- Email: [email protected]
Is Repeat Transurethral Resection Needed for Minimally Invasive T1 Urothelial Cancer?
Opposing Views
Is Repeat Transurethral Resection Needed for Minimally Invasive T1 Urothelial Cancer? PRO IS repeat (re-staging) transurethral resection (TUR) necessary for all T1 bladder tumors? The answer is an unequivocal yes. Re-staging TUR is recommended in the American Urological Association and European Association of Urology guidelines for T1 bladder cancer. Can some T1 tumors be cured with initial TUR alone (exception to the rule)? Undoubtedly a single TUR suffices for some low grade T1 tumors (focal invasion of papillary stalk) but for practical purposes, the answer is no. Even small, solitary, papillary tumors exhibiting limited invasion are at risk of incomplete resection. Of 409 T1 tumors 36 (9%) were low grade but a third of the cases had residual tumor on repeat TUR, half recurred within 2 years and 5% (2) progressed to muscle invasion.1 Most T1 tumors are high grade, solid, multiple or mixed with Ta tumors; invade the lamina propria with finger-like roots that extend beyond the margins of visible tumor; and are associated with carcinoma in situ (CIS). Cystoscopy may underestimate the true extent of disease, and in fact, suspected T1 is sometimes the tip of the iceberg of a muscle invasive cancer. TUR is a difficult operation, subject to unquantifiable surgeon, tumor and pathology related variables. Even T1 tumors that appear to invade the lamina propria above the level of the muscularis mucosa can be under staged, and it is dangerous to assume such tumors are minimally invasive based on tumor specimens submitted in pieces subject to errors (ie tangential cuts, retraction defects) on pathological evaluation. To overcome these limitations inherent in the stochastic nature of TUR dictates that all T1 cancers deserve a contemporary repeat TUR. A repeat TUR is a diagnostic, therapeutic, prognostic and predictive procedure. Let’s consider the evidence supporting each of these reasons for repeat resection of T1 bladder cancers. Repeat TUR is diagnostic because it detects disease missed on the initial resection. For example, of 701 suspected T1 cases only 22% had no (T0) tumor on repeat TUR, 23% had Ta/CIS, 25% had persistent 0022-5347/11/1863-0787/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
T1 and 15% to 30% were up staged to muscle invasion with or without muscle present in the first TUR specimen.1 Many studies estimate residual disease on repeat TUR in at least half of the cases of T1 cancer, with tumor at the same site of disease in 44% to 86% and at different locations in 14% to 56%. Incomplete resection is responsible for most early recurrences, providing a compelling argument for repeating the TUR. Also if the same surgeon who performed the initial TUR performs the repeat TUR, residual T1 cancer is still found on repeat TUR in 17% of those cases.2 Repeat TUR is therapeutic because by detecting more disease, it can effectively remove it. A randomized trial revealed longer recurrence and progression-free survival after 2 rather than 1 TURs,3 and a prospective cohort study showed better long-term response to bacillus Calmette-Guérin (BCG) therapy after a second TUR.4 BCG is used to treat diffuse CIS and not T1 tumors and is most effective against minimal residual disease. Repeat TUR is prognostic because outcome is better defined. Of 409 patients with T1 bladder cancer 67% remained disease-free and only 9% had disease progression when no tumor was found or tumor stage was less than T1 on second TUR.1 In contrast, of 106 patients with persistent T1 tumor 78% had disease progression usually within 2 years, despite 1 or more courses of BCG.5 Lastly, repeat TUR is predictive because owing to better staging and local tumor control, it leads to changes in therapy that improve outcomes. A second TUR may reveal stage less than T1, T1 or greater than T1 cancer. A single TUR considers T1 cancer as a single entity, usually treated with a single modality (ie BCG). However, each represents a spectrum of clinical T1 cancer that requires individualized treatment. For example, patients with no tumor or stage less than T1 are ideal candidates for BCG therapy and bladder preservation; those with residual T1 cancer, especially large volume or multiple lesions, are best treated with immediate cystectomy, which improves survival over BCG treatment; and patients with muscle invasion are treated Vol. 186, 787-789, September 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.06.016
www.jurology.com
787
788
OPPOSING VIEWS
with neoadjuvant chemotherapy and cystectomy. A second TUR is mandatory if trimodal therapy is required to preserve the bladder. Individualized and appropriate therapy is best directed by pathological evaluation from a repeat TUR. Why not do the TUR right the first time, making repeat TUR unnecessary? The answer lies in the technical difficulties of the procedure and the nature of bladder tumors. Many factors confound the adequacy of resection, including multiplicity and extent of disease, capability and perseverance of the urologist, quality of specimens provided and pathological analysis. Tumors may be overlooked, especially if they are extensive or involve difficult regions of the bladder, such as the dome, anterior wall or bladder neck. Tumor spread at the margins or invading lamina propria is not always seen at cystoscopy and is usually more extensive than the surface appearance of the tumor suggests. As the TUR proceeds, vision becomes obscured, owing to mucosal edema, bladder
spasms and bleeding, making it increasingly difficult to differentiate benign from tumor bearing mucosa and to achieve negative surgical margins. These uncertainties cannot be eliminated entirely but they can be substantially reduced by a timely second TUR. Repeat TUR of T1 tumors achieves optimal local control by removing residual tumor, improves staging accuracy, provides additional pathological material to allow for more accurate diagnosis, leads to changes in treatment with improved outcomes, facilitates response to intravesical therapy and provides important prognostic information. The benefits outweigh the potential risks to patients of not doing it, justifying a repeat TUR as essential to successful management of T1 cancer. Harry W. Herr Department of Urology Memorial Sloan-Kettering Cancer Center New York, New York
REFERENCES 1. Herr HW and Donat SM: Quality control in transurethral resection of bladder tumors. BJU Int 2008; 102: 1242. 2. Dalbagni G, Herr HW and Reuter VE: Impact of a second transurethral resection on staging T1 bladder cancer. Urology 2002; 60: 822.
3. Divrik RT, Sahin AF, Yildirim U et al: Impact of routine second TUR on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate, and disease-specific survival: a prospective randomized trial. Eur Urol 2010; 58: 185.
CON THE key concept behind the successful treatment of urothelial carcinoma of the bladder which invades the lamina propria (T1 tumor) is complete transurethral resection of all disease and not just visible disease. TUR is followed by adjuvant therapy (most commonly intravesical BCG) with response rates depending on various factors such as tumor grade, presence of concomitant carcinoma in situ, timing of adjuvant therapy and, notably, adequacy of tumor resection.1 Unfortunately, TUR of urothelial cancer as is currently performed is an oncologically imperfect surgery whereby only the visible tumor tissue is removed in pieces, and hundreds of thousands of tumor cells are allowed to float around in the bladder with potential to implant in the resection bed, resulting in early recurrence. It is also well recognized that a suboptimally performed TUR leaves behind residual tumor that can then manifest itself as a treatment failure. Furthermore, incomplete resection of tumor base results in clinical under staging whereby muscle invasive disease (T2) may be wrongly classified as T1 and treated as such, with
4. Herr HW: Re-staging TUR of high risk superficial bladder cancer improves the initial response to BCG therapy. J Urol 2005; 174: 2134. 5. Herr HW, Donat SM and Dalbagni G: Can restaging TUR of T1 bladder cancer select patients for immediate cystectomy? J Urol 2007; 177: 75.
potential disastrous consequence for the patient. It is in order to address these shortcomings, namely to compensate for inadequacy of TUR as a cancer surgery, that the concept of repeat TUR after initial TUR has grown in popularity.2 Unfortunately, this strategy of re-resection must be considered a failure on our part to refine our technique. It is in essence an admission that our initial resection of the bladder tumor is imperfect and that we must rely on repeat TUR to complete the job. An analogy would be to perform a partial nephrectomy without striving to achieve a negative margin and return for a planned re-resection to correct the error. In fact, in a recent presentation of the International Consultation of Urological DiseaseEuropean Association of Urology guidelines on bladder cancer the technique of TUR was discussed with a lament that “at present, there is insufficient information to support recommendation of a specific technique for TUR.”3 It was stated that during “routine TUR, bladder perforation should be avoided” and due to inadequacies of TUR, “a second TURBT should be performed in all patients with a highgrade Ta lesion or any T1 lesion.” It was also discussed that the technique of TUR needs to be refined
Is Repeat Transurethral Resection Needed for Minimally Invasive T1 Urothelial Cancer? PRO IS repeat (re-staging) transurethral resection (TUR) necessary for all T1 bladder tumors? The answer is an unequivocal yes. Re-staging TUR is recommended in the American Urological Association and European Association of Urology guidelines for T1 bladder cancer. Can some T1 tumors be cured with initial TUR alone (exception to the rule)? Undoubtedly a single TUR suffices for some low grade T1 tumors (focal invasion of papillary stalk) but for practical purposes, the answer is no. Even small, solitary, papillary tumors exhibiting limited invasion are at risk of incomplete resection. Of 409 T1 tumors 36 (9%) were low grade but a third of the cases had residual tumor on repeat TUR, half recurred within 2 years and 5% (2) progressed to muscle invasion.1 Most T1 tumors are high grade, solid, multiple or mixed with Ta tumors; invade the lamina propria with finger-like roots that extend beyond the margins of visible tumor; and are associated with carcinoma in situ (CIS). Cystoscopy may underestimate the true extent of disease, and in fact, suspected T1 is sometimes the tip of the iceberg of a muscle invasive cancer. TUR is a difficult operation, subject to unquantifiable surgeon, tumor and pathology related variables. Even T1 tumors that appear to invade the lamina propria above the level of the muscularis mucosa can be under staged, and it is dangerous to assume such tumors are minimally invasive based on tumor specimens submitted in pieces subject to errors (ie tangential cuts, retraction defects) on pathological evaluation. To overcome these limitations inherent in the stochastic nature of TUR dictates that all T1 cancers deserve a contemporary repeat TUR. A repeat TUR is a diagnostic, therapeutic, prognostic and predictive procedure. Let’s consider the evidence supporting each of these reasons for repeat resection of T1 bladder cancers. Repeat TUR is diagnostic because it detects disease missed on the initial resection. For example, of 701 suspected T1 cases only 22% had no (T0) tumor on repeat TUR, 23% had Ta/CIS, 25% had persistent 0022-5347/11/1863-0787/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
T1 and 15% to 30% were up staged to muscle invasion with or without muscle present in the first TUR specimen.1 Many studies estimate residual disease on repeat TUR in at least half of the cases of T1 cancer, with tumor at the same site of disease in 44% to 86% and at different locations in 14% to 56%. Incomplete resection is responsible for most early recurrences, providing a compelling argument for repeating the TUR. Also if the same surgeon who performed the initial TUR performs the repeat TUR, residual T1 cancer is still found on repeat TUR in 17% of those cases.2 Repeat TUR is therapeutic because by detecting more disease, it can effectively remove it. A randomized trial revealed longer recurrence and progression-free survival after 2 rather than 1 TURs,3 and a prospective cohort study showed better long-term response to bacillus Calmette-Guérin (BCG) therapy after a second TUR.4 BCG is used to treat diffuse CIS and not T1 tumors and is most effective against minimal residual disease. Repeat TUR is prognostic because outcome is better defined. Of 409 patients with T1 bladder cancer 67% remained disease-free and only 9% had disease progression when no tumor was found or tumor stage was less than T1 on second TUR.1 In contrast, of 106 patients with persistent T1 tumor 78% had disease progression usually within 2 years, despite 1 or more courses of BCG.5 Lastly, repeat TUR is predictive because owing to better staging and local tumor control, it leads to changes in therapy that improve outcomes. A second TUR may reveal stage less than T1, T1 or greater than T1 cancer. A single TUR considers T1 cancer as a single entity, usually treated with a single modality (ie BCG). However, each represents a spectrum of clinical T1 cancer that requires individualized treatment. For example, patients with no tumor or stage less than T1 are ideal candidates for BCG therapy and bladder preservation; those with residual T1 cancer, especially large volume or multiple lesions, are best treated with immediate cystectomy, which improves survival over BCG treatment; and patients with muscle invasion are treated Vol. 186, 787-789, September 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.06.016
www.jurology.com
787
788
OPPOSING VIEWS
with neoadjuvant chemotherapy and cystectomy. A second TUR is mandatory if trimodal therapy is required to preserve the bladder. Individualized and appropriate therapy is best directed by pathological evaluation from a repeat TUR. Why not do the TUR right the first time, making repeat TUR unnecessary? The answer lies in the technical difficulties of the procedure and the nature of bladder tumors. Many factors confound the adequacy of resection, including multiplicity and extent of disease, capability and perseverance of the urologist, quality of specimens provided and pathological analysis. Tumors may be overlooked, especially if they are extensive or involve difficult regions of the bladder, such as the dome, anterior wall or bladder neck. Tumor spread at the margins or invading lamina propria is not always seen at cystoscopy and is usually more extensive than the surface appearance of the tumor suggests. As the TUR proceeds, vision becomes obscured, owing to mucosal edema, bladder
spasms and bleeding, making it increasingly difficult to differentiate benign from tumor bearing mucosa and to achieve negative surgical margins. These uncertainties cannot be eliminated entirely but they can be substantially reduced by a timely second TUR. Repeat TUR of T1 tumors achieves optimal local control by removing residual tumor, improves staging accuracy, provides additional pathological material to allow for more accurate diagnosis, leads to changes in treatment with improved outcomes, facilitates response to intravesical therapy and provides important prognostic information. The benefits outweigh the potential risks to patients of not doing it, justifying a repeat TUR as essential to successful management of T1 cancer. Harry W. Herr Department of Urology Memorial Sloan-Kettering Cancer Center New York, New York
REFERENCES 1. Herr HW and Donat SM: Quality control in transurethral resection of bladder tumors. BJU Int 2008; 102: 1242. 2. Dalbagni G, Herr HW and Reuter VE: Impact of a second transurethral resection on staging T1 bladder cancer. Urology 2002; 60: 822.
3. Divrik RT, Sahin AF, Yildirim U et al: Impact of routine second TUR on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate, and disease-specific survival: a prospective randomized trial. Eur Urol 2010; 58: 185.
CON THE key concept behind the successful treatment of urothelial carcinoma of the bladder which invades the lamina propria (T1 tumor) is complete transurethral resection of all disease and not just visible disease. TUR is followed by adjuvant therapy (most commonly intravesical BCG) with response rates depending on various factors such as tumor grade, presence of concomitant carcinoma in situ, timing of adjuvant therapy and, notably, adequacy of tumor resection.1 Unfortunately, TUR of urothelial cancer as is currently performed is an oncologically imperfect surgery whereby only the visible tumor tissue is removed in pieces, and hundreds of thousands of tumor cells are allowed to float around in the bladder with potential to implant in the resection bed, resulting in early recurrence. It is also well recognized that a suboptimally performed TUR leaves behind residual tumor that can then manifest itself as a treatment failure. Furthermore, incomplete resection of tumor base results in clinical under staging whereby muscle invasive disease (T2) may be wrongly classified as T1 and treated as such, with
4. Herr HW: Re-staging TUR of high risk superficial bladder cancer improves the initial response to BCG therapy. J Urol 2005; 174: 2134. 5. Herr HW, Donat SM and Dalbagni G: Can restaging TUR of T1 bladder cancer select patients for immediate cystectomy? J Urol 2007; 177: 75.
potential disastrous consequence for the patient. It is in order to address these shortcomings, namely to compensate for inadequacy of TUR as a cancer surgery, that the concept of repeat TUR after initial TUR has grown in popularity.2 Unfortunately, this strategy of re-resection must be considered a failure on our part to refine our technique. It is in essence an admission that our initial resection of the bladder tumor is imperfect and that we must rely on repeat TUR to complete the job. An analogy would be to perform a partial nephrectomy without striving to achieve a negative margin and return for a planned re-resection to correct the error. In fact, in a recent presentation of the International Consultation of Urological DiseaseEuropean Association of Urology guidelines on bladder cancer the technique of TUR was discussed with a lament that “at present, there is insufficient information to support recommendation of a specific technique for TUR.”3 It was stated that during “routine TUR, bladder perforation should be avoided” and due to inadequacies of TUR, “a second TURBT should be performed in all patients with a highgrade Ta lesion or any T1 lesion.” It was also discussed that the technique of TUR needs to be refined