Bcl-2 predicts response to neoadjuvant chemotherapy and is overexpressed in lymph node metastases of urothelial cancer of the bladder

PurposeTo assess whether Bcl-2, an inhibitor of the apoptotic cascade, can predict response to neoadjuvant chemotherapy in patients with urothelial cancer of the bladder (UCB).MethodsBcl-2 expression was analyzed in 2 different tissue microarrays (TMAs). One TMA was constructed of primary tumors and their corresponding lymph node (LN) metastases from 152 patients with chemotherapy-naive UCB treated by cystectomy and pelvic lymphadenectomy (chemotherapy-naive TMA cohort). The other TMA was constructed of tumor samples obtained from 55 patients with UCB before neoadjuvant chemotherapy (transurethral resection of the bladder cancer) and after cystectomy with pelvic lymphadenectomy (residual primary tumor [ypT+], n = 38); residual LN metastases [ypN+], n = 24) (prechemotherapy/postchemotherapy TMA cohort). Bcl-2 overexpression was defined as 10% or more cancer cells showing cytoplasmic immunoreactivity.ResultsIn both TMA cohorts, Bcl-2 overexpression was significantly (P<0.05) more frequent in LN metastases than in primary tumors (chemotherapy-naive TMA group: 18/148 [12%] in primary tumors vs. 39/143 [27%] in metastases; postchemotherapy TMA: ypT+7/35 [20%] vs. ypN+11/19 [58%]). In the neoadjuvant setting, patients with Bcl-2 overexpression in transurethral resection of the bladder cancer specimens showed significantly (P = 0.04) higher ypT stages and less regression in their cystectomy specimens than did the control group, and only one-eighth (13%) had complete tumor regression (ypT0 ypN0). In survival analyses, only histopathological parameters added significant prognostic information.ConclusionsBcl-2 overexpression in chemotherapy-naive primary bladder cancer is related to poor chemotherapy response and might help to select likely nonresponders.     

Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: a comparative mapping study

Background

The value of lymph node dissection (LND) in the treatment of bladder urothelial carcinoma is well established. However, standards for the quality of LND remain controversial.

Objective

We compared the distribution of lymph node (LN) metastases in a two-institution cohort of patients undergoing radical cystectomy (RC) using a uniformly applied extended LND template.

Design, setting, and participants

Patients undergoing RC at the University of Southern California (USC) Institute of Urology and at Oregon Health Sciences University (OHSU) were included if they met the following criteria: (1) no prior pelvic radiotherapy or LND; (2) lymphatic tissue submitted from all nine predesignated regions, including the paracaval and para-aortic LNs; (3) bladder primary; and (4) category M0 disease. The number and location of LN metastases were prospectively entered into corresponding databases.

Measurements

LN maps were constructed and correlated with preoperative and pathologic characteristics. Kaplan-Meier curves were constructed to estimate overall survival (OS) and recurrence free survival (RFS) among LN-positive (LN+) patients.

Results and limitations

Inclusion criteria were met by 646 patients (439 USC, 207 OHSU), and 23% had LN metastases at time of cystectomy. Although there was a difference in the median per-patient LN count between institutions, there were no significant interinstitutional differences in the incidence or distribution of positive LNs, which were found in 11% of patients with ≤pT2b and in 44% of patients with ≥pT3a tumors. Among LN+ patients, 41% had positive LNs above the common iliac bifurcation. Estimated 5-yr RFS and OS rates for LN+ patients were 45% and 33%, respectively, and did not differ significantly between institutions.

Conclusions

LN metastases in regions outside the boundaries of standard LND are common. Adherence to meticulous dissection technique within an extended template is likely more important than total LN count for achieving optimal oncologic outcomes.     

Prognostic significance of Her2/neu overexpression in patients with muscle invasive urinary bladder cancer treated with radical cystectomy

Introduction The aim of the study was to evaluate the status of Her2/neu protein expression in patients with muscle-invasive urothelial carcinomas of the bladder treated with radical cystectomy and to determine its prognostic significance. Material and methods We retrospectively analyzed the data of 90 patients who had undergone cystectomy for invasive transitional cell carcinoma of the urinary bladder. Immunohistochemical analysis for Her2/neu was done on paraffin-fixed tissues with CB11 antibodies (BioGenex, San Ramon, CA, USA). Sections with grade 2 and grade 3 staining were considered positive for Her2/neu. Results Over a median follow-up period of 46 months (24–96 months) 46 patients are living without disease recurrence and six with recurrent disease either at the local site or with distant metastases. The remaining 38 patients have died. The median overall survival time was 50 months, and median disease-free survival time was 40 months. The Her2/neu status was significantly related to the tumor stage (P = 0.001), lymph node involvement (77% in N+ vs 23% in N0; P = 0.001) and the grade of the disease (32% of grade 2 vs 71% of grade 3; P = 0.037). Kaplan–Meier curves showed a significantly worse disease-related survival period (log rank P = 0.011) for patients with Her2 overexpressing tumors than for those without overexpression. In addition to tumor stage [P = 0.001; relative risk (RR) = 2.62] and lymph node status (P = 0.0001; RR = 2.95), Her2 status (P = 0.020; RR = 2.22) was identified as an independent predictor for disease-related survival in a multivariate analysis. Conclusion These results suggest that Her2 expression might provide additional prognostic information for patients with muscle-invasive bladder cancer. Future studies on Her2 expression with chemosensitivity and the efficacy of Her2-targeted therapies in urothelial carcinomas are warranted.     

Detection of C-erb B2 gene amplification in bilharzial associated bladder cancer using fluorescence in situ hybridization

BACKGROUND: Gene amplifications are common events in different tumor types and may confer diagnostic, prognostic, or therapeutic information for patient management. Fluorescence in situ hybridization (FISH) represents a standard methodologic approach for testing for this genetic alteration, as it is rapid, reproducible and extremely reliable in detecting presence of C-erb-B2 gene amplification for clinical utility. PATIENTS AND METHODS: In this study, FISH is used in a series of archival human bilharzial bladder cancer specimens to evaluate for the presence of cerbB-2 gene alterations in the most common malignant tumor in bilharzial endemic areas, e.g., Egypt and some other countries. The study included 40 cases, 30 males and 10 females. Their ages ranged between 30 years and 76 years (median: 51 years). Twenty-one cases had squamous cell carcinoma, 16 had transitional cell carcinoma, two had adenocarcinoma, and one case had undifferentiated carcinoma. RESULTS: Thirteen out of 40 tumor samples (32.5%) show evidence of true C-erb-B2 gene amplification. Of the remaining samples, 24 (60%) show no gene amplification and three (7.5%) fall into the borderline category with a ratio between one and two C-erb-B2 genes/cell relative to chromosome 17 centromeres. No evidence of chromosome 17 polysomy was found in any cases scored as single copy with the C-erb-B2 probe. CONCLUSION: No significant association was found between gene amplification and any of the tested clinicopathologic parameters or tumor recurrence except for tumor grade where higher tumor grades tended to be associated with more C-erb-B2 gene amplification (P = 0.01) thus reflecting more tumor aggressiveness. So, the amplification of C-erb-B2 in bilharzial associated bladder cancer is probably not independently related to clinical outcome of patients.     

膀胱尿路上皮癌组织中HMGA2蛋白表达及其临床意义

目的 探讨高迁移率族蛋白A2(high mobility group protein A2,HMGA2)在膀胱癌组织中的表达情况,并分析其与临床病理特征及复发的关系.方法 膀胱尿路上皮癌标本148例,正常膀胱组织标本30例,采用免疫组织化学方法检测2组标本组织中HMGA2蛋白的表达,并结合临床资料进行分析.结果 正常膀胱组织中无HMGA2蛋白表达,肿瘤组织中随病理分级和分期增加,HMGA2蛋白相对表达量逐渐增高.HMGA2蛋白在G1、G2、G3组织中表达阳性率分别为21.3%、60.3%、82.1%,差异有统计学意义(P＜0.001).非肌层浸润性膀胱尿路上皮癌和肌层浸润性膀胱尿路上皮癌中HMGA2蛋白表达的阳性率分别为43.3%和72.7%,差异有统计学意义(P=0.003).随访2～95个月,复发64例,复发组与未复发组中HMGA2蛋白表达阳性率分别为54.7%和25.0%,差异有统计学意义(P=0.007).结论 HMGA2蛋白表达在膀胱癌组织中明显高于正常组织,HMGA2蛋白表达与膀胱癌的分级、分期、复发有关;与患者年龄、性别、肿瘤数目无相关性.检测HMGA2蛋白有助于膀胱癌的诊断及预后的评估.

Abstract：

Objective This study was to explore the expression and significance of HMA2 in bladder cancer , analyze its correlations to clinicopathologic and recurrence of bladder cancer. Methods The expression of HMGA2 protein in 148 specimens of bladder cancer and 30 specimens of normal bladder tissues was detected by immunohistochemtry, its correlations to clinicopathologic features was analyzed. Results There was no expression of HMGA2 protein in normal bladder tissues,while the expression level of HMGA2 protein was getting higher with the increase of tumor pathology grade and stage. The positive rate of HMGA2 protein was 21.3% in G1 bladder cancer, 60. 3% in G2 bladder cancer, 82.1% in G3 bladder cancer, its difference is significant (P＜0. 001). It was significantly lower in non-muscle invasive bladder cancer than in muscle invasive bladder cancer (43.3% vs 72. 7%, P=0. 003). The patients were followed up for 2～95 months, patients of recurrence was 64,HMGA2 protein expression was significantly higher in patients with recurrence than with non-recurrence (54.7% vs 25.0%, P=0. 007). Conclusions The expression of HMGA2 protein was highly in bladder cancer, the positive rate of HMGA2 protein expression was related with classification,TMN stage and recurrence, but not with sex, age, tumor number (P＞0. 05). The detection of the expression of HMGA2 protein is in favor of diagnosis and prognostic evaluation of bladder cancer.     

Lymph node density affects cancer-specific survival in patients with lymph node-positive urothelial bladder cancer following radical cystectomy

Background

The prognosis for patients with lymph node (LN)–positive bladder cancer (BCa) is likely affected by the extent of lymphadenectomy in radical cystectomy (RC) cases. Specifically, the prognostic significance of the LN density (ratio of positive LNs to the total number removed) has been demonstrated.

Objective

To evaluate the prognostic signature of lymphadenectomy variables, including the LN density, for a large, multicentre cohort of RC patients with LN-positive BCa.

Design, setting, and participants

The clinical and histopathologic data from 477 patients with LN-positive urothelial BCa (pN1–2) were analysed. The median follow-up period for all living patients was 28 mo.

Measurements

Multivariable Cox regression analysis was used to test the effect of various pelvic lymph node dissection (PLND) variables on cancer-specific survival (CSS) based on colinearity in various models.

Results and limitations

The median number of LNs removed was 12 (range: 1–66), and the median number of positive LNs was 2 (range: 1–25). Two hundred ninety (60.8%) of the patients presented with stage pN2 disease. The median and mean LN density was 17.6% and 29% (range: 2.3–100), respectively, where 268 (56.2%) and 209 (43.8%) patients exhibited am LN density of ≤20% and >20%, respectively. In separate multivariable Cox regression models adjusted for age, sex, pTN stage, grade, associated Tis, and adjuvant chemotherapy, the interval-scaled LN density (hazard ratio [HR]: 1.01; p = 0.002) and the LN density, ordinal-scaled by 20% (HR: 1.65; p < 0.001) exhibit independent effects on CSS. In addition, an independent contribution appears from the pT but not the pN stage. Limitations include surgeon selection bias when determining the extent of lymphadenectomy.

Conclusions

Our results support the prognostic relevance of LN density in patients with LN-positive BCa, where a threshold value of 20% stratifies the population into two prognostically distinct groups. Before LN density is integrated into the clinical decision-making process, these results should be validated by prospective studies with defined LN templates and standardised histopathologic methods.     

Pattern of node metastases in patients treated with radical cystectomy and extended or superextended pelvic lymph node dissection due to bladder cancer

Background

Pelvic lymph node dissection (PLND) has a diagnostic and therapeutic role during radical cystectomy in bladder cancer patients. However, at the time, no prospective data supports the value of extended PLND in improving survival expectances. We sought to describe incidence and location of node metastases in patients treated with extended and superextended PLND.

直肠癌系膜淋巴结转移的临床病理学研究

目的探讨直肠癌系膜淋巴结转移的规律。方法 2 6例患者取淋巴结 4 4 3枚 ,应用淋巴结显示液处理全直肠系膜切除的直肠癌标本 ,对切取的淋巴结进行病理检测。结果 2 3例(88 5 % )患者的 1 2 8枚 (2 8 9% )淋巴结发现肿瘤转移 ,淋巴结直径≤ 0 5cm者 76枚 (5 9% )。转移病例中 ,后壁直肠癌 1 4例 ,71枚淋巴结有肿瘤转移 ,6 8枚分布于直肠上动脉旁。侧壁直肠癌 9例 ,5 7枚淋巴结有肿瘤转移 ,其中同侧直肠上动脉分支旁转移 2 9枚 ,对侧 7枚 ,同侧直肠中动脉旁转移4枚、对侧无转移。结论后壁直肠癌转移主要为上行扩散 ,侧壁直肠癌可伴有侧方淋巴结受累 ,并以肿瘤同侧淋巴结转移为主     

A nomogram is more accurate than a regression tree in predicting lymph node invasion in prostate cancer

OBJECTIVE

To compare the performance and discriminant properties of two instruments (a tree‐structured regression model and a logistic regression‐based nomogram), recently developed to predict lymph node invasion (LNI) at radical prostatectomy (RP), in a contemporary cohort of European patients.

PATIENTS AND METHODS

The cohort comprised 1525 consecutive men treated with RP and bilateral pelvic LN dissection (PLND) in two tertiary academic centres in Europe. Clinical stage, pretreatment prostate‐specific antigen (PSA) level and biopsy Gleason sum were used to test the ability of the regression tree and the nomogram to predict LNI. Accuracy was quantified by the area under the receiver operating characteristic curve (AUC). All analyses were repeated for each participating institution.

RESULTS

The AUC for the nomogram was 81%, vs 77% for the regression tree (P = 0.007). When data were stratified according to institution, the nomogram invariably had a higher AUC than the regression tree (Hamburg cohort: nomogram 82.1% vs regression tree 77.0%, P = 0.002; Milan cohort: 82.4% vs 75.9%, respectively; P = 0.03).

CONCLUSIONS

Nomogram‐based predictions of LNI were more accurate than those derived from a regression tree; therefore, we recommend the use of nomogram‐derived predictions.     

Circulating tumor cells in patients with advanced urothelial carcinoma of the bladder: Association with tumor stage,lymph node metastases,FDG-PET findings,and survival

Background

There are currently no methods in clinical use that can detect early systemic dissemination of urothelial tumor cells.

Mode of lymph node metastases in esophageal cancer induced in rabbits with Vx2 carcinoma

We carried out experimental studies in which Vx2 carcinoma was inoculated submucosally into the esophagi of 57 rabbits. The purpose was to clarify the mode of tumor growth and lymph node metastasis of esophageal cancer. The inoculation was given into five different segments of the esophagus and the cardia in six different groups of rabbits: the cervical (Ce), the cervicothoracic junction (Ce=Iu), the upper thoracic (Iu), the middle and lower thoracic (ImEi) and the abdominal (Ea) segments and the cardia (C). The lymph node metastatic pattern of the Vx2 carcinoma was then observed. The Ce and Ce=Iu located carcinomas metastasized mainly above the tracheal bifurcation; the ImEi located carcinomas metastasized equally above and below the tracheal bifurcation. In cases of the Ea and C located carcinomas, the lymph node metastasis was restricted to the abdomen when serosal invasion was excluded but it spread widely from the abdomen to the neck when serosal invasion was positive. Thus, in experimentally-induced carcinoma, tracheal lymph node metastasis occurred with a high frequency. As intraoperative assessment is closely related to anatomical factors and operative risk, care should be taken that such assessments are thoroughly carried out.     

Sentinel lymph node mapping of invasive urinary bladder cancer in animal models using invisible light

OBJECTIVES: With conventional methodology, sentinel lymph node (SLN) mapping of invasive urinary bladder cancer is technically challenging. This study was performed to determine the utility of invisible, near-infrared fluorescent (NIRF) light for patient-specific SLN mapping, in real time under complete image guidance. METHODS: Lymphatic tracers, injection volume, NIRF excitation fluence rate, light collection of emitted fluorescence, and degree of bladder distension were systematically optimized in normal dogs and pigs. SLN mapping was then performed in pet dogs with naturally occurring invasive transitional cell carcinoma (InvTCC) of the urinary bladder, which closely mimics the human disease. RESULTS: NIRF albumin (hydrodynamic diameter [HD], 7.4 nm) and NIRF quantum dots (15-20 nm HD) injected into the bladder wall resulted in identification of draining lymph nodes (LNs) in under 3 min. In both species, considerable variability in the lymphatic drainage was observed among individuals. Optimal SLN mapping was achieved with the use of superficial, serosal injection of NIRF tracer, with the bladder distended to an intraluminal pressure of 20-40 cm H(2)O. In dogs with InvTCC, NIRF tracers identified SLNs that were confirmed histologically to harbor metastases. CONCLUSIONS: The use of invisible NIRF light permits real-time, patient-specific identification of SLNs that drain bladder cancer. Intraluminal bladder pressure is a key parameter that needs to be controlled for optimal results.     

A patient with gallbladder cancer with paraaortic lymph node and hepatic metastases who has survived for more than 13 years after the primary extended radical operation

Gallbladder cancer is a disease with poor prognosis, especially when it is associated with distant metastasis. Here we report a rare case of a patient with gallbladder cancer with extensive local and distant lymph node metastases and multiple liver metastases who has survived for more than 13 years through aggressive treatments. A 54-year-old woman developed right upper quadrant pain. Computed tomography (CT) revealed a papillary tumor in the gallbladder. Low-density tumors in segments 4, 5, and 8 of the liver and extensive paraaortic lymph node swelling were observed. She underwent central hepatic bisectionectomy and paraaortic lymphadenectomy. Two months later, hepatic metastases were found in segments 2, 3, 6, and 7, and percutaneous ethanol injection and transcatheter arterial chemoembolization were performed. Twelve months after the first surgery, CT revealed lymph node swelling around the right external iliac artery and behind the left renal vein. Metastatic lymph node dissection and resection and reconstruction of the right external iliac artery and vein with artificial graft replacements were performed. Two months later, CT revealed a paraesophageal lymph node swelling, which was treated by radiotherapy. At present, 13 years after the first surgery, and 11 years after the last radiotherapy, she is alive without any sign of recurrence.     

Expression and prognostic significance of cancer stem cell markers CD24 and CD44 in urothelial bladder cancer xenografts and patients undergoing radical cystectomy

ObjectivesTo evaluate CD24/CD44/CD47 cancer stem cell marker expressions in bladder cancer (BCa) and provide data on their prognostic significance for clinical outcome in patients undergoing radical cystectomy (RC).Material and methodsPrimary BCa tissue was used for xenograft studies. A tissue microarray was prepared using specimens from a cohort of 132 patients. All patients underwent RC for urothelial BCa between 2001 and 2010. Expression of CD24, CD44, and CD47 was examined in primary samples and xenografts by fluorescence-activated cell sorting. Populations of CD24^low- and CD24^high- expressing cells were sorted and evaluated for tumorigenicity in vivo. Tissue microarray was analyzed for CD24/CD44 staining intensity and tumor-specific vs. stromal cell staining. Associations with BCa survival, BCa stage, and lymph node status were evaluated by univariate and multivariate analyses.ResultsCD24 and CD44/CD47 expressions mark distinct cell populations within the normal urothelium as well as in BCa. CD24^high/low expression was not sufficient to characterize CD24 as a BCa-initiating marker in in vivo primary xenotransplants. CD24 and CD44 expressions correlated with lower cancer-specific survival in patients. However, multivariate analyses of CD24 or CD44 did not demonstrate significantly increased hazards for cancer-specific death if analyzed together with stage, grade, and nodal status of patients.ConclusionsCancer stem cell markers CD24/CD44/CD47 are differentially expressed in cells of urothelial BCa in patients undergoing RC and influence cancer-specific survival of patients. Further evaluation of CD24/CD44/CD47 protein expression could be of high therapeutic value in BCa. However, both CD24 and CD44 expressions cannot be regarded as independent prognostic parameters for patients undergoing RC.     

乳腺癌原发灶及淋巴结转移灶中表皮生长因子受体、C-erbB-2的表达及临床意义

目的 探讨乳腺癌原发灶和淋巴结转移灶中表皮生长因子受体（EGFR）、C-erbB-2的表达及其与肿瘤类型、肿瘤分期的关系.方法 选择行手术治疗且术前均未行抗癌治疗,术后病理证实无同侧腋窝淋巴结转移的乳腺癌患者24例,伴有同侧腋窝淋巴结转移的乳腺癌患者36例,用免疫组化S-P法检测原发灶和淋巴结转移灶EGFR、C-erbB-2的表达.结果 有同侧腋窝淋巴结转移的乳腺癌原发灶EGFR、C-erbB-2的表达明显高于无同侧腋窝淋巴结转移的乳腺癌.乳腺癌原发灶EGFR、C-erbB-2的表达呈正相关（P=0.01）.原发灶和淋巴结转移灶之间的EGFR、C-erbB-2的表达无相关性.原发灶EGFR、C-erbB-2的表达在不同的肿瘤分期存在差异.浸润性导管癌和浸润性小叶癌之间EGFR、C-erbB-2的表达无差异.结论 乳腺癌细胞淋巴结转移的过程中由于体内某种机制的作用导致了恶性程度的变化;EGFR、C-erbB-2的表达正相关并共同促进了乳腺癌的淋巴结转移;原发灶EGFR、C-erbB-2的表达与肿瘤的分期呈正相关.     

Comparison of two models for the prediction of nonsentinel node metastases in breast cancer

BACKGROUND: It is debated whether all patients with a positive sentinel node dissection (SLND) should be submitted to axillary lymph node dissection (ALND). Models have been developed to estimate the likelihood of nonsentinel node (non-SLN) metastases. METHODS: The accuracy of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and MD Anderson scoring system for the prediction of non-SLN status was tested in a consecutive series of 186 SLN-positive breast cancer patients. A multivariate analysis was performed to assess which parameters independently predicted the presence of non-SLN metastases. RESULTS: The predictive accuracy of the MSKCC nomogram measured by the receiver operating characteristic curve was 0.71, and it was best in patients with <10% risk of non-SLN metastases (sensitivity 100% and specificity 96%). The MD Anderson score predicted non-SLN involvement with low accuracy because it classified 85% of the patients in the intermediate-risk groups. Only SLN macrometastases and tumor multifocality independently predicted non-SLNs involvement. CONCLUSIONS: The MSKCC nomogram can help individualize the surgical treatment of SLN-positive breast cancer when the likelihood of further axillary involvement is low or surgical risks are higher.     

The impact of lymph node metastases on the survival of breast cancer patients with ten or more positive lymph nodes

To investigate the impact of the number of involved lymph nodes on survival, we retrospectively reviewed the data for 37 patients with breast cancer and metastases of ten or more lymph nodes who underwent treatment between 1987 and 1995. Based on the number of positive lymph nodes, the patients were allocated to one of three groups. The 5-year disease-free and overall survival rates for all patients were both 53.0%. The 7 patients with 26 or more positive nodes had significantly poorer survival than either the 19 patients with 10–15 nodes, or the 11 with 16–25 nodes, although there were no differences in survival related to the extent of node involvement as defined using the Japanese staging system. Patients with 50%–75% frequency of metastasis, defined as the positive nodes/total resected nodes, had significantly better survival than those with <50% or >75% frequency. These results indicate that the number of involved lymph nodes is related to survival and that 25 positive nodes is a cutoff point in breast cancer patients with ten or more positive lymph nodes.     

Outcomes in patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection

OBJECTIVES: To evaluate the rates of local and systemic progression (LP and SP), recurrence-free survival and overall survival for patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection (PLND) in 1987-2000. PATIENTS AND METHODS: A consecutive series was analysed of 385 patients (median age 61.9 years, range 30.7-83.8) treated by limited bilateral PLND and radical cystectomy (RC) between 1987 and 2000, with negative surgical margins on final pathology. All patients were staged N0M0 before RC, and none received neoadjuvant radiotherapy or chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and bifurcation of iliac vessels to the circumflex iliac vein. LP was defined as a radiographic soft-tissue density of > or = 2 cm below the bifurcation of the aorta. Pathological characteristics, based on the 1997 Tumour-Nodes-Metastasis system, recurrence patterns, and recurrence-free and overall survival, were determined. RESULTS The median (range) overall follow-up was 45.1 (1.1-165.6) months; the number of lymph nodes (LNs) reported per patient was 12 (2-32). Of the 385 patients, 130 (33.8%) had evidence of LP and 60 (15.6%) of SP. The 5-year recurrence-free and overall survival rates were both 71% for patients with organ-confined, N0 tumours, and 23% and 26% for unconfined, N0 tumours. Positive LNs were found in 45 (12%) patients, who had a recurrence-free and overall survival rate of 9% at 5 years. CONCLUSION: Compared with published reports of similar cohorts of patients managed with RC and extended PLND, the present study suggests that limited PLND is associated with suboptimal staging, greater rates of LP, and lower rates of recurrence-free survival, particularly for patients with unconfined or LN-positive disease.