- Email: [email protected]
Re: Thomas F. Chromecki, Eugene K. Cha, Harun Fajkovic, et al. The Impact of Tumor Multifocality on Outcomes in Patients Treated with Radical Nephroureterectomy. Eur Urol 2012;61;245–53
EUROPEAN UROLOGY 62 (2012) e75–e76
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Letter to the Editor Re: Thomas F. Chromecki, Eugene K. Cha, Harun Fajkovic, et al. The Impact of Tumor Multifocality on Outcomes in Patients Treated with Radical Nephroureterectomy. Eur Urol 2012;61;245–53 In this paper, Chromecki et al [1] evaluated the impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy (RNU). The idea of studying the impact of location and multifocality in patients with upper-tract urothelial carcinoma (UTUC) undergoing RNU is old. Several years ago, two studies (with 84 and 72 patients, respectively) suggested that ureteral tumors are associated with a poorer prognosis than renal pelvis tumors [2,3]. However, more recent studies reported conflicting results on the same issue. For example, Van der Poel et al noted in their series of 149 patients that those with distal ureteral tumors had significantly better survival rates than patients with proximal ureteral or renal pelvis tumors [4]. Meanwhile, Catto et al and others reported no prognostic difference with respect to tumor location in patients with UTUC [5–8]. Ouzzane et al [9] compared ureteral, pelvic, and multifocal UTUC tumors in 609 patients and found that ureteral and multifocal tumors had worse prognosis than renal pelvic tumors. Novara et al [10] reported an independent prognostic value for tumor multifocality in 269 patients (organ-confined or not) treated with RNU for UTUC, whereas Chromecki et al [1] concluded that tumor multifocality is an independent prognostic factor of disease progression and cancer-specific mortality only in patients with organ-confined UTUC treated with RNU. The difference in conclusions is related to the difference in the methodology and its robustness. Referring readers to Table 1 in their paper, Chromecki et al reported that tumor multifocality was significantly associated with lymph node involvement ( p = 0.036), higher tumor stage ( p < 0.001), and higher tumor grade ( p < 0.001) [1]. The data in the table do not support this kind of conclusion; there are only a significant relationships between the status of multifocality and each variable (lymph node status, tumor stage, tumor grade) as a whole. The statistical analysis in Table 1 is based on the chi-square test for independence. The null hypothesis states that the status of multifocality and clinicopathologic characteristics
are independent. The alternative hypothesis is that the status of multifocality and clinicopathologic characteristics are not independent. Thus we would reject the null hypothesis that there is no relationship between the status of multifocality and the clinicopathologic characteristics, but no additional conclusion can be drawn. Support for the alternative hypothesis suggests that the variables are related, but the relationship is not necessarily causal in the sense that one variable causes the other. In Table 1, the authors reported that tumor multifocality was significantly associated with lymph node involvement ( p = 0.036), but one cannot conclude that from a chi-square test for independence. Additionally, the significant relationship between multifocality and lymph node status is probably due to the group labeled no lymph node performed. When comparing lymph node–positive and lymph node–negative, we do not find any association between multifocality and lymph node status. The authors wrote, ‘‘Tumor location was defined as either renal pelvic or ureteral,’’ and, ‘‘Tumor multifocality was defined as the synchronous presence of two or more pathologically confirmed tumors in any location (renal pelvis or ureter).’’ In case of multifocality, how did the authors attribute the primary location of multifocal tumors? Why they did not use location in the renal pelvis, ureter, and both together to verify which (multifocality or multilocation) was the independent prognostic factor? Last, the study population was composed of 2492 patients with UTUC who underwent RNU between 1987 and 2007. The median follow-up was 45 mo (interquartile range: 0–106; range: 0–271). The first quartile is equal to zero, which means that 25% of the population have never been followed-up and should be censored at time 0. This is an important percentage reflecting the missing data problem, mainly when we consider 2007 as last inclusion date. This is contrary to the number of patients at risk at 12 mo, mentioned in Figure 1a and 1b, where we find that <25% of patients were censored at 12 mo follow-up. Conflicts of interest: The author has nothing to disclose.
References [1] Chromecki TF, Cha EK, Fajkovic H, et al. The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy. Eur Urol 2012;61:245–53.
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2011.09.017 0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eururo.2012.06.042
e76
EUROPEAN UROLOGY 62 (2012) e75–e76
[2] Akdogan B, Dogan HS, Eskicorapci SY, Sahin A, Erkan I, Ozen H.
[8] Raman JD, Ng CK, Scherr DS, et al. Impact of tumor location on
Prognostic significance of bladder tumor history and tumor location
prognosis for patients with upper tract urothelial carcinoma man-
in upper tract transitional cell carcinoma. J Urol 2006;176:48–52.
aged by radical nephroureterectomy. Eur Urol 2010;57:1072–9.
[3] Park S, Hong B, Kim CS, Ahn H. The impact of tumor location on
[9] Ouzzane A, Colin P, Xylinas E, et al. Ureteral and multifocal tumours
prognosis of transitional cell carcinoma of the upper urinary tract.
have worse prognosis than renal pelvic tumours in urothelial
J Urol 2004;171:621–5.
carcinoma of the upper urinary tract treated by nephroureterec-
[4] Van der Poel HG, Antonini N, van Tinteren H, et al. Upper urinary tract cancer: location is correlated with prognosis. Eur Urol 2005;48:438–44. [5] Catto JW, Yates DR, Rehman I, et al. Behavior of urothelial carcinoma with respect to anatomical location. J Urol 2007;177: 1715–20. [6] Favaretto RL, Shariat SF, Chade DC, et al. The effect of tumor location
tomy. Eur Urol 2011;60:1258–65. [10] Novara G, De Marco V, Gottardo F, et al. Independent predictors of cancer-specific survival in transitional cell carcinoma of the upper urinary tract: multi-institutional dataset from 3 European centers. Cancer 2007;110:1715–22. Pascal Mouracade* Strasbourg University Hospital, Strasbourg, France
on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center. Eur Urol 2010;58: 574–80. [7] Isbarn H, Jeldres C, Shariat SF, et al. Location of the primary tumor is
*Strasbourg University Hospital, 1 place de l’Hoˆpital, Strasbourg, 67000, France. Tel. +33 614114341. E-mail address: [email protected]
not an independent predictor of cancer specific mortality in patients with upper urinary tract urothelial carcinoma. J Urol 2009;182: 2177–81.
June 19, 2012 Published online on June 28, 2012
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Letter to the Editor Re: Thomas F. Chromecki, Eugene K. Cha, Harun Fajkovic, et al. The Impact of Tumor Multifocality on Outcomes in Patients Treated with Radical Nephroureterectomy. Eur Urol 2012;61;245–53 In this paper, Chromecki et al [1] evaluated the impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy (RNU). The idea of studying the impact of location and multifocality in patients with upper-tract urothelial carcinoma (UTUC) undergoing RNU is old. Several years ago, two studies (with 84 and 72 patients, respectively) suggested that ureteral tumors are associated with a poorer prognosis than renal pelvis tumors [2,3]. However, more recent studies reported conflicting results on the same issue. For example, Van der Poel et al noted in their series of 149 patients that those with distal ureteral tumors had significantly better survival rates than patients with proximal ureteral or renal pelvis tumors [4]. Meanwhile, Catto et al and others reported no prognostic difference with respect to tumor location in patients with UTUC [5–8]. Ouzzane et al [9] compared ureteral, pelvic, and multifocal UTUC tumors in 609 patients and found that ureteral and multifocal tumors had worse prognosis than renal pelvic tumors. Novara et al [10] reported an independent prognostic value for tumor multifocality in 269 patients (organ-confined or not) treated with RNU for UTUC, whereas Chromecki et al [1] concluded that tumor multifocality is an independent prognostic factor of disease progression and cancer-specific mortality only in patients with organ-confined UTUC treated with RNU. The difference in conclusions is related to the difference in the methodology and its robustness. Referring readers to Table 1 in their paper, Chromecki et al reported that tumor multifocality was significantly associated with lymph node involvement ( p = 0.036), higher tumor stage ( p < 0.001), and higher tumor grade ( p < 0.001) [1]. The data in the table do not support this kind of conclusion; there are only a significant relationships between the status of multifocality and each variable (lymph node status, tumor stage, tumor grade) as a whole. The statistical analysis in Table 1 is based on the chi-square test for independence. The null hypothesis states that the status of multifocality and clinicopathologic characteristics
are independent. The alternative hypothesis is that the status of multifocality and clinicopathologic characteristics are not independent. Thus we would reject the null hypothesis that there is no relationship between the status of multifocality and the clinicopathologic characteristics, but no additional conclusion can be drawn. Support for the alternative hypothesis suggests that the variables are related, but the relationship is not necessarily causal in the sense that one variable causes the other. In Table 1, the authors reported that tumor multifocality was significantly associated with lymph node involvement ( p = 0.036), but one cannot conclude that from a chi-square test for independence. Additionally, the significant relationship between multifocality and lymph node status is probably due to the group labeled no lymph node performed. When comparing lymph node–positive and lymph node–negative, we do not find any association between multifocality and lymph node status. The authors wrote, ‘‘Tumor location was defined as either renal pelvic or ureteral,’’ and, ‘‘Tumor multifocality was defined as the synchronous presence of two or more pathologically confirmed tumors in any location (renal pelvis or ureter).’’ In case of multifocality, how did the authors attribute the primary location of multifocal tumors? Why they did not use location in the renal pelvis, ureter, and both together to verify which (multifocality or multilocation) was the independent prognostic factor? Last, the study population was composed of 2492 patients with UTUC who underwent RNU between 1987 and 2007. The median follow-up was 45 mo (interquartile range: 0–106; range: 0–271). The first quartile is equal to zero, which means that 25% of the population have never been followed-up and should be censored at time 0. This is an important percentage reflecting the missing data problem, mainly when we consider 2007 as last inclusion date. This is contrary to the number of patients at risk at 12 mo, mentioned in Figure 1a and 1b, where we find that <25% of patients were censored at 12 mo follow-up. Conflicts of interest: The author has nothing to disclose.
References [1] Chromecki TF, Cha EK, Fajkovic H, et al. The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy. Eur Urol 2012;61:245–53.
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2011.09.017 0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eururo.2012.06.042
e76
EUROPEAN UROLOGY 62 (2012) e75–e76
[2] Akdogan B, Dogan HS, Eskicorapci SY, Sahin A, Erkan I, Ozen H.
[8] Raman JD, Ng CK, Scherr DS, et al. Impact of tumor location on
Prognostic significance of bladder tumor history and tumor location
prognosis for patients with upper tract urothelial carcinoma man-
in upper tract transitional cell carcinoma. J Urol 2006;176:48–52.
aged by radical nephroureterectomy. Eur Urol 2010;57:1072–9.
[3] Park S, Hong B, Kim CS, Ahn H. The impact of tumor location on
[9] Ouzzane A, Colin P, Xylinas E, et al. Ureteral and multifocal tumours
prognosis of transitional cell carcinoma of the upper urinary tract.
have worse prognosis than renal pelvic tumours in urothelial
J Urol 2004;171:621–5.
carcinoma of the upper urinary tract treated by nephroureterec-
[4] Van der Poel HG, Antonini N, van Tinteren H, et al. Upper urinary tract cancer: location is correlated with prognosis. Eur Urol 2005;48:438–44. [5] Catto JW, Yates DR, Rehman I, et al. Behavior of urothelial carcinoma with respect to anatomical location. J Urol 2007;177: 1715–20. [6] Favaretto RL, Shariat SF, Chade DC, et al. The effect of tumor location
tomy. Eur Urol 2011;60:1258–65. [10] Novara G, De Marco V, Gottardo F, et al. Independent predictors of cancer-specific survival in transitional cell carcinoma of the upper urinary tract: multi-institutional dataset from 3 European centers. Cancer 2007;110:1715–22. Pascal Mouracade* Strasbourg University Hospital, Strasbourg, France
on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center. Eur Urol 2010;58: 574–80. [7] Isbarn H, Jeldres C, Shariat SF, et al. Location of the primary tumor is
*Strasbourg University Hospital, 1 place de l’Hoˆpital, Strasbourg, 67000, France. Tel. +33 614114341. E-mail address: [email protected]
not an independent predictor of cancer specific mortality in patients with upper urinary tract urothelial carcinoma. J Urol 2009;182: 2177–81.
June 19, 2012 Published online on June 28, 2012