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Lymphovascular Invasion in High Grade T1 Bladder Cancer: Are More Aggressive Treatments Needed?
Letter to the Editor
Lymphovascular Invasion in High Grade T1 Bladder Cancer: Are More Aggressive Treatments Needed? Marco Borghesi, Eugenio Brunocilla, Riccardo Schiavina, Giuseppe Martorana Clinical Genitourinary Cancer, Vol. 12, No. 2, e59-60 ª 2014 Elsevier Inc. All rights reserved.
We want to congratulate Brancherau et al1 on their article “Prognostic Value of the Lymphovascular Invasion in High-Stage pT1 Bladder Cancer” in which they contribute to the understanding of the role of lymphovascular invasion (LVI) in transurethral resection of the bladder (TURB) specimens as a significant prognostic factor for overall survival (OS) in patients with high-risk nonemuscle invasive (stage pT1) bladder cancer.1 LVI, defined as the presence of tumor cells within an endothelium-lined space in standard hematoxylin and eosinestained sections, is a critical and significant step in the systemic spread of cancer cells. Several studies have demonstrated the role of LVI as an independent predictor of oncologic outcomes (OS and disease-specific survival)2-4 and recurrence5 in patients who underwent radical cystectomy and pelvic lymph node dissection for bladder cancer; this finding has been widely demonstrated in patients with lymph node metastases and, interestingly, also in those who were found to have nodenegative disease at final pathologic examination. However, despite this evidence, LVI is not yet part of the TNM staging system and is not taken into consideration in the guidelines for bladder cancer. In their retrospective study, the authors evaluated a cohort of 108 patients with high-grade nonemuscle invasive (stage pT1) bladder cancer; of these patients, 89 (82.4%) were conservatively managed with TURB plus bacillus Calmette-Guérin (BCG) therapy, and 19 (17.6%) underwent early cystectomy. Eleven of the 89 patients had delayed cystectomy after bacillus Calmette-Guérin therapy failed. Lymphovascular invasion was demonstrated on the first bladder resection specimen in 36% of cases. At multivariate analysis, LVI was found to be the only statistically significant parameter able to influence the oncologic outcomes of the general population (P ¼ .003). This result is comparable to those in other similar studies.6,7 Interestingly, the presence of LVI significantly correlated with the presence of lymph node metastases on the cystectomy specimens in both early and delayed settings; furthermore, on univariate analysis, the presence of LVI on the first TURB specimen Department of Urology, Azienda Ospedaliero-Universitaria Policlinico S.Orsola-Malpighi, Bologna, Italy Submitted: Jan 30, 2013; Accepted: Mar 3, 2013; Epub: Nov 13, 2013
1558-7673/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2013.03.002
proved to be a poor prognostic factor in the delayed cystectomy group (P ¼ .01) but not in the early cystectomy group. We believe that these results confirm that LVI is a feature of biologically and clinically aggressive urothelial bladder cancer and is therefore independently associated with poor clinical outcomes after radical cystectomy. Consequently, several concerns regarding the clinical and surgical approach to high-grade pT1 bladder cancer should be taken into consideration. LVI can be regarded as a surrogate marker for the presence of micrometastases in the lymph nodes at the time of surgical treatment, and this could explain the differences in terms of survival outcomes in patients who undergo early cystectomy and pelvic lymph node dissection when compared with those who are treated with delayed cystectomy and pelvic lymph node dissection. We strongly believe that a higher prevalence of micrometastatic nodal disease could be observed in patients with LVI at the time of TURB, thus justifying the differences in terms of cancer-specific survival and OS in node-negative disease as well. Based on this critical statement as well as several previous clinical studies2,8,9 and the results of Brancherau et al’s study,1 should urologists perform a more extended pelvic lymph node dissection in patients with specimens that are positive for LVI and who are scheduled to undergo delayed radical cystectomy after conservative management failure? Should we offer a neoadjuvant treatment for stage pT1 LVIpositive, high-grade bladder cancer? As a criterion of severity, LVI might be used to identify high-risk patients who could benefit from “targeted” medical and surgical procedures.
References 1. Brancherau J, Larue S, Vayleux B, et al. Prognostic value of the lymphovascular invasion in high-grade stage pT1 bladder cancer. Clin Genitourin Cancer 2013; 11: 182-8. 2. Brunocilla E, Pernetti R, Martorana G. The role of pelvic lymph node dissection during radical cystectomy for bladder cancer. Anticancer Res 2011; 31:271-5. 3. Brunocilla E, Pernetti R, Martorana G. The prognostic role of lymphovascular invasion in urothelial-cell carcinoma of upper and lower urinary tract. Anticancer Res 2011; 31:3503-6. 4. Bolenz C, Herrmann E, Bastian PJ, et al. Lymphovascular invasion is an independent predictor of oncological outcomes in patients with lymph node-negative urothelial bladder cancer treated by radical cystectomy: a multicentre validation trial. BJU Int 2010; 106:493-9. 5. Tilki D, Shariat SF, Lotan Y, et al. Lymphovascular invasion is independently associated with bladder cancer recurrence and survival in patients with final stage T1 disease and negative lymph nodes after radical cystectomy. BJU Int 2013; 111:1215-21.
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Letter to the Editor 6. Streeper NM, Simons CM, Konety BR, et al. The significance of lymphovascular invasion in transurethral resection of bladder tumour and cystectomy specimens on the survival of patients with urothelial bladder cancer. BJU Int 2009; 103:475-9. 7. Kunju LP, You L, Zhang Y, et al. Lymphovascular invasion of urothelial cancer in matched transurethral bladder tumor resection and radical cystectomy specimens. J Urol 2008; 180:1928-32.
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8. Karl A, Carroll PR, Gschwend JE, et al. The impact of lymphadenectomy and lymph node metastasis on the outcomes of radical cystectomy for bladder cancer. Eur Urol 2009; 55:826-35. 9. Leissner J, Ghoneim MA, Abol-Enein H, et al. Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. J Urol 2004; 171:139-44.
Lymphovascular Invasion in High Grade T1 Bladder Cancer: Are More Aggressive Treatments Needed? Marco Borghesi, Eugenio Brunocilla, Riccardo Schiavina, Giuseppe Martorana Clinical Genitourinary Cancer, Vol. 12, No. 2, e59-60 ª 2014 Elsevier Inc. All rights reserved.
We want to congratulate Brancherau et al1 on their article “Prognostic Value of the Lymphovascular Invasion in High-Stage pT1 Bladder Cancer” in which they contribute to the understanding of the role of lymphovascular invasion (LVI) in transurethral resection of the bladder (TURB) specimens as a significant prognostic factor for overall survival (OS) in patients with high-risk nonemuscle invasive (stage pT1) bladder cancer.1 LVI, defined as the presence of tumor cells within an endothelium-lined space in standard hematoxylin and eosinestained sections, is a critical and significant step in the systemic spread of cancer cells. Several studies have demonstrated the role of LVI as an independent predictor of oncologic outcomes (OS and disease-specific survival)2-4 and recurrence5 in patients who underwent radical cystectomy and pelvic lymph node dissection for bladder cancer; this finding has been widely demonstrated in patients with lymph node metastases and, interestingly, also in those who were found to have nodenegative disease at final pathologic examination. However, despite this evidence, LVI is not yet part of the TNM staging system and is not taken into consideration in the guidelines for bladder cancer. In their retrospective study, the authors evaluated a cohort of 108 patients with high-grade nonemuscle invasive (stage pT1) bladder cancer; of these patients, 89 (82.4%) were conservatively managed with TURB plus bacillus Calmette-Guérin (BCG) therapy, and 19 (17.6%) underwent early cystectomy. Eleven of the 89 patients had delayed cystectomy after bacillus Calmette-Guérin therapy failed. Lymphovascular invasion was demonstrated on the first bladder resection specimen in 36% of cases. At multivariate analysis, LVI was found to be the only statistically significant parameter able to influence the oncologic outcomes of the general population (P ¼ .003). This result is comparable to those in other similar studies.6,7 Interestingly, the presence of LVI significantly correlated with the presence of lymph node metastases on the cystectomy specimens in both early and delayed settings; furthermore, on univariate analysis, the presence of LVI on the first TURB specimen Department of Urology, Azienda Ospedaliero-Universitaria Policlinico S.Orsola-Malpighi, Bologna, Italy Submitted: Jan 30, 2013; Accepted: Mar 3, 2013; Epub: Nov 13, 2013
1558-7673/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2013.03.002
proved to be a poor prognostic factor in the delayed cystectomy group (P ¼ .01) but not in the early cystectomy group. We believe that these results confirm that LVI is a feature of biologically and clinically aggressive urothelial bladder cancer and is therefore independently associated with poor clinical outcomes after radical cystectomy. Consequently, several concerns regarding the clinical and surgical approach to high-grade pT1 bladder cancer should be taken into consideration. LVI can be regarded as a surrogate marker for the presence of micrometastases in the lymph nodes at the time of surgical treatment, and this could explain the differences in terms of survival outcomes in patients who undergo early cystectomy and pelvic lymph node dissection when compared with those who are treated with delayed cystectomy and pelvic lymph node dissection. We strongly believe that a higher prevalence of micrometastatic nodal disease could be observed in patients with LVI at the time of TURB, thus justifying the differences in terms of cancer-specific survival and OS in node-negative disease as well. Based on this critical statement as well as several previous clinical studies2,8,9 and the results of Brancherau et al’s study,1 should urologists perform a more extended pelvic lymph node dissection in patients with specimens that are positive for LVI and who are scheduled to undergo delayed radical cystectomy after conservative management failure? Should we offer a neoadjuvant treatment for stage pT1 LVIpositive, high-grade bladder cancer? As a criterion of severity, LVI might be used to identify high-risk patients who could benefit from “targeted” medical and surgical procedures.
References 1. Brancherau J, Larue S, Vayleux B, et al. Prognostic value of the lymphovascular invasion in high-grade stage pT1 bladder cancer. Clin Genitourin Cancer 2013; 11: 182-8. 2. Brunocilla E, Pernetti R, Martorana G. The role of pelvic lymph node dissection during radical cystectomy for bladder cancer. Anticancer Res 2011; 31:271-5. 3. Brunocilla E, Pernetti R, Martorana G. The prognostic role of lymphovascular invasion in urothelial-cell carcinoma of upper and lower urinary tract. Anticancer Res 2011; 31:3503-6. 4. Bolenz C, Herrmann E, Bastian PJ, et al. Lymphovascular invasion is an independent predictor of oncological outcomes in patients with lymph node-negative urothelial bladder cancer treated by radical cystectomy: a multicentre validation trial. BJU Int 2010; 106:493-9. 5. Tilki D, Shariat SF, Lotan Y, et al. Lymphovascular invasion is independently associated with bladder cancer recurrence and survival in patients with final stage T1 disease and negative lymph nodes after radical cystectomy. BJU Int 2013; 111:1215-21.
Clinical Genitourinary Cancer April 2014
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Letter to the Editor 6. Streeper NM, Simons CM, Konety BR, et al. The significance of lymphovascular invasion in transurethral resection of bladder tumour and cystectomy specimens on the survival of patients with urothelial bladder cancer. BJU Int 2009; 103:475-9. 7. Kunju LP, You L, Zhang Y, et al. Lymphovascular invasion of urothelial cancer in matched transurethral bladder tumor resection and radical cystectomy specimens. J Urol 2008; 180:1928-32.
e60
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Clinical Genitourinary Cancer April 2014
8. Karl A, Carroll PR, Gschwend JE, et al. The impact of lymphadenectomy and lymph node metastasis on the outcomes of radical cystectomy for bladder cancer. Eur Urol 2009; 55:826-35. 9. Leissner J, Ghoneim MA, Abol-Enein H, et al. Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. J Urol 2004; 171:139-44.