The primary goal of treatment of muscle-invasive bladder cancer is cure of the cancer itself. Traditionally, this goal has been best achieved by radical cystectomy.1 Unfortunately, this approach requires diversion of urine by the creation of a substitute bladder. In our opinion, if cancer can be eradicated and satisfactory bladder function can be preserved, an optimum therapeutic goal has been achieved. In such a case, major surgery is avoided, which results in fewer possible complications, and reduced urological risks including no stoma and appliance problems such as infection, incontinence and leakage, as well as reduced erectile dysfunction and sexual dysfunction in female patients and renal dysfunction.1
Cure is most likely to be achieved if the cancer is confined to the bladder, as shown by a negative CT scan of the chest, abdomen and pelvis, and a negative bone scan. We recognize that there is a high probability of circulating cancer cells associated with muscle invasion and that it is not possible to completely rule out the presence of micrometastases at the time of pretreatment evaluation. Transurethral resection of the tumor is not only performed for diagnosis and clinical staging, but also for potential complete eradication of the tumor to the extent that this can be determined endoscopically.2 Cancer cells could certainly still be present within the bladder wall or in the vicinity of the bladder after transurethral resection of the bladder (TURB).
The rationale for chemoradiation after TURB is, therefore, to eradicate these cells. In addition to its local and systemic tumorcidal effects, chemotherapy permits radiosensitization of bladder cancer cells. Radiation therapy given immediately after chemotherapy potentially eradicates all cancer cells in the bladder wall and surrounding tissues more effectively than would radiation alone; however, if tumor cells resist the cidal effects of chemoradiation it is assumed that these surviving cells in the bladder wall will be visible or diagnosable by follow-up cystoscopy and reresection of the original tumor-bearing area. In such an instance, prompt cystectomy will probably prevent this residual nidus of tumor from metastasizing (Figure 1).
Objective and definitive re-evaluation of the bladder after the initial phase of therapy is central to assessing the success of the TURB and chemoradiation approach. Cytological evaluation of urine and/or bladder washings, and CT or MRI of the bladder and endoscopic reresection are required. Our concerns that residual or new cancers might be missed have been allayed over the past two decades by following patients closely with sequential cystoscopies and biopsies for at least a year after the initial treatment cycle.3 Thereafter, biopsies are performed if the surveillance cystoscopy findings indicate that they are necessary. If the initial evaluation fails to show persistent or recurrent disease, long-term local remission and cure are possible. All the protocols used at the Massachusetts General Hospital or by the Radiation Therapy Oncology Group (RTOG) call for salvage cystectomy if less than an initial complete success is achieved. This protocol also applies with each successive endoscopic evaluation in case an invasive recurrence is identified.
Patients with transitional-cell carcinoma clinical stage cT2NxM0 and cT3NxM0 are potentially eligible for entry to a bladder-preserving protocol. Results are best when a visibly complete TURB can be performed in the absence of tumor-related hydronephrosis. The successful ablation of carcinoma in situ is probably because of electrocauterization rather than chemoradiation. Post protocol, carcinoma in situ can be treated with intravesical therapy.4 Survival results correspond with clinical tumor stage at diagnosis, which correlates with the probability of nondiagnosable, micrometatastatic disease. Survival outcomes are similar for patients of similar clinical stages who undergo bladder-sparing therapy versus radical cystectomy (Table 1).5, 6, 7, 8
Over the past 22 years, treatment protocols have become more streamlined. For example, radiation and chemotherapy are administered as an outpatient procedure. In addition, the interval between commencing treatment and having the initial response evaluation has been shortened to 7 weeks, which minimizes the delay before recommending cystectomy, should that be necessary.
Salvage cystectomy is indicated if invasive cancer persists or recurs during follow-up. We have not encountered increased surgical complications caused by previous pelvic irradiation. Urinary diversion is preferable to an orthotopic bladder to avoid radiation-related healing problems. If possible, the ureters and bowel segment for the conduit should be cut high enough in order to avoid using tissue that has been heavily irradiated.
Treatment-related toxic effects are shown in Table 2 with bone-marrow toxicity (manifested as decreased blood counts) being the most prevalent.9 Fatigue can be considerable, especially during the consolidation phase of the protocol. The initial protocol treatment phase is demanding as it includes chemotherapy sessions given between radiation treatments in the morning and afternoon. Adhering to this treatment approach, which also includes four cycles of adjuvant chemotherapy, requires attentive, engaged treating clinicians because of its multispecialty involvement. Usually the patients are highly motivated to comply with protocol requirement because the driving force is the patient's desire not to lose the bladder. High motivation on the part of the urologist is also crucial. There is no part for a half-hearted TURB. Rather, TURB must be done with the determination to resect all visible tumor. Nothing less will suffice. The rewards for success include a happy, grateful and disease-free patient.10 Quality-of-life studies have also shown a significant degree of patient satisfaction.11
