BERKELEY, CA (UroToday.com) - The presence of lymph node (LN) metastases is critical for tumor staging and prediction of disease recurrence after radical cystectomy in patients with urothelial carcinoma of the bladder. The extent of pelvic lymphadenectomy during radical cystectomy has been shown to affect the accuracy of TNM staging as well as disease prognosis. In contrast to cancers of other organ systems (such as colorectal carcinoma, gastric, or breast cancer), there is no consensus regarding the requirement for the minimum number of LNs submitted for pathologic evaluation. Proposals for the required minimum number of LNs examined, and considered optimal for accurate pN staging and improved outcome, vary widely, and range from 10 to 27 LNs. The purpose of this study was: (1) to evaluate the adequacy of pathologic LN staging in radical cystectomy specimens from patients with urothelial carcinoma of the bladder; and (2) to analyze the frequency of LN metastases among different anatomic regions.
All radical cystectomies performed for primary urothelial bladder cancer over a 5-year period (January 2007 - September 2012) at a single institution were reviewed. Packet LNs from different drainage areas and levels were collected in different containers by urologists during the cystectomy procedure, including periaortic, paracaval, common iliac, external iliac, obturator/hypogastric, presacral, presciatic and Cloquet’s LN etc. Cases with LNs collected “en bloc” were excluded. Tumors were staged (pTNM staging) according to the 7th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. Particular attention was paid to the total number of LNs examined, the number and location of LNs with metastases (“positive LNs”), and the presence or absence of extranodal tumor extension and/or lymphovascular invasion in the cystectomy specimen. Results and data were analyzed with Origin 6.0 and Microsoft Office Excel 2007 software. A p-value < 0.05 was set for statistical significance.
A total of 248 radical cystectomies with 8 432 LNs were reviewed. A total of 60 (24%) cases, with 274 positive LNs out of 1 982 total (13.8%), were identified with a male to female ratio of 6.5:1 (52 male, 8 female patients). The average number LNs examined in each case was 33.0± 20.9 (range 5-112). The average number of positive LNs identified in each case was 4.5±4.8 (range 1-26).
Among all of the LNs, the hypogastric/obturator (internal iliac) LNs were the most commonly submitted (35.2%), followed by common iliac (19.9%) and external iliac (19.6%). Among all positive LNs identified, the highest percentage was derived from hypogastric / obturator (46.0%), followed by external iliac (20.8%) and common iliac (20.1%). The yield of positive LNs from each drainage area was also analyzed. For primary drainage LNs, 119/684 (17.4%) hypogastric / obturator LNs, 57/394 (14.5%) external iliac LNs, 12/125 (9.6%) presiatic LNs, 2/49 (4.1%) presacral LNs, and 1/101 (1.0%) Cloquet LNs were positive. Among secondary drainage LNs, i.e., common iliac LNs, 55/389 (14.1%) were positive. For distant LNs, 17/95 (17.9%) of periaortic LNs and 6/118 (5.1%) paracaval LNs were positive.
Lymph node density (LND) was analyzed according to pN and pM stage. The pN1 stage cases had a lower LND compared to those with those with a higher stage (5.61% in pN1 and 11.21% in pN2 compared to 22.85% in pN3, p=0.003 and 0.035, respectively). Based on the LND, the average number of examined LN corresponding to a yield of 1 positive LN can be calculated as 1/LND. On average, for cases staged pN1 and pN2, there was one positive LN per 17.8 and 8.9 LNs examined from the primary drainage LNs, respectively. The current (7th) edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual states that pN1 and pN2 represent one, and more than one, positive LN in the primary drainage LNs, respectively. Thus, to identify 2 or more positive primary drainage LNs among pN2 cases, 8.9 x 2 (i.e., 17.8) LNs from this area should be examined. For pN3 cases, one out of 4.4 secondary drainage LNs (common iliac) was found to be positive. Similarly, one out of 4.0 distant LNs (above the aortic bifurcation) was found to be positive in cases with pM1 staging. The LND was also higher in cases classified as pM1 stage when compared to pM0 (25.03% versus 15.21% respectively, p < 0.001)
Our study was limited by its retrospective design, as well as a number of other factors. These include the following: (i) the lymphadenectomies were not standardized; (ii) the extent of LN dissection from each case was dependent on the patient's clinical stage; (iii) other factors such as BMI, previous radiation, previous chemotherapy, etc.; and (iv) patient/surgeon preferences. Thus, the number of LNs examined is not an exact surrogate for the extent of LN dissection. Thus, there are several factors affecting the true LN count; these include the level of expertise of the surgeon, the person performing the gross examination, and the pathologist performing the microscopic examination. Although this study was conducted at a single institution, with only minor variation in the experience of pathologists and surgeons as compared to a multicenter study, the relatively small sample size remains a significant limitation.
Our study suggests that, on average, 23 LNs (including 18 primary drainage LNs and 5 secondary drainage LNs) should be submitted for optimal pN staging. For adequate pM1 staging, an average of 4 distal LNs should be evaluated. In total, an average of 27 LNs (23 for pN staging and 4 for pM staging) should be examined in radical cystectomy specimens. LND showed positive correlation with the increase of pN and pM stage. We also propose to stratify the number of positive LNs according to the drainage area. To the best of our knowledge, this is the first time that the number of LNs was stratified according to their drainage area.
Written by:
Lu Wang, MD,1 Kumaran Mudaliar, MD,1 Vikas Mehta, MD,1 Güliz A. Barkan, MD,1 Marcus L. Quek, MD,2 Robert C. Flanigan, MD,2 and Maria M. Picken, MD, PhD1* as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
1Department of Pathology and Laboratory Medicine, 2Department of Urology Loyola University Medical Center, 2160 S 1st Ave., Chicago, IL, 60153 USA
*Corresponding Author:
Maria M. Picken, MD, PhD
Department of Pathology and Laboratory Medicine
Loyola University Medical Center
2160 S 1st Avenue
Chicago, IL 60153
Tel: (708) 327-0267
Fax: (708) 327-2620
e-mail:
Seeking a standard for adequate pathologic lymph node staging in primary bladder carcinoma - Abstract
More Information about Beyond the Abstract