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.

Association between race and oncologic outcome following radical prostatectomy for clinically organ-confined prostate cancer: a long-term follow-up study.

PURPOSE: Few studies have evaluated prostate cancer oncologic outcomes in different ethnic groups following radical prostatectomy for clinically organ-confined disease. Existing studies lack long-term outcome data. We conducted this study to assess the impact of racial differences on risk profile and oncologic outcomes in a large cohort of patients with prostate cancer who underwent radical prostatectomy. METHODS: Using our institutional review board-approved prostate cancer database, we retrospectively reviewed the records of 3437 patients who underwent radical prostatectomy with curative intent in our institution between 1987 and 2009. Based on ethnicity, patients were divided into Asian Americans (n = 133), African Americans (n = 155) and Caucasians (n = 3149). Baseline characteristics and oncologic outcomes including biochemical recurrence free, clinical recurrence free and overall survival were compared between the study groups. RESULTS: A total of 3437 patients with a mean age of 63 ± 9.8 years and median follow-up period of 8.7 (range 0.1-24.1) years were included in the analysis. Pathologic stage and the frequency of poorly differentiated cancer were higher in Asian Americans; however, margin status did not differ significantly. Moreover, oncologic outcomes were comparable between different ethnic groups. In multivariate analysis, both pathologic stage and grade were independent predictors of oncologic outcomes, but race was not. CONCLUSIONS: In this large, ethnically diverse long-term follow-up study, we noted that Asian Americans compared to African Americans and Caucasians are more likely to have high risk prostate cancer; however, race was not an independent predictor of oncologic outcome following radical prostatectomy with curative intent.

Oncological Outcomes After Radical Prostatectomy for High-Risk Prostate Cancer Based on New Gleason Grouping System: A Validation Study From University of Southern California With 3,755 Cases.

BACKGROUNDS: To assess the prognostic value of new Gleason grade grouping system in high-risk prostate cancer patients, we compared oncological outcomes after radical prostatectomy for patients with Gleason score 8 versus 9-10. METHODS: Between 1987 and 2008, 3,755 men underwent radical prostatectomy with curative intent at University of Southern California. Patients who had Gleason score 8-10 at final histopathological evaluation (pT2-4N0) were included in this study. Eligible patients were divided into two groups; 226 with Gleason score 8 and 132 with Gleason score 9-10. Various patient and disease characteristics as well as oncological outcomes (biochemical recurrence, clinical recurrence, and overall survival) were compared between the groups. Impact of Gleason score on outcomes was controlled for preoperative prostate specific antigen, pathological stage, use of adjuvant radiotherapy, and neoadjuvant/adjuvant hormone therapy in multivariable analyses. RESULTS: A total of 358 patients (mean age: 65 years) were included in the analysis. Mean age and median duration of follow-up (9.6 years) were comparable between the study groups. Gleason 9-10 prostate cancer was associated with worse biochemical (HR 1.6; 95%CI [1.1-2.3]) and clinical recurrence free survival (HR = 1.9; 95%CI [1.1-3.3]); however, overall survival did not differ significantly between the groups. In addition, more patients with Gleason score 9-10 received adjuvant hormone therapy in the course of disease. CONCLUSIONS: Long-term follow-up after radical prostatectomy revealed significant differences in disease-specific outcomes between patients with Gleason score 8 versus 9-10. This sub-classification of high-risk patients might be helpful for patient counseling and determining therapeutic strategies. Prostate 77:743-748, 2017. © 2017 Wiley Periodicals, Inc.

Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era.

INTRODUCTION: We sought to determine predictors for early and late biochemical recurrence following radical prostatectomy among localized prostate cancer patients. METHODS: The study included localized prostate cancer patients treated with radical prostatectomy (RP) at the University of Southern California from 1988 to 2008. Competing risks regression models were used to determine risk factors associated with earlier or late biochemical recurrence, defined using the median time to biochemical recurrence in this population (2.9 years after radical prostatectomy). RESULTS: The cohort for this study included 2262 localized prostate cancer (pT2-3N0M0) patients who did not receive neoadjuvant or adjuvant therapies. Of these patients, 188 experienced biochemical recurrence and a subset continued to clinical recurrence, either within (n=19, 10%) or following (n=13, 7%) 2.9 years after RP. Multivariable stepwise competing risks analysis showed Gleason score ≥7, positive surgical margin status, and ≥pT3a stage to be associated with biochemical recurrence within 2.9 years following surgery. Predictors of biochemical recurrence after 2.9 years were Gleason score 7 (4+3), preoperative prostate-specific antigen (PSA) level, and ≥pT3a stage. CONCLUSIONS: Higher stage was associated with biochemical recurrence at any time following radical prostatectomy. Particular attention may need to be made to patients with stage ≥pT3a, higher preoperative PSA, and Gleason 7 prostate cancer with primary high-grade patterns when considering longer followup after RP.

Long-term cancer control after radical prostatectomy and bilateral pelvic lymph node dissection for pT3bN0M0 prostate cancer in the prostate-specific antigen era.

OBJECTIVES: We evaluated long-term cancer control outcomes of radical prostatectomy and bilateral pelvic lymph node dissection (RP) for pT3bN0M0 prostate cancer in the era of prostate-specific antigen (PSA) screening. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data from the University of Southern California Prostate Cancer Database was performed. Between 1987 and 2008, 229 men underwent open RP for pT3bN0M0 prostate cancer. The cohort was divided into early (1987-1997) and contemporary (1998-2008) PSA eras. The Kaplan-Meier method and Cox proportional regression models were used to analyze clinical recurrence (CR) and biochemical recurrence (BCR). RESULTS: The median follow-up duration was 14.5 years (range, 0.2-21.1y). The predicted 10-year freedom from CR and BCR rates for men treated in the early and contemporary PSA eras were 73% and 95% (Log-rank P = 0.001) and 65% and 73% (Log-rank P = 0.055), respectively. Multivariable analysis showed that pathologic Gleason grade 8-10 (CR: hazard ratio [HR] = 5.11; 95% confidence interval [CI] = 1.72-15.20; P = 0.003; BCR: HR = 3.47; 95% CI = 1.60-7.48; P = 0.002) and contemporary PSA era (CR: HR = 0.15; 95% CI = 0.06-0.41; P<0.001; BCR: HR = 0.49; 95% CI = 0.28-0.86; P = 0.013) were independently associated with cancer control. Adjuvant radiation therapy and positive surgical margins were not independently associated with outcomes. CONCLUSIONS: RP conferred long-term cancer control in men with pT3bN0M0 prostate cancer treated in the PSA era. Pathologic Gleason grade 8-10 and treatment in the early PSA era were independently associated with poorer cancer control outcomes.

Impact of micropapillary urothelial carcinoma variant histology on survival after radical cystectomy.

OBJECTIVES: The role of micropapillary urothelial carcinoma (MUC) variant histology as an independent prognostic factor for survival after radical cystectomy has not been studied. Our aim was to examine the impact of MUC on survival. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data from the University of Southern California (USC) Bladder Cancer Database was performed. Between 1985 and 2008, 1,380 patients underwent radical cystectomy and superextended pelvic lymph node dissection for bladder cancer. All surgical specimens underwent central pathologic review by dedicated genitourinary pathologists. Histologic type was categorized as urothelial carcinoma (UC; n = 1,347) or MUC (n = 33). The outcomes were overall survival (OS) and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data. RESULTS: The median follow-up duration was 10 years (range, 0-25 years). Baseline characteristics were similar between histologic types except MUC was associated with advanced clinical (cTanyN1-3: 2% vs. 9%, P = 0.03) and pathologic (pTanyN1-3: 22% vs. 46%, P = 0.01) TNM stage, multifocality (38% vs. 58%, P = 0.02), and high nuclear grade (83% vs. 97%, P = 0.03). The predicted 5-year OS (61% and 67%, Log rank P = 0.96) and RFS (69% and 58%, Log rank P = 0.33) rates did not differ between patients with UC and MUC. Multivariable analysis showed that histologic type was not independently associated with OS (HR 0.91, 95% CI 0.55-1.49, P = 0.70) or RFS (HR 0.97, 95% CI 0.55-1.73, P = 0.92). CONCLUSIONS: Outcomes of radical cystectomy for patients with MUC are similar to those with UC when controlling for other clinical and pathologic factors.

Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer with pathologically positive lymph nodes in the prostate-specific antigen era.

OBJECTIVES: To evaluate the outcomes of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for clinically organ confined prostate cancer (CaP) with regional lymph node metastases (pN1) treated in the era of prostate-specific antigen (PSA) screening. MATERIALS AND METHODS: A single institution cohort of 2,487 men with cT1-T2 CaP treated with open radical prostatectomy and pelvic lymph node dissection between 1988 and 2008 were analyzed. Kaplan-Meier and Cox proportional regression models were used to analyze overall survival (OS), clinical recurrence-free survival (cRFS), and biochemical recurrence-free survival (bRFS). RESULTS: Overall, 150 out of 2,487 patients (6%) had pN1 disease, with a median follow-up of 10.4 years. The predicted 10-year OS, cRFS, and bRFS rates for patients with pN0 and pN1 were 86% and 74% (Log rank P < 0.001), 97% and 84% (Log rank P < 0.001), and 88% and 57% (Log rank P < 0.001), respectively. In the subset of pN1 patients treated with surgery only (n = 49), the predicted 10-year OS, cRFS, and bRFS rates were 81%, 80%, and 59%, respectively. Exploratory univariate regression analysis showed that age (P = 0.003), total number of lymph nodes identified (P = 0.040), and total number of positive lymph nodes identified (P = 0.004) were associated with OS. Total number of positive lymph nodes (LNs) identified was also significantly associated with cRFS (P = 0.05). CONCLUSIONS: The incidence of pN1 in patients with cT1-T2 CaP treated with surgery in the era of PSA screening was low. RP and PLND demonstrated therapeutic efficacy in a subset of pN1 patients treated with surgery alone.

Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: a retrospective analysis from the University of Southern California.

OBJECTIVES: We evaluated pathologic and survival outcomes of GC (gemcitabine/cisplatin) and methotrexate/vinblastine/doxorubicin/cisplatin (M-VAC) neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: A retrospective analysis of prospectively collected data on 116 patients who received NAC (GC: n = 58; M-VAC: n = 58) before radical cystectomy and superextended pelvic lymph node dissection for clinical stage T2-4N0M0 bladder cancer was performed. The outcomes were complete response rate (CRR; pT0N0), partial response rate (PRR; pT0N0, pTaN0, pT1N0, or pTisN0), overall mortality (OM), and recurrence. The Kaplan-Meier method and multivariable Cox regression analysis were used to analyze OM. The cumulative incidence method and Fine and Gray's competing risk regression analysis were used to analyze recurrence. RESULTS: The median follow-up duration was 2.1 years for the GC group and 7.4 years for the M-VAC group (P < 0.001). There were no statistically significant differences between the GC and M-VAC groups with regard to CRR (27.3% vs. 17.1%, P = 0.419) or PRR (45.5% vs. 37.1%, P = 0.498). The predicted 5-year freedom from OM rate (P = 0.634) and cumulative incidence of recurrence rate (P = 0.891) did not differ between the GC and M-VAC groups. Multivariable analysis showed that there was no independent association between type of NAC and OM (P = 0.721) or recurrence (P = 0.065). CONCLUSIONS: Pathologic and survival outcomes did not differ in patients who received GC and M-VAC NAC. These data support the use of the GC regimen in the neoadjuvant setting.

Focal cryotherapy for clinically unilateral, low-intermediate risk prostate cancer in 73 men with a median follow-up of 3.7 years.

BACKGROUND: Evolution of cryotherapy for prostate cancer is likely to result in parenchyma-sparing modifications adjacent to the urethra and neurovascular bundle. Results of initial series of focal therapy to minimize cryosurgery-related morbidity without compromising oncologic control have been encouraging, but limited in short-term outcomes. OBJECTIVE: To retrospectively report (1) median 3.7-yr follow-up experience of primary focal cryotherapy for clinically unilateral prostate cancer with oncologic and functional outcomes, and (2) matched-pair analysis with contemporaneous patients undergoing radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: Over 8.5 yr (September 2002 to March 2011), focal cryoablation (defined as ablation of one lobe) was performed in 73 carefully selected patients with biopsy-proven, clinically unilateral, low-intermediate risk prostate cancer. All patients underwent transrectal ultrasound (TRUS) and Doppler-guided sextant and targeted biopsies at entry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-therapy follow-up included measuring prostate-specific antigen (PSA) level every 3-6 mo; TRUS biopsies at 6-12 mo and yearly, as indicated; and validated symptom questionnaires. Matched-pair analysis compared oncologic outcomes of focal cryotherapy and RP (matched for age, PSA, clinical stage, and biopsy Gleason score). RESULTS AND LIMITATIONS: Complete follow-up was available in 70 patients (median follow-up: 3.7 yr; range: 1-8.5 yr). No patient died or developed metastases. Precryotherapy mean PSA was 5.9 ng/ml and Gleason score was 6 (n=30) or 7 (n=43). Postcryotherapy mean PSA was 1.6 ng/ml (70% reduction compared to precryotherapy; p<0.001). Of 48 patients undergoing postcryotherapy biopsy, 36 (75%) had negative biopsies; positive biopsy for cancer (n=12) occurred in the untreated contralateral (n=11) or treated ipsilateral lobe (n=1). Complete continence (no pads) and potency sufficient for intercourse were documented in 100% and 86% of patients, respectively. Matched-pair comparison of focal cryotherapy and RP revealed similar oncologic outcome, defined as needing salvage treatment. CONCLUSIONS: Primary focal cryoablation for low-intermediate risk unilateral cancer affords encouraging oncologic and functional outcomes over a median 3.7-yr follow-up. Close surveillance with follow-up whole-gland biopsies is mandatory.

Long-term outcomes of open radical retropubic prostatectomy for clinically localized prostate cancer in the prostate-specific antigen era.

OBJECTIVE: To determine long-term oncological outcomes and complication rates for patients with clinically organ confined prostate adenocarcinoma (PCa) treated with open radical retropubic prostatectomy and pelvic lymph node dissection (RRP/PLND) in the prostate-specific antigen (PSA) era. METHODS: Outcomes data were obtained from a prospectively maintained prostate cancer database. Patients with cT1/cT2 PCa undergoing RRP/PLND without neoadjuvant therapy between July 1988 and June 2008 were included. Kaplan-Meier and Cox proportional regression models were used to evaluate factors influencing biochemical recurrence, clinical recurrence, and overall survival (OS). RESULTS: A total of 2487 patients met inclusion criteria, and median follow-up was 7.2 years (range 1-21 years). Of the patients, 49.7% were low risk, 33.2% intermediate risk, and 16.1% high risk by D'Amico criteria, and 6% were LN+. The 10-year biochemical recurrence-free survival (BCRFS) for low-, intermediate-, and high-risk patients was 92%, 83%, and 76%, respectively (P < .001), and 10 year OS was 91%, 83%, and 74%, respectively (P < .001). BCRFS at 10 years was 76% and 88% for patients with positive and negative margins, respectively (P < .001). Of the 2487 patients, 11% developed BCR, and 3.7% experienced CR, with 9 local recurrences. The overall complication rate was 2.3%, and the cancer specific mortality rate was 2%. CONCLUSION: D'Amico risk group, margin status, and LN status are significantly correlated with outcomes in patients undergoing RRP/PLND for clinically localized PCa. Local recurrence and death from prostate cancer are rare in patients undergoing open RRP/PLND for clinically organ confined disease in the PSA era.

Long-term outcome in patients with a Gleason score ≤ 6 prostate cancer treated by radical prostatectomy.

OBJECTIVE: • To determine the actual recurrence risk of patients with a Gleason score (GS) ≤ 6 treated with radical retropubic prostatectomy (RRP) and bilateral lymphadenectomy in a cohort with long-term follow-up. PATIENTS AND METHODS: • The USC/Norris Comprehensive Cancer Center database included 3235 consecutive patients who underwent RRP for prostate cancer between January 1972 and December 2005. We identified 1383 patients with a GS ≤ 6 in prostatectomy specimens. Median follow-up was 8.3 years. Data on pathological and clinical characteristics and outcome were prospectively recorded. • Statistical analysis was performed using the stratified log-rank test and stepwise Cox regression analysis. RESULTS: • A GS of 6 was present in 66%, 5 in 27%, 4 in 5% and 3 or 2 in 3% of cases. Tumour classification was pT2N0 (83%), pT3N0 (14%), pT4N0 (0.1%) and any TN1 (2%). • Positive margins were seen in 18%. Estimated PSA and clinical recurrence rate were 14% and 4% after 10 years and 18% and 6% after 15 years, respectively. In multivariate analysis, N-stage (P < 0.001), T-stage (P= 0.02) and margin status (P < 0.001) were associated with PSA recurrence. • N-stage (P < 0.001) and T-stage (P= 0.01) were associated with clinical recurrence. • Overall, patients with a GS ≤ 6 accounted for 26% of all PSA recurrences and for 20% of all patients with clinical recurrences in the database. CONCLUSION: • A relatively small proportion of patients with a GS ≤ 6 cancer developed PSA recurrence and/or overt metastasis. However, these patients account for a substantial minority of those who experienced recurrence and metastasis.

Subclinical haemostatic activation and current surgeon volume predict bleeding with open radical retropubic prostatectomy.

OBJECTIVE: To assess subclinical haemostatic activation and clinical variables to predict bleeding during radical retropubic prostatectomy (RP), as haemostatic activation is common in cancer and might be useful for predicting outcomes, but routine coagulation screening does not correlate with bleeding. PATIENTS AND METHODS: Clinical data and blood samples were collected from 153 patients (median age 63 years; prostate-specific antigen, PSA, level 5.92 ng/mL) before RP and lymph node dissection. Plasma was assayed for d-dimer and thrombin-antithrombin complex (TAT). Univariable then multivariable analyses were used to identify associations between plasma markers and clinical variables for bleeding and thrombosis. RESULTS: Most patients (77%) were stage T1c and most (76.5%) had organ-confined cancer (< or =pT2). Pathological Gleason scores were < or =6 in 68 (44.4%) and > or =8 in 14 (9%) of the patients. The median (range) estimated blood loss (EBL) was 400 (50-3000) mL, the median decrease in haemoglobin level 3.5 (-0.1, 6.6) g/dL, and eight men (5.2%) required a transfusion. In the univariable analysis, a lower TAT before RP (P < 0.001) and d-dimer level (P = 0.023) correlated with a greater decline in haemoglobin level. The platelet count, international normalised ratio, and activated partial thromboplastin time (aPTT) did not predict the EBL nor change in haemoglobin level; the eight transfused patients had lower platelet counts before RP (P = 0.004). Higher surgical volume predicted a lower EBL (P < 0.001) and lower decrease in haemoglobin (P < 0.05). Multivariable linear regression showed that TAT remained significant for the decrease in haemoglobin, and surgical volume for EBL and decrease in haemoglobin. CONCLUSIONS: Haemostatic activation before RP was associated with significantly less bleeding when assessed by objective measures, predicting the decrease in haemoglobin level better than prothrombin time, aPTT or platelet counts. Current surgeon volume might also predict both subjective and objective bleeding variables.

Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival.

Chemotherapy resistance is a significant contributor to treatment failure and death in men with hormone-refractory prostate cancer. One unexplored mechanism for drug resistance is the induction of stress response proteins referred to as the glucose-regulated proteins (GRPs). We sought to determine the level of expression of GRP78, the best characterized GRP in lymph node-positive prostate cancer. Archived, paraffin-embedded, radical prostatectomy specimens were obtained from 153 patients with lymph node-positive prostate cancer (stage D1). The level of GRP78 expression was determined by immunohistochemistry. We assessed the expression and specificity of GRP78 immunoreactivity in benign prostatic tissue, prostate cancer, and lymph node metastasis. We correlated the intensity of immunopositivity with prostate cancer recurrence and survival. Whereas immunohistochemical staining demonstrated that all prostate tissue was immunoreactive for GRP78, the intensity of expression was markedly higher in the primary tumor compared with areas of benign epithelium. GRP78 expression was also evident in lymph node metastases although less intensely than in the primary tumor. Patients with strong GRP78 immunoreactivity in the primary tumor are at higher risk for clinical recurrence (relative risk = 2.0, P = .019) and death (relative risk = 1.8, P = .024) than patients with weak GRP78 expression. This finding confirms that GRP78 protein expression is significantly higher in prostate cancer than in benign prostatic tissue. The intensity of expression is significantly associated with survival and clinical recurrence. GRP78 has considerable potential not only as a prognostic indicator but also as a potential therapeutic target.

Radical cystectomy with extended lymphadenectomy: evaluating separate package versus en bloc submission for node positive bladder cancer.

PURPOSE: To provide future mapping analysis of lymph node positive disease we modified our lymphadenectomy at radical cystectomy for bladder cancer from an en bloc packet to 13 separate nodal packets. We evaluated the clinical and pathological findings resulting from this modification. MATERIALS AND METHODS: A total of 1,359 patients underwent en bloc radical cystectomy and extended lymphadenectomy for bladder cancer. They were compared to 262 patients who underwent radical cystectomy and extended lymphadenectomy with lymph nodes submitted in 13 distinct nodal packets. Overall 317 patients (23%) of the en bloc group (group 1) and 66 of the 262 (25%) in the separately packaged group (group 2) had node positive disease. Clinical and pathological findings were analyzed to compare these 2 groups of patients. RESULTS: Although the incidence of lymph node positivity was not different, the median number of total lymph nodes removed in group 2 was significantly higher than that in group 1 (68, range 14 to 132 vs 31, range 1 to 96, p<0.001). A trend toward more lymph nodes involved was observed in group 2 compared to group 1 (3, range 1 to 91 vs 2, range 1 to 63, p=0.062). These findings significantly lowered median lymph node density in group 2 compared to that in group 1 (6% vs 9%, p=0.006). CONCLUSIONS: Although the overall incidence of lymph node positive disease was not different, the submission of 13 separate nodal packets at radical cystectomy significantly increased the total number of lymph nodes removed/analyzed and identified a slightly higher number of positive lymph nodes compared to en bloc submission.

Salvage radical prostatectomy: quality of life outcomes and long-term oncological control of radiorecurrent prostate cancer.

PURPOSE: We review our 20-year experience with salvage radical prostatectomy to determine prognostic variables predictive of oncological control of radiorecurrent prostate cancer. Using a standardized questionnaire we also evaluate outcome data regarding the long-term sexual and urinary effects of salvage radical prostatectomy. MATERIALS AND METHODS: Between 1983 and 2002 salvage radical prostatectomy was performed in 51 patients with locally recurrent prostate cancer following definitive radiotherapy. Clinical information was obtained from a prospective database. Quality of life data were collected using the UCLA Prostate Cancer Index, a validated, patient administered instrument. RESULTS: At 5 years 47% of patients were progression-free without androgen deprivation therapy. Among patients with pT2 disease 100% were progression-free at 5 years, compared with 35% of patients with pT3N0 disease or higher and 0% of patients with node positive (pTxN+) disease (p < 0.001). Preoperative PSA 5.0 ng/ml or less was predictive of organ confined disease, and strongly associated with prolonged progression-free and overall survival (p < 0.001 and 0.01, respectively). Mean urinary function scores for patients with or without an artificial urinary sphincter compared favorably with scores reported after standard, nonsalvage prostatectomy. Sexual dysfunction was nearly uniform in patients undergoing standard salvage radical prostatectomy but implantation of a penile prosthesis was associated with a clinically significant improvement in sexual function. CONCLUSIONS: When initiated early in the course of recurrent disease, salvage radical prostatectomy provides excellent oncological control of radiorecurrent prostate cancer without the need for androgen ablation. Implantation of an artificial urinary sphincter and inflatable penile prosthesis devices in patients with postoperative urinary incontinence or erectile dysfunction results in significantly improved quality of life parameters.

Detection of occult lymph node metastases in locally advanced node-negative prostate cancer.

PURPOSE: The purpose of this study was to determine the incidence and clinical significance of occult metastases in the lymph nodes of patients with prostate cancer originally considered node negative by routine histologic evaluation. METHODS: Two hundred seventy four patients with pT3 prostate carcinoma treated by radical prostatectomy and bilateral lymph node dissection were included in this study. One hundred eighty patients were staged node negative (N0), while 94 patients were lymph node positive (N+), based on routine histologic evaluation. All lymph nodes from the 180 N0 patients were evaluated for occult metastases by immunohistochemistry using antibodies to cytokeratins and, if positive, prostate-specific antigen. Recurrence and overall survival were compared among patients with occult tumor cells (OLN+), with patients whose lymph nodes remained negative (OLN-), and with the 94 N+ patients. RESULTS: A total of 3,914 lymph nodes were evaluated from 180 N0 patients (average, 21.7 lymph nodes per patient). Occult tumor cells were found in 24 of 180 patients (13.3%). The presence of OLN+ was significantly associated with increased recurrence and decreased survival compared with OLN- patients (P < .001 and P = .019, respectively; relative risk of recurrence, 2.27; relative risk of death 2.07, respectively). The presence of occult lymph node metastases was an independent predictor of recurrence and death in a multivariable analysis. The outcome for patients with OLN+ disease was similar to that for patients with N+ disease. CONCLUSION: The detection of occult lymph node metastases in patients with pT3N0 prostate cancer identifies those with significantly increased risk of prostate cancer recurrence and death.

Prognostic significance of neuroendocrine expression in lymph node-positive prostate cancer.

OBJECTIVES: To evaluate the expression of chromogranin A, a marker for neuroendocrine (NE) differentiation, in patients with lymph node-positive prostate cancer to determine its prognostic significance. NE cells are involved in cellular growth and differentiation in both normal and pathologic conditions of the prostate. METHODS: We reviewed the data of 140 patients with lymph node-positive prostate adenocarcinoma treated with radical prostatectomy and pelvic lymphadenectomy. The median follow-up was 10.9 years (range 0.8 to 19.7). Immunohistochemical staining for chromogranin A was evaluated in areas of benign epithelium, primary prostate cancer, and lymph node metastasis. The association between chromogranin A expression and the clinical and pathologic factors (preoperative serum prostate-specific antigen and prostatectomy Gleason score and stage) and clinical outcomes, including overall and recurrence-free survival, was evaluated. RESULTS: Staining was positive in 86% of benign areas, 61% of primary cancer specimens, and 12% of lymph node deposits. The preoperative serum prostate-specific antigen level and pathologic stage and grade of the primary tumor did not show any statistically significant correlation with NE staining in any of the areas. Only NE expression in the primary tumor was associated with clinical recurrence, with a 10-year recurrence-free survival rate for those with less than 5% staining of 67% compared with 35% for those with 5% staining or greater (P = 0.03). Furthermore, after adjusting for age, greater NE expression in the primary tumor (relative risk 2.15, P = 0.02) and lymph node deposit (relative risk 2.03, P = 0.03) was associated with poorer overall survival. CONCLUSIONS: NE expression in the primary tumor and lymph node metastasis of patients with node-positive prostate cancer may provide additional prognostic stratification.

A critical analysis of perioperative mortality from radical cystectomy.

PURPOSE: Operative mortality from radical cystectomy has decreased as a result of improvements in surgical and anesthetic care. We reviewed the perioperative deaths from a large group of patients treated with radical cystectomy for primary bladder cancer. MATERIALS AND METHODS: All perioperative mortalities from radical cystectomy were identified from a single high volume institution. The medical records were reviewed to assess the cause of death as well as possible contributing factors. RESULTS: From August 1971 to December 2001, 1,359 patients with primary bladder cancer were treated with radical cystectomy and pelvic iliac lymphadenectomy at our institution. Of these patients, 27 (2%) died within 30 days of surgery or before discharge from hospital. Median patient age at surgery was 67 years (range 47 to 78) and males accounted for 81% of the patients. The median time to death was 28 days from cystectomy (range 0 to 80). Most deaths were cardiovascular related (including acute myocardial infarction, cerebrovascular accident, arterial thrombosis) or due to septic complications with resulting multi-organ system failure, followed by pulmonary embolism, hepatic failure and hemorrhage. Septic related mortality was most often associated with postoperative urine or bowel leak. While most deaths occurred before hospital discharge, 2 patients died at home due to a late pulmonary embolus. No association was seen between pathological stage or type of urinary diversion and mortality. CONCLUSIONS: Perioperative mortality from radical cystectomy is low in this group of patients. Most deaths are due to cardiovascular or septic complications. Careful patient selection and meticulous surgical technique may help decrease the incidence of perioperative mortality.

Radical cystectomy in the elderly: comparison of clincal outcomes between younger and older patients.

BACKGROUND: The authors report their experience with radical cystectomy for transitional cell carcinoma (TCC) of the bladder comparing clinical outcomes, including complication rates, among older patients versus younger patients in a high-volume center specializing in the treatment of patients with advanced carcinoma of the urinary bladder. METHODS: A retrospective review was undertaken of 1054 patients who underwent radical cystectomy for bladder TCC from 1971 through 1997. Four age groups were compared; < 60 years at the time of cystectomy (n = 309 patients), age 60-69 years (n = 381 patients), age 70-79 years (n = 314 patients), and age > or = 80 years (n = 50 patients). RESULTS: The median length of hospital stay in patients ages < 60 years, 60-69 years, 70-79 years, and > or = 80 years was 10 days, 10 days, 11 days, and 11 days, respectively (P < 0.001). The corresponding rates of overall early complications were 24%, 25%, 37%, and 30%, respectively (P = 0.002); whereas the corresponding late complication rates were 36%, 30%, 22%, and 14%, respectively (P < 0.001). The rate of early diversion-related complications did not differ significantly (11%, 8%, 12%, and 6%, respectively; P = 0.14). The operative mortality rates were 1%, 3%, 4%, and 0%, respectively (P = 0.14). There was no difference with respect to early complications, early diversion-related complications, late complications, or operative mortality comparing patients age > 70 years who underwent ileal conduit versus orthotopic urinary diversion (P = 0.20, P = 0.61, P = 0.53, and P = 0.78, respectively). CONCLUSIONS: Elderly patients who underwent cystectomy for TCC had similar mortality and early diversion-related complication rates. Carefully selected elderly patients safely can be offered an orthotopic urinary diversion. Chronological age, per se, is not a contraindication for radical cystectomy in the setting of invasive bladder carcinoma.

Combined radical prostatectomy and bladder augmentation for concomitant prostate cancer and detrusor instability.

OBJECTIVES: To determine the outcomes of a select cohort of patients with severe voiding dysfunction, refractory to medical management, and a concomitant diagnosis of prostate cancer, who were treated with radical prostatectomy and augmentation enterocystoplasty. METHODS: Four men with biopsy-proven prostatic adenocarcinoma, as well as a diagnosis of severe overactive bladder, underwent combined radical retropubic prostatectomy and augmentation enterocystoplasty. All patients underwent fluorourodynamic testing confirming nonobstructive detrusor instability or hyperreflexia. Three patients underwent nerve-sparing radical retropubic prostatectomy with a clamshell ileocystoplasty, and one with neurogenic hyperreflexia underwent sigmoid cystoplasty with a continent catheterizable stoma at radical retropubic prostatectomy. RESULTS: The mean follow-up was 21.5 months (range 8 to 48). All patients had an undetectable prostate-specific antigen level postoperatively. The average hospitalization was 8 days. Perioperative complications occurred in 2 patients, including a prolonged urine leak managed with catheter drainage and postoperative hematuria requiring cystoscopic clot evacuation. Erectile function was preserved in 2 patients with good preoperative erections. At last follow-up, the 3 patients who voided per urethra had minimal postvoid residual urine volumes and maintained good continence, with only 1 patient describing occasional mild stress incontinence. At last follow-up, the patient with the sigmoid cystoplasty catheterized every 4 hours with volumes of about 300 mL and complete stomal continence. No patient required anticholinergic medications postoperatively. CONCLUSIONS: The concomitant diagnosis of prostate cancer and severe detrusor instability may be difficult to treat. The results of our study have shown that for those desiring surgical management for their prostate cancer, a combined bladder augmentation and radical prostatectomy may be performed with minimal added morbidity and significantly improved voiding function in the properly selected individual.