Urological Oncology
Risk stratification for bladder recurrence of upper urinary tract urothelial carcinoma after radical nephroureterectomy Junichiro Ishioka1, Kazutaka Saito1, Toshiki Kijima1, Yasukazu Nakanishi1, Soichiro Yoshida1, Minato Yokoyama1, Yoh Matsuoka1, Noboru Numao1, Fumitaka Koga1, Hitoshi Masuda1, Yasuhisa Fujii1, Yasuyuki Sakai2, Chizuru Arisawa3, Tetsuo Okuno4, Katsuhi Nagahama5, Shigeyoshi Kamata6, Mizuaki Sakura7, Junji Yonese7, Shinji Morimoto8, Akira Noro9, Toshihiko Tsujii1,10, Satoshi Kitahara11, Shuichi Gotoh12, Yotsuo Higashi13 and Kazunori Kihara1 1 Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, 2Department of Urology, National Cancer Centre Hospital East, Chiba, 3Department of Urology, East Tokyo Metropolitan Hospital, Tokyo, 4 Department of Urology, JA Toride Medical Centre, Ibaraki, 5Department of Urology, Kounodai Hospital, National Centre for Global Health and Medicine, Chiba, 6Department of Urology, Soka Municipal Hospital, Saitama, 7Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 8Department of Urology, Tsuchiura Kyodo General Hospital, Ibaraki, 9Department of Urology, Saitama Red Cross Hospital, Saitama, 10 Department of Urology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, 11Department of Urology, Tama-Nanbu Chiiki Hospital, Tokyo, 12Department of Urology, Hamamatsu Medical Centre, Shizuoka, and 13Department of Urology, Saitama Cancer Centre, Saitama, Japan
Objectives To identify risk factors and develop a model for predicting recurrence of upper urinary tract urothelial carcinoma (UTUC) in the bladder in patients without a history of bladder cancer after radical nephroureterectomy (RNU).
Patients and Methods We retrospectively reviewed 754 patients with UTUC without prior or concurrent bladder cancer or distant metastasis at 13 institutions in Japan. Univariate and multivariate Fine and Gray competing risks proportional hazards models were used to examine the cumulative incidence of bladder recurrence of UTUC. A risk stratification model and a nomogram were constructed. Two prediction models were compared using the concordance index (c-index) focusing on predictive accuracy and decision-curve analysis, which indicate whether a model is appropriate for decision-making and determining subsequent patient prognosis.
Multivariate analysis showed that papillary tumour architecture, absence of lymphovascular invasion and higher pathological T stage were both predictive factors for bladder cancer recurrence. The predictive accuracy of the risk stratification model and the nomogram for bladder cancer recurrence were not different (c-index: 0.60 and 0.62). According to the decision-curve analysis, the risk stratification was an acceptable model because the net benefit of the risk stratification was equivalent to that of the nomogram. The overall cumulative incidence rates of bladder cancer 5 years after RNU were 10, 26 and 44% in the low-, intermediate- and high-risk groups, respectively.
Conclusions We identified risk factors and developed a risk stratification model for UTUC recurrence in the bladder after RNU. This model could be used to provide both an individualised strategy to prevent recurrence and a risk-stratified surveillance protocol.
Results The cumulative incidence rates of bladder UTUC recurrence at 1 and 5 years were 15 and 29%, respectively; the median time to bladder UTUC recurrence was 10 months.
© 2014 The Authors BJU International © 2014 BJU International | doi:10.1111/bju.12707 Published by John Wiley & Sons Ltd. www.bjui.org
Keywords upper tract urothelial carcinoma, radical nephroureterectomy, bladder recurrence
BJU Int 2015; 115: 705–712 wileyonlinelibrary.com
Ishioka et al.
Introduction Rates of recurrence in the bladder after treatment of primary upper urinary tract urothelial carcinoma (UTUC) have been reported to be 15–50% [1,2]. In the management of UTUC, the bladder should be kept under surveillance in all cases after completion of the definitive treatment. The National Comprehensive Cancer Network 2012 guidelines recommend surveillance based on cystoscopy and urinary cytology every 3 months for 1 year, and then at increasing intervals [3]. Despite their importance, cystoscopies are invasive, costly and labour-intensive, therefore, identifying the risk factors for bladder recurrence may help physicians to reduce the number of follow-up cystoscopies for patients at low risk and physicians can provide a closer follow-up schedule based on solid evidence for patients at intermediate risk, whereas patients at high risk may benefit from prophylactic intravesical instillation therapy [4]. Despite the efforts of previous researchers, only a few consistent risk factors have thus far been found [2], partly because of the small number of patients and the resulting lack of statistical power. In particular, it is important to identify risk factors for patients without a history of bladder cancer because it is possible to manage UTUC recurrence in the bladder in patients with a history of bladder cancer using the prediction model for bladder cancer. In addition, the risk of the event of interest has been overestimated by previous studies in the presence of strong competing risks such as cancer-specific death, because almost all studies have applied standard Cox regression for statistical analysis. We hypothesised that a risk prediction model constructed with risk factors identified by competing risk regression would have high discriminative ability. The aim of the present multicentre study was to identify the risk factors for bladder recurrence of UTUC after radical nephroureterectomy (RNU) and to develop a simple prediction model for this recurrence [5,6].
Patients and Methods Between January 1995 and December 2010, 1135 patients with UTUC were treated at 13 institutions. We excluded patients who had not been treated with RNU (n = 173), who had lymph node metastasis (n = 76), or who had a history of bladder cancer (n = 186) or concurrent bladder cancer (n = 180) from the present analysis (some patients met more than one exlusion criterion). The remaining 754 patients with UTUC were eligible for the analysis. Minimally invasive RNU was carried out using an open transperitoneal or retroperitoneal approach and gasless two-port access [7,8]. RNU performed using an ordinary laparoscopic approach was not included. Ethical board review approval was obtained from each institution.
706
© 2014 The Authors BJU International © 2014 BJU International
We evaluated clinical variables to predict recurrence in the bladder after the definitive treatment of UTUC. The variables included were gender (male vs female), age (continuous), laterality, body mass index (continuous), smoking status (never vs former/current smoker), tumour location (renal pelvis vs ureter), presence of tumour multifocality (absent vs present), tumour architecture (papillary vs sessile), dominant pathological tumour grade (≥3 vs
Risk stratification for bladder recurrence of upper urinary tract urothelial carcinoma after radical nephroureterectomy Junichiro Ishioka1, Kazutaka Saito1, Toshiki Kijima1, Yasukazu Nakanishi1, Soichiro Yoshida1, Minato Yokoyama1, Yoh Matsuoka1, Noboru Numao1, Fumitaka Koga1, Hitoshi Masuda1, Yasuhisa Fujii1, Yasuyuki Sakai2, Chizuru Arisawa3, Tetsuo Okuno4, Katsuhi Nagahama5, Shigeyoshi Kamata6, Mizuaki Sakura7, Junji Yonese7, Shinji Morimoto8, Akira Noro9, Toshihiko Tsujii1,10, Satoshi Kitahara11, Shuichi Gotoh12, Yotsuo Higashi13 and Kazunori Kihara1 1 Department of Urology, Tokyo Medical and Dental University Graduate School, Tokyo, 2Department of Urology, National Cancer Centre Hospital East, Chiba, 3Department of Urology, East Tokyo Metropolitan Hospital, Tokyo, 4 Department of Urology, JA Toride Medical Centre, Ibaraki, 5Department of Urology, Kounodai Hospital, National Centre for Global Health and Medicine, Chiba, 6Department of Urology, Soka Municipal Hospital, Saitama, 7Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 8Department of Urology, Tsuchiura Kyodo General Hospital, Ibaraki, 9Department of Urology, Saitama Red Cross Hospital, Saitama, 10 Department of Urology, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, 11Department of Urology, Tama-Nanbu Chiiki Hospital, Tokyo, 12Department of Urology, Hamamatsu Medical Centre, Shizuoka, and 13Department of Urology, Saitama Cancer Centre, Saitama, Japan
Objectives To identify risk factors and develop a model for predicting recurrence of upper urinary tract urothelial carcinoma (UTUC) in the bladder in patients without a history of bladder cancer after radical nephroureterectomy (RNU).
Patients and Methods We retrospectively reviewed 754 patients with UTUC without prior or concurrent bladder cancer or distant metastasis at 13 institutions in Japan. Univariate and multivariate Fine and Gray competing risks proportional hazards models were used to examine the cumulative incidence of bladder recurrence of UTUC. A risk stratification model and a nomogram were constructed. Two prediction models were compared using the concordance index (c-index) focusing on predictive accuracy and decision-curve analysis, which indicate whether a model is appropriate for decision-making and determining subsequent patient prognosis.
Multivariate analysis showed that papillary tumour architecture, absence of lymphovascular invasion and higher pathological T stage were both predictive factors for bladder cancer recurrence. The predictive accuracy of the risk stratification model and the nomogram for bladder cancer recurrence were not different (c-index: 0.60 and 0.62). According to the decision-curve analysis, the risk stratification was an acceptable model because the net benefit of the risk stratification was equivalent to that of the nomogram. The overall cumulative incidence rates of bladder cancer 5 years after RNU were 10, 26 and 44% in the low-, intermediate- and high-risk groups, respectively.
Conclusions We identified risk factors and developed a risk stratification model for UTUC recurrence in the bladder after RNU. This model could be used to provide both an individualised strategy to prevent recurrence and a risk-stratified surveillance protocol.
Results The cumulative incidence rates of bladder UTUC recurrence at 1 and 5 years were 15 and 29%, respectively; the median time to bladder UTUC recurrence was 10 months.
© 2014 The Authors BJU International © 2014 BJU International | doi:10.1111/bju.12707 Published by John Wiley & Sons Ltd. www.bjui.org
Keywords upper tract urothelial carcinoma, radical nephroureterectomy, bladder recurrence
BJU Int 2015; 115: 705–712 wileyonlinelibrary.com
Ishioka et al.
Introduction Rates of recurrence in the bladder after treatment of primary upper urinary tract urothelial carcinoma (UTUC) have been reported to be 15–50% [1,2]. In the management of UTUC, the bladder should be kept under surveillance in all cases after completion of the definitive treatment. The National Comprehensive Cancer Network 2012 guidelines recommend surveillance based on cystoscopy and urinary cytology every 3 months for 1 year, and then at increasing intervals [3]. Despite their importance, cystoscopies are invasive, costly and labour-intensive, therefore, identifying the risk factors for bladder recurrence may help physicians to reduce the number of follow-up cystoscopies for patients at low risk and physicians can provide a closer follow-up schedule based on solid evidence for patients at intermediate risk, whereas patients at high risk may benefit from prophylactic intravesical instillation therapy [4]. Despite the efforts of previous researchers, only a few consistent risk factors have thus far been found [2], partly because of the small number of patients and the resulting lack of statistical power. In particular, it is important to identify risk factors for patients without a history of bladder cancer because it is possible to manage UTUC recurrence in the bladder in patients with a history of bladder cancer using the prediction model for bladder cancer. In addition, the risk of the event of interest has been overestimated by previous studies in the presence of strong competing risks such as cancer-specific death, because almost all studies have applied standard Cox regression for statistical analysis. We hypothesised that a risk prediction model constructed with risk factors identified by competing risk regression would have high discriminative ability. The aim of the present multicentre study was to identify the risk factors for bladder recurrence of UTUC after radical nephroureterectomy (RNU) and to develop a simple prediction model for this recurrence [5,6].
Patients and Methods Between January 1995 and December 2010, 1135 patients with UTUC were treated at 13 institutions. We excluded patients who had not been treated with RNU (n = 173), who had lymph node metastasis (n = 76), or who had a history of bladder cancer (n = 186) or concurrent bladder cancer (n = 180) from the present analysis (some patients met more than one exlusion criterion). The remaining 754 patients with UTUC were eligible for the analysis. Minimally invasive RNU was carried out using an open transperitoneal or retroperitoneal approach and gasless two-port access [7,8]. RNU performed using an ordinary laparoscopic approach was not included. Ethical board review approval was obtained from each institution.
706
© 2014 The Authors BJU International © 2014 BJU International
We evaluated clinical variables to predict recurrence in the bladder after the definitive treatment of UTUC. The variables included were gender (male vs female), age (continuous), laterality, body mass index (continuous), smoking status (never vs former/current smoker), tumour location (renal pelvis vs ureter), presence of tumour multifocality (absent vs present), tumour architecture (papillary vs sessile), dominant pathological tumour grade (≥3 vs
