Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases.

PURPOSE: Symptomatic, hormone refractory prostate cancer (HRCAP) is a major cause of morbidity with a median survival of less than 12 months and a 2-year survival of only up to 10% in most series. Mitoxantrone has been approved by the Food and Drug Administration for HRCAP. Preliminary data suggest that DPPE (N,N-diethyl-2-[4-(phenylmethyl) phenoxy]-ethanamine) or tesmilifene modulates cytotoxics to enhance the anticancer effect. In this phase II trial we assessed whether there is sufficient evidence of enhanced efficacy of DPPE and mitoxantrone to lead to a phase III clinical trial. MATERIALS AND METHODS: A total of 29 patients with a median age of 73 years, of whom 10% were older than 80 years, with progressive HRCAP received 5.3 mg/kg DPPE intravenously every 3 weeks, 12 mg/m mitoxantrone intravenously every weeks and 5 mg prednisone orally twice daily. All patients had pain at presentation, while 97% had bone metastases, 10% had liver metastases and 17% had lung metastases. Median prostate specific antigen (PSA) was 210 ng/ml (IQR 77 to 430). RESULTS: Of the patients 75% had some pain improvement, 66% had decreased analgesia, 59% had a PSA decrease of 50% or greater and 45% had a PSA decrease of 75% or greater. Actual (not actuarial) 2-year survival was 21%. CONCLUSIONS: Despite major limitations of historical comparison the PSA decrease and decreased symptoms with DPPE-mitoxantrone-prednisone compare favorably to those of mitoxantrone-prednisone and docetaxel-estramustine in the literature. The 2-year survival rate of 21% mandates further assessment. This will be tested in a phase III Southwest Oncology Group trial.

Comparison of surgery alone with surgery and adjuvant radiotherapy for pT3N0 prostate cancer.

OBJECTIVE: To compare the outcome between patients with pT3N0 adenocarcinoma of the prostate treated with radical prostatectomy (RP) and those receiving RP followed by a planned course of postoperative radiation therapy (RT). PATIENTS AND METHODS: During a period of 22 years 622 patients with pT3N0 prostate cancer were treated in one medical centre by RP. Of these, 199 (32%) were treated with surgery alone while 423 (68%) received planned postoperative pelvic RT (median 48 Gy). Patients were selected for RT by having a higher incidence of adverse prognostic factors than those undergoing RP alone. These prognostic factors included pathological stage (P = 0.001) preoperative prostate specific antigen (PSA) level (P < 0.001) and Gleason score (P = 0.18). The patients' median age was 66 years; the median follow-up was 6.1 years for all patients, 7 years for RP + RT and 5 years for the RP-alone. RESULTS: The 5- and 10-year actuarial survival was 92% and 73%, respectively, for RP + RT patients, and nearly identical for those in the RP-alone group (P = 0.73). The 5- and 10-year disease-free survival (DFS; PSA < 0.05 ng/mL) was 69% and 51%, respectively, for the former, and 71% and 60%, respectively, for the latter group. There was no significant difference in DFS between the treatment groups by pathological stage and Gleason score (P = 0.77). Likewise, there was no significant difference in mean and median time to relapse. A preoperative PSA level of < 10 vs 10-25 vs > 25 ng/mL did not influence overall survival but a PSA of > 25 ng/mL was predictive of DFS (P = 0.02). In a multivariate analysis the Gleason score was the most important predictor for overall survival and DFS (P < 0.001), while pathological stage was predictive of clinical recurrence and DFS (P < 0.001). After controlling for pathological stage and Gleason score, RP + RT patients were predicted to recur at 92% of the rate of RP-alone patients (P = 0.65). In all, 43 (10%) patients developed a clinical recurrence in the RP + RT group, including 30 (7%) patients with distant metastases alone, 13 (3%) with local recurrence, with an additional 88 (21%) who had PSA recurrence (PSA > 0.05 ng/mL). This compared with 13 (6.5%) patients with clinical recurrence, including seven (3.5%) with local recurrence and 23 (11.6%) with PSA > 0.05 ng/mL in the RP-alone group. Postoperative RT was well tolerated and did not add to the incidence of surgical complications. CONCLUSION: We propose that postoperative RT, as described here, helped to reduce the incidence of local recurrence and improved DFS to equal that of a lower-risk group of patients treated with RP alone. A randomized comparison is needed to define the role of adjuvant RT in patients with pT3N0 disease.

Her-2/neu expression in prostate cancer: high level of expression associated with exposure to hormone therapy and androgen independent disease.

PURPOSE: HER-2/neu is a proto-oncogene that encodes a transmembrane receptor belonging to the family of epidermal growth factor receptors. Increasing evidences indicates that HER-2/neu may contribute to hormone resistance in prostate cancer. We investigated HER-2/neu expression in primary, androgen dependent and advanced androgen independent prostate cancer, and its potential value as a marker of disease progression. MATERIALS AND METHODS: Immunohistochemical testing was performed to investigate HER-2/neu expression in 81 patients with prostate cancer, including 31 with pathological stage C disease treated with radical prostatectomy without preoperative androgen ablation therapy (untreated group), 30 with pathological stage C disease treated before surgery with androgen ablation therapy (treated group) and 20 with advanced androgen independent prostate cancer (androgen independent group). Tumors were classified based on the percent of tumor cells showing HER-2/neu membrane immunoreactivity as low (50% or less) and high (50% or greater) expression. RESULTS: Of the 31 prostate tumors in the untreated group 9 (29%) showed high HER-2/neu expression versus 15 of 30 (50%) in the treated and 17 of 20 (85%) in the androgen independent groups. The difference in HER-2/neu expression was significant in the untreated and androgen independent (p <0.001) and in the treated and androgen independent (p = 0.016) groups. There was a significant association of Gleason score with HER-2/neu expression in the untreated group (p = 0.038) but not in the treated group. No association was found of tumor substage with HER-2/neu expression. In the untreated group patients with tumors showing high HER-2/neu expression had a decreased survival rate (p = 0.044). CONCLUSIONS: High HER-2/neu expression is highly associated with exposure to hormone therapy and androgen independence. It may contribute to androgen independence in prostate cancer and identify patients with prostate cancer more likely to have disease progression, particularly those not exposed to previous hormone therapy.

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.

PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

Nonrandomized comparison of surgery with and without adjuvant pelvic irradiation for patients with pT3N0 adenocarcinoma of the prostate.

The purpose of this study was to evaluate the outcome of radical prostatectomy alone and compare it with that of surgery followed by planned adjuvant radiotherapy in patients with pT3N0 prostate cancer (CaP). A total of 402 patients with CaP were treated with prostatectomy, including 311 (77%) who received a planned course of adjuvant radiotherapy (RT) (surgery [S] + RT) to the prostatic fossa (median dose: 48 Gy) and 91 (23%) who had surgery alone. Patients in the former group had worse risk factors than those in the latter group, such as a higher clinical and pathologic stage (p = 0.001), higher Gleason score (p = 0.09), and higher preoperative prostate-specific antigen (PSA) level (p = 0.0001). PSA failure was defined as more than 0.05 ng/ml. Median follow-up was 59 months. The 5- and 10-year overall survival for the 311 S+RT patients was 91% and 81%, respectively, and it was similar for those 91 in the surgery-alone group, p = 0.59. The 5- and 10-year probability of freedom from PSA and/or clinical failure for the former group was 70% and 53%, respectively, whereas it was 66% and 46%, respectively, for the latter group, p = 0.72. Any recurrence developed in a total of 96 (31%) patients in the S+RT group as compared with 23 (25%) in the surgery-alone group. Local recurrence was noted in 10 (3.2%) S+RT and in 6 (6.6%) surgery-alone patients (N.S.). The time to clinical or chemical recurrence was also similar for both treatment groups (median time: 3.0 versus 3.8 years). Patients with pT3b tumors had relatively poor 5- and 10-year disease-free survival (53% and 32%, respectively, for S+RT and 38% and 0%, respectively, for surgery alone, p = 0.82). In multivariate analyses, pathologic stage and Gleason score were independent predictors of recurrence, each with p < 0.001 after controlling for the other. The worst prognostic category included patients with pT3bN0, Gleason score 7-10 disease who had 5.0 times the risk of recurrence as compared with pT3aN0, Gleason score 2-6 patients. No significant difference in disease-free survival by the treatment group was seen in Cox regression analysis controlling for pathologic stage (p = 0.59), Gleason score (p = 0.99), and PSA (p = 0.28). S+RT patients were predicted to have disease recurrence at 83% the rate of surgery-alone patients, p = 0.42. Preoperative PSA (>25 ng/ml) was predictive of recurrence (2.0 x risk) in univariate analysis, but it was not a significant predictor in multivariate analysis. It appears that moderate-dose, localized fields postoperative irradiation reduced the incidence of local recurrence in patients who were at a higher risk of recurrence as compared with those treated with surgery alone. New treatment strategies need to be developed to manage pT3bN0, Gleason score 7-10 patients whose 10-year disease-free survival was poor.

Update on impact of moderate dose of adjuvant radiation on urinary continence and sexual potency in prostate cancer patients treated with nerve-sparing prostatectomy.

OBJECTIVES: Adjuvant radiotherapy to the prostatic bed at moderate doses of 45 to 54 Gy achieves results comparable to higher doses. We studied the effect of moderate doses of postoperative radiation therapy on urinary continence and sexual potency in prostate cancer patients who had undergone nerve-sparing prostatectomy. METHODS: Between November 1983 and December 1992, 255 prostate cancer patients were selected to undergo nerve-sparing prostatectomy. A total of 94 (37%) patients had received adjuvant postoperative radiotherapy, 45 to 54 Gy to the prostatic bed, based on microscopic positive margins, seminal vesicle involvement, and/or Gleason score. Subjective patient reports regarding the potency and urinary continence status were recorded during a semistructured telephone interview at 3 or more years after treatment. The findings in irradiated and nonirradiated patients were compared and correlated to those obtained from the same patients preoperatively and 1 year postoperatively. RESULTS: At 3 or more years of follow-up no significant difference among irradiated and nonirradiated patients was detected. Most patients described optimal urinary continence and approximately one third had maintained potency after bilateral nerve-sparing prostatectomy. None of the patients who had undergone unilateral nerve-sparing surgery remained potent. Using a multivariable analysis, the significant predictors for maintaining potency were the status at 1 year postoperatively and bilateral versus unilateral nerve-sparing procedure. CONCLUSIONS: Doses of adjuvant radiation therapy in the range used (45 to 54 Gy) did not affect the long-term pattern of maintenance of either function.

Tube gastrostomy after radical cystectomy and urinary diversion: surgical technique and experience in 709 patients.

We describe our surgical technique of tube gastrostomy and report our experience with 709 patients who underwent cystectomy and urinary diversion with gastrostomy tube placement from January 1988 to December 1997. This modified Stamm technique provides an effective means of gastric decompression without the discomfort associated with nasogastric decompression, is associated with a low complication rate (0.05%), and may be considered as the procedure of choice when gastric drainage is required after radical cystectomy and lower urinary tract reconstruction.

Comparison of outcomes of radical prostatectomy with and without adjuvant pelvic irradiation in patients with pathologic stage C (T3N0) adenocarcinoma of the prostate.

Patients with localized adenocarcinoma of the prostate gland (CaP) are frequently (approximately 50%) found at radical prostatectomy to have extracapsular disease or positive surgical margins. The management of these patients is a subject of controversy because some question the impact of this manifestation of CaP on patient survival or disease-free survival. Between 1976 and 1991, 241 patients with pathologic stage C (T3N0) were treated in this medical center. Of these 241 patients, 201 (83%) received a planned postoperative pelvic irradiation consisting of 48 Gy given to the prostatic fossa, whereas 40 (17%) patients were treated with radical prostatectomy alone. The two study urologists selected these patients not to receive postoperative irradiation based on intraoperative findings and important prognostic factors. Comparison of treatment outcomes in these two treatment groups is a subject of this report. The 201 patients treated with surgery-radiotherapy (S+RT) combination had a higher pathologic stage, greater incidence of seminal vesicle involvement, p = 0.002, and higher mean and median preoperative prostate-specific antigen level, p < 0.0001, than the 40 surgery (S) alone patients. There was no significant difference in the incidence of higher Gleason's score by the treatment group, p = 0.14. In univariate analysis, there was no significant difference in survival, disease-free survival, and time to failure between the two treatment groups. In multivariate analysis after controlling for pathologic stage and Gleason's score, the 201 adjuvant radiotherapy patients were predicted to have recurrence at 68% (95% confidence interval 39%-118%) the rate of the 40 surgery-alone patients. Local recurrence with or without metastatic disease was found in 10% of surgery-alone patients as compared to 5% in those also receiving postoperative irradiation. Treatment tolerance was very good with minor radiotherapy complications only. There was no significant difference in the incidence of incontinence between the two treatment arms. In summary: (a) The use of moderate-dose postoperative radiotherapy was of low toxicity and it did not increase the incidence of incontinence. (b) Local recurrence was 5% in S+RT and 10% in S-alone patients. (c) In multivariate analysis, S+RT patients had 68% rate of recurrence of S-alone patients. (d) Adjuvant RT probably reduces the risk of recurrence in patients with poor prognostic factors. (e) These data need to be interpreted with caution because of the nonrandomized nature of the study.

Quality of life after radical cystectomy for bladder cancer in patients with an ileal conduit, cutaneous or urethral kock pouch.

PURPOSE: Radical cystectomy for bladder cancer is associated with many changes in bodily function with sexual and urinary dysfunction most prevalent. However, little research has been done on how efforts to improve erectile function relate to quality of life. Also, the psychological benefits associated with continent urinary diversion have not been fully explored. We compared long-term quality of life outcomes among 3 urinary diversion groups, and between patients who had and had not received an inflatable penile prosthesis. MATERIALS AND METHODS: The 224 participating patients completed 4 self-reporting questionnaires, including the profile of mood states, and adapted versions of the sexual history form, body image dissatisfaction scale and quality of life questionnaire. We compared self-reports of emotional distress, global quality of life, sexuality, body image dissatisfaction, urinary diversion problems, and problems with social, physical and functional activities in patients with advanced bladder cancer who underwent urinary diversion, including an ileal conduit in 25, cutaneous Kock pouch in 93 and urethral Kock pouch in 103. Patients who had or had not received an inflatable penile prosthesis after cystectomy were also compared in regard to quality of life variables. RESULTS: Regardless of type of urinary diversion the majority of patients reported good overall quality of life, little emotional distress and few problems with social, physical or functional activities. Problems with urinary diversion and sexual functioning were identified as most common. After controlling for age analysis of variance showed no significant differences among urinary diversion subgroups in any quality of life area. However, t tests controlling for age indicated that penile prosthesis placement was significantly associated with better sexual function and satisfaction. CONCLUSIONS: Quality of life appears good in these long-term survivors of advanced bladder cancer. The type of urinary diversion does not appear to be associated with differential quality of life. Findings suggest that physicians may wish to discuss urinary diversion problems and sexual dysfunction as long-term correlates of radical cystectomy for bladder cancer. Furthermore, they may also wish to discuss the option of erectile aids in men with erectile dysfunction after cystectomy.

Adjuvant radiotherapy in patients with pathologic Stage C (pT3N0) adenocarcinoma of the prostate.

OBJECTIVES: This report is an update on the outcomes in the management of pathologic Stage C (T3N0) prostate cancer (CaP) with postoperative irradiation. METHODS: Between 1976 and 1994, 311 patients with pathologic Stage C CaP were treated with radical prostatectomy. Pathologic stage was as follows: C1, 60 patients (19%), C2, 146 patients (47%), and C3, 105 patients (34%). Gleason score was 2 to 4 in 10 patients (3.2%), 5 to 6 in 121 (39%), 7 in 101 (32%), and 8 to 10 in 76 (24%); median prostate-specific antigen (PSA) level was 11.9 ng/mL. Postoperative irradiation consisted of a median dose of 48 Gy. Follow-up was up to 18 years (median 5). RESULTS: The 10-year actuarial survival was 81% and 10-year disease-free survival was 51%. Pathologic stage and Gleason score were independently predictive of recurrence, each with P >0.001 after controlling for the other. Patients with pathologic Stage C3 and Gleason score 7 to 10 were in the worst prognostic category and had 5.4 times the risk of recurrence compared with patients with pathologic Stage C1-C2, Gleason score 2 to 6. Preoperative PSA was a good (P = 0.02) predictor of disease-free survival. Clinical recurrence was seen in 28 patients (9%), including 10 (3.2%) with local recurrence. PSA recurrence (PSA greater than 0.05 ng/mL) developed in 68 patients (22%). CONCLUSIONS: With the known limitations of a nonrandomized clinical trial, on the basis of the experience of this study we recommend the use of moderate dose, limited-field postoperative radiotherapy in patients with pathologic Stage C disease with Gleason score greater than 4.

Orthotopic urinary diversion with preservation of erectile and ejaculatory function in men requiring radical cystectomy for nonurothelial malignancy: a new technique.

PURPOSE: Nerve sparing techniques to preserve sexual function in men undergoing cystoprostatectomy have been well documented. The patient who desires to remain fertile with ejaculatory function poses an additional challenge. We describe a new technique for radical cystectomy and orthotopic diversion with preservation of the vasa deferentia, seminal vesicles, posterior prostate and neurovascular bundles. MATERIALS AND METHODS: Four men with a median age of 26 years presented with bladder pathology necessitating cystectomy, including signet ring carcinoma of the bladder dome, leiomyosarcoma of the anterior bladder wall, leiomyosarcoma of the lateral bladder wall, and extensive polypoid cystitis glandularis of the trigone and posterior wall refractory to conservative and transurethral management. All patients wished to maintain fertility and ejaculatory function. We detail the surgical technique of extirpation of the bladder and anterior proximal prostate en bloc with preservation of the vasa deferentia, seminal vesicles, posterior prostate and neurovascular bundles as well as construction of an orthotopic reservoir. RESULTS: Followup ranges from 4 months to 5 years. All patients remain completely continent and void to completion without difficulty. Erectile function is normal in all cases. Of 3 patients who ejaculate antegrade 1 has fathered a child. The remaining patient ejaculates retrograde. There has been no tumor recurrence. CONCLUSIONS: The technique of cystectomy with preservation of the vasa deferentia, seminal vesicles, posterior prostate and neurovascular bundles is an excellent option in men with nonurothelial malignancy or another pathological condition that necessitates cystectomy, and in whom preservation of fertility and potency is desirable. All of our patients are fully potent and achieve ejaculation. Even the patient with retrograde ejaculation remains fertile. In terms of practicality semen retrieval from urine is much simpler than epididymal sperm aspiration and in vitro fertilization.

Hydronephrosis as a prognostic indicator in bladder cancer patients.

PURPOSE: Pathological stage is the standard measure of prognosis in patients who have undergone radical cystectomy for bladder cancer. Despite the development of new imaging techniques, clinical staging for bladder cancer continues to be inaccurate. We investigated whether the presence of unilateral or bilateral upper tract obstruction could accurately predict advanced cancer stage (extravesical extension, stage greater than p3b or N+). MATERIALS AND METHODS: A retrospective study of 415 patients diagnosed with transitional cell carcinoma of the bladder who were treated with radical cystectomy between 1983 and 1993 was conducted. All patients were followed for survival. The criteria for analysis included hydronephrosis status (no obstruction, unilateral, bilateral) as well as pathological stage of the tumor. RESULTS: Of 415 patients 72% presented with no, 22.7% unilateral and 5.3% bilateral obstruction. Our results showed a significant correlation between hydronephrosis and advanced cancer stage (p <0.0001), and decreased patient survival (p <0.0001). More than 90% of patients with bilateral obstruction had disease with extravesical extension. Of the patients with unilateral obstruction a third had disease confined to the bladder with a significant proportion confined to the bladder mucosa. CONCLUSIONS: The presence of unilateral or bilateral hydronephrosis is a clinical datum that is already available to help accurately stage bladder tumors. The presence of bilateral obstruction is an ominous sign, while a significant proportion of patients presenting with unilateral obstruction have disease confined to the bladder.

Radical cystectomy for elderly patients with bladder carcinoma: an updated experience with 404 patients.

BACKGROUND: The authors evaluated the experiences at their institution with radical cystectomy and urinary diversion performed on elderly bladder carcinoma patients to determine whether age had an impact on the clinical or functional results for this group of patients. METHODS: Between August 1971 and December 1996, 404 patients age 70 years or older (median age, 74 years) underwent radical cystectomy and urinary diversion for invasive bladder carcinoma: 352 (87%) were ages 70-79 years and 52 (13%) were age 80 years or older. Data analyzed included the following: perioperative mortality; early (within 90 days after surgery) and late (more than 90 days after surgery) postoperative complications, related and unrelated to the urinary diversion; length of hospital stay; pathologic staging; and clinical outcome. These data were then compared with those for 762 patients younger than 70 years (median age, 61 years) who underwent the same procedure during the same time period. RESULTS: The overall mortality rate for patients age 70 years or older was 2.8% (3.2% for those ages 70-79 years, 0% for those age 80 years or older), compared with 2% for patients younger than 70 years. The early complication rate for patients age 70 years or older was 32%, compared with 25% for patients younger than 70 years. Patients age 80 years or older had a similar early complication rate of 29%. Late postoperative complications occurred in 12.4% of patients age 70 years or older, compared with 22.8% of patients younger than 70 years. There was no significant difference between the two groups with regard to pathologic stage or length of hospital stay. The 3-year and 5-year overall survival rates for patients age 70 years or older were 60% and 53%, respectively, compared with 68% and 63%, respectively, for patients younger than 70 years (P=0.001). There was no statistical difference between the groups when rates of disease recurrence were compared (P=0.3627). The 5-year recurrence rate for patients age 70 years or older was 35%, compared with a 5-year recurrence rate of 31% for patients younger than 70 years. CONCLUSIONS: These data suggest that an aggressive, curative, radical surgical approach and urinary diversion may be a viable treatment strategy for properly selected elderly patients who are in generally good health and require definitive therapy for invasive bladder carcinoma.

Salvage radical cystoprostatectomy and orthotopic urinary diversion following radiation failure.

PURPOSE: Salvage surgery followed by lower urinary tract reconstruction is a viable therapeutic option for patients in whom definitive radiation therapy for localized bladder or prostate cancer has failed. Improvements in surgical technique and postoperative care have significantly improved overall outcome. An enhanced understanding of the rhabdoid sphincteric mechanism responsible for maintaining urinary continence following cystoprostatectomy has helped make the orthotopic neobladder the procedure of choice for patients requiring lower urinary tract reconstruction. We describe our experience with salvage surgery and orthotopic bladder substitution following failed radical radiation therapy. MATERIALS AND METHODS: We evaluated the complications of 18 patients in whom definitive radiation therapy (total minimum dose 60 Gy. or greater) for bladder or prostate cancer had failed. All patients underwent a salvage procedure with creation of an orthotopic neobladder. RESULTS: Operative characteristics, postoperative outcomes and postoperative complications related or unrelated to urinary reconstruction were similar between irradiated and nonirradiated patients. Good day and night continence following surgery was reported by 67 and 56% of irradiated patients, respectively. Patients with poor postoperative continence were successfully treated with the placement of an artificial urinary sphincter. CONCLUSIONS: Salvage surgery with orthotopic urinary reconstruction is a safe, effective procedure that provides a functional lower urinary tract in patients in whom definitive pelvic radiation therapy has failed.

Prospective pathologic analysis of female cystectomy specimens: risk factors for orthotopic diversion in women.

OBJECTIVES: To prospectively evaluate our previously established pathologic risk factors in women undergoing cystectomy for bladder cancer and to determine if these criteria identify appropriate female candidates for orthotopic diversion. METHODS: Prospective pathologic evaluation was performed on 71 consecutive female cystectomy specimens removed for primary transitional cell carcinoma of the bladder. The histologic grade, pathologic stage, presence of carcinoma in situ, number, and location of tumors were determined. In addition, final pathologic analysis of the bladder neck and proximal urethra was performed and compared with the intraoperative frozen-section analysis of the distal margin (proximal urethra). RESULTS: Tumor at the bladder neck and proximal urethra was seen in 14 (19%) and 5 (7%) cystectomy specimens, respectively. Bladder neck tumor involvement was found to be the most significant risk factor for tumor involving the urethra (P <0.001). All patients with urethral tumors demonstrated concomitant bladder neck tumors. However, more than 60% of patients with bladder neck tumors had a normal (tumor-free) proximal urethra. Furthermore, no patient with a normal bladder neck demonstrated tumor involvement of the urethra. Intraoperative frozen-section analysis of the distal surgical margin was performed on 47 patients: 45 without evidence of tumor and 2 patients with urethral tumor involvement. In all cases, the intraoperative frozen-section analysis was correctly confirmed by final permanent section. CONCLUSIONS: We prospectively demonstrate that bladder neck tumor involvement is a significant risk factor for urethral tumor involvement in women. However, despite bladder neck tumor involvement, a number of women undergoing cystectomy for bladder cancer have a normal urethra and may be candidates for orthotopic diversion. Furthermore, our data demonstrate that intraoperative frozen-section analysis of the distal surgical margin accurately and reliably evaluates the proximal urethra and currently determines which patients undergo orthotopic diversion at our institution.

The T pouch: an orthotopic ileal neobladder incorporating a serosal lined ileal antireflux technique.

PURPOSE: At our institution the Kock ileal neobladder has been the primary form of urinary diversion after cystectomy. The few associated complications are primarily related to the intussuscepted antireflux afferent limb, including stones, stenosis and extussusception of the afferent nipple. We present a novel orthotopic ileal neobladder, the T pouch, with an innovative antireflux technique designed to prevent complications of the intussuscepted afferent nipple. MATERIAL AND METHODS: From November 1996 through August 1997, 40 patients an average of 67 years old underwent construction of an orthotopic ileal neobladder (T pouch). Mean followup is 10.5 months (range 8 to 14). The T pouch incorporates an antireflux mechanism using a serosal lined ileal tunnel technique. Urinary reflux is prevented without ileal intussusception and with complete preservation of the blood supply to the afferent ileal segment. Followup in all cases includes clinical and functional results, and radiographic evaluation of the urinary reservoir and upper urinary tracts. RESULTS: One perioperative death (2.5%) and 5 early complications (12.5%) were unrelated to urinary diversion. There have been no late complications. All T pouch reservoirs had excellent capacity without evidence of urinary reflux. The upper urinary tracts remain unchanged or improved in all patients. CONCLUSIONS: The T pouch is an orthotopic ileal neobladder that incorporates an effective, innovative antireflux mechanism created by a serosal lined ileal tunnel. Early clinical and functional results of this type of urinary diversion have been excellent. Furthermore, we suspect that this antireflux technique may eliminate the complications associated with an intussuscepted afferent nipple and maintain an effective antireflux mechanism.

Radical prostatectomy and postoperative irradiation in patients with pathological stage C (T3) carcinoma of the prostate.

PURPOSE: Adenocarcinoma of the prostate is the most common human cancer of internal organs. Radical surgery is regarded by many to be the treatment of choice for capsule confined disease. Since accurate preoperative assessment of tumor stage is difficult to define, many patients are subsequently found to have pathological stage C (T3) disease. These patients should be considered for adjuvant radiotherapy. METHODS AND MATERIALS: A group of 201 PS C (T3) unselected patients, treated with radical prostatectomy and limited pelvic lymphadenectomy, received postoperative irradiation to the prostate bed. This radiotherapy was given between 42-90 days after surgery and consisted of a median dose of 48 Gy. Patient survival, disease free survival, time to clinical and chemical relapse and the incidence of local and systemic relapse were analyzed. The influence of multiple parameters on the treatment outcome including patient age, treatment period, clinical stage, pathological stage, Gleason's score, prostate specific antigen (PSA), radiotherapy techniques and radiation dose were examined using univariate and multivariate analysis. Follow-up ranged from 3 to 15 years, with a median of 5 years. RESULTS: The overall 5- and 10-year actuarial survival was 92% and 83% (median > 10 years), respectively and the 5- and 10-year disease-free survival (clinical and PSA) was 67% and 53% (median > 10 years), respectively. A total of 61 (30%) patients had a recurrence, including 23 (11%) patients who had clinical and 38 (19%) who had PSA recurrence. Of the 23 patients with clinical recurrence, 10 (5%) had local recurrence, including two patients who had local and systemic recurrence. Pathological stage and Gleason's score were independently predictive of recurrence (each with p < 0.001 after controlling for the other). Patients in the worst prognostic category with pathological stage C3 and Gleason's score 8-10 were predicted to be at 7.2 times the risk of recurrence, compared to stage C1 or C2 and Gleason's score 2-7 patients. Preoperative PSA level (> 25 ng/ml) was also an important independent factor predicting tumor recurrence, p = 0.05. All other investigated parameters were not significant in predicting tumor recurrence. This treatment program was very well tolerated by the study patients, with seven (3.5%) recorded with major and 18 (9%) with minor surgical complications, while 65% of patients had minor and clinically insignificant radiation complications. CONCLUSION: Surgery followed by moderate dose radiotherapy in patients with PS C (T3) prostatic carcinoma was well tolerated and resulted in excellent overall and disease free survival, with a low incidence of local recurrence. New treatment strategies need to be developed for patients with C3 tumors and those with high (8-10) Gleason's score and those with high (> 25 ng/ml) PSA level at diagnosis.

Quality of life and sexuality following radical prostatectomy in patients with prostate cancer who use or do not use erectile aids.

OBJECTIVES: It is well established that prostate cancer patients undergoing radical prostatectomy may experience disruptive side effects, most notably urinary incontinence and erectile dysfunction. The purpose of this study is to compare relevant outcomes between patients awaiting radical prostatectomy for prostate cancer and patients who already underwent the surgery, taking into account type of prostatectomy and use of erectile aids. METHODS: We compared self-reports of global quality of life, sexuality, urinary continence, and physical capabilities in 86 nerve-sparing patients, 89 standard-prostatectomy patients, 74 prostatectomy patients who used erectile aids, and a comparison group of 45 patients awaiting radical prostatectomy. RESULTS: Regardless of type of surgery, use of erectile aid, or preoperative status, most patients reported good quality of life. The best outcomes in sexuality were reported by patients who used erectile aids, who appeared similar in sexuality to patients awaiting surgery. When differences were detected, standard prostatectomy patients who did not use erectile aids scored worse in most areas of sexuality than nerve-sparing patients who did not use erectile aids. There were no differences in frequency of urinary leakage among the three surgery subgroups. CONCLUSIONS: Although most patients reported problems in sexual and urinary function, global quality of life does not appear to be compromised following radical prostatectomy. Findings suggest that postsurgical sexuality differs depending on type of prostatectomy and use of erectile aids, while urinary function is similar across surgery groups. We conclude that erectile aids should be offered routinely to patients who are ineligible for nerve-sparing surgery or experience erectile difficulties following the nerve-sparing procedure.