DOI: 10.1089/end.2015.1507 CROES COUNCIL Chairman Jean de la Rosette, M.D. Amsterdam (The Netherlands) Adrian Joyce, M.S. Leeds (UK)
JOIN THE PREMIER RESEARCH OFFICE IN THE FIELD OF ENDOUROLOGY
Stavros Gravas, M.D. Larissa (Greece) Jorge Gutierrez-Aceves, M.D. Winston Salem (USA) Dean Assimos, M.D. Birmingham (USA) Ying-Hao Sun, M.D. Shanghai (China) Tadashi Matsuda, M.D. Osaka ( Japan)
Take part in publications and presentations that offer exposure to your institution Become a member of the global research network of Endourologists Be recognized as a centre of excellence in the field of Endourology
TREASURER John Denstedt, M.D. London (Canada)
EXECUTIVE DIRECTOR Sonja van Rees Vellinga Amsterdam (The Netherlands) [email protected]
259
CURRENT DIAGNOSTICS AND FOLLOW-UP FOR NONMUSCLE-INVASIVE BLADDER CANCER: ARE WE ‘‘AS GOOD AS IT GETS’’? Carl-Jørgen Arum and Jean de la Rosette Every article ever written about nonmuscle-invasive bladder cancer (NMIBC)—i.e., carcinoma in situ (CIS), Ta, and T1—cites recurrence rates of 15% to 61% (http://www.eortc.be/tools/bladdercalculator/) within a few years and progression rates of 10% to 54%.1 As physicians responsible for treating this patient group, we should certainly not be satisfied with such ‘‘bad’’ rates. The bases for these variable results are: 1. 2. 3. 4. 5.
Nature of the disease Accuracy of histopathologic classification Individual visual acuity Individual intraoperative responses based on the information perceived Sensitivity of our instruments
The nature of NMIBC and its multifocality is explained by two nonmutually exclusive theories.2 The field cancerization effect theory3 asserts that the urothelium in patients with NMIBC may be unstable because of genetic hits and progressive outgrowth of genetically unstable cells throughout the entire urothelium. The clonal expansion theory suggests that multifocal tumors (both synchronous and metachronous) are the result of intraluminal spread from a single transformed cell, namely seeding.4 NMIBC should, therefore, not just be considered a tumor or even multiple tumors but rather a disease of the entire urothelium with varying propensity to generate malignancies. Optimal diagnosis, treatment, and follow-up of NMIBC are highly dependent on staging and grading the tumor. Unfortunately, the reproducibility of both staging and grading is low and needs improvement for optimal treatment and follow-up.5 In spite of well-defined criteria for the diagnosis of CIS, there remains significant variability among pathologists, for which agreement is achieved in only 70% to 78% of cases.6 In regard to stage classification, there is also a significant interobserver variability in both the 1973 and the 2004 classifications.7 Considering that the general conformity of histopathologic grading and staging is between 50% and 60%1 suggests that our current ability to classify, diagnose, and thereby facilitate correct management decisions is less than ‘‘optimal.’’ Endoscopy is dependent on visual acuity, a subject not often addressed in urologic literature. The prevalence of visual impairment in US adults (National Health Interview Survey, 2002) is for those aged 45 to 54 years: 11.5% (confidence interval [CI ]10.5–12.5); 55 to 64: 10.4% (CI 9.3–11.4); 65 to 74: 14.5% (CI 13.0–16.0); 75: 21.1% (19.4–22.8).8–10 Should we not only personalize our glasses but also consider what individual adjustments can be done with current endoscopic technologies? White light (WL) cystoscopy is still the gold standard for visualizing and establishing a diagnosis of bladder cancer. This is supported by the 100% sensitivity and 100% specificity of WL evaluation in discriminating between dysplastic/malignant and benign/reactive lesions by an experienced urolo260
gist.11 In spite of these findings, when second-look transurethral resection of the bladder (TUR-b) is performed for T1 disease, residual tumor rates of 43% to 62% are noted,12–14 suggesting that WL sensitivity is not optimal. CIS may also be overlooked in up to 50% of lesions, leading to inadequate treatment and follow-up.15 Individual intraoperative responses based on the information perceived is dependent on the experience and skills of the urologist performing the TUR-b.16,17 Complete TUR-b is essential to obtain diagnostic accuracy and to reduce recurrence as well as disease progression. Optimal TUR-b should also be augmented with prompt ‘‘single-shot’’ intravesical chemotherapy and in high-risk disease, immunotherapy, as indicated by guidelines (http://www.uroweb.org/gls/pdf/05%20Non-muscle% 20Invasive%20BC_TaT1_LR.pdf).1 To address the limits of WL cystoscopy, several new technologies have been or are being developed:
Photodynamic diagnosis (fluorescence cystoscopy) (PDD) Narrow-band imaging (NBI) STORZ professional image enhancement system (SPIES) Emerging technologies (optical coherence tomography, confocal laser endomicroscopy, and Raman spectroscopy)
All of the above mentioned new technologies, including new resection techniques, contribute to more complete TUR-b.18 According to European Association of Urology (EAU) guidelines (2014), PDD is now recommended in patients who are suspected of harboring a high-grade tumor—e.g., for biopsy guidance in patients with positive cytology results or with a history of high-grade tumor.1 In the EAU 2014 update, it is noted that NBI-guided biopsies and resection have demonstrated improved cancer detection. In a study by Geavlete and associates,19 it was noted that using NBI cystoscopy significantly improved diagnostic accuracy and decreased 1-year recurrence rates. Recently STORZ has developed an endoscopic image enhancement system (SPIES) that potentially will improve TUR-b results. All of the above mentioned confounding factors contribute to the variability in reoccurrence rates and progression for NMIBC. This variability makes studying the effects of new endoscopic technologies difficult and necessitates either very restrictive patient selection or very large randomized trials to provide convincing evidence of the increased efficacy of new technologies. A multicenter international randomized study will be conducted by the Clinical Research Office of the Endourological Society (CROES) comparing WL with SPIES. Close to 2000 patients will be included, aiming at addressing many questions on the added value of imaging enhanced endoscopy. Moreover, this technology can be used to evaluate upper tract urinary urothelial cell (UTUUC) tumors. CROES is therefore pleased that the STORZ company also supports a registry to study the indications in treatment and outcomes for UTUUC tumors. The sites that have access to ureteroscopes that are enabled with SPIES will thus also evaluate the added value of SPIES in those patients. The oncoming SPIES projects will enable us to provide the best possible care for our patients. This is made possible through a partnership with STORZ and illustrates the importance of these collaborations. In addition, this opens the doors for every urologist involved in the management of UTUUC tumors to contribute through CROES to new insights and knowledge of this condition. References
1. Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: Update 2013. Eur Urol 2013;64:639–653. 2. Kakizoe T. Development and progression of urothelial carcinoma. Cancer Sci 2006;97:821–828. 3. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium. Clinical implications of multicentric origin. Cancer 1953;6:963–968. 4. Sidransky D, Frost P, Von Eschenbach A, et al. Clonal origin bladder cancer. N Engl J Med 1992;326:737–740. 5. Mangrud OM, Waalen R, Gudlaugsson E, et al. Reproducibility and prognostic value of WHO1973 and WHO2004 grading systems in TaT1 urothelial carcinoma of the urinary bladder. PloS One. 2014;9:e83192. 6. Witjes JA, Moonen PM, van der Heijden AG. Review pathology in a diagnostic bladder cancer trial: Effect of patient risk category. Urology 2006;67:751–755. 7. May M, Brookman-Amissah S, Roigas J, et al. Prognostic accuracy of individual uropathologists in noninvasive urinary bladder carcinoma: A multicentre study comparing the 1973 and 2004 World Health Organisation classifications. Eur Urol 2010;57:850–858. 261
8. Klein R, Klein BE. The prevalence of age-related eye diseases and visual impairment in aging: Current estimates. Invest Ophthalmol Vis Sci 2013;54:ORSF5-ORSF13. 9. Owsley C. Aging and vision. Vision Res 2011;51:1610–1622. 10. Sjostrand J, Laatikainen L, Hirvela H, et al. The decline in visual acuity in elderly people with healthy eyes or eyes with early age-related maculopathy in two Scandinavian population samples. Acta Ophthalmol 2011;89:116–123. 11. Cina SJ, Epstein JI, Endrizzi JM, et al. Correlation of cystoscopic impression with histologic diagnosis of biopsy specimens of the bladder. Hum Patholo 2001;32:630–637. 12. Dobruch J, Borowka A, Herr HW. Clinical value of transurethral second resection of bladder tumor: Systematic review. Urology 2014;84:881–885. 13. Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999;162:74–76. 14. Mariappan P, Finney SM, Head E, et al. Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new nonmuscle-invasive bladder cancer: Validation across time and place and recommendation for benchmarking. BJU Int 2012;109:1666–1673. 15. Rink M, Babjuk M, Catto JW, et al. Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: A critical review of the current literature. Eur Urol 2013;64:624–638. 16. Yeo L, Jain S. Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: Validation across time and place and recommendation for benchmarking. BJU Int 2012;109:E27. 17. Brausi M, Collette L, Kurth K, et al. Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: A combined analysis of seven EORTC studies. Eur Urol 2002;41:523–531. 18. Lerner SP, Goh A. Novel endoscopic diagnosis for bladder cancer. Cancer 201;121:169–178. 19. Geavlete B, Multescu R, Georgescu D, et al. Narrow band imaging cystoscopy and bipolar plasma vaporization for large nonmuscle-invasive bladder tumors—results of a prospective, randomized comparison to the standard approach. Urology 2012;79:846–851.
The Global Ureteroscopy Study, Global GreenLightÔ Laser Study, and the Global Renal Mass Study were closed in 2012. The first five articles on ureteroscopy and the first one on the Renal Mass Study have been published. The first two articles of the GreenLightÔ Laser Study are under review. The randomized study on Narrow Band Imaging vs White Light Imaging closed in 2013. The first results are being analyzed. Ongoing project: The Irreversible Electroporation Study for Focal Therapy, including a pilot study, a randomized controlled trial, and a registry. New project: The randomized study on SPIES vs White Light Imaging. New project: The Global Upper Tract-Transitional-Cell Carcinoma Study. For further information, please visit: www.croesoffice.org or contact the Executive Director of CROES, Mrs. Sonja van Rees Vellinga ([email protected]).
262
Copyright of Journal of Endourology is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
JOIN THE PREMIER RESEARCH OFFICE IN THE FIELD OF ENDOUROLOGY
Stavros Gravas, M.D. Larissa (Greece) Jorge Gutierrez-Aceves, M.D. Winston Salem (USA) Dean Assimos, M.D. Birmingham (USA) Ying-Hao Sun, M.D. Shanghai (China) Tadashi Matsuda, M.D. Osaka ( Japan)
Take part in publications and presentations that offer exposure to your institution Become a member of the global research network of Endourologists Be recognized as a centre of excellence in the field of Endourology
TREASURER John Denstedt, M.D. London (Canada)
EXECUTIVE DIRECTOR Sonja van Rees Vellinga Amsterdam (The Netherlands) [email protected]
259
CURRENT DIAGNOSTICS AND FOLLOW-UP FOR NONMUSCLE-INVASIVE BLADDER CANCER: ARE WE ‘‘AS GOOD AS IT GETS’’? Carl-Jørgen Arum and Jean de la Rosette Every article ever written about nonmuscle-invasive bladder cancer (NMIBC)—i.e., carcinoma in situ (CIS), Ta, and T1—cites recurrence rates of 15% to 61% (http://www.eortc.be/tools/bladdercalculator/) within a few years and progression rates of 10% to 54%.1 As physicians responsible for treating this patient group, we should certainly not be satisfied with such ‘‘bad’’ rates. The bases for these variable results are: 1. 2. 3. 4. 5.
Nature of the disease Accuracy of histopathologic classification Individual visual acuity Individual intraoperative responses based on the information perceived Sensitivity of our instruments
The nature of NMIBC and its multifocality is explained by two nonmutually exclusive theories.2 The field cancerization effect theory3 asserts that the urothelium in patients with NMIBC may be unstable because of genetic hits and progressive outgrowth of genetically unstable cells throughout the entire urothelium. The clonal expansion theory suggests that multifocal tumors (both synchronous and metachronous) are the result of intraluminal spread from a single transformed cell, namely seeding.4 NMIBC should, therefore, not just be considered a tumor or even multiple tumors but rather a disease of the entire urothelium with varying propensity to generate malignancies. Optimal diagnosis, treatment, and follow-up of NMIBC are highly dependent on staging and grading the tumor. Unfortunately, the reproducibility of both staging and grading is low and needs improvement for optimal treatment and follow-up.5 In spite of well-defined criteria for the diagnosis of CIS, there remains significant variability among pathologists, for which agreement is achieved in only 70% to 78% of cases.6 In regard to stage classification, there is also a significant interobserver variability in both the 1973 and the 2004 classifications.7 Considering that the general conformity of histopathologic grading and staging is between 50% and 60%1 suggests that our current ability to classify, diagnose, and thereby facilitate correct management decisions is less than ‘‘optimal.’’ Endoscopy is dependent on visual acuity, a subject not often addressed in urologic literature. The prevalence of visual impairment in US adults (National Health Interview Survey, 2002) is for those aged 45 to 54 years: 11.5% (confidence interval [CI ]10.5–12.5); 55 to 64: 10.4% (CI 9.3–11.4); 65 to 74: 14.5% (CI 13.0–16.0); 75: 21.1% (19.4–22.8).8–10 Should we not only personalize our glasses but also consider what individual adjustments can be done with current endoscopic technologies? White light (WL) cystoscopy is still the gold standard for visualizing and establishing a diagnosis of bladder cancer. This is supported by the 100% sensitivity and 100% specificity of WL evaluation in discriminating between dysplastic/malignant and benign/reactive lesions by an experienced urolo260
gist.11 In spite of these findings, when second-look transurethral resection of the bladder (TUR-b) is performed for T1 disease, residual tumor rates of 43% to 62% are noted,12–14 suggesting that WL sensitivity is not optimal. CIS may also be overlooked in up to 50% of lesions, leading to inadequate treatment and follow-up.15 Individual intraoperative responses based on the information perceived is dependent on the experience and skills of the urologist performing the TUR-b.16,17 Complete TUR-b is essential to obtain diagnostic accuracy and to reduce recurrence as well as disease progression. Optimal TUR-b should also be augmented with prompt ‘‘single-shot’’ intravesical chemotherapy and in high-risk disease, immunotherapy, as indicated by guidelines (http://www.uroweb.org/gls/pdf/05%20Non-muscle% 20Invasive%20BC_TaT1_LR.pdf).1 To address the limits of WL cystoscopy, several new technologies have been or are being developed:
Photodynamic diagnosis (fluorescence cystoscopy) (PDD) Narrow-band imaging (NBI) STORZ professional image enhancement system (SPIES) Emerging technologies (optical coherence tomography, confocal laser endomicroscopy, and Raman spectroscopy)
All of the above mentioned new technologies, including new resection techniques, contribute to more complete TUR-b.18 According to European Association of Urology (EAU) guidelines (2014), PDD is now recommended in patients who are suspected of harboring a high-grade tumor—e.g., for biopsy guidance in patients with positive cytology results or with a history of high-grade tumor.1 In the EAU 2014 update, it is noted that NBI-guided biopsies and resection have demonstrated improved cancer detection. In a study by Geavlete and associates,19 it was noted that using NBI cystoscopy significantly improved diagnostic accuracy and decreased 1-year recurrence rates. Recently STORZ has developed an endoscopic image enhancement system (SPIES) that potentially will improve TUR-b results. All of the above mentioned confounding factors contribute to the variability in reoccurrence rates and progression for NMIBC. This variability makes studying the effects of new endoscopic technologies difficult and necessitates either very restrictive patient selection or very large randomized trials to provide convincing evidence of the increased efficacy of new technologies. A multicenter international randomized study will be conducted by the Clinical Research Office of the Endourological Society (CROES) comparing WL with SPIES. Close to 2000 patients will be included, aiming at addressing many questions on the added value of imaging enhanced endoscopy. Moreover, this technology can be used to evaluate upper tract urinary urothelial cell (UTUUC) tumors. CROES is therefore pleased that the STORZ company also supports a registry to study the indications in treatment and outcomes for UTUUC tumors. The sites that have access to ureteroscopes that are enabled with SPIES will thus also evaluate the added value of SPIES in those patients. The oncoming SPIES projects will enable us to provide the best possible care for our patients. This is made possible through a partnership with STORZ and illustrates the importance of these collaborations. In addition, this opens the doors for every urologist involved in the management of UTUUC tumors to contribute through CROES to new insights and knowledge of this condition. References
1. Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: Update 2013. Eur Urol 2013;64:639–653. 2. Kakizoe T. Development and progression of urothelial carcinoma. Cancer Sci 2006;97:821–828. 3. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium. Clinical implications of multicentric origin. Cancer 1953;6:963–968. 4. Sidransky D, Frost P, Von Eschenbach A, et al. Clonal origin bladder cancer. N Engl J Med 1992;326:737–740. 5. Mangrud OM, Waalen R, Gudlaugsson E, et al. Reproducibility and prognostic value of WHO1973 and WHO2004 grading systems in TaT1 urothelial carcinoma of the urinary bladder. PloS One. 2014;9:e83192. 6. Witjes JA, Moonen PM, van der Heijden AG. Review pathology in a diagnostic bladder cancer trial: Effect of patient risk category. Urology 2006;67:751–755. 7. May M, Brookman-Amissah S, Roigas J, et al. Prognostic accuracy of individual uropathologists in noninvasive urinary bladder carcinoma: A multicentre study comparing the 1973 and 2004 World Health Organisation classifications. Eur Urol 2010;57:850–858. 261
8. Klein R, Klein BE. The prevalence of age-related eye diseases and visual impairment in aging: Current estimates. Invest Ophthalmol Vis Sci 2013;54:ORSF5-ORSF13. 9. Owsley C. Aging and vision. Vision Res 2011;51:1610–1622. 10. Sjostrand J, Laatikainen L, Hirvela H, et al. The decline in visual acuity in elderly people with healthy eyes or eyes with early age-related maculopathy in two Scandinavian population samples. Acta Ophthalmol 2011;89:116–123. 11. Cina SJ, Epstein JI, Endrizzi JM, et al. Correlation of cystoscopic impression with histologic diagnosis of biopsy specimens of the bladder. Hum Patholo 2001;32:630–637. 12. Dobruch J, Borowka A, Herr HW. Clinical value of transurethral second resection of bladder tumor: Systematic review. Urology 2014;84:881–885. 13. Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999;162:74–76. 14. Mariappan P, Finney SM, Head E, et al. Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new nonmuscle-invasive bladder cancer: Validation across time and place and recommendation for benchmarking. BJU Int 2012;109:1666–1673. 15. Rink M, Babjuk M, Catto JW, et al. Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: A critical review of the current literature. Eur Urol 2013;64:624–638. 16. Yeo L, Jain S. Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: Validation across time and place and recommendation for benchmarking. BJU Int 2012;109:E27. 17. Brausi M, Collette L, Kurth K, et al. Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: A combined analysis of seven EORTC studies. Eur Urol 2002;41:523–531. 18. Lerner SP, Goh A. Novel endoscopic diagnosis for bladder cancer. Cancer 201;121:169–178. 19. Geavlete B, Multescu R, Georgescu D, et al. Narrow band imaging cystoscopy and bipolar plasma vaporization for large nonmuscle-invasive bladder tumors—results of a prospective, randomized comparison to the standard approach. Urology 2012;79:846–851.
The Global Ureteroscopy Study, Global GreenLightÔ Laser Study, and the Global Renal Mass Study were closed in 2012. The first five articles on ureteroscopy and the first one on the Renal Mass Study have been published. The first two articles of the GreenLightÔ Laser Study are under review. The randomized study on Narrow Band Imaging vs White Light Imaging closed in 2013. The first results are being analyzed. Ongoing project: The Irreversible Electroporation Study for Focal Therapy, including a pilot study, a randomized controlled trial, and a registry. New project: The randomized study on SPIES vs White Light Imaging. New project: The Global Upper Tract-Transitional-Cell Carcinoma Study. For further information, please visit: www.croesoffice.org or contact the Executive Director of CROES, Mrs. Sonja van Rees Vellinga ([email protected]).
262
Copyright of Journal of Endourology is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
