淺層膀胱癌與同時性或異時性上泌尿道上皮癌的預測發生率與列線圖

鄭偉權¹、張殷綸¹、劉惠瑛¹、王弘仁¹、莊燿吉¹、陳彥達¹、吳彥廷¹、蘇祐立²、黃俊杰³、羅浩倫¹

高雄長庚紀念醫院 ¹泌尿科, ²血液腫瘤科, ³放射腫瘤科

The incidence and multiplex nomogram for prediction of metachronous and synchronous upper tract urothelial cancer in patients with non-muscle invasive urinary bladder cancer

Wei Quen Tee¹, Yin-Lun Chang¹, Hui-Ying Liu¹, Hung-Jen Wang¹, Yao Chi Chuang¹, Yen Ta Chen¹, Yen-Ting Wu¹, Yu Li Su², Chun Chieh Huang³, Hao Lun Luo¹*

 ^1. Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

^2. Department of Hematology and Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

^3. Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

Introduction:

Patients with urinary bladder urothelial carcinoma (UBUC) developed with synchronous or metachronous upper tract urothelial carcinoma (UTUC) is relatively low incidence but should not be ignored. Development of synchronous or metachronous UTUC confers a poor prognosis which is partly attributable to delay in diagnosis and further development of advanced disease. Therefore, the aim of this study is to identify the associated factors for metachronous and synchronous UTUC in patients with non-muscle invasive UBUC (NMIBC). Identifying the clinical features of patients at risk of synchronous and metachronous UTUC is an important public health issue especially in Taiwan, an UTUC endemic area, and helps avoid delayed diagnosis and establish a better follow-up protocol for NMIBC.

Materials and Methods:

We retrieved the data of all patients with the diagnosis of NMIBC (ICD-10:C67, stage 0 or 1) and synchronous/metachronous UTUC (ICD-10: C65 - C66) from the cancer registry database within the CGRD from 2005 to 2019. The inclusion criteria were the patient with NMIBC who were managed with transurethral resection (TUR) was reviewed. Patients’ files were further reviewed to identify those who had synchronous UTUC or metachronous UTUC in follow-up.  Synchronous UTUC was defined as a concurrent disease within 3 months of the diagnosis of UBUC while metachronous UTUC was defined as a disease occurring > 3 months after the diagnosis of UBUC. The patients were classified into 3 groups: NMIBC only, synchronous UTUC-NMIBC, and NMIBC-metachronous UTUC. Potential risk factors for synchronous and metachronous UTUC were analyzed. Univariate and multivariate logistic regression addressed the prediction of synchronous and metachronous UTUC. The ROC analysis predicts high risk in metachronous and synchronous UTUC. A novel predictive nomogram was constructed by incorporating these features.

Results:

A total of 3260 patients were enrolled including 3038 cases of NMIBC only, 124 cases of synchronous UTUC-NMIBC, and 99 cases of NMIBC-metachronous UTUC. Significant differences were found between these three groups in gender, age, tumor stage, CCI, CCR, and solid organ transplantation. In group synchronous UTUC-NMIBC, the multivariate logistic regression analysis showed female (HR=3.27, 95% CI: 2.23-4.79, P < 0.001), T stage Tis (HR=3.88, 95% CI: 1.82-8.3, P < 0.001), organ transplantation (HR=7.28, 95% CI: 3-17.67, P < 0.001), and Cr eGFR < 60 (HR=3.9, 95% CI: 2.52-6.02, P < 0.001) were independently associated with synchronous UTUC. In group NMIBC with metachronous UTUC, the multivariate logistic regression analysis showed that age > 68 (HR=2.08, 95% CI: 1.36-3.2, P < 0.001), female (HR=1.82, 95% CI: 1.2-2.75, P = 0.005), T stage Tis (HR=2.24, 95% CI: 0.92-5.45, P = 0.075), Cr eGFR < 60 (HR=5.05, 95% CI: 3.12-8.17, P<0.001) were independent risk factors. We used these predictors to create the novel nomogram and ROC curve.

Conclusion

NMIBC with metachronous or synchronous UTUC is uncommon but cannot be negligible especially in high-risk (female, CIS, organ transplant status, CKD stage≥3) patients. We established and validated an accurate tool for the prediction of NMIBC with metachronous or synchronous UTUC.