In favour of bladder preservation using combined modality treatment.
|Article Type:||Clinical report|
Radiotherapy (Health aspects)
Bladder cancer (Care and treatment)
Bladder cancer (Patient outcomes)
Bladder cancer (Research)
Quality of life (Health aspects)
Quality of life (Research)
Cancer (Health aspects)
|Publication:||Name: Canadian Urological Association Journal (CUAJ) Publisher: Canadian Urological Association Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 Canadian Urological Association ISSN: 1911-6470|
|Issue:||Date: Oct, 2009 Source Volume: 3 Source Issue: 5|
|Topic:||Event Code: 310 Science & research|
|Geographic:||Geographic Scope: Canada Geographic Code: 1CANA Canada|
Author(s): Himu Lukka, MBCLB, FRCP(UK), FRCR(UK), FRCPC
All health care professionals would agree that the primary goal of bladder cancer treatment should be to maximize patient survival while minimizing toxicity and negative impact on a patient's quality of life (QOL). Bladder preservation (and its impact on QOL) can only be considered an important secondary objective. Bladder cancer management has seen a significant change with the increasing use of multimodality treatment (e.g., surgery, radiotherapy and/or chemotherapy) as opposed to unimodality treatment.
To enable all treatment options to be discussed and to avoid unnecessary delays in treatment, ideally patients should be seen by urologists, radiation oncologists and medical oncologists in a multidisciplinary setting. Urologists would be strongly encouraged to refer their patients with invasive bladder cancer for a multidisciplinary opinion with the understanding that patients requiring a cystectomy would be referred back to the referring urologists.
Cystectomy as a treatment option
Radical cystectomy remains the primary treatment in the local management of bladder cancer in North America. In contrast, bladder preservation with salvage cystectomy in Europe has had a longer history--in some centres, it is the recommended approach. In North America, the centre with the largest experience with bladder preservation using a trimodality treatment is Massachusetts General Hospital (MGH) in Boston. While continent urinary tract reconstruction using cutaneous urinary reservoirs or orthotopic diversion is a step up from urinary diversion with an ileal conduit and urostoma, limited number of patients, in practice, have continent urinary tract reconstruction.
Results of cystectomy
Two large recent radical cystectomy series provide the best data outcomes (Table 1). The University of Southern California (USC) series of 633 patients with pT2-T4a reported 5 and 10 years overall survival of 48% and 32%.¹ The Memorial Sloan Kettering Cancer Center (MSKCC) series of 184 patients with pT2-4 reported overall 5-year survival rates of 36%.[sup.2] While the operative and perioperative care has improved, operative mortality in modern series ranges from 1% to 2% and postoperative complications range from 15% to 32%.[sup.3,4] Studies confirm that the most serious side effects are urinary diversion and loss of sexual function in men and women; these effects also have a significant impact on QOL. Continent urinary procedures achieve 82% continence rates, yet complications require reoperation in 10% to 15% of these patients.
Radiotherapy in the local management of bladder cancer has seen a significant change over the last couple of decades, evolving from the use of radiotherapy alone to preoperative radiotherapy, and more recently the use of trimodality treatment. The modern approach to bladder preservation involves careful cystoscopic evaluation, transurethral resection of the bladder to minimize the extent of residual disease, concurrent chemoradiotherapy followed by regular cystoscopic evaluation, and salvage cystectomy for recurrence. These strategies require the active participation of the urologist in the preradiotherapy assessment, decisionmaking, postradiotherapy monitoring and surgical intervention for salvage radiotherapy.
Concurrent cisplatinum with radiotherapy is recommended to improve local control based on the National Cancer Institute of Canada randomized study.[sup.5] One of the clearest indications of the potential for chemoradiotherapy came from the University of Paris, where the concurrent chemoradiotherapy approach (as a planned preoperative approach) did not identify any residual disease at cystectomy in the first 18 patients.[sup.6] These results led to a prospective study of selective bladder presentation using a trimodality strategy.[sup.7] The University of Erlangen reported the results of its trimodality treatment in 2002.[sup.8] In this protocol, patients completed the full course of chemoradiotherapy and underwent transurethral resection of bladder cancer (TURBT) restaging at 6 weeks to 8 weeks and salvage cystectomy for recurrence. The overall survival of the 245 patients at the 5-year point and the 10-year point was 47% and 26%, respectively. The Paris, MGH and Radiation Therapy Oncology Group (RTOG) approaches are a variation of this trimodality approach (Fig. 1). Patients commence chemoradiotherapy and undergo cystoscopy after 6 weeks. Patients found to have a complete response (CR) go on to complete their chemoradiotherapy while patients with residual disease proceed to cystectomy. The advantage with this approach is that it selects patients with CRs as candidates for bladder preservation while the remaining patients undergo early salvage cystectomy. The overall survival of the modern bladder preserving series at 5 years ranges from 45% to 52% (Table1) and 54% to 67% of surviving patients have a tumour-free normally functioning bladder. [sup.7,9]-[sup.12]
Unfortunately, in the absence of a randomized study directly comparing radical cystectomy (with or without chemotherapy) with trimodality treatment, it is not possible to have a definite answer that would guide patient care and inform patients. Differences in patient selection and reporting based on pathologic staging (surgical series) versus clinical staging (bladder-preserving trimodality treatment) makes comparability of results from these treatment approaches difficult.
The MGH and RTOG studies show that 70% to 80% of patients achieve CR with chemoradiotherapy and 80% to 89% of these patients remain free from recurrent invasive disease at 5 years. In addition, 60% of patients remained free of any noninvasive or invasive recurrence and 84% of patients with recurrent noninvasive recurrences are maintained in remission with transurethral resection and intravesical therapy.[sup.13,14] Invasive recurrences generally require salvage cystectomy. Salvage cystectomy results in 40% to 50% survival rates at 5 years and local regional control rates of 60%.[sup.12] Interestingly, the 5-year metastatic rate in the early cystectomy patients (who did not complete the full course of chemoradiotherapy) and the later salvage cystectomy patient were similar, at 50%.[sup.12]
A criticism of the chemoradiotherapy approach is that the treated bladder becomes poorly functioning. The MGH group has performed QOL and urodynamic studies (UDS) in 71 patients who are alive with a functioning bladder.[sup.15] The median time from trimodality treatment was 6.3 years, long enough for late effects to arise. Of interest, 75% of patients had normally functioning bladders by UDS. Reduced bladder capacity was identified in 22% of patients, and only in a third of these patients did distressing symptoms arise. Bowel symptoms occurred in 22% of patients with 14% recording any level of distress. Only 8% of patients reported dissatisfaction with their sex lives. In contrast, in the Swedish and Italian series, 13% and 8%, respectively, of cystectomised controls retained useful erection.[sup.16,17]
Overall, most men treated with trimodality treatment retain good bladder function and maintain sexual functioning. A proportion of patients may experience bowel symptoms that may affect their QOL; however, this should to be weighed against the benefits of bladder preservation. A small proportion of patients (2%) will experience unacceptable bladder toxicity requiring a cystectomy.[sup.8] Modern radiotherapy approaches with meticulous attention to planning, shielding of normal structures, intensity-modulated radiation therapy and image guided radiotherapy has the potential to further reduce doses to the bowel and reduce toxicity.
A further criticism of this strategy is that it delays definite surgical treatment. For patients who have an inadequate response, early cystectomy enables this delay to be minimized. In these early salvage patients, the treatment can be considered to be a preoperative chemoradiotherapy approach and randomized studies have failed to show that preoperative radiotherapy is detrimental for important outcomes.
Organ-preserving approaches to manage cancer are well-established and are recognized standards of care in other cancer, such as breast, anal and laryngeal cancers. In contrast, this is less well-established in the management of bladder cancer in North America. Patients have the right to be made aware of all available options in the management of their cancers and should be informed of the pros and cons of the various treatment strategies in a shared decision-making model. Given the complexity of the issues, this discussion is best done in a multidisciplinary setting. Tumour characteristics associated with favourable response to tri-modality treatment include primary T2-3a tumours that are unifocal, tumours less than 5 cm in maximum diameter, no ureteric obstruction, good capacity bladder and visibly complete TURBT.[sup.12]
The reported neoadjuvant series and the meta-analysis have shown a 5% survival benefit regardless of the local modality employed (surgery or concurrent chemoradiotherapy).[sup.18]-[sup.27] Thus neoadjuvant chemotherapy needs to be seriously considered in addition to local treatment strategies. The treatment options boil down to radical cystectomy (with neoadjuvant chemotherapy or adjuvant chemotherapy for selected patients) or TURBT and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy and salvage cystectomy.
In conclusion, patients have the right to be informed of all treatment options in the management of their bladder cancer. Organ preservation is a well-recognized treatment strategy in some cancers. While radical cystectomy is considered the standard of care in North America, results of tri-modality treatment (involving TURBT, neoadjuvant chemotherapy, concurrent chemoradiotherapy and salvage cystectomy) have demonstrated comparable results (though the series are not directly comparable) and 54% to 67% of surviving patients have a tumour-free, normally functioning bladder. Patients with residual or recurrent disease are candidates for either early cystectomy (before completion of their full course of chemoradiotherapy) or later salvage treatment. This maintains the surgical option for recurrent patients while providing patients who achieve a CR the opportunity for bladder preservation. Urodynamic studies and QOL studies have shown that these patients have well-functioning bladders and have mild bowel symptoms following radio-therapy. Besides the obvious benefits of organ preservation, the reported sexual functioning of the trimodality approach is good in contrast to the surgical approach. Patients should be evaluated both for cystectomy and bladder preservation based on patient and tumour characteristics to optimize survival and QOL and minimize toxicity.
This paper has been peer-reviewed.
Competing interests: None declared.
1.. Stein JP, Lieskoversusky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001;19:666-75.
2.. Dalbagni G, Genega E, Hashibe M. Cystectomy for bladder cancer: a contemporary series. J Urol 2001;165:1111-6.
3.. Frazier HA, Robertson JE, Paulson DF. Complications of radical cystectomy and urinary diversion: a retrospective review of 675 cases in 2 decades. J Urol 1992;148:1401-5.
4.. Chang SS, Cookson MS, Baumgartner RG, et al. Analysis of early complications after radical cystectomy: results of a collaborative care pathway. J Urol 2002;167:2012-2016.
5.. Coppin C, Gospodarowicz M, James K, et al. Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. J Clin Oncol 1996;14:2901-7.
6.. Housset M, Maulard C, Chretien YC, et al. Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study. J Clin Oncol 1993;11:2150-2157.
7.. Houssett M, Maulard C, Chretien Y, et al. Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study. J Clin Oncol 1993;11:2150-7.
8.. Rodel C, Grabenbauer GG, Kuhn R, et al. Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol 2002;20:3061.
9.. Shipley WU, Winter KA, Lee R, et al. Initial results of RTOG 89-03: a phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy [abstract 41]. Int J Radiat Oncol Biol Phys 1997;39:155.
10.. Rodel C, Grabenbauer GG, Kuhn R, et al. Invasive bladder cancer: organ preservation by radiochemotherapy. Front Radiat Ther Oncol 2002;36:118-30.
11.. Shipley WU, Kaufman DS, Thakral HK, et al. Long-term outcome of patients treated for muscle-invasive bladder cancer by trimodality therapy. Urology 2002;60:62-8.
12.. Zeitman A, Shipley W. Clinical Radiation Oncology Gunderson & Tepper eds : Churchill Livingstone Elsevier; 2007:1237-60.
13.. Pisters LL, Tykochinsky G, Wajsman Z. Intravesical bacillus Calmette-Guerin or mitomycin C in the treatment of carcinoma in situ of the bladder following prior pelvic radiation therapy. J Urol 1991;146:1514-7.
14.. Zietman AL, Grocela J, Zehr E, et al. Selective bladder conservation using trans-urethral resection, chemotherapy, and radiation: the risk and consequences of superficial recurrences within the retained bladder. Urology 2001;58:380-5.
15.. Zietman AL, Sacco D, Skowronski U, et al. Organ-conservation in invasive bladder cancer treated by trans-urethral resection, chemotherapy, and radiation: results of urodynamic and quality of life study on long-term survivors. J Urol 2003;170:1772-6.
16.. Caffo O, Fellin G, Graffer U, et al. Assessment of quality of life after cystectomy or conservative therapy for patients with infiltrating bladder carcinoma. Cancer 1996;78:1089-97.
17.. Henningsohn L, Wijkstrom H, Dickman PW, et al. Distressful symptoms after radical radiotherapy for urinary bladder cancer. Radiother Oncol 2002;60:215-25.
18.. GISTV (Italian Bladder Cancer Study Group). Neoadjuvant treatment for locally advanced bladder cancer: a randomized prospective clinical trial. J Chemother 1996;8:345-66.
19.. Shipley WU, Winter KA, Lee R, et al. Initial results of RTOG 89-03: a phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy [abstract 41]. Int J Radiat Oncol Biol Phys 1997;39:155.
20.. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349:85.
21.. Stockle M, Meyenburg W, Wellek S, et al. Fortgeschrittenes Blasenkarzinom (Stadien pT3b, pT4a, pN1, pN2). Verbesserte berlebensrten nach radikaler Zystektomie durch 3 adjuvante Zyklen M-VAC/M-VEC-Erste Ergebnisse einer kontrollierten Studie. Akt Urol 1991;22:201.
22.. Bassi P, Pagano F, Pappagallo G. Neo-adjuvant M-VAC of invasive bladder cancer: The G.U.O.N.E. multi-center phase III trial. Eur Urol 1998;33Suppl1:142.
23.. Orsatti M, Curotto A, Canobbio L. Alternating chemo-radiotherapy in bladder cancer: a conservative approach. Int J Radiat Oncol Biol Phys 1995;33:173-8.
24.. Per-Uno Malmstrom, Rintala EMembers of the Nordic Cooperative Bladder Cancer Study Group. Five-year follow-up of a prspective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial 1. J Urol 1996;115:1903.
25.. Sherif A, Rintala E, Mestad O, et al. Neoadjuvant cisplatin-methotrexate chemotherapy of invasive bladder cancer--Nordic cystectomy trial 2. Scand J Urol Nephrol 2002;36:419-25.
26.. Abol-Enein H, El Makresh M, El Baz M, et al. Neoadjuvant chemotherapy in treatment of invasive transitional bladder cancer: a controlled, prospective randomized study. Br J Urol 1997;80Suppl2:49.
27.. Raghavan D, Quinn D, Skinner DG, et al. Surgery and adjunctive chemotherapy for invasive bladder cancer. Surg Oncol 2002;11:55.
Figure and Table
Fig. 1.: Schema for bladder-preserving therapy. TURBT = transurethral resection of the bladder; XRT = radiotherapy. [Figure omitted]
Table 1.: Muscle-invasive bladder cancer: survival outcomes in contemporary series [Table omitted]
 McMaster University, Department of Oncology, Hamilton, ON
Correspondence: Dr. Himu Lukka, Juravinski Cancer Centre, 3rd Floor, 699 Concession St., Hamilton, ON L8V 5C2; fax: 905-575-6326;firstname.lastname@example.org
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