Assessing the minimum number of lymph nodes needed at radical cystectomy in patients with bladder cancer.

OBJECTIVE: To identify the likelihood of finding one or more positive lymph nodes (LNs) according to the number of LNs removed at radical cystectomy (RC), as the number of LNs removed affects disease progression and survival after RC. PATIENTS AND METHODS: Between 1984 and 2003, 731 assessable patients had RC and bilateral pelvic lymphadenectomy at three different institutions. ROC curve coordinates were used to determine the probability of identifying one or more positive LNs according to the total number of removed LNs. RESULTS: Of the 731 patients, 174 (23.8%) had LNs metastases. The mean (median, range) number of LNs removed was 18.7 (17, 1-80). The ROC coordinate-based plots of the number of removed LNs and the probability of finding one or more LNs metastases indicated that removing 45 LNs yielded a 90% probability. Conversely, removing either 15 or 25 LNs indicated, respectively, 50% and 75% probability of detecting one or more LNs metastases. CONCLUSIONS: These data indicate that removing 25 LNs might represent the lowest threshold for the extent of lymphadenectomy at RC. Our findings confirm the importance of an extended lymph node dissection.

Adjuvant chemotherapy for bladder cancer does not alter cancer-specific survival after cystectomy in a matched case-control study.

OBJECTIVE: To assess the effect of adjuvant chemotherapy (ACHT; methotrexate, vinblastine, adriamycin and cisplatin, MVAC, or gemcitabine/cisplatin, GC) on the rate of cancer-specific survival and overall survival, as the benefit of ACHT after radical cystectomy (RC) for bladder cancer is controversial. PATIENTS AND METHODS: Within a study group of 958 patients treated with RC between 1984 and 2003, we identified 274 (29.0%) with a high risk of progression due to pT3 or pT4 and/or pN1-3 stages. Of these, 129 (46.6%) received ACHT (MVAC in 103, GC in 26). These patients were then matched with the remaining patients who were unexposed to ACHT. Exact matches were made for pT stage, tumour grade, pN stage and lymphovascular invasion. Age (+/-5 years) and year of surgery (+/-5 years) were calliper-matched. Matching resulted in 62 patients treated with RC/ACHT and 65 treated with RC alone. Kaplan-Meier, life-table and Cox regression analyses were used to assess cancer-specific and overall survival. RESULTS: There was no statistically significant difference in cancer-specific survival probabilities at 5 years after RC between the two groups (relative risk 1.2; P = 0.5). There was also no difference in overall survival at 5 years (1.1; P = 0.7). In multivariable analyses the delivery of adjuvant chemotherapy was not an independent predictor for survival endpoints (P = 0.3 for cancer-specific and 0.3 for overall survival). CONCLUSIONS: This matched case-control analysis showed that either MVAC or GC chemotherapy had no effect on cancer-specific or overall survival after RC in high-risk patients. Further randomized long-term studies are necessary to confirm these results.

Macroscopic, but not microscopic, perivesical fat invasion at radical cystectomy is an adverse predictor of recurrence and survival.

OBJECTIVE: To examine whether the presence of microscopic (pT3a) or macroscopic (pT3b) disease worsens the prognosis relative to pT2 disease at radical cystectomy, as the prognostic significance of pT3a vs pT3b perivesical fat invasion (pT3) is controversial. PATIENTS AND METHODS: In all, 242 patients with pT3 disease (pT3a in 88, pT3b in 121) had radical cystectomy and bilateral pelvic lymphadenectomy for transitional cell carcinoma of the urinary bladder; they were compared with 172 who had organ-confined muscle-invasive disease (pT2). For the analyses we used univariable and multivariable Cox regression models of recurrence and cancer-specific survival, adjusted for age, tumour grade, lymphovascular invasion and the presence of lymph node metastases. RESULTS: In multivariable analyses, microscopic perivesical fat extension (pT3a) was not associated with higher recurrence (P = 0.3) or the mortality rate (P = 0.06) vs pT2 disease. Conversely, the presence of deep perivesical fat extension (pT3b) was associated with 1.8 times the rate of recurrence (P = 0.002) and with twice the rate of death (P = 0.001) vs pT2 disease. CONCLUSION: These findings imply that a detailed assessment of the cystectomy specimen for the presence of microscopic perivesical fat invasion might not be necessary, as the presence of pT3a disease has no strong effect on recurrence or mortality. Moreover, patients with pT3a disease might not require more aggressive therapy than their counterparts with pT2 disease. However, further validation of our data is required.

Discrepancy between clinical and pathologic stage: impact on prognosis after radical cystectomy.

OBJECTIVES: We compared clinical and pathologic staging in a large, contemporary, consecutive series of patients who were treated with radical cystectomy and pelvic lymphadenectomy, and determined the effect of stage discrepancy on outcomes. METHODS: We collected retrospective data from 778 consecutive patients with bladder transitional cell carcinoma who were treated with radical cystectomy and pelvic lymphadenectomy, and for whom the clinical and pathologic stage were available. RESULTS: Pathologic upstaging occurred in 42% of patients, and pathologic downstaging occurred in 22%. Forty percent of patients with non-muscle-invasive clinical stage had muscle-invasive pathologic stage. Thirty-six percent of patients with organ-confined clinical stage had non-organ-confined pathologic stage (> or =pT3N0 or pTanyN-positive). Patients with higher clinical stage were more likely to be upstaged to non-organ-confined disease (p<0.001). Patients were stratified into three groups: pathologically upstaged, same clinical and pathologic stage, and pathologically downstaged. When adjusted for the effects of standard postoperative features, upstaged patients were at a significantly higher risk of disease recurrence and bladder cancer-specific death than patients who had the same pathologic and clinical stage, who in turn were at significantly higher risk than downstaged patients. This observation remained true within each clinical stage strata. Within each pathologic stage strata, clinical stage did not substratify into different risk groups. CONCLUSIONS: Clinical to pathologic stage discrepancy is a relatively common finding after extirpative surgery for bladder cancer. Clinical outcomes after radical cystectomy are largely driven by pathologic stage. Better clinical staging is necessary to improve patient evaluation and management.

Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy.

OBJECTIVES: Carcinoma in situ (CIS) is a nonpapillary, high-grade, potentially aggressive, and unpredictable manifestation of transitional cell carcinoma (TCC) of the bladder. The aim of this study was to assess whether presence of concomitant CIS has a detrimental effect on cancer control after radical cystectomy. METHODS: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder TCC at three US academic centres were reviewed. Ninety-nine of 812 (12%) patients had CIS only at radical cystectomy and were excluded from the analyses. RESULTS: Three hundred thirty of the 713 (46.3%) patients had concomitant CIS at radical cystectomy. Patients with TCC involvement of the urethra were more likely to have concomitant CIS than not (61% vs. 40%, p=0.018). Concomitant CIS was significantly more common in patients with lower cystectomy stages and higher tumour grades. In univariate, but not multivariate, analysis, patients with concomitant CIS versus those without were at increased risk of disease recurrence (p=0.0371). In patients with organ-confined disease, concomitant CIS was an independent predictor of disease recurrence (p=0.048 and p=0.012, respectively) but not bladder cancer-specific mortality (p=0.160 and p=0.408, respectively) after adjusting for the effects of standard postoperative features. CONCLUSIONS: Concomitant CIS in the cystectomy specimen is common, and patients with concomitant CIS are at increased risk of urethral TCC involvement. The presence of concomitant CIS appears to confer a worse prognosis in patients with non-muscle-invasive TCC treated with radical cystectomy.

Advanced age is associated with poorer bladder cancer-specific survival in patients treated with radical cystectomy.

OBJECTIVE: Bladder cancer (BCa) is a disease of older persons, the incidence of which is expected to increase as the population ages. There is controversy, however, regarding the outcomes of radical cystectomy (RC), the gold standard treatment of high-risk BCa, in patients of advanced chronological age. The aim of our study was to assess the impact of patient age on pathological characteristics and recurrence-free and disease-specific survival following RC. METHODS: The records of 888 consecutive patients who underwent RC for transitional cell carcinoma (TCC) were reviewed. Age at RC was analyzed both as a continuous (yr) and categorical (< or =60 yr old, n=240; 60.1-70 yr old, n=331; 70.1-80 yr old, n=266; >80 yr old, n=51) variable. Logistic regression and survival analyses were performed. RESULTS: Higher age at RC, analyzed as a continuous or categorical variable, was associated with extravesical disease and pathological upstaging (all p<0.02). Older patients were less likely to receive postoperative chemotherapy (< or =60 yr: 32% vs. >80 yr: 14%, p=0.008). In both pre- and postoperative multivariate models, higher age at RC as a categorical variable was associated with BCa-specific survival (p<0.05). Patients >80 yr old had a significantly greater risk of disease recurrence than patients aged < or =60 yr (p<0.05). CONCLUSION: Greater patient age at the time of RC for BCa is independently associated with adverse outcomes. Better understanding of factors associated with postoperative outcomes in this growing segment of the population is necessary. Prospective corroboration and further refinement of similar analyses in other large datasets is needed.

Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium.

PURPOSE: We present the characteristics and outcomes of a large, contemporary, consecutive series of patients treated with radical cystectomy and pelvic lymphadenectomy for transitional cell carcinoma of the bladder. MATERIALS AND METHODS: We developed a multi-institutional database and collected retrospective and prospective data on 888 consecutive patients with bladder transitional cell carcinoma who were treated with radical cystectomy and pelvic lymphadenectomy at 3 academic centers in the United States between 1984 and 2003. RESULTS: Of the patients 25% had extravesical tumor extension with negative lymph nodes and 23% had lymph node metastasis. The rate of lymph node involvement increased with advancing pathological stage. Mean recurrence-free and bladder cancer specific survival +/- SE was 58% +/- 2% and 66% +/- 2% at 5 years, respectively. On preoperative multivariate analysis clinical tumor stage and neoadjuvant systemic chemotherapy were associated with cancer recurrence, while more advanced age, clinical tumor stage and preoperative carcinoma in situ were associated with bladder cancer specific mortality. On postoperative multivariate analysis pathological tumor stage, lymph node metastasis, lymphovascular invasion, adjuvant radiotherapy and adjuvant chemotherapy were associated with cancer recurrence, while higher pathological tumor stage, more advanced age, lymph node metastasis, lymphovascular invasion and adjuvant radiotherapy were associated with disease specific survival. Patients with metastasis to regional lymph nodes (pT any N1-3) were at significantly higher risk for bladder cancer recurrence and death than patients with extravesical tumor extension (pT3N0), who in turn were at significantly higher risk than patients with organ confined disease (pT2 N0 or less). CONCLUSIONS: The results of this large, contemporary, multi-institutional series show that radical cystectomy and pelvic lymphadenectomy provide durable local control and disease specific survival in patients with localized invasive transitional cell carcinoma.

Nomograms provide improved accuracy for predicting survival after radical cystectomy.

AIMS: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer-specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging. METHODS: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation. RESULTS: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.663). CONCLUSIONS: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.

Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder.

PURPOSE: American Joint Committee on Cancer staging represents the gold standard for prediction of recurrence after radical cystectomy in patients with invasive bladder cancer. We tested the hypothesis that American Joint Committee on Cancer stage based predictions may be improved when pathological tumor and node stage information is combined with additional clinical and pathological variables within a prognostic nomogram. MATERIALS AND METHODS: We used Cox proportional hazards regression analysis to model variables of 728 patients with transitional cell carcinoma of the bladder treated with radical cystectomy and bilateral pelvic lymphadenectomy at 1 of 3 participating institutions. Standard predictors, pT and pN, were complemented by age, gender, tumor grade at cystectomy, presence of lymphovascular invasion, presence of carcinoma in situ in the cystectomy specimen, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy. The concordance index was used to quantify the accuracy of regression coefficient based nomograms. A total of 200 bootstrap resamples were used to reduce overfit bias and for internal validation. Calibration plots were used to graphically explore the performance characteristics of the multivariate nomogram. RESULTS: Followup ranged from 0.1 to 183.4 months (median 24.9, mean 36.4). Recurrence was recorded in 249 (34.2%) patients with a median time to recurrence of 108 months (range 0.8 to 131.9). Actuarial recurrence-free probabilities were 69.6% (95% CI 65.8%-73.0%), 60.2% (55.8%-64.3%) and 52.9% (47.3%-58.1%) at 2, 5 and 8 years after cystectomy, respectively. Two-hundred bootstrap corrected predictive accuracy of American Joint Committee on Cancer stage based predictions was 0.748. Accuracy increased by 3.2% (0.780) when age, lymphovascular invasion, carcinoma in situ, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy were added to pathological stage information and used within a nomogram. CONCLUSIONS: A nomogram predicting bladder cancer recurrence after cystectomy is 3.2% more accurate than American Joint Committee on Cancer stage based predictions. Moreover, a nomogram approach combines several advantages such as easy and precise estimation of individual recurrence probability at key points after cystectomy, which all patients deserve to know and all treating physicians need to know.

Characteristics and outcomes of patients with carcinoma in situ only at radical cystectomy.

OBJECTIVES: To describe the cancer-specific outcomes of patients with pathologic carcinoma in situ (CIS) only at radical cystectomy. METHODS: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder transitional cell carcinoma at three U.S. academic centers were reviewed. Of the 812 patients, 99 (12%) had CIS only at radical cystectomy. RESULTS: The distribution of clinical stage for the 99 patients with CIS only at radical cystectomy was as follows: 47% of patients had CIS only, 8% had cT1, 15% had cT1 plus CIS, 10% had cT2, 13% had cT2 plus CIS, 6% had cTa, and 1% had Ta plus CIS. Two patients had lymphovascular invasion in the radical cystectomy specimen, and three had metastases to the lymph nodes. The actuarial recurrence-free survival estimates were 89.8% (95% confidence interval [CI] 83.0% to 96.6%) at 3 years and 83.0% (95% CI 73.2% to 92.8%) at 5 and 7 years after radical cystectomy. Six patients (6%) had died of bladder cancer at analysis and 13 (13%) had died of other causes without evidence of disease recurrence. The actuarial disease-specific survival estimates were 95.8% (95% CI 91.2% to 99.9%) at 3 years, 90.7% (95% CI 82.4% to 98.9%) at 5 years, and 87.2% (95% CI 76.8% to 97.5%) at 7 years after surgery. On univariate Cox regression analyses, only metastasis to lymph nodes was associated with bladder cancer recurrence and death (P <0.001). CONCLUSIONS: Disease control seemed durable for patients with pathologic CIS only at radical cystectomy in the absence of metastases to the lymph nodes, even in the case of failure after intravesical therapy.

Precystectomy nomogram for prediction of advanced bladder cancer stage.

OBJECTIVE: To evaluate precystectomy prediction of pT and pN stages at cystectomy. METHODS: Multivariate logistic regression analyses modelled variables of 726 evaluable patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. The first set of models predicted pT(3-4) stage at cystectomy, and the second set predicted pN(1-3) stages at cystectomy. Transurethral resection (TUR) predictors consisted of 2002 T stage, 1973 WHO tumour grade, presence of carcinoma in situ, age, gender, and delivery of neo-adjuvant chemotherapy. The area under the ROC curve quantified nomogram accuracy. Two hundred bootstrap resamples were used to reduce overfit bias. RESULTS: At TUR, 11% of patients were staged as pT(3-4) versus 42% at cystectomy. Lymph node metastases were found in 24% of patients at cystectomy (pN(1-3)). The multivariate pT(3-4) nomogram was 75.7% accurate versus 71.4% for TUR T stage. The multivariate pN(1-3) nomogram was 63.1% accurate versus 61.0% for TUR T stage. CONCLUSION: Multivariate nomograms are not perfect, but they do predict more accurately than TUR T stage alone.

Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder.

PURPOSE: The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. MATERIALS AND METHODS: A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. RESULTS: Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. CONCLUSIONS: NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.

Cancer specific outcomes in patients with pT0 disease following radical cystectomy.

PURPOSE: We assessed clinical outcomes in patients found to have no evidence of disease, ie pT0, in the cystectomy specimen following radical cystectomy for transitional cell carcinoma. MATERIALS AND METHODS: Between 1984 and 2003, 955 consecutive patients underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer at 3 institutions, namely The Johns Hopkins Hospital, University of Texas Southwestern Medical Center and Baylor College of Medicine. Excluding nonTCC histology and patients with missing data resulted in 888 evaluable cases. Primary end points were recurrence-free survival and bladder cancer specific survival. RESULTS: Final pathological evaluation revealed absent transitional cell carcinoma in the cystectomy specimen, ie pT0, in 59 patients (7%), of whom 2 (3%) had pathologically positive lymph nodes. Transurethral resection stage or clinical stage data were available on 56 patients (95%), including Tis in 5 (9%), Ta in 2 (4%), T1 in 18 (32%), T2 in 29 (52%) and T3 in 2 (4%). Overall 6 recurrences (10%) were noted, including cTis in 1 case, cT1 in 1, cT2 in 3 and cT3 in 1. Median followup in patients with pT0 disease was 56 months (range 3 to 183). Three patients (5%) died of bladder cancer and another 4 (7%) died of other causes. Five and 10-year bladder cancer progression-free and cancer specific survival estimates in patients with pT0 disease were 90% and 81%, and 95% and 85%, respectively. CONCLUSIONS: Despite excellent clinical outcomes in the majority of patients with no evidence of tumor on final pathological evaluation not all patients with pT0 disease in the cystectomy specimen are cured of bladder cancer. These events may even occur in patients with nonmuscle invasive or muscle invasive organ confined pathology at staging transurethral resection. Further study is needed to identify prognostic factors in this population.

Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy.

PURPOSE: We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. METHODS: A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. RESULTS: LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P < .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. CONCLUSION: LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node-negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy.

Stage specific lymph node metastasis mapping in radical cystectomy specimens.

PURPOSE: We provide an accurate map of lymph node (LN) metastasis in patients with bladder cancer undergoing radical cystectomy and pelvic lymph node dissection. MATERIALS AND METHODS: We analyzed data on 176 consecutive patients operated on by the same surgeon. The extent of node dissection included presacral, bilateral common iliac and pelvic, and perivesical. The number of LNs removed from each site and the number of metastases bearing nodes were recorded separately. Stage specific maps were constructed. RESULTS: The median number of LNs removed was 25 (range 2 to 80). Metastases were found in the lymph nodes of 43 patients (24.4%) and the median number of positive nodes was 3 (range 1 to 63). Of these patients 22 (51%) had lymph node involvement at more than 1 site. The mean number of positive/total LNs sampled +/- SD in LN positive cases was 26% +/- 28% and the median was 13% (range 1.9 to 100%). Only 1 of the patients with pT1 (3.6%) had LN metastases, which was in the pelvic region. Only 2 of the patients with pT2 (3%) had LN metastases outside of the true pelvis and perivesical sites. Of patients with pT3 or pT4 16% had LN metastases outside the common boundaries for standard LN dissection, namely the common iliac artery and at or above aortic bifurcation. CONCLUSIONS: We present a detailed map of regional LN involvement in patients treated with radical cystectomy and lymph node dissection for transitional cell cancer of the bladder. Extensive LN dissection is essential for the complete removal of disease and accurate staging.

Analysis of polymorphic patterns in candidate genes in Israeli patients with prostate cancer.

BACKGROUND: The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known. OBJECTIVES: To evaluate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters. METHODS: Jewish Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters. RESULTS: The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner. CONCLUSIONS: In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.