VOLUME
32
䡠
NUMBER
34
䡠
DECEMBER
1
2014
JOURNAL OF CLINICAL ONCOLOGY
E
D
I
T
O
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I
A
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Organ-Sparing Multimodality Treatment for Muscle-Invasive Bladder Cancer: Can We Continue to Ignore the Evidence? Claus Rödel and Christian Weiss, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany See accompanying article on page 3801
Radical cystectomy with pelvic lymph node dissection is currently viewed as the standard of care for muscle-invasive bladder cancer, with 5-year overall survival rates in contemporary cystectomy series in the range of 55% to 60%. However, although sophisticated techniques for urinarydiversionhavebeendeveloped,eventheconstructionofanorthotopic neobladder with continent urinary diversion cannot substitute for the patient’s original bladder. Removal of the entire organ may lead to significant morbidity and affects patients’ comfort and quality of life.1 In recent decades, organ-preserving multimodality therapies have been established in many malignancies, including breast cancer, anal cancer, head and neck cancer, and soft tissue sarcoma, among others. Meanwhile, we have learned from experiences with these tumor entities that the best results for each patient can be achieved in a multidisciplinary setting, where surgeons, medical and radiation oncologists, and other specialists jointly assess whether limited forms of organ-sparing surgery, supplemented by local radiotherapy and systemic therapy, can allow radical and partially mutilating extirpation to be avoided without compromising the survival of the patient. As an organ-preserving treatment alternative to radical surgery for muscle-invasive bladder cancer, a trimodality therapy (TMT) approach that includes initial maximal transurethral tumor resection of the bladder tumor (TURBT) followed by radiotherapy combined with various forms of neoadjuvant, concurrent, and adjuvant chemotherapy protocols has been tested in series at single institutions and in prospective clinical trials by cooperative groups, such as the Radiation Therapy Oncology Group (RTOG), over several decades.2 With this approach, radical cystectomy is reserved as a salvage option for patients with incomplete responses to (induction) chemoradiotherapy or with invasive local recurrence. In the article that accompanies this editorial, Mak et al3 describe a pooled analysis with long-term outcomes of one of the largest cohorts of patients (n ⫽ 468) treated for bladder preservation in five prospective, multi-institutional RTOG phase II studies and one phase III study. With a median follow-up of 7.8 years for survivors, the 5-year and 10-year overall survival rates were 57% and 37%, respectively, and 80% of patients retained an intact bladder at 5 years. A complete response on rebiopsy after initial TURBT and induction chemoradiotherapy was achieved in 69% of patients, and prompt salvage cystectomy for nonresponders or local invasive recurrences (the latter restricted to 14% of patients at 10 years) still Journal of Clinical Oncology, Vol 32, No 34 (December 1), 2014: pp 3787-3788
resulted in 5-year and 10-year disease-free survival rates of 60% and 47%, respectively. Moreover, a previously published pooled analysis of the RTOG studies demonstrated a low incidence of late pelvic toxicity in patients retaining their bladder (late grade ⱖ 3 genitourinary and GI toxicity in 5.7% and 1.9% of patients, respectively).4 Almost identical results have been reported from the largest singlecenterseries(n⫽415)oftheTMTapproachattheUniversityofErlangen: complete response at restaging biopsy after TMT was achieved in 72% of patients, overall and disease-specific survival rates were 51% and 56% at 5 years, and 31% and 42% at 10 years, respectively, and more than 80% of survivorspreservedtheirintact,well-functioningbladder(cystectomyasa result of a contracted bladder was restricted to 2% of patients).5 A recent systematic review of all available retrospective and prospective series and studies of TMT for muscle-invasive bladder cancer confirmed cancerspecific and overall survival rates in the range of 50% to 82% and 36% to 74%, respectively, with salvage cystectomy restricted to 25% to 30% of patients.6 As more experience is acquired with organ-sparing treatment in bladder cancer, it is clear that future clinical and basic research will focus on two main topics: first, the proper selection of patients who will most likely benefit from the respective treatment alternatives, and second, the optimization of the respective treatment components, including optimization of radiation techniques and fractionation schedules as well as incorporation of novel cytotoxic and biologic agents. As demonstrated in the pooled analysis by Mak et al,3 clinical criteria that are helpful in determining which patients are appropriate candidates for bladder preservation include such variables as early tumor stage, a visibly complete TURBT, and absence of ureteral obstruction. Other series identified associated carcinoma in situ and diffuse multifocal disease as poor prognostic markers for organ-preservation therapies.6 Interestingly, Mak et al showed that patients age 75 years and older had excellent compliance with radiotherapy and similar bladder-preservation and disease-freesurvivalratescomparedwithyoungerpatients,indicatingthat elderly patients, who are often not well suited for radical surgery, are excellent candidates for a curative bladder-preservation approach. Inclusion of molecular markers that predict response and innovative imaging techniques, such as diffusion-weighted magnetic resonance imaging, to monitor response to TMT may also help to improve patient selection and management.7-9 © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at NEW YORK UNIVERSITY MED CTR on April 15, 2015 Copyright © 2014 Americanfrom Society of Clinical Oncology. All rights reserved. 128.122.253.228
3787
Editorial
To date, the current radiation protocols comprise once or twice per day fractions of 1.5 to 2 Gy to an initial dose of 40 to 45 Gy to the bladder and pelvic lymph nodes. Consolidation radiotherapy, either as a split or continuous course, is continued to the bladder (tumor) to a full dose of approximately 65 Gy in most series.2,6 New treatment techniques, such as image-guided and intensity-modulated radiotherapy as well as interstitial radiotherapy in selected patients (with unifocal, small bulk disease) may allow dose escalation with the expectation of further reducing toxicity and improvingtumorresponseandlong-termlocalcontrol.10,11 Protonbeam therapyhasalsobeenassessed,butreportsremainpreliminary.12 Concurrent cisplatin is currently used in most protocols as a radiosensitizing drug in those with adequate renal function. Recently, a regimen using concurrent fluorouracil and mitomycin in addition to radiotherapy demonstrated benefit in a randomized phase III trial.13 Use of carbogen and nicotinamide as hypoxia-reducing agents has also been supported by evidence from a randomized trial.14 Clearly, the concept of TMT for bladder preservation is evolving and being refined through the work of many groups around the world. No treatment concept in oncology is without risks and limitations. Successful implementation of a bladder-preserving program requires a dedicated team and careful coordination among all disciplines involved. Patients who achieve an initial complete response should be encouraged to undergo lifelong surveillance cystoscopies with prompt salvage therapy on recurrence of disease. Most patients will in fact remain free from muscle-invasive recurrences; however, nonmuscle-invasive recurrences in the retained bladder occurred in up to 36% of patients after 10 years in thepooledanalysisoftheRTOGtrials.3 Althoughtheserecurrencescanbe managed conservatively with TURBT and intravesical therapy, patients remain at risk of requiring delayed cystectomy.15 Another concern is that orthotopic neobladder reconstruction (although feasible) after pelvic radiotherapy is often not advocated by surgeons because of a higher risk of functional complications.16 There are no randomized trials that have directly compared radical surgery and the TMT bladder-preservation approach; the recent United Kingdom SPARE (Selective Bladder Preservation Against Radical Excision) phase III trial unfortunately failed to accrue patients.17 Any indirect comparison between the procedures is difficult because of selection bias and clinicopathologic stage discordance. Nevertheless, the long-term data of the RTOG trials in concert with a growing body of accumulated data from other groups should help to further promote TMT as a reasonable alternative to radical cystectomy and as a curative treatment option in patients with muscle-invasive bladder cancer. Given that the adoption of organ-preserving TMT for bladder cancer has been limited, Gospodarowicz asked in her editorial commenting on the long-term results of our bladder-preserving strategy more than a decade ago in this journal: “Are we ignoring the evidence?”18(p3048) European Association of Urology consensus guidelines and the updated National Comprehensive Cancer Network guidelines now accept bladder preservation for selected patients with muscle-invasive bladder cancer.19,20 The researchers of the RTOG bladder-preservation trials are to be congratulatedfortheirmajorcontributionsinthisfield.Whencounseling patients with muscle-invasive bladder cancer concerning their treatment options, organ-sparing TMT cannot be ignored.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. AUTHOR CONTRIBUTIONS
Manuscript writing: All authors Final approval of manuscript: All authors REFERENCES 1. Shabsigh A, Korets R, Vora KC, et al: Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 55:164-176, 2009 2. Rödel C, Weiss C, Sauer R: Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol 24:5536-5544, 2006 3. Mak RH, Hunt D, Shipley WU, et al: Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: A pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol 32:3801-3809, 2014 4. Efstathiou JA, Bae K, Shipley WU, et al: Late pelvic toxicity after bladdersparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol 27:4055-4061, 2009 5. Rödel C, Grabenbauer GG, Kühn R, et al: Combined-modality treatment and selective organ preservation in invasive bladder cancer: Long-term results. J Clin Oncol 20:3061-3071, 2002 6. Ploussard G, Daneshmand S, Efstathiou JA, et al: Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: A systematic review. Eur Urol 66:120-137, 2014 7. Laurberg JR, Brems-Eskildsen AS, Nordentoft I, et al: Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int 110:E1228E1236, 2012 8. Keck B, Wach S, Taubert H, et al: Neuropilin-2 and its ligand VEGF-C predict treatment response after transurethral resection and radiochemotherapy in bladder cancer patients. Int J Cancer [epub ahead of print on May 27, 2014] 9. Yoshida S, Koga F, Kobayashi S, et al: Diffusion-weighted magnetic resonance imaging in management of bladder cancer, particularly with multimodal bladder-sparing strategy. World J Radiol 6:344-354, 2014 10. Søndergaard J, Holmberg M, Jakobsen AR, et al: A comparison of morbidity following conformal versus intensity-modulated radiotherapy for urinary bladder cancer. Acta Oncol 1:1-8, 2014 11. Aluwini S, van Rooij PH, Kirkels WJ, et al: Bladder function preservation with brachytherapy, external beam radiation therapy, and limited surgery in bladder cancer patients: Long-term results. Int J Radiat Oncol Biol Phys 88:611-617, 2014 12. Hata M, Miyanaga N, Tokuuye K, et al: Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy. Int J Radiat Oncol Biol Phys 64:1371-1379, 2006 13. James ND, Hussain SA, Hall E, et al: Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 366:1477-1488, 2012 14. Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI: Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. J Clin Oncol 28:4912-4918, 2010 15. Weiss C, Wittlinger M, Engehausen DG, et al: Management of superficial recurrences in an irradiated bladder after combined-modality organ-preserving therapy. Int J Radiat Oncol Biol Phys 70:1502-1506, 2008 16. Eisenberg MS, Dorin RP, Bartsch G, et al: Early complications of cystectomy after high dose pelvic radiation. J Urol 184:2264-2269, 2010 17. Huddart RA, Hall E, Lewis R, et al: Life and death of SPARE (Selective Bladder Preservation Against Radical Excision): Reflections on why the SPARE trial closed. BJU Int 106:753-755, 2010 18. Gospodarowicz M: Radiotherapy and organ preservation in bladder cancer: Are we ignoring the evidence? J Clin Oncol 20:3048-3050, 2002 19. Gakis G, Efstathiou J, Lerner SP, et al: ICUD-EAU International Consultation on Bladder Cancer 2012: Radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol 63:45-57, 2013 20. National Comprehensive Cancer Network: Bladder cancer. http://www.nccn.org/ professionals/physician_gls/f_guidelines.asp#site.
DOI: 10.1200/JCO.2014.58.5521; published online ahead of print at www.jco.org on November 3, 2014
■ ■ ■
3788
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at NEW YORK UNIVERSITY MED CTR on April 15, 2015 Copyright © 2014 Americanfrom Society of Clinical Oncology. All rights reserved. 128.122.253.228
Editorial
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Organ-Sparing Multimodality Treatment for Muscle-Invasive Bladder Cancer: Can We Continue to Ignore the Evidence? The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Claus Rödel No relationship to disclose
www.jco.org
Christian Weiss Honoraria: Roche, Merck Serono
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at NEW YORK UNIVERSITY MED CTR on April 15, 2015 Copyright © 2014 Americanfrom Society of Clinical Oncology. All rights reserved. 128.122.253.228
32
䡠
NUMBER
34
䡠
DECEMBER
1
2014
JOURNAL OF CLINICAL ONCOLOGY
E
D
I
T
O
R
I
A
L
Organ-Sparing Multimodality Treatment for Muscle-Invasive Bladder Cancer: Can We Continue to Ignore the Evidence? Claus Rödel and Christian Weiss, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany See accompanying article on page 3801
Radical cystectomy with pelvic lymph node dissection is currently viewed as the standard of care for muscle-invasive bladder cancer, with 5-year overall survival rates in contemporary cystectomy series in the range of 55% to 60%. However, although sophisticated techniques for urinarydiversionhavebeendeveloped,eventheconstructionofanorthotopic neobladder with continent urinary diversion cannot substitute for the patient’s original bladder. Removal of the entire organ may lead to significant morbidity and affects patients’ comfort and quality of life.1 In recent decades, organ-preserving multimodality therapies have been established in many malignancies, including breast cancer, anal cancer, head and neck cancer, and soft tissue sarcoma, among others. Meanwhile, we have learned from experiences with these tumor entities that the best results for each patient can be achieved in a multidisciplinary setting, where surgeons, medical and radiation oncologists, and other specialists jointly assess whether limited forms of organ-sparing surgery, supplemented by local radiotherapy and systemic therapy, can allow radical and partially mutilating extirpation to be avoided without compromising the survival of the patient. As an organ-preserving treatment alternative to radical surgery for muscle-invasive bladder cancer, a trimodality therapy (TMT) approach that includes initial maximal transurethral tumor resection of the bladder tumor (TURBT) followed by radiotherapy combined with various forms of neoadjuvant, concurrent, and adjuvant chemotherapy protocols has been tested in series at single institutions and in prospective clinical trials by cooperative groups, such as the Radiation Therapy Oncology Group (RTOG), over several decades.2 With this approach, radical cystectomy is reserved as a salvage option for patients with incomplete responses to (induction) chemoradiotherapy or with invasive local recurrence. In the article that accompanies this editorial, Mak et al3 describe a pooled analysis with long-term outcomes of one of the largest cohorts of patients (n ⫽ 468) treated for bladder preservation in five prospective, multi-institutional RTOG phase II studies and one phase III study. With a median follow-up of 7.8 years for survivors, the 5-year and 10-year overall survival rates were 57% and 37%, respectively, and 80% of patients retained an intact bladder at 5 years. A complete response on rebiopsy after initial TURBT and induction chemoradiotherapy was achieved in 69% of patients, and prompt salvage cystectomy for nonresponders or local invasive recurrences (the latter restricted to 14% of patients at 10 years) still Journal of Clinical Oncology, Vol 32, No 34 (December 1), 2014: pp 3787-3788
resulted in 5-year and 10-year disease-free survival rates of 60% and 47%, respectively. Moreover, a previously published pooled analysis of the RTOG studies demonstrated a low incidence of late pelvic toxicity in patients retaining their bladder (late grade ⱖ 3 genitourinary and GI toxicity in 5.7% and 1.9% of patients, respectively).4 Almost identical results have been reported from the largest singlecenterseries(n⫽415)oftheTMTapproachattheUniversityofErlangen: complete response at restaging biopsy after TMT was achieved in 72% of patients, overall and disease-specific survival rates were 51% and 56% at 5 years, and 31% and 42% at 10 years, respectively, and more than 80% of survivorspreservedtheirintact,well-functioningbladder(cystectomyasa result of a contracted bladder was restricted to 2% of patients).5 A recent systematic review of all available retrospective and prospective series and studies of TMT for muscle-invasive bladder cancer confirmed cancerspecific and overall survival rates in the range of 50% to 82% and 36% to 74%, respectively, with salvage cystectomy restricted to 25% to 30% of patients.6 As more experience is acquired with organ-sparing treatment in bladder cancer, it is clear that future clinical and basic research will focus on two main topics: first, the proper selection of patients who will most likely benefit from the respective treatment alternatives, and second, the optimization of the respective treatment components, including optimization of radiation techniques and fractionation schedules as well as incorporation of novel cytotoxic and biologic agents. As demonstrated in the pooled analysis by Mak et al,3 clinical criteria that are helpful in determining which patients are appropriate candidates for bladder preservation include such variables as early tumor stage, a visibly complete TURBT, and absence of ureteral obstruction. Other series identified associated carcinoma in situ and diffuse multifocal disease as poor prognostic markers for organ-preservation therapies.6 Interestingly, Mak et al showed that patients age 75 years and older had excellent compliance with radiotherapy and similar bladder-preservation and disease-freesurvivalratescomparedwithyoungerpatients,indicatingthat elderly patients, who are often not well suited for radical surgery, are excellent candidates for a curative bladder-preservation approach. Inclusion of molecular markers that predict response and innovative imaging techniques, such as diffusion-weighted magnetic resonance imaging, to monitor response to TMT may also help to improve patient selection and management.7-9 © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at NEW YORK UNIVERSITY MED CTR on April 15, 2015 Copyright © 2014 Americanfrom Society of Clinical Oncology. All rights reserved. 128.122.253.228
3787
Editorial
To date, the current radiation protocols comprise once or twice per day fractions of 1.5 to 2 Gy to an initial dose of 40 to 45 Gy to the bladder and pelvic lymph nodes. Consolidation radiotherapy, either as a split or continuous course, is continued to the bladder (tumor) to a full dose of approximately 65 Gy in most series.2,6 New treatment techniques, such as image-guided and intensity-modulated radiotherapy as well as interstitial radiotherapy in selected patients (with unifocal, small bulk disease) may allow dose escalation with the expectation of further reducing toxicity and improvingtumorresponseandlong-termlocalcontrol.10,11 Protonbeam therapyhasalsobeenassessed,butreportsremainpreliminary.12 Concurrent cisplatin is currently used in most protocols as a radiosensitizing drug in those with adequate renal function. Recently, a regimen using concurrent fluorouracil and mitomycin in addition to radiotherapy demonstrated benefit in a randomized phase III trial.13 Use of carbogen and nicotinamide as hypoxia-reducing agents has also been supported by evidence from a randomized trial.14 Clearly, the concept of TMT for bladder preservation is evolving and being refined through the work of many groups around the world. No treatment concept in oncology is without risks and limitations. Successful implementation of a bladder-preserving program requires a dedicated team and careful coordination among all disciplines involved. Patients who achieve an initial complete response should be encouraged to undergo lifelong surveillance cystoscopies with prompt salvage therapy on recurrence of disease. Most patients will in fact remain free from muscle-invasive recurrences; however, nonmuscle-invasive recurrences in the retained bladder occurred in up to 36% of patients after 10 years in thepooledanalysisoftheRTOGtrials.3 Althoughtheserecurrencescanbe managed conservatively with TURBT and intravesical therapy, patients remain at risk of requiring delayed cystectomy.15 Another concern is that orthotopic neobladder reconstruction (although feasible) after pelvic radiotherapy is often not advocated by surgeons because of a higher risk of functional complications.16 There are no randomized trials that have directly compared radical surgery and the TMT bladder-preservation approach; the recent United Kingdom SPARE (Selective Bladder Preservation Against Radical Excision) phase III trial unfortunately failed to accrue patients.17 Any indirect comparison between the procedures is difficult because of selection bias and clinicopathologic stage discordance. Nevertheless, the long-term data of the RTOG trials in concert with a growing body of accumulated data from other groups should help to further promote TMT as a reasonable alternative to radical cystectomy and as a curative treatment option in patients with muscle-invasive bladder cancer. Given that the adoption of organ-preserving TMT for bladder cancer has been limited, Gospodarowicz asked in her editorial commenting on the long-term results of our bladder-preserving strategy more than a decade ago in this journal: “Are we ignoring the evidence?”18(p3048) European Association of Urology consensus guidelines and the updated National Comprehensive Cancer Network guidelines now accept bladder preservation for selected patients with muscle-invasive bladder cancer.19,20 The researchers of the RTOG bladder-preservation trials are to be congratulatedfortheirmajorcontributionsinthisfield.Whencounseling patients with muscle-invasive bladder cancer concerning their treatment options, organ-sparing TMT cannot be ignored.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. AUTHOR CONTRIBUTIONS
Manuscript writing: All authors Final approval of manuscript: All authors REFERENCES 1. Shabsigh A, Korets R, Vora KC, et al: Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 55:164-176, 2009 2. Rödel C, Weiss C, Sauer R: Trimodality treatment and selective organ preservation for bladder cancer. J Clin Oncol 24:5536-5544, 2006 3. Mak RH, Hunt D, Shipley WU, et al: Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: A pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol 32:3801-3809, 2014 4. Efstathiou JA, Bae K, Shipley WU, et al: Late pelvic toxicity after bladdersparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol 27:4055-4061, 2009 5. Rödel C, Grabenbauer GG, Kühn R, et al: Combined-modality treatment and selective organ preservation in invasive bladder cancer: Long-term results. J Clin Oncol 20:3061-3071, 2002 6. Ploussard G, Daneshmand S, Efstathiou JA, et al: Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: A systematic review. Eur Urol 66:120-137, 2014 7. Laurberg JR, Brems-Eskildsen AS, Nordentoft I, et al: Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int 110:E1228E1236, 2012 8. Keck B, Wach S, Taubert H, et al: Neuropilin-2 and its ligand VEGF-C predict treatment response after transurethral resection and radiochemotherapy in bladder cancer patients. Int J Cancer [epub ahead of print on May 27, 2014] 9. Yoshida S, Koga F, Kobayashi S, et al: Diffusion-weighted magnetic resonance imaging in management of bladder cancer, particularly with multimodal bladder-sparing strategy. World J Radiol 6:344-354, 2014 10. Søndergaard J, Holmberg M, Jakobsen AR, et al: A comparison of morbidity following conformal versus intensity-modulated radiotherapy for urinary bladder cancer. Acta Oncol 1:1-8, 2014 11. Aluwini S, van Rooij PH, Kirkels WJ, et al: Bladder function preservation with brachytherapy, external beam radiation therapy, and limited surgery in bladder cancer patients: Long-term results. Int J Radiat Oncol Biol Phys 88:611-617, 2014 12. Hata M, Miyanaga N, Tokuuye K, et al: Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy. Int J Radiat Oncol Biol Phys 64:1371-1379, 2006 13. James ND, Hussain SA, Hall E, et al: Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 366:1477-1488, 2012 14. Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI: Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. J Clin Oncol 28:4912-4918, 2010 15. Weiss C, Wittlinger M, Engehausen DG, et al: Management of superficial recurrences in an irradiated bladder after combined-modality organ-preserving therapy. Int J Radiat Oncol Biol Phys 70:1502-1506, 2008 16. Eisenberg MS, Dorin RP, Bartsch G, et al: Early complications of cystectomy after high dose pelvic radiation. J Urol 184:2264-2269, 2010 17. Huddart RA, Hall E, Lewis R, et al: Life and death of SPARE (Selective Bladder Preservation Against Radical Excision): Reflections on why the SPARE trial closed. BJU Int 106:753-755, 2010 18. Gospodarowicz M: Radiotherapy and organ preservation in bladder cancer: Are we ignoring the evidence? J Clin Oncol 20:3048-3050, 2002 19. Gakis G, Efstathiou J, Lerner SP, et al: ICUD-EAU International Consultation on Bladder Cancer 2012: Radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol 63:45-57, 2013 20. National Comprehensive Cancer Network: Bladder cancer. http://www.nccn.org/ professionals/physician_gls/f_guidelines.asp#site.
DOI: 10.1200/JCO.2014.58.5521; published online ahead of print at www.jco.org on November 3, 2014
■ ■ ■
3788
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at NEW YORK UNIVERSITY MED CTR on April 15, 2015 Copyright © 2014 Americanfrom Society of Clinical Oncology. All rights reserved. 128.122.253.228
Editorial
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Organ-Sparing Multimodality Treatment for Muscle-Invasive Bladder Cancer: Can We Continue to Ignore the Evidence? The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Claus Rödel No relationship to disclose
www.jco.org
Christian Weiss Honoraria: Roche, Merck Serono
© 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at NEW YORK UNIVERSITY MED CTR on April 15, 2015 Copyright © 2014 Americanfrom Society of Clinical Oncology. All rights reserved. 128.122.253.228
