Indian Journal of Cancer Medknow Publications on behalf of Indian Cancer Society ISSN: 0019-509X EISSN: 1998-4774 Vol. 48, Num. 2, 2011, pp. 230-233

Indian Journal of Cancer, Vol. 48, No. 2, April-June, 2011, pp. 230-233

Original Article

Does extended lymph node dissection affect the lymph node density and survival after radical cystectomy?

A Dharaskar, V Kumar, R Kapoor, M Jain, A Mandhani

Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India

Correspondence Address:A Mandhani Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP India mandhani@sgpgi.ac.in

Code Number: cn11055

DOI: 10.4103/0019-509X.82896

Abstract

Keywords: Extended lymph node dissection, lymph node density, radical cystectomy

Introduction

Radical cystectomy (RC) is considered as one of the most complex uro-oncological procedures with high morbidity and mortality. Over the years, the role of RC is getting clearer in terms of indication, technique, and the ultimate output of surgery. Pelvic lymphadenectomy has been recently debated over the issues such as extended lymphadenectomy, technique of lymph node (LN) harvesting, and the impact of number of LN on overall survival.

The extended lymphadenectomy is LN dissection till the bifurcation of aorta ^[1] or up to the origin of inferior mesenteric artery. ^[2] It is accepted that it does not add to the overall operative time and morbidity of RC. However, its real benefit remains to be seen in the light of survival advantage to patients with bladder cancer. It is therefore thought worthwhile to compare extended lymphadenectomy to standard lymphadenectomy in terms of LN yield, density, and effect on survival.

Materials and Methods

For this study, the patients who have undergone RC from Jan 2004 to July 2009 were considered. Indications of RC were muscle invasive transitional cell carcinoma of bladder and high-grade superficial tumor not responding to intravesical therapy.

Radical cystectomy was done with an open approach, the only exception being the difference in extent of lymphadenectomy and the technique used in submitting the LNs to histopathological examination. Patients of RC were divided into three groups conforming to the change of practice of lymphadenectomy. Group I had 28 patients who had lymphadenectomy with the standard template and all the LNs were sent together (no separate packets were made before histopathological examination). Group II had 23 patients wherein LNs harvested by standard template lymphadenectomy were sent in four different packets (external iliac vessel and obturator with the presacral group from both the sides). Extended lymphadenectomy was started from July 2007, and LNs were sent in six different packets (external iliac, obturator with presacral, and common iliac till the bifurcation of the aorta from both the sides). All the cases of extended lymphadenectomy were done by a single surgeon (AM). This cohort formed the group III with 27 patients.

Demographic data of all the patients were retrieved from the hospital information system (HIS) and the patients′ case sheets. The neoadjuvant chemotherapy or radiotherapy was not given to any patient. All the patients were followed up in an out patient department at 3-month interval. The total number of LN harvested and the number of positive LN were recorded. LN density was calculated as the number of positive LNs divided by the total number of LNs expressed as percentage. Adjuvant chemotherapy in the form of MVAC/GC was given to the patients with LN involvement and/or T3 and T4 diseases. Follow-up data were collected from case sheets and HIS.

Analysis was performed for total number of LNs harvested, positive LNs, and LN density using the SPSS 15 commercial software. Survival analysis was done with Kaplan-Meier and the significance was calculated by log rank test.

Results

Seventy-eight patients were included for this study. The demographic data of these patients along with T-stage of the tumor were comparable in all three groups [Table - 1] and [Figure - 1]. The median number of LNs removed was 5(1-25), 9(3-28), and 16(1-25) in groups I, II, and III, respectively (P < 0.005). The LN positive rate was 25%, 26%, and 25.9% in groups I, II, and III, respectively. The mean LN density was 13.12%, 4.83%, and 6.93% in groups I, II, and III, respectively. Although there was an increase in the number of LN retrieved in group III, there was no difference in the yield rate of positive LN. Density of the LN was also not different in three groups [Table - 2]. The median duration of follow-up in group I was 24 months (0-49 months), group II was 14 months (0-43 months), and group III was 6 months (0-37 months). Overall survival was not significantly different in these three groups [Figure - 2].

Discussion

Radical cystectomy with pelvic lymphadenectomy provides the best local control and long-term survival in patients with LN positive and node negative disease. After RC and PLND, involvement of LN was seen in 25% of cases of bladder cancer. ^{[2],[3],[4],[5]} Preoperatively, lymph nodal assessment is done by computed tomography (CT) and magnetic resonance imaging (MRI) which, at times can be false negative in approximately 25% of cases. The survival of patients with LN involvement is poor when compared to patients with no nodal involvement. This highlights the importance of pelvic lymphadenectomy in patients with bladder cancer. Surgery is the best method to stage the local disease and plan further adjuvant therapy.

The therapeutic or prognostic significance of lymphadenectomy is extensively debated in almost all urological tumors and bladder cancer in particular. To further narrow down this debate, LN count is being considered as a benchmark of surgical quality of RC and proposed as a measure of adequacy of lymphadenectomy. The number of LNs pathologically evaluated at RC depends on several factors, i.e., (1) the extent of LND (extended or standard), (2) diligence and method of the pathologist in searching and preparing LNs for evaluation, and (3) how the specimen is submitted to the pathologist (en bloc or separate nodal packages). Therefore, the surgeon and the pathologist can influence the LN count and degree of LN involvement.

Traditionally, pelvic LN dissection is performed with the standard template and all the LNs are sent in one packet. This practice is challenged recently and many variations are reported in the way PLND is performed. Stein et al. defined an extended lymphadenectomy as including all LNs in the boundaries of the aortic bifurcation and common iliac vessels (proximally), the genitofemoral nerve (laterally), the circumflex iliac vein and the LN of Cloquet (distally), the hypogastric vessels (posteriorly) including the obturator fossa, the presciatic nodes bilaterally, and the presacral LNs. ^[1]

The oncological impact of this variation in PLND is very controversial. Leissner et al. observed that extended LN dissection improved the survival for both lymph node-negative and lymph node-positive patients, with a reduced local recurrence rate, when a greater number of LNs were removed. ^[3] Similarly other studies have shown that there is a survival advantage, with increasing the number of LNs, irrespective of them being positive or negative. ^[4],[6],[7]

Studies showing association between survival and more number of LNs removed during PLND are far from perfect. There is no randomised control trial available yet to prove this point. Most of the studies ^{[6],[7],[8],[9],[10]} were retrospective except a study by Leissner et al., ^[3] which was prospective nonrandomized. One possible explanation for increased survival with extended lymphadenectomy could be the removal of LNs with micrometastasis which are not picked up by pathologists. It is possible that with increase in the total number of LN removed, pathologists get very vigilant in analyzing all the LNs diligently and there is increase in number of positive LN also. However, the actual biology of the disease may not change by increasing the mere number of LNs. Tumor, once has gone beyond the bladder, becomes a systemic disease and extending the LN dissection and getting more LNs may not be of actual advantage.

LN dissection up to the inferior mesenteric artery is time-consuming and simultaneous dissection of all the lymph nodal stations may not be of advantage as described in a study from Egypt which has found that endopelvic (obturator and internal iliac) LNs were sentinel drainage for bladder. If the nodes in sentinel region were disease-free by frozen section examination, more proximal lymphadenectomy may be unnecessary. ^[2] No case of skip lesion was seen. Therefore, it was concluded that more extensive lymphadenectomy was only needed in patients with positive LN in the obturator and internal iliac group.

LN yield is a measure of an extent of LN dissection, which could be a reflection of a surgeon′s experience and number of procedures performed by him. This could bring in a selection bias toward the routine use of extended lymphadenectomy as against those who are infrequently doing RC. Hollenbeck ^[11] published hospital survey done in SEER database for LN count after RC. Hospitals were ranked and sorted into three evenly sized groups on the basis of the number of LNs. Low LN count hospitals tended to treat older, sick patients of lower socioeconomic strata. These hospitals had higher admission acuity, and had lower procedure volumes. After adjusting for these differences, low LN count hospitals tended to have slightly higher mortality (adjusted HR, 1.12; 95% CI: 0.99-1.27), although this finding did not reach statistical significance. In our study, extended lymphadenectomy was done by particular surgeon in the study period which reduces the selection bias.

Conclusions

Extended lymphadenectomy did increase the number of LNs retrieved, but it did not influence the positivity rate and density which are the predictors for better survival. Although micrometastasis is said to be the reason for better survival with extended lymphadenectomy even in negative LN, no difference was found in the survival with extending the LN dissection limit in our study. Although removal of positive LN has survival advantages, merely increasing the yield rate may not translate in improving survival. Therefore, more rational approach in terms of extended LN dissection needs to be explored further.

References

Copyright 2011 - Indian Journal of Cancer

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