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.16–2.40, P = .006), an age 60 years (HR 0.70, 95% CI 0.49–0.99, P = .045) and presence of visceral metastasis (HR 1.54, 95% CI 1.11–2.13, P = .009) were independent factors facilitating OS prediction. The presence of histopathological variants indicates poor survival outcomes in patients with metastatic UC. Accordingly, VUC should be integrated into and considered an independent factor in a predictive model of survival. In the United States, genitourinary tract cancer was the fourth and eighth most common cancer in men and women, respectively [1] The major histopathological type of genitourinary tract cancer, including that of the upper urinary tract and the bladder, is urothelial carcinoma (UC). Previous studies have shown that UC has the propensity for divergent differentiation into various histologic subtypes [2], with an incidence of 7%–81% [3, 4] The most common histopathological variant is squamous differentiation, followed by glandular differentiation [5, 6]. Furthermore, several studies have revealed that compared with pure UC (PUC), variants of UC (VUC) harbored aggressive biological features, such as advanced stage, higher grade, more tumor necrosis, tumor multifocality, lymphovascular invasion and lymph node metastasis [7, 8] Recent evidence suggested that VUC can be used to predict survival, regardless of whether patients have upper urinary tract UC (UUTUC) or UC of the bladder (UCB). In studies investigating radical cystectomy or nephroureterectomy series, approximately 25% of patients with UCB or UUTUC had histopathological variants, and the oncologic outcomes were significantly poorer than those of patients with PUC [8, 9]. Regarding histopathological variants, UC patients with squamous, glandular, micropapillary, and nested differentiation had similar survival outcomes [9–13], whereas patients with plasmacytoid differentiation had the worst prognosis [14, 15]. Notably, all of the aforementioned studies were mainly focused on patients treated with radical surgery. However, the prognostic role of histopathological variants in patients with metastatic UC has never been investigated. Because no conclusive study exists at present, the purpose of the current study was to investigate the impact of histopathological variants on the survival of patients with metastatic VUC. Materials and Methods Study population We conducted a retrospective review of a database comprising information about patients who received systemic chemotherapy for metastatic UC at Kaohsiung Chang Gung Memorial Hospital between January 1997 and December 2013. Patients with unresectable and/or metastatic UCB or UUTUC were enrolled and stratified according to histopathological variants labeled as VUC and PUC, respectively (Fig 1). Patient characteristics wer (...truncated)


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Meng-Che Hsieh, Ming-Tse Sung, Po-Hui Chiang, Cheng-Hua Huang, Yeh Tang, Yu-Li Su. The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma, PLOS ONE, 2015, 6, DOI: 10.1371/journal.pone.0129268