Gary Lieskovsky

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.

The Role of Adjuvant Chemotherapy Following Cystectomy for Invasive Bladder Cancer: A Prospective Comparative Trial

We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2 cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection.

Vena caval involvement by renal cell carcinoma. Surgical resection provides meaningful long-term survival.

In 1972 we first reported that vena caval extension by tumor thrombus was a potentially curable lesion provided that complete removal could be achieved. We have developed a technique for safe removal of extensive vena caval thrombi extending up to the right atrium without the need for cardiopulmonary bypass or hypothermic cardioplegia. Cardiopulmonary bypass, however, is advocated for some type III thrombi, but the addition of the pump and heparinization compounds the magnitude of the procedure. We use a right thoracoabdominal approach for tumors arising from either kidney with vascular isolation of the vena cava from its insertion into the right atrium to the iliac bifurcation. From 1972 to 1988, 56 patients ranging in age from 31 to 76 years were evaluated and 53 underwent radical nephrectomy with en bloc vena caval tumor thrombectomy. Of these patients, 21 had subhepatic caval thrombus extension (level 1); 24 had extension into the intrahepatic vena cava (level 2), and 8 had thrombi extending into the heart (level 3). Overall 1-, 3-, and 5-year survival was 56%, 34%, and 25%, respectively. Crucial to survival was complete surgical excision. Successful extirpation of all apparent tumor was possible in 75% of the patients in this series. With an expected 5-year survival rate of 57% for those without metastatic disease to other organs, we continue to advocate an aggressive optimistic approach for patients if there is no preoperative evidence of metastatic disease.

The Rationale for EN Bloc Pelvic Lymph Node Dissection for Bladder Cancer Patients with Nodal Metastases: Long-Term Results

From August 1971 through June 1989, 591 consecutive patients underwent curative pelvic lymphadenectomy with en bloc radical cystectomy for bladder cancer. Of these patients 132 (22%) had pathologically proved nodal metastases. The incidence of positive nodes increased with increasing pathological stage of the primary tumor: stage PIS (0.75%), stage P1 (13%), stage P2 (20%), stage P3a (24%), stage P3b (42%) and stage P4 (45%). The median followup for the 31 patients still alive was 5.5 years (range 2.6 to 18.8). Recurrent bladder cancer was documented in 89 patients (67%) with a median interval to progression of 1.5 years. Pelvic recurrence as the first site of progression was uncommon, occurring in 15 patients (11%). The actuarial 2, 3, 5 and 10-year survival rates were 55%, 38%, 29% and 20%, respectively. Increased risk of progression and death was associated with advanced pathological tumor stage (stage P3b or greater, p < 0.001 and p < 0.001, respectively) and 6 or more positive nodes (p < 0.001 and p = 0.012, respectively). There was no significant difference in survival and interval to progression among patients who received preoperative irradiation or adjuvant chemotherapy compared to those treated with surgery alone. This retrospective analysis further substantiates the philosophy that single stage pelvic lymphadenectomy with en bloc radical cystectomy can provide long-term progression-free survival, particularly for patients with localized primary tumors and minimal metastatic nodal disease.

International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy

PURPOSE We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

QUALITY OF LIFE AFTER RADICAL CYSTECTOMY FOR BLADDER CANCER IN PATIENTS WITH AN ILEAL CONDUIT, OR 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.

Continent urinary diversion.

From August 1982 through March 1988, 531 patients have undergone continent urinary diversion using an ileal reservoir constructed according to the method of Kock. For the last 18 months we have used the principle of Kock reservoir construction for primary lower urinary tract reconstruction after cystectomy in 39 highly selected male patients by means of a ureteroileal urethrostomy. Early complications occurred in 86 of 531 patients (16.2 per cent), resulting in an operative mortality rate of 1.9 per cent (10 of 531). The early complication rate was 16.5 per cent among patients undergoing 1-stage cystectomy and Kock pouch construction, and 15.2 per cent among patients undergoing Kock pouch conversion. Late complications have been analyzed in 489 patients who have undergone Kock cutaneous diversion. The complications unique to continent urinary diversion, their incidence and the effect of technical modifications in reducing the number of late complications are shown. Note that since the last modification in July 1985 the over-all incidence of late complication has decreased to 22 per cent. Based on this ongoing experience we conclude that the continent ileal reservoir, as conceived by Kock, remains the ideal internal reservoir for bladder replacement in terms of volume accommodation with the lowest internal pressures, and the intussuscepted ileal nipple valve mechanism is a reproducible, highly effective mechanism that prevents reflux and pyelonephritis in greater than 95 per cent of the patients and produces excellent continence. Our enthusiasm remains tempered by the need for reoperation in approximately 10 to 15 per cent of the patients, usually due to a pinhole fistula or false passage at the base of the efferent nipple valve mechanism. Electrolyte abnormalities rarely occur and in the absence of radiation gastrointestinal dysfunction is unusual. Continent urinary diversion is a viable concept that provides a real alternative in terms of quality of life and self-image for the patient who requires urinary diversion for any reason.

Clinical Experience with the Kock Continent Ileal Reservoir for Urinary Diversion

From August 1982 through January 1984, 51 patients underwent urinary diversion that included creation of a continent reservoir from an ileal segment, according to the method described originally by Kock. An important modification included removal of a narrow strip of mesentery for 8 cm. along the afferent and efferent limbs of the pouch to allow adequate ileal intussusception, and fixation to prevent reflux and to ensure continence. Previous urinary diversion was by ureterosigmoidostomy in 3 patients, standard ileal conduit in 7 and suprapubic cystotomy in 1. A total of 39 patients underwent simultaneous anterior exenteration for pelvic malignancy. There was 1 postoperative death and early complications occurred in 10 patients. Of these 10 patients 4 required reoperation: 2 for drainage of a pelvic abscess, 1 for conversion to a standard ileal conduit and 1 for bleeding. Late complications occurred in only 8 patients: 5 required reoperation and revision of the continence valve mechanism, and 3 required hospitalization for brief episodes of pyelonephritis. The end result in 49 of 50 patients has been an overwhelming success. Patients perform self-catheterization every 4 to 6 hours during the day and once at night for volumes ranging up to 1,400 cc. Serum electrolytes have remained normal and hyperchloremic acidosis has been encountered in only 1 patient who had had compromised renal function preoperatively with hyperchloremic acidosis as a result of previous ureterosigmoidostomy. X-rays of the Kock pouch have shown evidence of reflux in only 1 patient, and all excretory urograms have demonstrated either normal upper tracts without obstruction or improvement in patients with preoperative hydronephrosis. Although preliminary, this clinical trial suggests that the quality of life for patients considered previously to be candidates for cutaneous diversion can be improved markedly by a modified Kock continent ileal reservoir.

Contemporary Cystectomy with Pelvic Node Dissection Compared to Preoperative Radiation Therapy Plus Cystectomy in Management of Invasive Bladder Cancer

Between August 1971 and August 1982, 197 consecutive patients underwent single stage radical cystectomy with pelvic lymph node dissection and urinary diversion as definitive management of high grade, invasive bladder cancer. In 100 patients 1,600 rad of radiation therapy were given for 4 days preoperatively and 97 patients underwent an operation only. Although not constituting a prospective randomized study, an analysis of these 2 groups of patients managed during an 11-year period by the same surgical team, using identical surgical technique, provides useful information that questions the benefit of preoperative radiation therapy in the management of high grade, invasive bladder cancer. Other factors, such as improved surgical technique with meticulous pelvic node dissection as well as better preoperative and postoperative care, may be responsible for survival results of contemporary surgery only that equal those reported following combination therapy protocols using preoperative radiation therapy. Contemporary surgery with or without preoperative radiation therapy yielded a 5-year survival rate free of tumor of 75 per cent for patients with pathologic stages P2 and P3A disease, 44 per cent with P3A and P3B disease, and 36 per cent with P4 disease and positive pelvic nodes.

Quality of Life Survey of Urinary Diversion Patients: Comparison of Ileal Conduits versus Continent Kock Ileal Reservoirs

There has been a recent marked increase in interest in continent urinary diversions. While considerable time has been spent on the technical aspects of these diversions the psychological impact has not yet been fully explored. We describe an extensive survey that was conducted among 100 consecutive adults (87 respondents) who had undergone urinary diversion via an ileal conduit and 100 consecutive adults (85 respondents) in whom a continent Kock ileal reservoir was created during the last 3 to 5 years at our university by the same surgeons. The Kock pouch patients were stratified further into 63 with primary diversion and 22 who underwent conversion from previous conduit diversions. The survey consisted of a questionnaire that included a social and sexual survey, the Beck Depressive Inventory, the Profile of Mood States and a physical impact study. The results revealed that all patients surveyed generally were satisfied with the diversions and they had adapted reasonably socially, physically and psychologically. The key to adaptation seemed to be a detailed, realistic preoperative education about the type of diversion used. Patients with ileal conduit diversions had the lowest expectations of the form of diversion as defined by the preoperative awareness of the need to wear an external ostomy appliance with its associated inconveniences and change in the external body image. Postoperatively, ileal conduit patients also had the poorest self images as defined by a decrease in sexual desire and in all forms of physical contact (sexual and nonsexual). The subset of patients who underwent conversion from conduit diversions to Kock pouches, however, were statistically the most satisfied, and they were the most physically and sexually active. We conclude that the Kock continent urostomy offers an important alternative to noncontinent forms of diversion.