Development and external validation of a preoperative nomogram for predicting pathological locally advanced disease of clinically localized upper urinary tract carcinoma

Yoshida, Takashi; Kobayashi, Takashi; Kawaura, Takayuki; Miyake, Makito; Ito, Katsuhiro; Okuno, Hiroshi; Mizutani, Takashi; Makita, Noriyuki; Kawakita, Mutsushi; Kawa, Gen; Kitawaki, Tomoki; Fujimoto, Kiyohide; Matsuyama, Hideyasu; Shiina, Hìroaki; Azuma, Haruhito; Ogawa, Osamu; Kinoshita, Hidefumi; Matsuda, Tadashi

doi:10.1002/cam4.2988

Cited by 19 publications

(13 citation statements)

References 27 publications

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“…The number of patients with multiple upper urothelial carcinomas who had recurrent urothelial carcinomas was signi cantly higher than that of patients with single urothelial carcinomas [38]. In addition, tumor size, preoperative hydronephrosis and ureterorenoscopy are more likely to lead to postoperative recurrence in the bladder [39][40][41]. Some of those conclusions are consistent with ours.…”

Section: Discussionsupporting

confidence: 87%

The predictive value of preoperative positive urine cytology for development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma: A retrospective multi-center case-control study and meta-analysis

Fan

Huang

Wen

et al. 2020

Preprint

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Background: Upper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Urine cytology is a common clinical method for the early diagnosis of urologic neoplasms. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in Northeast China are rare. Methods: In this retrospective case-control study, we first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 142 patients with UUT-UC after radical nephroureterectomy (RNU). A nomogram model was established and we evaluated its effectiveness. Subsequently, after searching several databases, including PubMed, Embase, and Ovid, we quantitatively combined our results with the published data in a meta-analysis. Results: Our case-control study demonstrated that patients with muscle-invasive tumors (T2-T4) were more prone to preoperative positive urine cytology than those with non-muscle-invasive tumors (Tis-T1), suggesting that preoperative positive urine cytology may be associated with the aggressive form of UUT-UC. Kaplan-Meier curves demonstrated that the patients with positive urine cytology had significantly poorer intravesical recurrence-free survival (IV-RFS). Additionally, preoperative urine cytology (hazard ratio, HR=3.24) and lymph node status (HR=2.67) were validated as significant independent predictors of intravesical recurrence by multivariate analysis. Nomogram, calibration plots, AUC values and the C-index demonstrated that the predictive accuracy was significantly improved when preoperative urine cytology was combined. Subsequently, adding to our study, 11 eligible articles from 2010 to 2016 containing 2942 patients were sifted out for our meta-analysis. Overall analysis showed that preoperative positive urine cytology was associated with a 56% increased risk of intravesical recurrence (HR=1.56). In the subgroup analysis by region, study type, and sample size, the pooled HR was statistically significant for the Japan subgroup (HR=1.45), China subgroup (HR=1.66), cohort study subgroup (HR=1.44), and case-control study subgroup (HR=1.77), the subgroup with sample size greater than or equal to 100 (HR=1.42), and the subgroup with sample size less than 100 (HR=2.95). Conclusions: Preoperative urine cytology significantly correlated with intravesical recurrence in patients with UUT-UC after RNU, although these results need to be interpreted with caution. Large, prospective trials are required to further confirm its prognostic significance.

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Section: Discussionsupporting

confidence: 87%

The predictive value of preoperative positive urine cytology for development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma: A retrospective multi-center case-control study and meta-analysis

Fan

Huang

Wen

et al. 2020

Preprint

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“…NLR is considered to reflect systemic inflammation caused by cancer 13 . High NLRs have been reported to be significant discriminators of the response to chemotherapy or survival in various types of cancers, 13 including UC 14‐17 . In this study, NLR ≥3.5 was adopted as the optimal cutoff because a cutoff of 3.0 resulted in an extremely small proportion of patients with PS ≥2.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

et al. 2021

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BackgroundThe benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum‐refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug.MethodsThis retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0–1, 2, and 3–4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2.ResultsThe numbers of patients with PS 0–1, 2, and 3–4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil–lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors.ConclusionsPS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.

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“…The present study utilized 2 independent cohorts to develop and validate a prognostic model. This method is commonly used in this kind of studies on prognostic models 8‐10 . Our analyses would have been statistically more powered if we had utilized all 755 patients from the initial setting.…”

Section: Discussionmentioning

confidence: 99%

“…Least Absolute Shrinkage and Selection Operator (LASSO) methods were used for automatic variable selection to establish a prognostic model 8 . The prognostication model established based on discovery cohort was externally validated using an independent validation cohort by calibration plots that compared the predicted prognosis with the actual prognosis 9,10 . The prognostication accuracies of survival models were compared using Harrell C‐index 7 .…”

Section: Methodsmentioning

confidence: 99%

Risk stratification for the prognosis of patients with chemoresistant urothelial cancer treated with pembrolizumab

et al. 2020

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The use of immune checkpoint inhibitors to treat urothelial carcinoma (UC) is increasing rapidly without clear guidance for validated risk stratification. This multicenter retrospective study collected clinicopathological information on 463 patients, and 11 predefined variables were analyzed to develop a multivariate model predicting overall survival (OS). The model was validated using an independent dataset of 292 patients. Patient characteristics and outcomes were well balanced between the discovery and validation cohorts, which had median OS times of 10.2 and 12.5 mo, respectively. The final validated multivariate model was defined by risk scores based on the hazard ratios (HRs) of independent prognostic factors including performance status, site of metastasis, hemoglobin levels, and the neutrophil‐to‐lymphocyte ratio. The median OS times (95% confidence intervals [CIs]) for the low‐, intermediate‐, and high‐risk groups (discovery cohort) were not yet reached (NYR) (NYR–19.1), 6.8 mo (5.8‐8.9), and 2.3 mo (1.2‐2.6), respectively. The HRs (95% CI) for OS in the low‐ and intermediate‐risk groups vs the high‐risk group were 0.07 (0.04‐0.11) and 0.23 (0.15‐0.37), respectively. The objective response rates for in the low‐, intermediate‐, and high‐risk groups were 48.3%, 28.8%, and 10.5%, respectively. These differential outcomes were well reproduced in the validation cohort and in patients who received pembrolizumab after perioperative or first‐line chemotherapy (N = 584). In conclusion, the present study developed and validated a simple prognostic model predicting the oncological outcomes of pembrolizumab‐treated patients with chemoresistant UC. The model provides useful information for external validation, patient counseling, and clinical trial design.

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Development and external validation of a preoperative nomogram for predicting pathological locally advanced disease of clinically localized upper urinary tract carcinoma

Cited by 19 publications

References 27 publications

The predictive value of preoperative positive urine cytology for development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma: A retrospective multi-center case-control study and meta-analysis

The predictive value of preoperative positive urine cytology for development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma: A retrospective multi-center case-control study and meta-analysis

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

Risk stratification for the prognosis of patients with chemoresistant urothelial cancer treated with pembrolizumab

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