|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2002 American Society for Clinical Oncology
Radiotherapy and Organ Preservation in Bladder Cancer: Are We Ignoring the Evidence?Princess Margaret Hospital, Toronto, Ontario, Canada BLADDER CANCER IS one of the most common malignancies, and it is associated with substantial morbidity and mortality. There will be 56,500 new cases diagnosed in the United States in 2002; 12,600 men and women will die of the disease.1 Although the majority of patients are managed with conservative measures, patients with muscle-invasive bladder cancer require radical local treatment. In the United States, this almost always involves a radical cystectomy with pelvic lymph node dissection. Although radiation therapy has been used in the management of bladder cancer for decades, it has not been widely accepted as a means to achieve bladder preservation. Indeed, in the quest for cure of locally advanced bladder cancer, the pursuit of organ preservation has largely been ignored. Organ preservation has been in the forefront of modern cancer care for the past two decades. Conservative management is now the standard of care in numerous malignancies including breast cancer, larynx cancer, anal canal cancer, and soft tissue sarcomas of the limb.2-5 Advances in combined-modality therapy in head and neck cancer and esophageal cancer now offer improved local tumor control without the routine use of extensive surgical resection.2,6 To be accepted, organ-conserving therapy must not compromise survival. To be generally adopted in bladder cancer, as with other diseases, organ-conserving therapy must have a high likelihood of eradicating the tumor, have a low risk of recurrence, and not compromise organ function. Rödel et al,7 in this issue of the Journal of Clinical Oncology, describe a large experience with organ-sparing treatment of invasive bladder cancer, documenting long-term outcome of 415 patients treated over a 20-year time period. As a retrospective study, this report provides at most level III evidence to support the use of radiotherapy in advanced bladder cancer. It should be noted that although Rödel’s experience has been collected over a 20-year period, and before the current era of precision in radiation therapy, a 72% complete response rate and sustained local control in 64% of those who achieved complete response is documented. In addition, 80% of surviving patients preserved their bladder, with only 2% requiring cystectomy for late toxicity. Zietman et al8 and Shipley et al9 from Massachusetts General Hospital have been reporting similar results for the past 15 years. These results certainly offer hope and indeed opportunity for bladder preservation in a significant proportion of patients who currently undergo cystectomy. Despite the work of Shipley et al10 and Zietman8 in the United States and Sauer et al,11 Rödel et al,12 and Dunst et al13 in Erlangen, the adoption of bladder conserving approaches has been limited. It is of interest to reflect on the potential reasons for this. Patients with bladder cancer are primarily diagnosed and managed by urologists. Improvements in technical aspects of urinary diversion, including the increased use of continent diversion, have reduced the pressure for bladder preservation. Patients are now offered a new bladder to replace a diseased one. However, not all patients with muscle invasive tumor have a diseased bladder that requires cystectomy. In fact, population-based studies comparing symptoms experienced by patients who received radiotherapy to those who had cystectomy showed satisfactory urinary, rectal, and sexual function in those treated without cystectomy.14 The perceived barriers to the adoption of radiotherapy-based bladder preservation protocols include concerns that radiotherapy-based protocols compromise cure, belief that accurate staging of bladder cancer is not possible without cystectomy, and apprehension about the risk of late relapse of cancer. In addition, the infrequent use of radiotherapy in bladder cancer may have resulted in inexperience among radiation oncologists and urologists in the application of radiotherapy-based bladder conserving protocols in the community. The prevailing opinion that radiotherapy-based approaches are inferior leads to referral of patients who are either not or poor candidates for cystectomy for bladder conserving approaches. In turn, this may lead to a self-fulfilling prophecy resulting in inferior outcomes in patients treated with radiotherapy. In fact, two population-based studies from Canada report significant use of radiotherapy in the management of bladder cancer which fail to document a significant survival disadvantage.15,16 A definitive trial comparing radical cystectomy alone to radiotherapy alone has never been performed. The reported randomized trials have involved comparisons of radiotherapy alone to cystectomy with preoperative radiotherapy and were conducted over 20 years ago. No appropriate selection of patients suitable for bladder preservation was involved and radiotherapy planning methods were inadequate. However, perceptions of compromised survival remain. These have been fueled further by the recent Cochrane Collaboration report by Shelley et al,17 in which the question of surgery versus radiotherapy for muscle invasive bladder cancer was addressed. The authors concluded that there was an overall survival benefit with radical surgery compared with radical radiotherapy in patients with muscle-invasive bladder cancer. The authors noted that only three trials (none directly addressing the question) were included for analysis, the patient numbers were small, and that many patients did not receive the treatment they were randomized to. These facts did not affect their conclusions. The fact that the use of radiotherapy alone for an unselected population of patients with muscle invasive bladder cancer is unsatisfactory has been documented in a number of published reports.18-20 The outcomes for large locally advanced bladder tumors with extravesical extension (T3b) are poor regardless of whether radiotherapy or surgery is used.18,19,21,22 In the past decade, the use of transurethral resection before radiotherapy and the use of concurrent radiotherapy and cisplatin have been shown to improve local control in bladder cancer, changing the standard approach from that of radiotherapy alone to combined-modality therapy.12,23,24 As noted above, the default referral of patients for radiotherapy-based approaches (ie, those unfit for or who refuse cystectomy) further compounds the prevailing impression of inferior outcomes. Where organ preservation is the goal, the selection of suitable patients is a paramount element for success. The goal should not be organ preservation for every patient, but for those who are most likely to benefit from this approach. Surgery, radiotherapy, and chemotherapy should be seen as complementary, rather than competing, treatment modalities. Our own and others’ experience show that local control and the opportunity for bladder preservation is best in patients with T2-T3a tumors less than 5 cm in diameter, located away from the dome of the bladder, and without associated diffuse carcinoma-in-situ.10,18,19 In addition to the lack of selection for radiotherapy, many local failures may have been due to inadequate radiotherapy by today’s standards. Improvements in imaging, especially magnetic resonance imaging (MRI) of the bladder and pelvis, to define anatomic disease extent allow more accurate radiotherapy planning. In addition, it is now feasible to precisely target radiotherapy to the tumor while sparing normal tissues. The implementation of three-dimensional conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT) techniques offer possibilities of further improvements in bladder preservation.25-28 MRI of the bladder offers more accurate clinical staging, and three-dimensional CRT and IMRT allow for radiotherapy dose escalation without an increase in morbidity and with resulting improved local control.29 Adoption of these techniques in bladder cancer has the potential to improve the probability of bladder conservation without sacrificing cure. Patients referred for bladder preservation protocols should be entered on prospective trials investigating radiotherapy dose escalation with three-dimensional CRT with the use of MRI-based radiotherapy planning, fiducial markers, and real-time target verification with portal imaging to optimize normal tissue protection. It is important to note that these improvements may be achieved by using existing technologies without the need for discovery of new molecular prognostic factors, therapeutic targets, or drugs. In fact, optimization of current strategies would lead towards "achieving the achievable" in muscle invasive bladder cancer (W.J. Mackillop, personal communication, 2000). However, progress in molecular characterization of bladder cancer and definition of new targeted therapies would provide new opportunities to tailor treatment to the individual. Introduction of chemoprevention strategies in patients with dysplasia and recurrent transitional cell cancer may reduce the rate of late cystectomies for new tumors, further improving the efficacy of bladder preserving strategies. Those involved in the management of muscle invasive bladder cancer should "take a leaf from the book" on sarcoma and breast cancer management, where multidisciplinary collaborative approach with knowledge and respect for the benefits and shortcomings of individual treatment modalities has led to a standard of organ preservation. Unless urologists, radiation oncologists and medical oncologists decide to collaborate and further optimize bladder conserving approaches, cystectomy may remain as the only option for patients with muscle invasive bladder cancer, regardless of the prospects for organ preservation. REFERENCES
1. Jemal A, Thomas A, Murray T, et al: Cancer statistics, 2002. CA Cancer J Clin 52: 23-47, 2002
2. Forastiere A, Koch W, Trotti A, et al: Head and neck cancer. N Engl J Med 345: 1890-1900, 2001 3. O’Sullivan B, Bell R, Bramwell V: Sarcomas of the soft tissues, in Souhami R, Tannock I, Hohenberger P, et al (eds): Oxford Textbook of Oncology, ed 2. Oxford, United Kingdom, Oxford University Press, 2002, pp 2495-2523 4. Singletary SE: Minimally invasive techniques in breast cancer treatment. Semin Surg Oncol 20: 246-250, 2001[CrossRef][Medline] 5. Willett CG: Organ preservation in anal and rectal cancers. Curr Opin Oncol 8: 329-333, 1996[Medline] 6. Rich T: Chemoradiation in conservation therapy for esophageal cancer. Hematol Oncol Clin North Am 15: 291-302, 2001[CrossRef][Medline]
7. 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 8. Zietman AL, Shipley WU, Kaufman DS: The combination of cisplatin based chemotherapy and radiation in the treatment of muscle-invading transitional cell cancer of the bladder. Int J Radiat Oncol Biol Phys 27: 161-170, 1993[Medline] 9. Shipley WU, Rose MA, Perrone TL, et al: Full-dose irradiation for patients with invasive bladder carcinoma: Clinical and histological factors prognostic of improved survival. J Urol 134: 679-683, 1985[Medline] 10. Shipley WU, Zietman AL, Kaufman DS, et al: Invasive bladder cancer: Treatment strategies using transurethral surgery, chemotherapy and radiation therapy with selection for bladder conservation. Int J Radiat Oncol Biol Phys 39: 937-943, 1997[CrossRef][Medline] 11. Sauer R, Birkenhake S, Kuhn R, et al: Efficacy of radiochemotherapy with platin derivatives compared to radiotherapy alone in organ-sparing treatment of bladder cancer. Int J Radiat Oncol Biol Phys 40: 121-127, 1998[CrossRef][Medline] 12. Rödel C, Grabenbauer GG, Kuhn R, et al: Invasive bladder cancer: Organ preservation by radiochemotherapy. Front Radiat Ther Oncol 36: 118-130, 2002[Medline] 13. Dunst J, Sauer R, Schrott KM, et al: Organ-sparing treatment of advanced bladder cancer: A 10-year experience. Int J Radiat Oncol Biol Phys 30: 261-266, 1994[Medline] 14. Henningsohn L, Wijkstrom H, Dickman PW, et al: Distressful symptoms after radical radiotherapy for urinary bladder cancer. Radiother Oncol 62: 215-225, 2002[CrossRef][Medline] 15. Hayter CR, Paszat LF, Groome PA, et al: The management and outcome of bladder carcinoma in Ontario, 1982-1994. Cancer 89: 142-151, 2000[CrossRef][Medline] 16. Scrimger RA, Murtha AD, Parliament MB, et al: Muscle-invasive transitional cell carcinoma of the urinary bladder: A population-based study of patterns of care and prognostic factors. Int J Radiat Oncol Biol Phys 51: 23-30, 2001[Medline] 17. Shelley MD, Barber J, Wilt T, et al: Surgery versus radiotherapy for muscle invasive bladder cancer (Cochrane Review). Cochrane Database Syst Rev CD002079, 2002 18. Fung CY, Shipley WU, Young RH, et al: Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy. J Clin Oncol 9: 1533-1542, 1991[Abstract] 19. Gospodarowicz MK, Hawkins NV, Rawlings GA, et al: Radical radiotherapy for muscle invasive transitional cell carcinoma of the bladder: Failure analysis. J Urol 142:1448-1453; discussion 1453-1454, 1989 20. Gospodarowicz MK, Quilty PM, Scalliet P, et al: The place of radiation therapy as definitive treatment of bladder cancer. Int J Urol 2: 41-48, 1995 21. Bassi P, Ferrante GD, Piazza N, et al: Prognostic factors of outcome after radical cystectomy for bladder cancer: A retrospective study of a homogeneous patient cohort. J Urol 161: 1494-1497, 1999[CrossRef][Medline] 22. Gschwend J, Dahm P, Fair W: Disease specific survival as endpoint of outcome for bladder cancer patients following radical cystectomy. Eur Urol 41: 440-448, 2002[CrossRef][Medline] 23. Zietman AL, Grocela J, Zehr E, et al: Selective bladder conservation using transurethral resection, chemotherapy, and radiation: Management and consequences of Ta, T1, and Tis recurrence within the retained bladder. Urology 58: 380-385, 2001[CrossRef][Medline] 24. Coppin CM, Gospodarowicz MK, James K, et al: Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation: The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 14: 2901-2907, 1996[Abstract]
25. Barentsz JO, Jager GJ, van Vierzen PB, et al: Staging urinary bladder cancer after transurethral biopsy: Value of fast dynamic contrast-enhanced MR imaging. Radiology 201: 185-193, 1996 26. Barentsz JO, Jager GJ, Witjes JA: MR imaging of the urinary bladder. Magn Reson Imaging Clin N Am 8: 853-867, 2000[Medline] 27. Tubiana M, Eschwege F: Conformal radiotherapy and intensity-modulated radiotherapy–clinical data. Acta Oncol 39: 555-567, 2000[CrossRef][Medline] 28. Shu HK, Lee TT, Vigneauly E, et al: Toxicity following high-dose three-dimensional conformal and intensity-modulated radiation therapy for clinically localized prostate cancer. Urology 57: 102-107, 2001[Medline] 29. Zelefsky MJ, Fuks Z, Happersett L, et al: Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer. Radiother Oncol 55: 241-249, 2000[CrossRef][Medline]
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
