Of note, the vast majority of patients included in these studies received cisplatin, methotrexate, and vinblastine with or without doxorubicin. It is not known whether the doublet regimen of cisplatin plus gemcitabine offers any benefit when administered in the preoperative setting, nor is there any evidence of benefit for carboplatin-based chemotherapy regimens.
On the basis of these findings, preoperative cisplatin-based combination chemotherapy followed by radical cystectomy represents a standard therapeutic option for patients with muscle-invasive bladder cancer who are fit for chemotherapy and for whom the priority is to maximize survival.
External-beam radiation therapy (EBRT) with or without concomitant chemotherapy
Definitive radiation therapy is a standard option that yields a 5-year survival of approximately 30% to 40%. When radiation therapy and chemotherapy are administered concomitantly, the results are better. However, while the addition of chemotherapy to radiation therapy has been shown to reduce local relapse rates, it has not been shown to result in increased survival, decreased mortality, or improved quality of life.
Most protocols for bladder preservation that use combined chemotherapy and radiation therapy have followed a relatively complex algorithm. After the initial stage TUR of the bladder tumor, patients undergo a repeat TUR to maximally resect the tumor. The patient is then treated with synchronous chemoradiation therapy to a dose of roughly 40 Gy followed by a repeat cystoscopy with biopsies to assess for residual cancer. If residual cancer is detected histopathologically, then the chemoradiation therapy is judged to have failed and the patient is advised to undergo a radical cystectomy. If the biopsies at 40 Gy are benign, then chemoradiation therapy is completed to a dose of about 65 Gy.
With definitive radiation therapy, best results are seen in patients with solitary lesions and without carcinoma in situ or hydronephrosis
After radiation therapy, approximately 50% of patients have dysuria and urinary frequency during treatment, which resolves several weeks after treatment, and 15% report acute toxic effects of the bowel.
Randomized trials that directly compare the bladder-preserving chemoradiation therapy approach with radical cystectomy have not been performed; the relative effectiveness of these two treatments is thus unknown.