AB045. Extended lymphadenectomy versus non-extended lymphadenectomy in radical cystectomy for bladder cancer: a meta-analysis

Objective: Bladder cancer (BCa) is the most common tumor of male urinary reproductive system. Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard treatment for muscle invasive and high-risk non-muscle invasive bladder cancer. But the 5-year overall survival is only about 50%, the majority of the death causes are the tumor local recurrence and metastasis. Local residual micro-lesions and lymph node metastasis are the most important factors of tumor local recurrence and metastasis. At present, radical cystectomy with pelvic lymph node dissection is a necessary step and an important part of radical cystectomy to remove lymph node metastases, an effective means to accurately determine the clinical stage, and is also effective in reducing tumor recurrence and improve the disease-free survival. At present, the extent of lymph node dissection for radical cystectomy remains controversial and has not formed a conclusion. Now the common extent of lymph node dissection including local pelvic lymph node dissection (lPLND, including the obturator and internal iliac lymph nodes), standard pelvic lymph node dissection (sPLND, including the obturator, internal iliac and external iliac lymph nodes), and extended pelvic lymph node dissection (ePLND, including the obturator, internal iliac, external iliac, common iliac, presacral and para-aortic lymph nodes to the inferior mesenteric artery lymph nodes). That lPLND is inaccurate for clinical staging, tumor cured and recurrence rate. sPLND is the most often used clinical technique. In recent years, a growing number of studies have shown that ePLND not only able to provide more accurate tumor clinical staging, but also may complete removal of lymph node metastasis, and the micrometastases can not be detected, thereby reducing the local recurrence, distant metastasis and improve survival, especially non-organ confirmed, and even the patients with lymph node metastasis. However, with extended the extent of lymph node dissection, operative difficulty, operative time, blood loss and surgical complications are bound to increase too far. In pursuing a thorough lymph node dissection may affect the recovery of postoperative urinary control and sexual function. Surgical complications and postoperative lower quality of life, which also will affect the patients received the confidence and motivation for further treatment. Moreover, there is no large sample of multi-center prospective randomized controlled study confirms the cure effect of EL arm is better than the non-EL arm.

Methods: A comprehensive literature search was performed in electronic databases including PubMed, EMBASE and the Cochrane Library (last search March 2012). There were no restrictions to publication time or language. Radical cystectomy with EL was the trial arm (extended lymphadenectomy, EL group), and radical cystectomy with non-EL (standard or local lymph node dissection, non-EL group) was the control arm. The software of RevMan5.1 and Stata11 were used for this meta-analysis (MTA). Data including 5-year overall survival (5-year OS), and 5-year recurrence-free survival (5-year RFS) and total recurrence (TR) were extracted from the EL arm and non-EL arm respectively. Useing the index of hazards ratio (HR), odds ratio (odds ratio, OR) or the weighted mean difference (WMD) to express the result for the categorical variable.

Results: Ten studies published from 1998 to 2012 fulfilled the inclusion criteria and were included in the meta-analysis. There was one prospective non-randomized controlled study, and the remaining studies were retrospective. Analysis was performed on 1865 patients in the EL arm and 1,524 in the non-EL arm. The results show that the lymph node numbers (LNs) increased significantly, and there were significant differences (WMD16.79, 95% CI, 11.14–22.43; P<0.00001); lymph node density (LD) were no significant differences (OR 1.39, 95% CI, 0.97–2.01; P=0.07); There were no significant differences in 5-year overall survival (HR 0.84,95% CI, 0.66–1.08; P=0.17); 5-year recurrence-free survival were higher in EL arm (HR 0.81, 95% CI, 0.68–0.98; P=0.03); There were no significant differences in total recurrence (OR 0.89, 95% CI, 0.75–1.05; P=0.17). There was no significant difference in peri-operative complication (P=0.08).

Conclusions: This study showed that radical cystectomy with extended lymph node dissection can improve the patient’s 5-year recurrence-free survival, but no sufficient evidence can improve the 5-year overall survival and reduce the overall recurrence. Extended lymph node dissection does not increase peri-operative morbidity and mortality.

Keywords: Bladder cancer; lymphadenectomy; survival; meta analysis