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Commentary (Corica/Keane): Organ Preservation in Muscle-Invasive Bladder Cancer

Commentary (Corica/Keane): Organ Preservation in Muscle-Invasive Bladder Cancer

This is a timely review on the current status of selective bladder preservation for muscleinvasive bladder cancer. Although controversial, the concept is extremely attractive to patients, and evidence from retrospective and/or small series demonstrate its efficacy. Most of these trials, however, have included highly selected patients. Unfortunately, there are few, if any, ongoing randomized controlled trials comparing radical cystectomy to bladder-preserving protocols. Although the overall 5-year survival rate for radical cystectomy and trimodality therapy is approximately 50%, patients with pure T2 disease frequently achieve 5-year survival rates approaching 70%.[1-3] While it is clearly beyond the scope of this editorial to go into an in-depth analysis of all the studies reported to date, several significant questions remain. Issues for Debate
First, the stalwart of bladder preservation has been the assertion that quality of life is considerably improved in this group of patients, as compared to radical cystectomy series. However, improvements in surgical technique and postoperative care have resulted in current perioperative mortality rates of less than 2%[2,3] and potency rates up to 64% after nerve-sparing radical cystectomy.[ 4] Furthermore, recent reports show similar subjective quality-of-life results after orthotopic urinary diversion compared to matched controls[5] and similar rates of patient-reported urinary incontinence among those who underwent trimodality therapy (18% vs 19%).[6] Second, bladder cancer staging is inaccurate and may result in significant understaging of T1 (75%) and T2 (55%) cancers on transurethral resection specimens.[2,7] Such patients would be denied the opportunity of a beneficial surgical approach with lymph node dissection were they to undergo a bladder-preserving protocol. Third, evidence from nonrandomized studies suggests that subtotal transurethral resection[8] and noncompletion or reduced-dose completion of chemoradiation protocols are associated with poorer survivals.[9,10] Recent series report 15% to 20% noncompletion rates,[11-13] up to 30% dose reduction, and 4% to 5% mortality rates during induction therapy due to toxicity.[13] Additionally, cancer may progress during chemoradiation in up to 10% of patients.[13] Finally, reported local invasive recurrence rates of 15% after complete response to trimodality therapy[11] exposes patients to the risk of metastasis that would have been eliminated by primary cystectomy. Fourth, salvage cystectomy rates, even with the most up-to-date treatment protocols, remain in the area of 20% to 30%[11,13] due primarily to failure to control disease but also due to treatment complications (up to 10%).[14] Mortality of salvage cystectomy is close to 8%[14] and has remained stable. The procedure is typically more difficult with fewer reconstructive options available, particularly as they relate to continent orthotopic neobladders. Fifth, the cost and time commitment required for multimodality bladder- preserving strategies, including diagnosis, treatment, and surveillance, greatly surpasses that of radical cystectomy. Zietman et al admit that such strategies require the coordinated efforts of at least three specialties and more than 6 months to complete incurring costs twice that of radical cystectomy.[ 15] Patients are committed to intensive, lifelong surveillance for cancer recurrence, which may arise 10 to 15 years later. Other Considerations
Although survival with current multimodality, bladder-sparing approaches appears to be comparable to radical cystectomy, considerations such as complexity, cost, and morbidity of bladder- sparing approaches must be taken into account and compared to the putative improvement in quality of life achieved with bladder retention. Current advances in surgical approaches must also be taken into consideration. Finally, while bladder-preserving strategies are an extremely attractive option for patients wishing to retain their bladders in the face of muscleinvasive bladder cancer, these patients should be aware that the chemotherapeutic protocols being undertaken have achieved, at best, modest success when applied to more advanced forms of the disease and that the ideal combination of chemotherapy and radiation has yet to be devised. With the development of newer more effective chemo- and radiotherapy protocols, it may well be that such a strategy ultimately will prove successful, but at the present time, the standard of care should remain a radical surgical approach. Conclusions
In the absence of definitive data such as that provided by a randomized trial, the debate will continue, using retrospective small analyses to scrutinize outcome. Protagonists will claim that bladder-conservation strategies deal adequately with a potentially fatal disease with enhanced quality of life through bladder preservation. Antagonists will claim that the bladder-sparing strategy places patients' lives at unnecessary risk, given that quality of life has improved considerably with the development of nerve-sparing orthotopic neobladder techniques. Presently, both strategies are appropriate, but only provided that the patient is fully educated as to the risks and benefits of each strategy. Unlike prostate cancer, in which time to death is frequently measured in decades, a considerable number of patients will die within 5 years. Some might not if they have undergone standard treatment with radical cystectomy, as no study to date has suggested an improved outlook with bladder-sparing protocols.

Disclosures

The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References

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2. Pagano F, Bassi P, Galetti TP, et al: Results of contemporary radical cystectomy for invasive bladder: A clinicopathological study with an emphasis on the inadequacy of the TNM classification. J Urol 145:45-50, 1991.
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4. Brendler CB, Steinberg GD, Marshall FF, et al: Local recurrence and survival following nerve-sparing cystoprostatectomy. J Urol 144:1137-1140 1990.
5. Henningsohn L, Stevan K, Kallestrup EB, et al: Distressful symptoms and well being after radical cystectomy and orthotopic bladder substitution compared with a matched control population. J Urol 168:168-174, 2002.
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12. Hussain SA, Stocken DD, Peake DR, et al: Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer. Br J Cancer 90:2106-2111, 2004.
13. Hagan MP, Winter KA, Kaufman DS, et al: RTOG 97-06: Initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys 57:665-672, 2003.
14. Chahal R, Sundaram SK, Iddenden R, et al: A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire. Eur Urol 43:246-257, 2003.
15. Zietman AL, Shipley WU, Kaufman DS, et al: A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil, and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer. J Urol 160:1673-1677, 1998.

 
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