腫瘤多發性對上泌尿道尿路上皮癌患者預後之影響

陳人傑¹、黃逸修^1,2、黃子豪^1,2、魏子鈞^1,2、黃奕燊^1,2、范玉華^1,2、林志杰^1,2、林子平^1,2、
鍾孝仁^1,2、郭俊逸^1,2、吳宏豪^1,2、張延驊^1,2、林登龍^1,2、黃志賢^1,2

¹臺北榮民總醫院 泌尿部; ²國立陽明交通大學醫學院 泌尿學科 書田泌尿科學研究中心

The Impact of Multifocality on Outcomes in Patients with Upper Tract Carcinoma Treated with Radical Nephroureterectomy

Jen‑Chieh Chen¹, Eric Yi‑Hsiu Huang^1,2, Tzu‑Hao Huang^1,2, Tzu‑Chun Wei^1,2, I‑Shen Huang^1,2,
Yu‑Hua Fan^1,2, Chih‑Chieh Lin^1,2, Tzu‑Ping Lin^1,2, Hsiao‑Jen Chung^1,2, Junne‑Yih Kuo^1,2,
Howard H. H. Wu^1,2, Yen‑Hwa Chang^1,2, Alex T. L. Lin^1,2, William J. Huang^1,2

¹Department of Urology, Taipei Veterans General Hospital

²Department of Urology, College of Medicine and Shu‑Tien Urological Research Center,

National Yang Ming Chiao Tung University, Taipei, Taiwan

Purpose:

The definition of multifocality in upper tract urothelial carcinoma (UTUC) is inconsistent in the literature. Moreover, the impact of multifocality on UTUC outcomes is inconclusive and has not been thoroughly evaluated in the Asian population. Therefore, we aim to use different definitions of multifocality in UTUC to evaluate the prognosis of UTUC patients treated with radical nephroureterectomy (RNU).

Materials and Methods:

This was a retrospective single-center study involving 532 UTUC patients who underwent RNU between January 2004 and December 2018. Three different definitions of multifocality in UTUC were utilized. Definition 1 was that tumors affecting both the kidney and ureter. Definition 2 considered the synchronous presence of multiple tumors in either the kidney or ureter. Lastly, definition 3 was synchronous presence of multiple tumors, including focal carcinoma in situ (CIS) alone, in either the kidney or ureter. Overall survival (OS), Cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS) were investigated. Fisher’s exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model (CRM) were used for data analysis.

Results:

The median follow-up was 50 months. Forty-seven patients were categorized as having multifocal UTUC using definition 1, 93 patients using definition 2, and 132 patients using definition 3. Regardless of which definition was used, patients with multifocal UTUC were associated with the presence of previous/synchronous bladder cancer and concomitant CIS. However, other clinicopathological features were not different between groups, including age, sex, smoking, preoperative ureterorenoscopic (URS) biopsy, T stage, lymph node positivity, tumor grade, concomitant CIS, presence of poor histological feature, presence of lymphovascular invasion, and type of surgery. Multivariate CRM showed that only definition 3 of multifocality was an independent significant adverse factor of OS (Hazard ratio [HR] = 1.60, 95% confidence interval [CI] = 1.20-2.15, p = 0.001). In respect of CSS and DFS, multifocality was not associated with CSS and DFS regardless of which definition was used. Concerning IVRFS, multivariate CRM revealed that multifocality in all definitions was an independent poor predictor (Definition 1: HR = 1.80, 95% CI = 1.18-2.77, p = 0.007; Definition 2: HR = 1.45, 95% CI = 1.02-2.06, p = 0.036; Definition 3: HR = 1.46, 95% CI = 1.06-2.00, p = 0.02). Other prognostic factors for poor IVRFS were preoperative positive voiding urine cytology, preoperative URS biopsy, and concomitant CIS.

Conclusion:

In our experience, tumor multifocality significantly affects IVRFS but not CSS or DFS in UTUC patients treated with RNU. Specifically, when tumor multifocality is defined by the synchronous presence of multiple tumors, including focal carcinoma in situ, it is associated with adverse prognostic outcomes following the surgeries.