Controversies Regarding Primary Treatment of Muscle-invasive Urothelial Carcinoma of the Bladder
Radical cystectomy remains the standard of care in the United States for the primary treatment of muscleinvasive urothelial bladder cancer in patients who are medically operable. However, prospective results from multi-institutional bladder preservation trials suggest that this is also a reasonable approach. Table 3 shows equivalent long-term survival with radical cystectomy compared with bladder preservation. When comparing studies of each approach, there are two main caveats. First, surgical series involve pathologically staged tumors as opposed to clinically staged tumors in the chemoradiation trials, favoring the surgical series because many cancers are upstaged at the time of surgery. Second, retrospective radical cystectomy series do not report an intent-to-treat analysis, which is in contrast to prospective chemoradiation trials. Randomized trials comparing these two treatments are unlikely to be forthcoming in the near future and are based, in part, on physician biases.
Inappropriate surgical candidates include patients who have poor nutrition, high anesthesia risk, multiple comorbidities, and loss of cognitive function. However, age alone should not necessarily rule out surgery because the rates of major and minor surgical complications are no different in patients with bladder cancer who are 80 years of age compared with those who are younger. Treatment decisions should be based on patient preferences and an understanding of the QOL issues associated with each treatment modality.
Quality of Life
For patients undergoing radical cystectomy, three sur gical urinary reconstructions have been developed to eliminate urine. Typically, the preferred method is to construct an orthotopic neobladder. In this procedure, a neobladder is created from the small bowel and subsequently connected to the ureters and urethra in an attempt to maintain continence via the urethra. Urination is performed similarly to an intact bladder, although catheterization of the urethra is sometimes necessary for emptying. A second approach is an ileal conduit (urostomy) in which the bladder is removed or bypassed and a conduit is constructed of small bowel or colon that carries urine to an opening on the abdominal wall. The urine is collected in a drainable pouch secured to the abdomen. A third approach involves a continent urinary diversion. This reconstruction involves the creation of an internal pouch from loops of the intestine connected to the abdominal wall. There is a "one-way" passage between the opening on the abdominal wall (stoma) and the internal pouch so that urine is contained within the pouch. Urine is drained by passing a catheter through the stoma and into the pouch every 3 to 4 hours.
Several QOL studies have evaluated these reconstructive methods. A study in Japan assessed 85 patients following radical cystectomy, 48 with an orthotopic neobladder (26 with an ileal neobladder and 22 with a colon neobladder) and 37 with an ileal conduit. QOL was evaluated using the Short Form-36 survey that contains 36 questions assessing physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning, and mental health. No significant difference existed in any scale scores between the neobladder and ileal conduit groups. However, general health and social functioning in both the neobladder and ileal conduit groups were significantly lower than those in the United States general population. Another study evaluated QOL in 49 neobladder and 23 ileal conduit patients. The researchers found on multivariate analysis that no significant difference was present in QOL between the two groups (P = .09). A third study evaluated 224 patients following radical cystectomy and also found no difference regarding the type of diversion used.
In addition to urinary function, erectile function is a major concern following radical cystectomy. One study evaluated 49 sexually active men who underwent radical cystectomy; 33% of those had undergone a nerve-sparing procedure. With a median followup of 47 months, the mean sexual health inventory scores decreased from 22 to 4 (P < .05), with 86% of men unable to perform vaginal penetration. This is supported by a Swedish cross-sectional comparison study that found 13% of patients receiving radical cystectomy had intercourse in the previous month compared with 38% of patients receiving chemoradiation therapy. In an Italian series, 8% of patients who underwent radical cystectomy had erectile function. This is in contrast to a Massachusetts QOL study of chemoradiation therapy that revealed that 8% of men reported dissatisfaction with their sex lives and 50% of men had normal erectile function.
Toxicity
A surgical series involving 1,142 patients reported that 64% of patients had more than one complication in the 90 days following surgery. Of those patients, 13% had major complications (grades 3 to 5). In addition, the readmission rate was 26% with a 90-day mortality of 2%. The perioperative morbidity and mortality rates of salvage cystectomy after previous bladder chemoradiation therapy were no different from primary cystectomy.
A major criticism of maximal TURBT followed by chemoradiation therapy is that the preserved bladder ultimately becomes a poorly functioning bladder. However, a group in Massachusetts published results of QOL and urodynamic studies on 71 patients with intact bladders after chemoradiation therapy. With a median follow-up of 6.3 years, they found that 75% of patients had normally functioning bladders based on urodynamic studies, and 85% reported no urgency or occasional urgency. In addition, 22% had a reduced bladder capacity, with 7 of the patients reporting significant symptoms. Efstathiou et al published late pelvic toxicity from 157 prospectively followed patients from an RTOG protocol after bladder preservation treatment with a median follow-up of 5.2 years. They reported a 6% grade 3 or higher genitourinary system toxicity. This report is consistent with findings by Weiss et al who found that 4% of patients were dissatisfied with their bladder function following chemoradiation therapy. In addition, Rödel et al reported that 2% of patients experienced unacceptable bladder toxicity requiring palliative cystectomy. Ultimately, patient preference should drive modality selection.