In an editorial accompanying the recently reported UK phase III Bladder Cancer 2001 (BC2001) trial, Shipley and Zietman, from Massachusetts General Hospital and Harvard Medical School, point out that this trial shows that “the addition of a very tolerable regimen of chemotherapy to radiotherapy cures significantly more patients than radiotherapy alone and at a rate similar to those in the best cystectomy series.” ^1,2 It is noted that many patients with bladder cancer do not currently receive potentially curative therapy, including some 35% of patients aged 70 to 80 years and 55% of those aged 80 years or older, and that a large majority of such patients would probably tolerate the regimen used in BC2001. Indeed, this approach can likely be recommended for younger, healthier patients with invasive disease if it can be shown that long-term survival is not compromised and if patients accept that should salvage cystectomy be required, it may be a more challenging procedure after chemoradiotherapy.

In this regard, long-term follow-up of series of patients with invasive bladder cancer indicate similar 10-year rates of disease-free survival of 55% to 60% irrespective of whether initial treatment was radical cystectomy or chemoradiotherapy, with rates of complications of salvage surgery being somewhat higher with chemoradiotherapy, but not as high as predicted. Additional factors may eventually play a role in deciding between initial cystectomy and chemoradiotherapy. It recently has been found that high expression of the MRE11 protein (which is active in cellular response to radiotherapy) predicted improved eradication for bladder tumors and cancer-specific survival after radiotherapy but not after cystectomy. Analysis of the effect of MRE11 expression on outcome after chemoradiotherapy with 5FU/mitomycin is planned in both an NCI Bladder Cancer Task Force project and a future BC2001 analysis.

Historical Perspective

According to the commentators, given the important history of cisplatin as a radiosensitizer in invasive bladder cancer, its use should not be overturned rashly. Until a direct comparison of chemotherapy regimens is performed, it may be that physicians will use 5-FU/mitomycin in elderly patients and cisplatin in younger patients, who tend to have better renal function and overall health.

Finally, the commentators state “The development of organ-sparing procedures in breast and prostate cancer was promoted by vocal patient advocacy groups with the use of the Internet and social networking. We anticipate that the publication of this important study will help patients with bladder cancer to find their voice. Cystectomy will always remain part of an organ-sparing approach, but this trial shows that as a primary treatment, it can now be regarded as one of several options for the patient.” ■

Disclosure: Drs. Shipley and Zietman reported no potential conflicts of interest.

References

1. 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.

2. Shipley WU, Zietman AL: Old drugs, new purpose—bladder cancer turning a corner. Editorial. N Engl J Med 366:1540-1541, 2012.