Detection of occult tumor cells in lymph nodes from bladder cancer patients by MUC7 nested RT-PCR

OBJECTIVE: Systemic progression is the prevalent form of bladder tumor recurrence after radical cystectomy. The detection of occult bladder tumor cells in histopathologically normal lymph nodes could be of prognostic value. We examined the possibility that mucin 7 (MUC7) RNA might reflect the presence of occult tumor cells in lymph nodes from bladder cancer patients. We used the polymerase chain reaction (RT-PCR), a highly sensitive assay, to monitor MUC7 RNA. METHODS: We collected 240 pelvic lymph nodes from 25 bladder cancer patients undergoing radical cystectomy. We also obtained 20 lymph nodes from patients with prostate cancer and interstitial cystitis to use as negative controls. Each lymph node was divided in two parts to provide tissue for both histopathological and PCR analysis. RESULTS: 166/240 lymph nodes from bladder cancer patients were usable for MUC7 RT-PCR. By conventional histopathology, six of these nodes contained metastases. MUC7 RT-PCR analysis was positive for five of the six histologically proven lymph node metastases. Histopathological reevaluation of the sixth node revealed tumor in an adjacent vein, not in the lymph node, itself. In contrast, 46/160 (29%) histologically classified normal lymph nodes (pN0) from 17 bladder cancer patients were positive for MUC7. All 20 lymph nodes from control patients were MUC7-negative. CONCLUSION: MUC7 RT-PCR is a specific and sensitive method for the detection of occult tumor cells in lymph nodes from bladder cancer patients. Long-term observation will be necessary to evaluate the clinical value of MUC7 as a prognostic indicator of lymph node metastasis and disease progression.     

The role of lymphadenectomy in high-grade invasive bladder cancer

Radical cystectomy with bilateral pelvic iliac lymphadenectomy is a standard treatment for high-grade, invasive bladder cancer. Cystectomy arguably provides the best survival outcomes and the lowest local recurrence rates. Although the extent or absolute limits of the lymph node dissection are unknown and remain to be better defined, an ever-growing body of data supports a more extended lymphadenectomy at the time of cystectomy in all patients who are appropriate surgical candidates. An extended lymph node dissection should include the distal para-aortic and paracaval lymph nodes as well as the pre-sacral nodes, known anatomic sites of lymph node drainage from the bladder and potential sites of lymph node metastases in patients with bladder cancer. An extended dissection may provide a survival advantage in patients with node-positive and node-negative tumors without significantly increasing the morbidity or mortality of the surgery. The extent of the primary bladder tumor (p stage), the number of lymph nodes removed, and the lymph node tumor burden are important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastases. Lymph node density may become an even more useful prognostic variable in these high-risk, node-positive patients with bladder cancer. This concept simultaneously incorporates the lymph node tumor burden (number of lymph nodes involved) and the number of lymph nodes removed (extent of the lymphadenectomy), improving the stratification of lymph node-positive patients following radical cystectomy. This notion may also be useful in future staging systems. Adjuvant therapies and clinical trials should consider applying these concepts, because they may help reduce bias and incorporate the extent of the lymphadenectomy, which currently is not standardized.     

Anatomic Extent of Pelvic Lymphadenectomy in Bladder Cancer

ContextThe rationale for locoregional staging lymphadenectomy in bladder cancer lies in the accurate diagnosis of occult micrometastases to stratify patients who might benefit from adjuvant therapeutic measures. In bladder cancer, pelvic lymphadenectomy (PLA) as a common procedure of radical cystectomy has not been standardized, although evidence supports a relationship between the extent of lymph node dissection and therapeutic outcome.Evidence acquisitionRecent retrospective and prospective clinical trials have carefully analyzed the distribution of lymph node metastases at time of radical cystectomy, thereby identifying those regions that should be included in a standard pelvic lymph node dissection.Evidence synthesisDissecting all lymphatic tissue along the common iliac region—with the aortic bifurcation as cranial margin—along the external, internal iliac region, and the obturator fossae bilaterally will completely clear 80% of all positive nodes. Only if frozen section examination will demonstrate micrometastases at these regions will extending lymphadenectomy further cranially be worthwhile.ConclusionsCurrently, extended PLA in bladder cancer has been shown to improve progression-free survival if >14 lymph nodes are removed. For the future, prospective trials have to demonstrate a benefit with regard to cancer-specific and overall survival and in terms of regional versus distant recurrences.     

Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: concept of lymph node density

PURPOSE: We evaluated the clinical outcomes and risk factors for progression in a large cohort of patients with lymph node metastases following en bloc radical cystectomy and bilateral pelvic lymphadenectomy. MATERIALS AND METHODS: From July 1971 through December 1997, 1,054 patients underwent radical cystectomy and bilateral pelvic-iliac lymphadenectomy for high grade, invasive transitional cell carcinoma of the bladder. Of these patients 244 (23%) with a median age of 66 years (range 36 to 90) had pathological lymph node metastases. Overall 139 of the 244 patients (57%) received some form of chemotherapy. At a median followup of greater than 10 years (range 0 to 28) outcomes data were analyzed in univariate analysis according to tumor grade, carcinoma in situ, primary bladder tumor stage, pathological subgroups, total number of lymph nodes removed and involved with tumor, and lymph node density (total number of positive lymph nodes/total number removed). In addition, the form of urinary diversion and the administration of chemotherapy were also evaluated. Multivariate analysis was then performed to analyze these variables independently. RESULTS: The incidence of positive lymph nodes increased with higher p stage and pathological subgroups. Of 669 patients 75 (11%) with organ confined primary tumors and 169 of 385 (44%) with extravesical tumor extension had involved lymph nodes. The median number of lymph nodes removed in the 244 lymph node positive cases was 30 (range 1 to 96), while the median number of positive lymph nodes was 2 (range 1 to 63). Overall recurrence-free survival at 5 and 10 years for the 244 patients with lymph node positive disease was 35% and 34%, respectively. Patients with lymph node positive disease and an organ confined primary bladder tumor had significantly improved 10-year recurrence-free survival compared with those with extravesical tumor extension (44% vs 30%, p = 0.003). The total number of lymph nodes removed at surgery was also prognostic. Patients with 15 or less lymph nodes removed had 25% 10-year recurrence-free survival compared with 36% when greater than 15 lymph nodes were removed. Recurrence-free survival at 10 years for patients with 8 or less positive lymph nodes was significantly higher than in those with greater than 8 positive lymph nodes (40% vs 10%, p <0.001). The novel concept of lymph node density was also a significant prognostic factor. Patients with a lymph node density of 20% or less had 43% 10-year recurrence-free survival compared with only 17% survival at 10 years when lymph node density was greater than 20% (p <0.001). On multivariate analysis the total number of lymph nodes involved, pathological subgroups of the primary bladder tumor, lymph node density and adjuvant chemotherapy remained significant and independent risk factors for recurrence-free and overall survival. CONCLUSIONS: Patients with lymph node tumor involvement following radical cystectomy may be stratified into high risk groups based on the primary bladder tumor, pathological subgroup, number of lymph nodes removed and total number of lymph nodes involved. Lymph node density, which is a novel prognostic indicator, may better stratify lymph node positive cases because this concept collectively accounts for the total number of positive lymph nodes (tumor burden) and the total number of lymph nodes removed (extent of lymphadenectomy). Future staging systems and the application of adjuvant therapies in clinical trials should consider applying lymph node density to help standardize this high risk group of patients following radical cystectomy.     

膀胱癌盆腔淋巴结转移的规律及影响因素分析

目的通过分析膀胱尿路上皮癌淋巴结转移的规律及其相关影响因素,结合盆腔淋巴清扫的研究进展,探讨盆腔淋巴清扫策略。 方法收集我院2008年至2016年由同一术者完成腹腔镜根治性膀胱切除和盆腔淋巴清扫的膀胱尿路上皮癌患者的资料,回顾性分析淋巴结转移的规律及其相关影响因素。 结果共收集患者285例,69例（24.2%）发生淋巴结转移。最常见的淋巴结转移部位为髂内/闭孔淋巴结（57/69,82.6%）,其次是髂外淋巴结（37/69,53.6%）;真骨盆外淋巴结转移均伴随髂内/闭孔或髂外淋巴结转移;单侧壁膀胱癌可以向对侧盆腔淋巴结转移。T1组淋巴结转移率4.6%（4/87）,T2组18.0%（18/100）;T3组50.8%（30/59）;T4组68.0%（17/25）。多因素回归分析显示淋巴结转移与肿瘤分期呈正相关,与分级、年龄、性别、体质量指数、吸烟等因素无关。 结论髂内/闭孔和髂外淋巴结是膀胱癌最主要的淋巴结转移部位,肿瘤高分期是影响膀胱癌淋巴结转移的主要因素。根治性膀胱切除术应行至少包括双侧髂内、闭孔、髂外淋巴结的标准淋巴清扫。     

Lymphadenectomy in bladder cancer: How high is “high enough”?

PURPOSE: The role of a regional lymphadenectomy in the surgical treatment of high-grade, invasive transitional cell carcinoma of the bladder has evolved over the last several decades. Although the application of a lymphadenectomy for bladder cancer is not significantly debated, the absolute extent or level of proximal dissection of the lymphadenectomy remains a controversial issue. MATERIAL AND METHODS: A review of the literature should help elucidate the rationale and extent of an appropriate lymphadenectomy in patients undergoing radical cystectomy for bladder cancer. Various surgical issues of lymphadenectomy as well as prognostic factors in patients undergoing radical cystectomy for bladder cancer are examined. RESULTS: A growing body of evidence, spanning from early autopsy and cadaveric studies to recent retrospective series and multicenter prospective trials, suggests that an extended lymph node dissection (cephalad extent to include the common iliac arteries) may provide not only prognostic information but also provide a therapeutic benefit for both patients with lymph node-positive and lymph node-negative disease undergoing radical cystectomy for bladder cancer. Although the absolute boundaries of the lymphadenectomy remain a subject of controversy, historical reports confirmed by recent lymphatic mapping studies suggest the inclusion of the common iliac as well as possibly presacral nodes in the routine lymphadenectomy for transitional cell carcinoma of the bladder. The need to extend the dissection higher to include the distal para-aortic and paracaval lymph nodes may be important in select individuals but remains more controversial. The extent of the primary bladder tumor (p-stage), number of lymph nodes removed, the lymph node tumor burden (tumor volume), and lymph node density (number of lymph nodes involved/number of lymph nodes removed) are all important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastases. Systemic adjuvant chemotherapy remains a mainstay of treatment of patients with lymph node metastases. CONCLUSIONS: Radical cystectomy with an appropriately performed lymphadenectomy provides the best survival outcomes and lowest local recurrence rates. Although the absolute limits of the lymph node dissection remain to be determined, evidence supports a more extended lymphadenectomy to include the common iliac vessels and presacral lymph nodes at cystectomy in patients who are appropriate surgical candidates. When feasible, adjuvant chemotherapy is warranted in patients with positive nodal metastasis.     

PELVIC LYMPH NODE METASTASES FROM BLADDER CANCER: OUTCOME IN 83 PATIENTS AFTER RADICAL CYSTECTOMY AND PELVIC LYMPHADENECTOMY

PURPOSE: We evaluate the outcome in patients with node positive bladder cancer with particular reference to the effect of individual characteristics of positive nodes on survival after meticulous pelvic lymphadenectomy at cystectomy. MATERIALS AND METHODS: This prospective analysis contains 452 cases of bladder cancer staged preoperatively as N0M0, managed with pelvic lymphadenectomy and cystectomy between 1984 and 1997. A total of 83 (18%) patients with histologically confirmed node positive disease are included in our study. RESULTS: The median overall survival of patients with positive nodes was 20 months. Median 5-year survival was 29%. Patients who survived were found with positive nodes at each site in the pelvis. The median survival of 57 patients with less than 5 positive nodes was 27 months, compared with 15 months for 26 with 5 nodes or more (log-rank test p = 0.0027). Median survival of 26 patients with no lymph node capsule perforation was 93 months, compared with 16 months for 57 with capsule perforation (p = 0.0004). The median survival of 18 patients with a maximum diameter of lymph node metastasis up to 0.5 cm. was 64 months, compared with 16 months for 65 with nodal metastasis greater than 0.5 cm. (p = 0.024). Contralateral positive nodes were found in 16 of 39 (41%) patients with unilateral bladder cancer. CONCLUSIONS: Long-term survival is possible with node positive bladder cancer. Those patients with few as well as smaller and, therefore, unsuspected nodal metastases, and those without lymph node capsule perforation have the best results after removal of pelvic metastatic nodal disease. Because patients who survive may be found regardless of the site of pelvic nodal metastases, meticulous bilateral pelvic lymphadenectomy is warranted in all patients at the time of attempted curative cystectomy for bladder cancer, particularly if there is no clinical evidence of nodal involvement.     

根治性膀胱切除术前淋巴结转移预测的相关指标分析

目的 探讨根治性膀胱切除术前临床指标在预测淋巴结转移方面的价值.方法 对2000年7月至2014年1月间在中山大学附属第三医院行根治性膀胱切除加盆腔淋巴结清扫术的67例患者进行回顾性分析,利用Logistic regression分析明确术前预测淋巴结转移的临床指标,并采用受试者操作曲线（ROC）来确定预测指标的临床应用价值.结果 入组患者中存在淋巴结转移的共计10例（14.9％）.术前经尿道膀胱肿瘤电切术（TUR）病理分级、术前CT中淋巴结大小作为独立的临床指标与术后的淋巴结转移有密切的关系,与其他指标相比具有统计学差异（P＜0.05）.ROC分析明确术前TUR病理分级、术前CT中淋巴结大小曲线下面积（AUC）分别为0.378（95％CI 0.194～0.562）,0.76 （95％CI 0.569～0.950）.结论 术前TUR病理分级以及影像学中淋巴结大小作为独立的预测指标,能为淋巴结转移判断提供可靠的依据.     

Anatomical Basis for Pelvic Lymphadenectomy in Prostate Cancer: Results of an Autopsy Study and Implications for the Clinic

Purpose

Pelvic lymphadenectomy remains the most reliable method to prove lymph node metastases in prostate cancer. However, evaluation of lymphadenectomy to be complete and sufficient as judged by the number of removed lymph nodes is hampered by the fact that, in contrast to other malignancies (for example breast or gastric cancer), anatomical studies investigating the regular and average number of pelvic lymph nodes are missing. We established an anatomically based standard for pelvic lymphadenectomy.

Materials and Methods

Standard pelvic lymphadenectomy was performed on 30 human cadavers and 59 consecutive patients with clinically organ confined prostate cancer during radical retropubic prostatectomy. Number, size and topography of the lymph nodes were noted separately for each anatomical region of both iliac fossas.

Results

The mean number of lymph nodes removed in the autopsy series plus or minus standard deviation (22.7 plus/minus 10.2, range 8 to 56) was nearly identical to that from patients with prostate cancer (20.5 plus/minus 6.6, range 10 to 37) but striking interindividual differences were observed. Patients with prostate cancer demonstrated enlarged nodes regardless of whether they did or did not contain tumor. Interestingly, pelvic lymph node metastases were more common on the left side regardless of the primary tumor site.

Conclusions

Approximately 20 pelvic lymph nodes may serve as a guideline for a sufficient standard pelvic lymph node dissection. Lymphadenopathy in prostate cancer patients is not always a result of metastases but, rather, hyperplastic or regressive alterations. A preferential distribution of lymph node metastases along the left iliac vessels regardless of the primary tumor site in the prostate warrants further investigation.     

Stellenwert der extendierten pelvinen Lymphadenektomie beim Harnblasenkarzinom

Despite radical surgery, invasive urothelial carcinoma has a high risk of systemic progression. This might be due to the presence of occult but already disseminated tumor cells in lymph nodes, blood, or bone marrow. In all retrospective series presented here, extended pelvic lymphadenectomy seems to provide a clear benefit for survival in pN0 and pN+ patients. Lymph node density and absolute number of positive lymph nodes appear to affect patient outcome and survival. However, only the randomized, prospective German LEA study will hopefully provide conclusive new data.     

Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study

PURPOSE: Previous studies demonstrate a positive correlation between postoperative survival and the extent of pelvic lymphadenectomies in patients with bladder cancer. However, the distribution of nodal metastases has not been examined in sufficient detail. Therefore, we conducted a comprehensive prospective analysis of lymph node metastases to obtain precise knowledge about the pattern of lymphatic tumor spread. MATERIALS AND METHODS: Between 1999 and 2002 we performed 290 radical cystectomies and extended lymphadenectomies. Cranial border of the lymphadenectomy was the level of the inferior mesenteric artery, lateral border was the genitofemoral nerve and caudal border was the pelvic floor. We made every effort to excise and examine microscopically all lymph nodes from 12 well-defined anatomical locations. RESULTS: Mean total number and standard deviation of lymph nodes removed was 43.1 +/- 16.1. Nodal metastases were present in 27.9% of patients. The percentage of metastases at different sites ranged from 14.1% (right obturator nodes) to 2.9% (right paracaval nodes above the aortic bifurcation). By studying cases of unilateral primary tumors or with only 1 metastasis we observed a preferred pattern of metastatic spread. However, there were many exceptions to the rule and we did not identify a well-defined sentinel lymph node. CONCLUSIONS: We strongly recommend extended radical lymphadenectomy to all patients undergoing radical cystectomy for bladder cancer to remove all metastatic tumor deposits completely. The operation can be conducted in routine clinical practice and our data may serve as a guideline for future standardization and quality control of the procedure.     

IMPACT OF SEPARATE VERSUS EN BLOC PELVIC LYMPH NODE DISSECTION ON THE NUMBER OF LYMPH NODES RETRIEVED IN CYSTECTOMY SPECIMENS

PURPOSE: Pelvic lymphadenectomy during radical cystectomy yields a various number of lymph nodes depending on the extent of lymph node dissection and pathologist aggressiveness when searching the specimen. How the surgeon submits lymph nodes for pathological evaluation may also affect how many are retrieved. MATERIALS AND METHODS: Bilateral pelvic lymph node dissection and radical cystectomy for transitional cell carcinoma of the bladder was performed in 32 patients. The extent of lymph node dissection involved standard and extended lymphadenectomy in 20 and 12 cases, respectively. In patients who underwent standard dissection unilateral en bloc submission of the lymph nodes was done with the contralateral lymph node dissection sent as an individual discrete packet. In those who underwent extended dissection all lymph nodes from each side were submitted en bloc or as 6 packets. RESULTS: Standard lymphadenectomy en bloc specimens yielded a mean of 2.4 lymph nodes compared with 8.5 retrieved from individual lymph node specimens (p = 0.003). Extended lymphadenectomy en bloc specimens yielded a mean of 22.6 lymph nodes compared with 36.5 retrieved from the individually submitted packets (p = 0.02). CONCLUSIONS: Submitting pelvic lymph nodes as separate specimens optimizes pathological evaluation of the number of lymph nodes that may be involved with metastatic cancer. Such information is important for identifying patients who may benefit from adjuvant chemotherapy.     

Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis

OBJECTIVE: To determine the need to standardize the number and location of lymph nodes to be removed during radical cystectomy in patients with invasive bladder carcinoma. PATIENTS AND METHODS: The pelvic lymph nodes from 447 patients (mean age 62.8 years) who underwent radical cystectomy between 1986 and 1997 were evaluated. The number of lymph nodes was correlated with the depth of invasion of the primary tumour (pT), occurrence of nodal metastases, clinical outcome, the operating surgeons and the pathologists dissecting the nodes. RESULTS: The clinical follow-up was available for 302 patients (mean follow-up 38.7 months). The mean (range) number of lymph nodes removed was 14.7 (1-46). The number of lymph nodes removed varied significantly among different surgeons but not among pathologists. In pT3 and pT4 tumours, a more extended lymphadenectomy (>/= 16 lymph nodes) correlated with a higher percentage of patients with documented nodal metastases. There was a significant correlation between the number of lymph nodes removed and the tumour-free 5-year survival in patients with pT1, pT2 or pT3 tumours, and in patients with 1-5 positive lymph nodes (P < 0.01). CONCLUSION: Extensive lymphadenectomy significantly improves the prognosis of patients with invasive bladder cancer and represents a potentially curative procedure in patients with nodal metastases, including micrometastases that may escape detection during routine histopathological evaluation. The results indicate the need for a standardized lymph node dissection.     

The role of lymph node density in bladder cancer prognostication

Pelvic lymph node metastases from bladder cancer occur in about 25% of patients undergoing radical cystectomy. While the majority of patients with lymph node metastases will develop progressive disease, some patients do exhibit long-term survival with and without adjuvant chemotherapy. The concept of lymph node density has been proposed as a means to stratify patient prognosis since it takes into account two important factors—the number of positive nodes (tumor burden) and the total number of nodes removed/examined (extent of dissection). Due to the lack of agreement on the extent of lymphadenectomy, lymph node density facilitates standardization of lymph node staging, thus allowing for adjuvant therapies and clinical trials to be more uniformly applied. Whether lymph node density provides improved prognostication over the standard nodal staging or absolute number of positive lymph nodes remains controversial. We review the literature regarding the role of lymph node density in the prognostic stratification of node-positive bladder cancer.     

The prognostic impact of pelvic lymph node metastasis and lymphovascular invasion on bladder cancer

Objectives:   To present long-term results of a single-center series of patients undergoing bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer and to analyze the impact of pelvic lymph node metastasis and lymphovascular invasion on clinical outcome.
Methods:   Between 1986 and 2005 833 patients were treated with bilateral pelvic lymphadenectomy and radical cystectomy at our institution. 614 of them with valid clinical follow-up information and no neoadjuvant therapy could be evaluated.
Results:   Disease-free and overall survival in the entire cohort was 56.7% and 49.5% at 5 years and 52.4% and 38.2% at 10 years, respectively. 28.1% of all patients had pelvic lymph node metastasis. We found organ-confined tumor stages (≤pT2) in 43.8%. Patients with non-organ-confined tumor stages (≥pT3) and positive pelvic lymph nodes had a significantly shorter overall survival than those without lymph node metastasis ( P  < 0.0001). In the subgroup of ≤pT2, the presence of pelvic lymph node metastasis did not show a statistically significant effect on overall survival ( P  = 0.618). The presence of lymphovascular invasion was associated with an impaired survival ( P  < 0.0001). In multivariate analysis, pathological tumor stage ( P  < 0.0001), lymph node stage (≥pT3) ( P  = 0.004) and lymphovascular invasion ( P  = 0.001) were independent prognostic parameters.
Conclusions:   According to the present series, survival for patients with ≤pT2 does not depend on the lymph node stage. Lymphovascular invasion is an independent parameter of impaired survival and should be determined routinely in cystectomy specimens to identify patients, who may benefit from adjuvant systemic therapy.     

Lymph node metastasis in bladder cancer

OBJECTIVE: We reviewed the literature on nodal staging in patients with bladder cancer treated with radical cystectomy and lymphadenectomy. RESULTS: Fractionating the lymph node specimen significantly increases the node count, whereas results are contradictory as to whether that increase improves detection of positive nodes. Pathoanatomic data indicate that extending lymph node dissection to the aortic bifurcation improves nodal staging. That approach might be beneficial, especially in cases of T3/T4a tumours, which more often have lymph node metastases above the iliac bifurcation as compared to less advanced tumours. In node-negative patients, extended lymph node dissection probably removes undetected micrometastases and thereby increases disease-free survival. Four studies suggested that a minimum of 8, 10, 10-14, and 16 nodes must be removed, to improve survival, and in another investigation aortic bifurcation was proposed as the upper limit for dissection. Some patients with positive nodes can be cured by surgery alone, even those with gross adenopathy. There is no evidence that extended lymphadenectomy increases surgery-related morbidity. The TNM classification is apparently insufficient for stratifying node-positive patients because several larger cystectomy series could not verify differences in survival between N groups. CONCLUSIONS: Fractionating the lymphadenectomy specimen increases the lymph node count. In node-negative patients, more meticulous and extended lymph node dissection (8-16 nodes or to the aortic bifurcation) probably improves disease-free survival by removing undetected micrometastases. Patients with positive lymph nodes should also be offered radical cystectomy.     

Rolle der Lymphadenektomie bei Patienten mit invasivem Urothelkarzinom der Harnblase

High-grade urothelial carcinomas of the bladder represent high-risk tumors and despite radical surgery and pelvic lymph node dissection patients have a lifelong risk for tumor progression and metastases. Since extended lymph node dissection detected metastases outside the fields of normal pelvic lymphadenectomy, it was concluded that all patients undergoing radical cystectomy should receive extended lymph node dissection. The article reviews published data discussing the question of whether lymph node dissection has prognostic or therapeutic relevance.     

The Impact of Lymphadenectomy and Lymph Node Metastasis on the Outcomes of Radical Cystectomy for Bladder Cancer

Context

The presence of lymph node metastases and the extent of lymphadenectomy have both been shown to influence the outcome of patients with muscle-invasive bladder cancer.

Objective

Current standards for detection of lymph node metastases, lymph-node mapping studies, histopathologic techniques, and risk factors in relation to lymph node involvement are discussed. The impact of lymph node metastases and the extent of lymphadenectomy on the outcome of patients treated with radical cystectomy are analyzed.

Evidence acquisition

A systematic literature review of bladder cancer and lymph nodes was performed searching the electronic databases Pubmed/Medline, Cochrane, and Embase. Articles were selected based on title, abstract, study format, and content by a consensus of all participating authors.

Evidence synthesis

Lymph node status is highly consequential in bladder cancer patients because the presence of lymph node metastases is predictive of poor outcome. Knowledge of primary landing sites of lymph node metastases is important for optimum therapeutic management. Accurate pathologic work-ups of resected lymph node tissue are mandatory. Molecular markers could potentially guide therapeutic decisions in the future because they may enable the detection of micrometastatic disease. In current series, radical cystectomy with an extended lymphadenectomy seems to provide a clinically meaningful therapeutic benefit compared with a limited approach. However, the anatomic boundaries of lymph node dissection are still under debate. Therefore, large prospective multicenter trials are needed to validate the influence of extended lymph node dissection on disease-specific survival.

Conclusions

An extended pelvic lymph node dissection (encompassing the external iliac vessels, the obturator fossa, the lateral and medial aspects of the internal iliac vessels, and at least the distal half of the common iliac vessels together with its bifurcation) can be curative in patients with metastasis or micrometastasis to a few nodes. Therefore, the procedure may be offered to all patients undergoing radical cystectomy for invasive bladder cancer.     

The usefulness of pelvic lymphadenectomy in bladder cancer

ObjetiveTo assess the usefulness of pelvic lymphadenectomy in bladder cancer.Methods and ResultsWith the followings key words: “bladder cancer, lymphadenectomy, lymph node metastasis” we search in Medline/PubMed database for papers published during the last ten years. Thirty three papers fulfilling the search criteria were selected.ConclusionsIt does not exist any randomized prospective study comparing different pelvic lymphadenectomy techniques. Nodal metastasis in bladder cancer after radical cystectomy and pelvic lymphadenectomy ranged between 18% and 28%. Standard lymphadenectomy could improve tumor staging and probably survival in selected patients. It is advisable to remove, as a quality parameter, at least 10 to 14 nodes in a pelvic lymphadenectomy. Lymph node density seems to predict survival better than TNM staging system. It is advisable to perform separate lymph node dissection rather than en-bloc.