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1.
J Urol ; 195(2): 493-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26459038

ABSTRACT

PURPOSE: Due to the high recurrence risk of nonmuscle invasive urothelial carcinoma it is crucial to distinguish patients at high risk from those with indolent disease. In this study we used a machine learning algorithm to identify the genes in patients with nonmuscle invasive urothelial carcinoma at initial presentation that were most predictive of recurrence. We used the genes in a molecular signature to predict recurrence risk within 5 years after transurethral resection of bladder tumor. MATERIALS AND METHODS: Whole genome profiling was performed on 112 frozen nonmuscle invasive urothelial carcinoma specimens obtained at first presentation on Human WG-6 BeadChips (Illumina®). A genetic programming algorithm was applied to evolve classifier mathematical models for outcome prediction. Cross-validation based resampling and gene use frequencies were used to identify the most prognostic genes, which were combined into rules used in a voting algorithm to predict the sample target class. Key genes were validated by quantitative polymerase chain reaction. RESULTS: The classifier set included 21 genes that predicted recurrence. Quantitative polymerase chain reaction was done for these genes in a subset of 100 patients. A 5-gene combined rule incorporating a voting algorithm yielded 77% sensitivity and 85% specificity to predict recurrence in the training set, and 69% and 62%, respectively, in the test set. A singular 3-gene rule was constructed that predicted recurrence with 80% sensitivity and 90% specificity in the training set, and 71% and 67%, respectively, in the test set. CONCLUSIONS: Using primary nonmuscle invasive urothelial carcinoma from initial occurrences genetic programming identified transcripts in reproducible fashion, which were predictive of recurrence. These findings could potentially impact nonmuscle invasive urothelial carcinoma management.


Subject(s)
Artificial Intelligence , Carcinoma, Transitional Cell/pathology , Gene Expression Profiling , Neoplasm Invasiveness/pathology , Urinary Bladder Neoplasms/pathology , Aged , Algorithms , Biopsy , Carcinoma, Transitional Cell/surgery , Female , Humans , Machine Learning , Male , Neoplasm Staging , Polymerase Chain Reaction , Predictive Value of Tests , Prognosis , Risk Assessment , Sensitivity and Specificity , Urinary Bladder Neoplasms/surgery
2.
J Urol ; 194(2): 433-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25823791

ABSTRACT

PURPOSE: The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy. MATERIALS AND METHODS: This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate. RESULTS: Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries. CONCLUSIONS: T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures.


Subject(s)
Carcinoma, Transitional Cell/surgery , Colonic Pouches , Urinary Bladder Neoplasms/surgery , Urinary Diversion/methods , Urinary Reservoirs, Continent , Adult , Aged , Aged, 80 and over , Cystectomy/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
3.
BJU Int ; 116(1): 44-9, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25413313

ABSTRACT

OBJECTIVES: To investigate the association between lymphovascular invasion (LVI) and clinical outcome in organ-confined, node-negative urothelial cancer of the bladder (UCB) in a post hoc analysis of a prospective clinical trial. To explore the effect of adjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) on outcome in the subset of patients whose tumours exhibited LVI. PATIENTS AND METHODS: Surgical and tumour factors were extracted from the operative and pathology reports of 499 patients who had undergone radical cystectomy (RC) for pT1-T2 N0 UCB in the p53-MVAC trial (Southwest Oncology Group 4B951/NCT00005047). The presence or absence of LVI was determined by pathological examination of transurethral resection or RC specimens. Variables were examined in univariate and multivariate Cox proportional hazards models for associations with time to recurrence (TTR) and overall survival (OS). RESULTS: Among 499 patients with a median follow-up of 4.9 years, a subset of 102 (20%) had LVI-positive tumours. Of these, 34 patients had pT1 and 68 had pT2 disease. LVI was significantly associated with TTR with a hazard ratio (HR) of 1.78 [95% confidence interval (CI) 1.15-2.77; number of events (EV) 95; P = 0.01) and with OS with a HR of 2.02 (95% CI 1.31-3.11; EV 98; P = 0.001) after adjustment for pathological stage. Among 27 patients with LVI-positive tumours who were randomised to receive adjuvant chemotherapy, receiving MVAC was not significantly associated with TTR (HR 0.70, 95% CI 0.16-3.17; EV 7; P = 0.65) or with OS (HR 0.45, 95% CI 0.11-1.83; EV 9; P = 0.26). CONCLUSIONS: Our post hoc analysis of the p53-MVAC trial revealed an association between LVI and shorter TTR and OS in patients with pT1-T2N0 disease. The analysis did not show a statistically significant benefit of adjuvant MVAC chemotherapy in patients with LVI, although a possible benefit was not excluded.


Subject(s)
Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Doxorubicin/therapeutic use , Methotrexate/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Vinblastine/therapeutic use , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/pathology , Prospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/pathology , Urothelium/pathology
4.
J Surg Oncol ; 111(7): 923-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25873574

ABSTRACT

BACKGROUND AND OBJECTIVES: Previous studies have shown that variability in surgical technique can affect the outcomes of cooperative group trials. We analyzed measures of surgical quality and clinical outcomes in patients enrolled in the p53-MVAC trial. METHODS: We performed a post-hoc analysis of patients with pT1-T2N0M0 urothelial carcinoma of the bladder following radical cystectomy (RC) and bilateral pelvic and iliac lymphadenectomy (LND). Measures of surgical quality were examined for associations with time to recurrence (TTR) and overall survival (OS). RESULTS: We reviewed operative and/or pathology reports for 440 patients from 35 sites. We found that only 31% of patients met all suggested trial eligibility criteria of having ≥15 lymph nodes identified in the pathologic specimen (LN#) and having undergone both extended and presacral LND. There was no association between extent of LND, LN#, or presacral LND and TTR or OS after adjustment for confounders and multiple testing. CONCLUSIONS: We demonstrated that there was substantial variability in surgical technique within a cooperative group trial. Despite explicit entry criteria, many patients did not undergo per-protocol LNDs. While outcomes were not apparently affected, it is nonetheless evident that careful attention to study design and quality monitoring will be critical to successful future trials.


Subject(s)
Cystectomy/mortality , Lymph Node Excision/mortality , Lymph Nodes/pathology , Neoplasm Recurrence, Local/surgery , Pelvic Neoplasms/surgery , Quality Assurance, Health Care/trends , Urinary Bladder Neoplasms/surgery , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Pelvic Neoplasms/mortality , Pelvic Neoplasms/pathology , Prognosis , Survival Rate , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
5.
J Urol ; 192(3): 682-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24704114

ABSTRACT

PURPOSE: Inferior vena cava tumor thrombectomy requires experienced surgical teams due to complex hemodynamic considerations. The teams often use vascular bypass techniques that introduce additional risk. Inferior vena caval control in the pericardium obviates the need for cardiopulmonary bypass. We reviewed our experience with intrapericardial control during inferior vena caval tumor thrombectomy to evaluate perioperative outcomes and determine factors associated with overall survival. MATERIALS AND METHODS: We retrospectively reviewed the records of 87 patients who underwent nephrectomy with inferior vena caval tumor thrombectomy using intrapericardial inferior vena caval control from 1978 to 2012. This technique was performed in all 43 and 35 cases of intrahepatic and supradiaphragmatic thrombi, respectively, and in 9 select cases of intra-atrial thrombi. Patient demographics, operative variables and postoperative outcomes were examined. Multivariate regression analysis was used to determine associations between clinical variables and overall survival. RESULTS: Mortality 30 days perioperatively was 9.2% and the incidence of high grade complications was 19.5%. Median survival was 3.1 and 2.5 years in patients with pT3bN0 and pT3cN0, respectively. Extended regional lymphadenectomy, which was performed in all cases, revealed nodal metastasis in 38%. On multivariate analysis ECOG greater than 2 and pT3c stage were associated with worse survival. Histological grade, perinephric fat invasion and lymph node involvement were not associated with worse survival. CONCLUSIONS: Intrapericardial control of the inferior vena cava enables a single surgical team to safely perform tumor thrombectomy for intrahepatic and supradiaphragmatic thrombi, eliminating the risk and morbidity related to cardiopulmonary bypass. Although supradiaphragmatic extent and ECOG greater than 2 are associated with worse survival, complete resection with lymphadenectomy can allow for long-term survival in patients with locally advanced disease.


Subject(s)
Neoplastic Cells, Circulating , Thrombectomy/methods , Thrombosis/mortality , Thrombosis/surgery , Vena Cava, Inferior , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/secondary , Cardiopulmonary Bypass , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Pericardium , Retrospective Studies , Survival Rate , Time Factors
6.
BJU Int ; 113(1): 65-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23937628

ABSTRACT

OBJECTIVE: To evaluate oncological outcomes of patients with carcinoma in situ (CIS) exclusively at radical cystectomy (RC) and no previous history of ≥T1 disease. PATIENTS AND METHODS: Patients undergoing RC with curative intent for CIS between 1971 and 2008 at the University of Southern California were included if they met all the following criteria: (i) pathological CIS-only disease at RC, (ii) preoperative clinical stage cCIS and/or cCIS + cTa, and (iii) no previous history of lamina propria invasion (≥pT1). Kaplan-Meier plots were used to estimate the probabilities of recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of the 1964 consented patients 52 met the inclusion criteria with a median (range) follow-up of 8.5 (0.008-34) years. A median (range) of 36 (10-95) lymph nodes were identified per patient but no metastases found. Estimated 5- and 10-year RFS rates were 94% and 90%, respectively and estimated 5- and 10-year OS rates were 85% and 66%, respectively. Different mechanisms of recurrence were found in four (8%) patients after a median (range) interval of 2.4 (0.6-7.1) years. While two patients had metachronous recurrence within the urinary tract, the first of the other two had early systemic recurrence and the second late local recurrence. CONCLUSIONS: We noticed excellent outcomes after RC for CIS-only disease. However, patients may have synchronous and/or develop metachronous tumours, as well as local and/or distant/systemic recurrence that can be cured but may also lead to fatal outcomes.


Subject(s)
Carcinoma in Situ/mortality , Carcinoma in Situ/surgery , Cystectomy , Lymph Nodes/pathology , Neoplasm Recurrence, Local/mortality , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , California/epidemiology , Carcinoma in Situ/pathology , Cystectomy/mortality , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Risk Factors , Treatment Outcome , Urinary Bladder Neoplasms/pathology
7.
BJU Int ; 113(4): 554-60, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24131453

ABSTRACT

OBJECTIVE: To analyse the long-term outcomes of patients with lymph node (LN)-positive bladder cancer, who did not receive any adjuvant therapy after radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND). PATIENTS AND METHODS: We conducted a retrospective, combined cohort analysis based on two prospectively maintained cystectomy databases from the University of Southern California and the University of Bern. Eligible patients underwent RC with ePLND for cN0M0 disease but were found to have LN-positive disease. No patient had neoadjuvant therapy, and all had negative surgical margins. Kaplan-Meier plots were used to estimate recurrence-free survival (RFS) and overall survival (OS). Subgroup comparisons were performed using log-rank tests, and multivariable analysis was based on Cox proportional hazard models. RESULTS: Of 521 patients with LN-positive disease, 251 (48%) never received adjuvant therapy. Although the pathological stage distribution was similar, the 251 patients who did not receive adjuvant therapy were older and had both fewer total and positive LNs than those who underwent adjuvant therapy. The median RFS for patients treated with RC alone was 1.6 years. Recurrences mainly occurred <2 years after RC, resulting in 5- and 10-year RFS rates of 32 and 26%, respectively. Pathological T stage, the total number of LNs and the number of positive LNs detected were independent predictors of RFS and OS. CONCLUSIONS: In this study, 25% of patients with documented LN metastases who did not receive adjuvant therapy were cured with RC and ePLND; however, a few relapses may occur later than 3 years. Predictors of survival were pathological T stage, the number of total LNs and the number of positive LNs identified.


Subject(s)
Cystectomy/methods , Lymph Node Excision/methods , Urinary Bladder Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Retrospective Studies , Treatment Outcome , Treatment Refusal , Urinary Bladder Neoplasms/pathology
8.
World J Urol ; 32(1): 221-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24317553

ABSTRACT

PURPOSE: The ratio between orthotopic and non-orthotopic diversions in women is far lower than in male patients. Data on urinary function in female patients with neobladders are therefore sparse. METHODS: We investigated the urinary function of female neobladder patients utilizing the Bladder Cancer Index, a validated and reliable health-related quality-of-life (HRQOL) questionnaire. Furthermore, we tried to identify preoperative factors that may influence functional results. All living female patients with an orthotopic neobladder (N = 82) from the University of Southern California Bladder Cancer Database were sent a questionnaire including the University of Michigan Bladder Cancer Index. Univariate analyses were performed using the Kruskal-Wallis test followed by a multivariate stepwise regression model. RESULTS: Fifty-six patients (68.3%) responded and were included in the analysis. Thirty-five (62.5%) of these patients had to catheterize their neobladder to a certain amount, while 25 patients (44.6%) depend on catheterization to empty their neobladder. Univariate analyses showed that patient age (>65 years) was the only variable associated with a statistically significant lower rate of neobladder catheterization. Better urinary bother scores were associated with organ-confined disease (p = 0.038) and education level (p = 0.01). However, these variables were not significant in a multivariate stepwise linear regression model. CONCLUSION: Considerably more women require urinary catheterization to void than previously reported. In this study, representing the largest investigated cohort in this topic, we were unable to identify any predictors of this outcome or any other urinary HRQOL in this cohort.


Subject(s)
Intestines/physiology , Intestines/surgery , Plastic Surgery Procedures/methods , Urinary Bladder Neoplasms/surgery , Urinary Bladder/surgery , Urination/physiology , Urodynamics/physiology , Adult , Aged , Aged, 80 and over , Cohort Studies , Cystectomy , Female , Follow-Up Studies , Humans , Middle Aged , Predictive Value of Tests , Quality of Life , Regression Analysis , Retrospective Studies , Surveys and Questionnaires , Treatment Outcome , Urinary Catheterization
9.
Cancer ; 119(4): 756-65, 2013 Feb 15.
Article in English | MEDLINE | ID: mdl-23319010

ABSTRACT

BACKGROUND: Traditional single-marker and multimarker molecular profiling approaches in bladder cancer do not account for major risk factors and their influence on clinical outcome. This study examined the prognostic value of molecular alterations across all disease stages after accounting for clinicopathological factors and smoking, the most common risk factor for bladder cancer in the developed world, in a population-based cohort. METHODS: Primary bladder tumors from 212 cancer registry patients (median follow-up, 13.2 years) were immunohistochemically profiled for Bax, caspase-3, apoptotic protease-activating factor 1 (Apaf-1), Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. "Smoking intensity" quantified the impact of duration and daily frequency of smoking. RESULTS: Age, pathological stage, surgical modality, and adjuvant therapy administration were significantly associated with survival. Increasing smoking intensity was independently associated with worse outcome (P < .001). Apaf-1, E-cadherin, and p53 were prognostic for outcome (P = .005, .014, and .032, respectively); E-cadherin remained prognostic following multivariable analysis (P = .040). Combined alterations in all 9 biomarkers were prognostic by univariable (P < .001) and multivariable (P = .006) analysis. A multivariable model that included all 9 biomarkers and smoking intensity had greater accuracy in predicting prognosis than models composed of standard clinicopathological covariates without or with smoking intensity (P < .001 and P = .018, respectively). CONCLUSIONS: Apaf-1, E-cadherin, and p53 alterations individually predicted survival in bladder cancer patients. Increasing number of biomarker alterations was significantly associated with worsening survival, although markers comprising the panel were not necessarily prognostic individually. Predictive value of the 9-biomarker panel with smoking intensity was significantly higher than that of routine clinicopathological parameters alone.


Subject(s)
Biomarkers, Tumor/analysis , Smoking , Urinary Bladder Neoplasms/mortality , Aged , Apoptotic Protease-Activating Factor 1/metabolism , Biomarkers, Tumor/metabolism , Cadherins/metabolism , Cohort Studies , Follow-Up Studies , Humans , Los Angeles , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prognosis , Registries , Treatment Outcome , Tumor Suppressor Protein p53/metabolism , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery
10.
BJU Int ; 112(2): E51-8, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23795798

ABSTRACT

OBJECTIVE: To evaluate oncological outcome trends over the last three decades in patients after radical cystectomy (RC) and extended pelvic lymph node (LN) dissection. PATIENTS AND METHODS: Retrospective analysis of the University of Southern California (USC) RC cohort of patients (1488 patients) operated with intent to cure from 1980 to 2005 for biopsy confirmed muscle-invasive urothelial bladder cancer. To focus on outcomes of unexpected (cN0M0) LN-positive patients, the USC subset was extended with unexpected LN-positive patients from the University of Berne (UB) (combined subgroup 521 patients). Patients were grouped and compared according to decade of surgery (1980-1989/1990-1999/≥2000). Survival probabilities were calculated with Kaplan-Meier plots, log-rank tests compared outcomes according to decade of surgery, followed by multivariable verification. RESULTS: The 10-year recurrence-free survival was 78-80% in patients with organ-confined, LN-negative disease, 53-60% in patients with extravesical, yet LN-negative disease and ≈30% in LN-positive patients. Although the number of patients receiving systemic chemotherapy increased, no survival improvement was noted in either the entire USC cohort, or in the combined LN-positive USC-UB cohort. In contrast, patient age at surgery increased progressively, suggesting a relative survival benefit. CONCLUSIONS: Radical surgery remains the mainstay of therapy for muscle-invasive bladder cancer. Yet, our study reveals predictable outcomes but no survival improvement in patients undergoing RC over the last three decades. Any future survival improvements are likely to result from more effective systemic treatments and/or earlier detection of the disease.


Subject(s)
Cystectomy , Lymph Node Excision , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Lymph Node Excision/methods , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
11.
J Urol ; 186(4): 1261-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21849183

ABSTRACT

PURPOSE: There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage. MATERIALS AND METHODS: Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed. RESULTS: Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%). CONCLUSIONS: Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.


Subject(s)
Carcinoma, Transitional Cell/surgery , Cystectomy , Lymph Node Excision , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/secondary , Female , Humans , Lymph Node Excision/methods , Male , Middle Aged , Neoplasm Recurrence, Local , Pelvis , Survival Rate , Urinary Bladder Neoplasms/mortality
12.
BJU Int ; 108(5): 660-4, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21223479

ABSTRACT

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.


Subject(s)
Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Disease-Free Survival , Follow-Up Studies , Humans , Lymph Node Excision , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prognosis , Prostatectomy/methods , Risk Factors , Time Factors , Treatment Outcome
13.
J Urol ; 181(5): 2052-8; discussion 2058-9, 2009 May.
Article in English | MEDLINE | ID: mdl-19286213

ABSTRACT

PURPOSE: We compared oncological outcomes in women undergoing radical cystectomy and orthotopic diversion for bladder transitional cell carcinoma. MATERIALS AND METHODS: From 1990 to 2005, 201 women underwent radical cystectomy, including 120 with an orthotopic neobladder. Median followup was 8.6 years. The clinical course, and pathological and oncological outcomes in these 120 women were analyzed and compared to those in 81 women undergoing radical cystectomy and cutaneous diversion during the same period. RESULTS: Overall 3 of 120 women (2.5%) who received a neobladder died perioperatively. In this group the tumor was pathologically organ confined in 73 patients (61%), extravesical in 18 (15%) and lymph node positive in 29 (24%). Overall 5 and 10-year recurrence-free survival was 62% and 55%, respectively. Five and 10-year recurrence-free survival in patients with organ confined and extravesical disease was similar at 75% and 67%, and 71% and 71%, respectively. Patients with lymph node positive disease had significantly worse 5 and 10-year recurrence-free survival (24% and 19%, respectively). One woman had recurrence in the urethra and 2 (1.7%) had local recurrence. As stratified by pathological subgroups, similar outcomes were observed when comparing women with an orthotopic neobladder to the 81 who underwent cutaneous diversion. CONCLUSIONS: Orthotopic diversion does not compromise the oncological outcome in women after radical cystectomy for bladder transitional cell carcinoma. Excellent local and urethral control may be expected. Women with node positive disease are at highest risk for recurrence. Similar outcomes were observed in women undergoing cutaneous diversion.


Subject(s)
Carcinoma, Transitional Cell/surgery , Cystectomy/methods , Neoplasm Recurrence, Local/mortality , Urinary Bladder Neoplasms/surgery , Urinary Diversion/methods , Urinary Reservoirs, Continent , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Cohort Studies , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Probability , Retrospective Studies , Risk Assessment , Survival Rate , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Urinary Diversion/adverse effects
14.
J Urol ; 182(5): 2182-7, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19758623

ABSTRACT

PURPOSE: Lymph node metastasis in patients who undergo radical cystectomy for bladder transitional cell carcinoma is considered a poor prognostic factor. However, patients with minimal lymph node involvement likely have a better outcome than those with extensive disease. We examined outcomes in patients with low volume lymph node metastasis and identified variables associated with disease recurrence. MATERIALS AND METHODS: Our institution maintains a database of 1,600 patients with bladder transitional carcinoma who underwent radical cystectomy from 1971 to 2005 with intent to cure. All patients with low volume lymph node metastasis, defined as 1 or 2 positive lymph nodes, without concomitant distant metastasis were included in study. RESULTS: A total of 181 patients were identified. Median followup was 12.8 years, during which 96 patients experienced recurrence. Estimated 5 and 10-year recurrence-free survival was 43.8% and 40.9%, respectively. Multivariate analysis indicated that pathological stage/subgroup (RR 1.733, p = 0.015), lymph node density (RR 1.935, p = 0.014) and adjuvant chemotherapy (RR 0.538, p = 0.004) were significant independent predictors of recurrence-free survival. CONCLUSIONS: A considerable proportion of patients with low volume lymph node metastasis in our cohort remained free of recurrence during followup. Extravesical tumor extension and lymph node density greater than 4% were associated with a higher recurrence risk and adjuvant chemotherapy was associated with a lower risk. Although some patients with low volume lymph node metastasis may be cured by surgery alone, these data support adjuvant chemotherapy in these patients.


Subject(s)
Carcinoma, Transitional Cell/secondary , Cystectomy , Neoplasm Recurrence, Local/epidemiology , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/epidemiology , Carcinoma, Transitional Cell/surgery , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Treatment Outcome , Urinary Bladder Neoplasms/surgery
15.
World J Urol ; 27(1): 51-5, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19002689

ABSTRACT

PURPOSE: Orthotopic neobladder reconstruction has become a standard form of urinary diversion in many centers for patients undergoing radical cystectomy for bladder cancer. There is still controversy about the best technique for construction of the neobladder, and especially whether it is necessary to include an antireflux mechanism. METHODS: We designed a prospective randomized clinical trial comparing two forms of ileal neobladder: the Studer pouch and the T-pouch. The latter includes an extraserosal tunneled afferent limb which prevents reflux from the pouch to the kidneys. The primary endpoint of the study is renal function and anatomy at 3 years following surgery, with secondary endpoints including early and late postoperative complications, renal infections and need for secondary procedures. RESULTS: To date we have randomized 462 patients over approximately 6 years, with a planned full enrollment of 550 patients. Ten percent of patients have been withdrawn because they did not undergo the planned orthotopic diversion due to a positive urethral margin on frozen section. We expect approximately 70% of patients to be alive and available for follow-up at 3 years, which will give us ample power to detect clinically meaningful differences in the outcome of these two diversions. CONCLUSION: This trial has been feasible and randomization has been acceptable to most patients. Long-term follow-up of the patients on this trial should be able to definitively answer the question of the importance of an antireflux mechanism in the orthotopic neobladders construction.


Subject(s)
Urinary Diversion/methods , Urinary Reservoirs, Continent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies
16.
World J Urol ; 27(1): 21-5, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19066905

ABSTRACT

OBJECTIVES: To report the long-term oncological efficacy of radical cystectomy for patients with presumed clinical CIS only disease, to characterize the likelihood of clinical understaging, and to characterize the pattern of recurrence. METHODS: One thousand six hundred patients have undergone radical cystectomy and pelvic lymph node dissection with intent to cure from August 1971 to December 2005 at the University of Southern California; 27 patients from this cohort who satisfied both the inclusion and exclusion criteria were identified. Relevant clinical and pathological data at time of cystectomy and during follow-up were reported. Overall and recurrence-free survival was estimated using the Kaplan-Meier method. RESULTS: At time of cystectomy, 33% of patients were found to be clinically understaged. Median follow-up was 94 months. Estimated 5- and 10-year overall survival was 87 and 56%, respectively. Estimated 5- and 10-year recurrence-free survival was 100 and 83%, respectively. CONCLUSIONS: Excellent long-term survival outcomes can be achieved with radical cystectomy. Radical cystectomy should be strongly considered for patients who have failed prior intravesical therapy. Long-term surveillance of the retained urethra and of the upper tract is essential, as recurrence can occur years following cystectomy. Patients who recur are at high risk of dying from disease.


Subject(s)
Carcinoma in Situ/surgery , Cystectomy , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Time Factors , Treatment Outcome
17.
World J Urol ; 27(1): 39-44, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19020886

ABSTRACT

OBJECTIVES: To describe the tolerability of two chemotherapy regimens, gemcitabine and cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) for adjuvant treatment of patients with locally advanced urothelial cancer after radical cystectomy. METHODS: The USC Department of Urology bladder cancer database was searched for subjects who received adjuvant chemotherapy following cystectomy for transitional cell carcinoma with extravesical and/or lymph node involvement, yielding 187 cases. Clinical details regarding toxicity, number of cycles administered, and cancer outcome were analyzed. RESULTS: The majority of subjects had lymph node involvement (70%). Sixty-eight percent of subjects received MVAC and 32% received GC, the latter regimen was predominant after 2000. Fifty-six percent of subjects received all four planned cycles (51% GC and 58% MVAC). With a median follow-up of 11.2 years (range 1.9-19.6), 96 patients (51%) have suffered a relapse, with no significant difference between chemotherapy regimens. Median time to recurrence for the population was 3.7 years and median overall survival is 4.6 years (3.0-9.3). The median time from recurrence to death was 6.7 months and was not significantly different between MVAC and GC. CONCLUSIONS: Both MVAC and GC are tolerated after cystectomy for advanced urothelial carcinoma. A significant proportion of high-risk patients survive, free of disease, beyond 10 years. At recurrence, patients previously treated with adjuvant chemotherapy have a survival that appears much shorter than patients who develop metastases in the absence of this exposure, suggesting resistance to salvage chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , California , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Doxorubicin/therapeutic use , Feasibility Studies , Female , Humans , Male , Methotrexate/therapeutic use , Middle Aged , Retrospective Studies , Universities , Vinblastine/therapeutic use , Gemcitabine
18.
World J Urol ; 27(1): 9-20, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19039591

ABSTRACT

Bladder cancer remains a significant health problem. Currently, conventional histopathologic evaluation criteria (tumor grade and stage) are limited in their ability to accurately predict tumor behavior. A significant number of patients with muscle-invasive or extravesical disease treated by radical cystectomy alone die of metastasis. Intense research efforts are being made to better identify and categorize tumors by their molecular alterations and biological characteristics. A majority of the aggressive, invasive bladder carcinomas have alterations in the p53 and retinoblastoma pathways that regulate the cell cycle by interacting with signal transduction pathways. Angiogenesis further contributes to the neoplastic growth by providing a constant supply of oxygen and nutrients. It is becoming apparent that the accumulation of genetic and molecular changes ultimately determines a tumor's phenotype and subsequent clinical behavior. We provide a contemporary outline of our current understanding of the molecular and genetic events associated with tumorigenesis and progression. We emphasize the ways by which molecular biology is likely to affect the development of future therapies that will be able to target molecular alterations in individual tumors based on their respective profiles. The current status of targeted therapies for bladder cancer is also presented as well as the ongoing clinical trials.


Subject(s)
Urinary Bladder Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Cell Cycle/physiology , Humans , Molecular Biology , Signal Transduction
20.
BJU Int ; 102(9): 1086-91, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18671791

ABSTRACT

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.


Subject(s)
Blood Loss, Surgical/prevention & control , Fibrin Fibrinogen Degradation Products/metabolism , Peptide Hydrolases/blood , Prostatectomy/adverse effects , Prostatic Neoplasms/surgery , Antithrombin III , Blood Transfusion , Enzyme-Linked Immunosorbent Assay , Hemoglobins/metabolism , Humans , Male , Middle Aged , Multivariate Analysis , Prostate-Specific Antigen/blood , Prostatectomy/methods , Prostatic Neoplasms/blood , Treatment Outcome
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