The Value of Preoperative Local Symptoms in Prognosis of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Retrospective, Multicenter Cohort Study

Hsin-Chih Yeh; Chao-Hsiang Chang; Jen-Kai Fang; I-Hsuan Alan Chen; Jen-Tai Lin; Jian-Hua Hong; Chao-Yuan Huang; Shian-Shiang Wang; Chuan-Shu Chen; Chi-Wen Lo; Chih-Chin Yu; Jen-Shu Tseng; Wun-Rong Lin; Yeong-Chin Jou; Ian-Seng Cheong; Yuan-Hong Jiang; Chung-You Tsai; Thomas Y Hsueh; Yung-Tai Chen; Hsu-Che Huang; Yao-Chou Tsai; Wei-Yu Lin; Chia-Chang Wu; Po-Hung Lin; Te-Wei Lin; Wen-Jeng Wu

doi:10.3389/fonc.2022.872849

The Value of Preoperative Local Symptoms in Prognosis of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Retrospective, Multicenter Cohort Study

Front Oncol. 2022 Jun 2:12:872849. doi: 10.3389/fonc.2022.872849. eCollection 2022.

Authors

Hsin-Chih Yeh^{1

2

3

4}, Chao-Hsiang Chang^{5

6

7}, Jen-Kai Fang⁷, I-Hsuan Alan Chen⁸, Jen-Tai Lin⁸, Jian-Hua Hong^{9

10}, Chao-Yuan Huang¹⁰, Shian-Shiang Wang^{11

12

13}, Chuan-Shu Chen^{11

12

14}, Chi-Wen Lo¹⁵, Chih-Chin Yu^{15

16}, Jen-Shu Tseng^{17

18

19}, Wun-Rong Lin^{17

18}, Yeong-Chin Jou^{20

21}, Ian-Seng Cheong²⁰, Yuan-Hong Jiang²², Chung-You Tsai^{23

24}, Thomas Y Hsueh^{25

26}, Yung-Tai Chen²⁷, Hsu-Che Huang^{28

29}, Yao-Chou Tsai^{30

31}, Wei-Yu Lin^{32

33

34}, Chia-Chang Wu^{30

35

36}, Po-Hung Lin^{37

38

39}, Te-Wei Lin⁴⁰, Wen-Jeng Wu^{2

3

4

41}

Affiliations

¹ Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
² Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁵ Department of Urology, China Medical University, Taichung, Taiwan.
⁶ School of Medicine, China Medical University, Taichung, Taiwan.
⁷ Department of Urology, China Medical University Hospital, Taichung, Taiwan.
⁸ Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
⁹ Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
¹⁰ Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹¹ Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
¹² Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
¹³ Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan.
¹⁴ Department of Senior Citizen Service Management, National Taichung University of Science and Technology, Taichung, Taiwan.
¹⁵ Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, New Taipei City, Taiwan.
¹⁶ School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan.
¹⁷ Department of Urology, MacKay Memorial Hospital, Taipei, Taiwan.
¹⁸ Mackay Medical College, New Taipei City, Taiwan.
¹⁹ Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan.
²⁰ Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
²¹ Department of Health and Nutrition Biotechnology, Asian University, Taichung, Taiwan.
²² Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.
²³ Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
²⁴ Department of Healthcare Information & Management, Ming Chuan University, Taoyuan, Taiwan.
²⁵ Division of Urology, Department of Surgery, Taipei City Hospital renai branch, Taipei, Taiwan.
²⁶ Department of Urology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
²⁷ Department of Urology, Taiwan Adventist Hospital, Taipei, Taiwan.
²⁸ Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan.
²⁹ Department of Life Science, College of Science, National Taiwan Normal University, Taipei, Taiwan.
³⁰ Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³¹ Department of Urology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
³² Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
³³ Chang Gung University of Science and Technology, Chiayi, Taiwan.
³⁴ Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³⁵ Department of Urology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
³⁶ Taipei Medical University Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei, Taiwan.
³⁷ Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
³⁸ Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³⁹ School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁴⁰ School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴¹ Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

Purpose: We aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC).

Methods: This retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models.

Results: The median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis (p <0.001), more dialysis status (p = 0.027), renal pelvic tumors (p <0.001), and early pathological tumor stage (p = 0.001). Symptomatic hydronephrosis was associated with female patients (p <0.001), less dialysis status (p = 0.001), less bladder cancer history (p <0.001), ureteral tumors (p <0.001), open surgery (p = 0.006), advanced pathological tumor stage (p <0.001), and postoperative chemotherapy (p = 0.029). Kaplan-Meier analysis showed that patients with hematuria or without symptomatic hydronephrosis had significantly higher rates of OS, CSS, and DFS (all p <0.001). Multivariate analysis confirmed that presence of hematuria was independently associated with better OS (HR 0.789, 95% CI 0.661-0.942) and CSS (HR 0.772, 95% CI 0.607-0.980), while symptomatic hydronephrosis was a significant prognostic factor for poorer OS (HR 1.387, 95% CI 1.142-1.683), CSS (HR 1.587, 95% CI 1.229-2.050), and DFS (HR 1.378, 95% CI 1.122-1.693).

Conclusions: Preoperative local symptoms were significantly associated with oncological outcomes, whereas symptomatic hydronephrosis and hematuria had opposite prognostic effects. Preoperative symptoms may provide additional information on risk stratification and perioperative treatment selection for patients with UTUC.

Keywords: flank pain; hematuria; prognosis; radical nephroureterectomy (RNU); symptomatic hydronephrosis; upper tract urothelial carcinoma (UTUC).