Pattern and risk factors of local recurrence after nephroureterectomy for upper tract urothelial carcinoma

Xiaoying Li, Ming Cui, Xiaobin Gu, Dong Fang, Hongzhen Li, Shangbin Qin, Kunlin Yang, Tianzhao Zhu, Xuesong Li, Liqun Zhou, Xian-Shu Gao, Dian Wang, Xiaoying Li, Ming Cui, Xiaobin Gu, Dong Fang, Hongzhen Li, Shangbin Qin, Kunlin Yang, Tianzhao Zhu, Xuesong Li, Liqun Zhou, Xian-Shu Gao, Dian Wang

Abstract

Purpose: This study aims to identify predictive local recurrence risk factors and site-specific local recurrence pattern of upper tract urothelial carcinoma (UTUC) with different primary tumor locations.

Methods: Three hundred and eighty-nine UTUC patients with radical nephroureterectomy were included in this study. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of local recurrence. We also mapped the position of local recurrence sites stratified by primary tumor locations.

Results: A total of 73 patients (18.7%) developed local recurrence within a median follow-up of 41 months (range, 3-80 months). For patients with local recurrence, the median interval of local recurrence was 9 months. Ureter tumor, multifocality, T stage, G grade, lymph node metastasis (LNM), lymph node dissection (LND), and lymph vascular invasion (LVI) were all significantly associated with increased local recurrence by univariable analyses (P < 0.05). Only multifocality, T3-4, G3, and LNM remained independent predictors of increased local recurrence by multivariable analyses. Adjuvant radiotherapy could reduce the local recurrence (HR = 0.177; 95% CI 0.064-0.493, P = 0.001). Patients with local recurrence had poorer cancer-specific survival (4-year cancer-specific survival rate 36 ± 7.5% vs 88.4 ± 2.2%, P = 0.000). We evaluated local recurrence pattern stratified by tumor locations. Para-aortic lymph node region was the most common recurrence area for all the patients. Left-sided UTUC had more than 70% recurrent lymph nodes in the left para-aortic region (LPA). For right-sided UTUC patients, recurrent para-aortic lymph nodes distributed in the LPA (33.3%), aortocaval (AC) (41.5%), and right paracaval (RPC) (25.2%) regions. Recurrence in the internal and external iliac regions was only found in the distal ureter group (P < 0.05). Renal pelvic fossa recurrence was only found in renal pelvic tumor (22.2%, P = 0.007). The ureter tumor bed recurrence rate was higher for ureter patients (P = 0.001).

Conclusions: Multifocality, T3-4, G3, and LNM are predictors of higher local recurrence rate of UTUC. Adjuvant radiotherapy can reduce local recurrence rate. Local recurrence patterns are different according to primary tumor locations.

Keywords: Local recurrence; Primary tumor location; Risk factor; Upper tract urothelial carcinoma.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The Kaplan-Meier survival curves of local recurrence-free survival stratified by T stage (a), G grade (b), multifocality (c); radiation therapy (RT) (d); lymph node status (e); cancer specific-free survival stratified by local recurrence (LR) (f)
Fig. 2
Fig. 2
Recurrence lymph node distribution map stratified by primary tumor location. a Recurrence lymph nodes of pelvic tumor. b Recurrence lymph nodes of proximal ureter tumor. c Recurrence lymph nodes of middle ureter tumor. d Recurrence lymph nodes of distal ureter tumor (red, artery; blue, vein)
Fig. 3
Fig. 3
Recurrence lymph node distribution ratio stratified by primary tumor site. a Recurrence lymph node distribution ratio of left UTUC patients. b Recurrence lymph node distribution ratio of right UTUC patients (red, left para-aortic; yellow, aortocaval; blue, right paracaval)

References

    1. Genega Elizabeth M., Porter Christopher R. Urothelial Neoplasms of the Kidney and Ureter. Pathology Patterns Reviews. 2002;117(suppl_1):S36–S48.
    1. Chou YH, Huang CH. Unusual clinical presentation of upper urothelial carcinoma in Taiwan. Cancer. 1999;85(6):1342–1344.
    1. Yang MH, Chen KK, Yen CC, Wang WS, Chang YH, Huang WJ, Fan FS, Chiou TJ, Liu JH, Chen PM. Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan. Urology. 2002;59(5):681–687.
    1. Chen CH, Dickman KG, Moriya M, Zavadil J, Sidorenko VS, Edwards KL, Gnatenko DV, Wu L, Turesky RJ, Wu XR, et al. Aristolochic acid-associated urothelial cancer in Taiwan. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(21):8241–8246.
    1. Lai MN, Wang SM, Chen PC, Chen YY, Wang JD. Population-based case-control study of Chinese herbal products containing aristolochic acid and urinary tract cancer risk. J Natl Cancer Inst. 2010;102(3):179–186.
    1. Li CC, Chang TH, Wu WJ, Ke HL, Huang SP, Tsai PC, Chang SJ, Shen JT, Chou YH, Huang CH. Significant predictive factors for prognosis of primary upper urinary tract cancer after radical nephroureterectomy in Taiwanese patients. European urology. 2008;54(5):1127–1134.
    1. Rouprêt M., Zigeuner R., Palou J., Boehle A., Kaasinen E., Sylvester R., Babjuk M., Oosterlinck W. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Actas Urológicas Españolas (English Edition) 2012;36(1):2–14.
    1. Wu Ching-Fang, Pang See-Tong, Chen Chih-Shou, Chuang Cheng-Keng, Chen Yu, Lin Paul-Yann. The Impact Factors on Prognosis of Patients With pT3 Upper Urinary Tract Transitional Cell Carcinoma. Journal of Urology. 2007;178(2):446–450.
    1. Jang NY, Kim IA, Byun SS, Lee SE, Kim JS. Patterns of failure and prognostic factors for locoregional recurrence after radical surgery in upper urinary tract transitional cell carcinoma: implications for adjuvant radiotherapy. Urol Int. 2013;90(2):202–206.
    1. Ozsahin M, Zouhair A, Villa S, Storme G, Chauvet B, Taussky D, Gouders D, Ries G, Bontemps P, Coucke PA, et al. Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study. Eur J Cancer. 1999;35(5):738–743.
    1. Xie J, Zhang XB, Wen J, Zhang YS, Li HZ. Comparison of clinicopathological features in metastatic upper tract urothelial carcinoma and urothelial bladder cancer. Int Urol Nephrol. 2016;48(4):481–487.
    1. Kondo T, Nakazawa H, Ito F, Hashimoto Y, Toma H, Tanabe K. Primary site and incidence of lymph node metastases in urothelial carcinoma of upper urinary tract. Urology. 2007;69(2):265–269.
    1. Matin SF, Sfakianos JP, Espiritu PN, Coleman JA, Spiess PE. Patterns of lymphatic metastases in upper tract urothelial carcinoma and proposed dissection templates. The Journal of urology. 2015;194(6):1567–1574.
    1. Catton CN, Warde P, Gospodarowicz MK, Panzarella T, Catton P, McLean M, Milosevic M. Transitional cell carcinoma of the renal pelvis and ureter: outcome and patterns of relapse in patients treated with postoperative radiation. Urologic Oncol. 1996;2(6):171–176.
    1. Yoo S, You D, Jeong IG, Hong B, Hong JH, Ahn H, Kim CS. Impact of tumor location on local recurrence after nephroureterectomy for upper tract urothelial carcinoma: implications for adjuvant radiotherapy. Clin Genitourin Cancer. 2017;15(2):e199–e204.
    1. Dominguez-Escrig JL, Peyronnet B, Seisen T, Bruins HM, Yuan CY, Babjuk M, Böhle A, Burger M, Compérat EM, Gontero P, et al. Potential benefit of lymph node dissection during radical nephroureterectomy for upper tract urothelial carcinoma: a systematic review by the European Association of Urology guidelines panel on non-muscle-invasive bladder cancer. Eur Urol Focus. 2019;5(2):224–241.
    1. Tanaka N, Kikuchi E, Kanao K, Matsumoto K, Kobayashi H, Ide H, Miyazaki Y, Obata J, Hoshino K, Shirotake S, et al. Metastatic behavior of upper tract urothelial carcinoma after radical nephroureterectomy: association with primary tumor location. Ann Surg Oncol. 2014;21(3):1038–1045.
    1. Rouprêt M, Babjuk M, Compérat E, Zigeuner R, Sylvester RJ, Burger M, Cowan NC, Gontero P, Van Rhijn BWG, Mostafid AH, et al. European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2017 update. European urology. 2018;73(1):111–122.
    1. Wein AJ, Kavoussi LR, Novick AC, Partin AW, CA. P: Campbell-Walsh urology 9th ed 2007.
    1. Scheidler J, Hricak H, Yu KK, Subak L, Segal MR. Radiological evaluation of lymph node metastases in patients with cervical cancer A meta-analysis. Jama. 1997;278(13):1096–1101.
    1. Williams AD, Cousins C, Soutter WP, Mubashar M, Peters AM, Dina R, Fuchsel F. McIndoe GA, deSouza NM: Detection of pelvic lymph node metastases in gynecologic malignancy: a comparison of CT, MR imaging, and positron emission tomography. AJR Am J Roentgenol. 2001;177(2):343–348.
    1. Bipat S, Glas AS, van der Velden J, Zwinderman AH, Bossuyt PM, Stoker J. Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: a systematic review. Gynecol Oncol. 2003;91(1):59–66.
    1. Lengele B, Scalliet P. Anatomical bases for the radiological delineation of lymph node areas. Part III: Pelvis and lower limbs. Radiother Oncol. 2009;92(1):22–33.
    1. Takiar V, Fontanilla HP, Eifel PJ, Jhingran A, Kelly P, Iyer RB, Levenback CF, Zhang Y, Dong L, Klopp A. Anatomic distribution of fluorodeoxyglucose-avid para-aortic lymph nodes in patients with cervical cancer. International journal of radiation oncology, biology, physics. 2013;85(4):1045–1050.
    1. Margulis V, Shariat SF, Matin SF, Kamat AM, Zigeuner R, Kikuchi E, Lotan Y, Weizer A, Raman JD, Wood CG. Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer. 2009;115(6):1224–1233.
    1. Munoz JJ, Ellison LM. Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. The Journal of urology. 2000;164(5):1523–1525.
    1. Fang D, Xiong GY, Li XS, Chen XP, Zhang L, Yao L, He ZS, Zhou LQ. Pattern and risk factors of intravesical recurrence after nephroureterectomy for upper tract urothelial carcinoma: a large Chinese center experience. J Formos Med Assoc. 2014;113(11):820–827.
    1. Seisen T, Granger B, Colin P, Leon P, Utard G, Renard-Penna R, Comperat E, Mozer P, Cussenot O, Shariat SF, et al. A systematic review and meta-analysis of clinicopathologic factors linked to intravesical recurrence after radical nephroureterectomy to treat upper tract urothelial carcinoma. Eur Urol. 2015;67(6):1122–1133.
    1. Wang Q, Zhang T, Wu J, Wen J, Tao D, Wan T, Zhu W. Prognosis and risk factors of patients with upper urinary tract urothelial carcinoma and postoperative recurrence of bladder cancer in central China. BMC Urol. 2019;19(1):24.
    1. Fang D, Zhang L, Li X, Yu W, Singla N, Zhao G, Xiong G, Song Y, He Q, He Z, et al. Presence of concomitant non-muscle-invasive bladder cancer in Chinese patients with upper tract urothelial carcinoma: risk factors, characteristics, and predictive value. Ann Surg Oncol. 2015;22(8):2789–2798.
    1. Hung SY, Yang WC, Luo HL, Hsu CC, Chen YT, Chuang YC. Segmental ureterectomy does not compromise the oncologic outcome compared with nephroureterectomy for pure ureter cancer. Int Urol Nephrol. 2014;46(5):921–926.
    1. Burger M, Shariat SF, Fritsche H-M, Martinez-Salamanca JI, Matsumoto K, Chromecki TF, Ficarra V, Kassouf W, Seitz C, Pycha A, et al. No overt influence of lymphadenectomy on cancer-specific survival in organ-confined versus locally advanced upper urinary tract urothelial carcinoma undergoing radical nephroureterectomy: a retrospective international, multi-institutional study. World J Urol. 2011;29(4):465–472.
    1. Pearce Shane M., Pariser Joseph J., Patel Sanjay G., Steinberg Gary D., Shalhav Arieh L., Smith Norm D. The effect of surgical approach on performance of lymphadenectomy and perioperative morbidity for radical nephroureterectomy. Urologic Oncology: Seminars and Original Investigations. 2016;34(3):121.e15-121.e21.
    1. Tamhankar AS, Patil SR, Ahluwalia P, Gautam G. Current status of lymphadenectomy during radical nephroureterectomy for upper tract urothelial cancer-yes, no or maybe? Indian J Surg Oncol. 2018;9(3):418–426.
    1. Roscigno M, Brausi M, Heidenreich A, Lotan Y, Margulis V, Shariat SF, Van Poppel H, Zigeuner R. Lymphadenectomy at the time of nephroureterectomy for upper tract urothelial cancer. Eur Urol. 2011;60(4):776–783.
    1. Huang YC, Chang YH, Chiu KH, Shindel AW, Lai CH. Adjuvant radiotherapy for locally advanced upper tract urothelial carcinoma. Sci Rep. 2016;6:38175.
    1. Jwa E, Kim YS, Ahn H, Kim CS, Lee JL, Kim SO, S DOA: Adjuvant radiotherapy for stage III/IV urothelial carcinoma of the upper tract. Anticancer Res 2014, 34(1):333-38.
    1. Chen B, Zeng ZC, Wang GM, Zhang L, Lin ZM, Sun LA, Zhu TY, Wu LL, Zhang JY, Ji Y. Radiotherapy may improve overall survival of patients with T3/T4 transitional cell carcinoma of the renal pelvis or ureter and delay bladder tumour relapse. BMC cancer. 2011;11:297.
    1. Kim M, Kim JK, Lee J, Kim YS, Lee JL, Kwak C, Jeong CW, Byun SS, Lee SC, Ohyama C, et al. Adjuvant treatments for advanced stage, non-metastatic upper tract urothelial carcinoma: a multicenter study. International journal of radiation oncology, biology, physics. 2019;104(4):819–827.
    1. Edward Halperin, Perez C, Brady L: Perez and Brady’s principles and practice of radiation oncology. 2007:2368.
    1. Park S, Hong B, Kim CS, Ahn H. The impact of tumor location on prognosis of transitional cell carcinoma of the upper urinary tract. J Urol. 2004;171(2 Pt 1):621–625.

Source: PubMed

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