Histological variants and lymphovascular invasion in upper tract urothelial carcinoma can stratify prognosis after radical nephroureterectomy.

Patients with histological variants (HV) of bladder cancer have more advanced disease and poorer survival rates than those with pure urothelial carcinoma (UC). Moreover, lymphovascular invasion (LVI) is an important biomarker after RNU in systematic reviews and meta-analyses. Thus, here we investigated the clinical and prognostic impact of HV and LVI in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Data from 223 UTUC patients treated with RNU without neoadjuvant chemotherapy were retrospectively evaluated. We analyzed differences in clinicopathological features and survival rates between patients with pure UC and those with HV. Conditional survival (CS) analysis was performed to obtain prognostic information over time. A total of 32 patients (14.3%) had HV, with the most common variant being squamous differentiation, followed by glandular differentiation. UTUC with HV was significantly associated with advanced pathological T stage (pT ≥ 3), higher tumor grade (G3), and LVI, compared to pure UC (all P < 0.01). Progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were all significantly worse in the HV group compared to the pure UC group (all, P < 0.001). In multivariable analysis, HV and LVI were independent predictors of CSS and OS. We classified the patients into three groups using these two predictors: low-risk (neither HV nor LVI), intermediate-risk (either HV or LVI), and high-risk (both HV and LVI). Significant differences in PFS, CSS, and OS rates were found among the 3 groups. In CS analysis, the conditional PFS, CSS, and OS rates at 1, 2, 3, 4, and 5 years improved with increased duration of event-free survival. CS analysis revealed that most progression events occurred within 2 years after RNU, and patients with risk factors had worse PFS at all time points. A risk model using HV and LVI can stratify PFS, CSS, and OS of patients treated with RNU. In addition, CS analysis revealed that HV and LVI were poor prognostic factors over time after RNU.

Takemoto K ，Hayashi T ，Hsi RS ，Kobatake K ，Sekino Y ，Kitano H ，Ikeda K ，Goto K ，Hieda K ，Sentani K ，Kajiwara M ，Nishizaka T ，Teishima J ，Oue N ，Hinata N ... -  《-》

Association between lymphovascular invasion and oncological outcome in node-negative upper tract urothelial carcinoma with different stage.

To evaluate the prognostic impact of lymphovascular invasion (LVI) on node-negative upper tract urothelial carcinoma (UTUC) in patients treated with radical nephroureterectomy (RNU). A retrospective study was performed in single tertiary referral center of middle Taiwan between 2001 and 2015. Seven hundred and twenty-eight patients were diagnosed of UTUC and underwent RNU with ipsilateral bladder cuff excision including 303 and 195 patients with N0 and Nx status respectively. LVI status was assessed as a prognostic factor for cancer-specific (CSS) and overall survival (OS) using univariate and multivariate Cox regression analysis. LVI was observed in 82 patients (16.5%). LVI presentation associated with smoking status, advanced tumor stage, high tumor grade, positive surgical margin, and consequence lung/liver/bone metastasis. In the multivariate analysis, LVI was failed to predict CSS, OS, and disease-free survival (DFS) (hazard ratio [HR] [95% confidence interval [CI]: 1.07 [0.55-2.09], 1.05 [0.62-1.79], 1.15 [0.69-1.92], in CSS, OS, DFS, respectively). In the subgroup analysis of pT1-2 disease, the CSS, OS, and DFS were associated with LVI status (HR [95% CI]: 2.29 [0.44-11.84], 3.17 [1.16-8.67], 2.66 [1.04-6.79], in CSS, OS, DFS, respectively). In contrast, there was no difference in pT3 disease. In conclusion, LVI status was not associated with survival outcomes of node-negative UTUC in our study. The subgroup analysis showed different prognostic impacts of LVI status in node-negative UTUC with T1-2 and T3 stage. Further evidence to clarify the prognostic effect is needed to make LVI became a practical factor in clinical decision-making.

Chen CS ，Lin CY ，Wang CL ，Wang SS ，Li JR ，Yang CK ，Cheng CL ，Chiu KY ，Yang SF ... -  《-》

The impact of histological variants in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

To investigate the impact of histological variants (HV) in patients with upper tract urothelial carcinoma (UTUC) and analyze the potential association between HV and postoperative bladder recurrence. The medical records of UTUC patients treated with RNU at our center from January 2012 to December 2019 were retrospectively analyzed. Patients were grouped according to the types of HV. Clinicopathological features and prognostic factors were compared among groups. A total of 629 patients were included in the study: 458 (73%) patients had pure urothelial carcinoma (PUC) and 171 (27%) patients had UTUC with HV. Squamous differentiation was the most common type (124 cases, 19%), followed by glandular differentiation (29 cases, 5.0%). Patients with HV had a higher proportion of T3 and T4 pathologic stages (P < 0.001) as well as high-grade disease (P = 0.002). In the univariate analysis, squamous differentiation and glandular differentiation were significantly associated with worse cancer-specific survival (CSS) (HR 2.22, 95% CI 1.62-3.04, P < 0.001; HR 1.90, 95% CI 1.13-3.20, P = 0.016). However, the multivariate analysis showed that this association became non-significant. We found that HV were associated with recurrent muscle-invasive bladder cancer (MIBC) after RNU and all patients had T2 and T3 initial tumor stages (P = 0.008, P < 0.001). We found that UTUC patients with HV were associated with biologically aggressive disease and recurrent MIBC after RNU. The detection of bladder recurrence following surgery needs to be given more attention in advanced UTUC patients with HV.

Wang J ，Zuo X ，Zhang Y ，Wang W ，Zhou D ，Liu W ，Han G ，Wu C ，Tian D ... -  《-》

Prognostic indicators for upper tract urothelial carcinoma after radical nephroureterectomy: the impact of lymphovascular invasion.

What's known on the subject? and What does the study add? In an array of urological and non-urological malignancies, lymphovascular invasion (LVI) is a pathological feature known to be associated with adverse outcomes for recurrence and survival. For some cancers, LVI has therefore been incorporated into American Joint Committee on Cancer TNM staging algorithms. This study presents an analysis of the impact of LVI in upper urinary tract urothelial carcinoma (UTUC) treated at our institution over a 20-year period. In addition to known associations with features of aggressive disease and overall survival, we were able to show that LVI-positive status upsets the TNM staging for UTUC. Namely, patients with superficial stage and LVI-positive disease have overall survival outcomes similar to those of patients with muscle-invasive LVI-negative carcinoma. Such evidence may support the addition of LVI to future TNM staging algorithms for UTUC. To assess the impact of lymphovascular invasion (LVI) on the prognosis of patients with upper urinary tract urothelial cell carcinoma (UTUC) treated with radical nephroureterectomy (RNU). The Columbia University Medical Center Urologic Oncology database was queried and 211 patients undergoing RNU for UTUC between 1990 and 2010 were identified. These cases were retrospectively reviewed, and the prognostic significance of relevant clinical and pathological variables was analysed using log-rank tests and Cox proportional hazards regression models. Actuarial survival curves were calculated using the Kaplan-Meier method. LVI was observed in 68 patients (32.2%). The proportion of LVI increased with advancing stage, high grade, positive margin status, concomitant carcinoma in situ, and lymph node metastases. The 5- and 10-year overall survival rates were 74.7% and 53.1% in the absence of LVI, and 35.7% and 28.6% in the presence of LVI, respectively. In multivariate analysis, age, race and LVI were independent predictors of overall survival. The presence of LVI on pathological review of RNU specimens was associated with worse overall survival in patients with UTUC. LVI status should be included in the pathological report for RNU specimens to help guide postoperative therapeutic options. With confirmation from large international studies, inclusion of LVI in the tumour-node-metastasis staging system for UTUC should be considered.

Godfrey MS ，Badalato GM ，Hruby GW ，Razmjoo M ，McKiernan JM ... -  《-》

Impact of lymphovascular invasion on survival in surgically treated upper tract urothelial carcinoma: a nationwide analysis.

Cirulli GO ，Corsi N ，Rakic I ，Stephens A ，Chiarelli G ，Finati M ，Davis M ，Tinsley S ，Sood A ，Buffi N ，Lughezzani G ，Carrieri G ，Salonia A ，Briganti A ，Montorsi F ，Rogers C ，Abdollah F ... -  《-》