Joseph A. Smith

BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

BACKGROUND: In carcinoma of the bladder, both intravesical chemotherapy and immunotherapy can induce tumor regression and reduce the rate of recurrence, but the relative merits of these two therapies are unclear. We conducted a multi-institutional study to address this question. METHODS: Patients with rapidly recurrent (stage Ta and T1) or in situ transitional-cell carcinoma of the bladder were randomly assigned to receive either doxorubicin administered intravesically or bacille Calmette-Guérin (BCG) administered both intravesically and percutaneously. The 262 eligible patients were followed for a median of 65 months. Complete responses to treatment of carcinoma in situ were confirmed by biopsy and cytologic analysis of the urine. RESULTS: For patients with Ta and T1 tumors without carcinoma in situ, the estimated probability of being disease free at five years was 17 percent after doxorubicin, as compared with 37 percent after immunotherapy with BCG (P = 0.015). The median times to treatment failure (termination of treatment, due to persistence, recurrence, or progression of disease) were 10.4 and 22.5 months, respectively. For patients with carcinoma in situ the complete-response probability estimates (i.e., the estimated probability of documented disappearance of disease) were 34 percent for doxorubicin (23 of 67 patients) and 70 percent for BCG (45 of 64 patients) (P less than 0.001); the median times to treatment failure were 5.1 and 39 months, respectively. The probability of being disease-free at five years survival among the patients with carcinoma in situ was 18 percent after treatment with doxorubicin and 45 percent after BCG therapy. Patients treated with BCG had a higher incidence of toxic systemic effects and a larger number of local irritative symptoms than patients treated with doxorubicin, but few of these adverse reactions were severe. CONCLUSIONS: As compared with intravesical doxorubicin, immunotherapy with BCG provides improved protection against the recurrence of superficial bladder cancer.

PURPOSE: We examined our recent series of patients who underwent radical cystectomy to determine and analyze the early perioperative morbidity of the procedure in a contemporary series treated with the guidance of a clinical pathway. MATERIALS AND METHODS: We reviewed the records of 304 consecutive patients who underwent radical cystectomy from December 1995 to July 2000. We specifically evaluated complications that developed within 30 days of the procedure. Potential variables predictive of early morbidity were analyzed, including patient age, gender, race, American Society of Anesthesiologists score, type of urinary diversion, smoking history, estimated blood loss, transfusion requirement, pathological stage and operative time. RESULTS: The overall minor complication rate was 30.9% (94 of 304 patients). Postoperative ileus was the most common minor complication, affecting 54 patients (18%). Increased blood loss and major complications predicted a significantly higher likelihood of ileus on multivariate analysis (p = 0.02 and 0.001, respectively). Major complications in 15 patients (4.9%) correlated with higher American Society of Anesthesiologists score, surgical intensive care unit admission and transfusion requirement (p = 0.01, <0.001 and 0.001, respectively). The early mortality rate was 0.3% (1 patient). CONCLUSIONS: Within the framework of a clinical pathway, radical cystectomy can be performed safely with an acceptable rate of early minor and major complications. Delay in the return of bowel function is the most common minor complication. Increased estimated blood loss, transfusion requirement and a major complication predicted a higher likelihood of postoperative ileus. The acceptable rate of early morbidity in this series in a 5-year period validates its use in patients undergoing radical cystectomy.