Laparoscopic pelvic lymph node dissection system based on preoperative primary tumour stage (T stage) by computed tomography in urothelial bladder cancer: results of a single-institution prospective study

Authors


Correspondence: Xiong-Bing Zu, Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008.

e-mail: csuxyzuxb@yahoo.cn

Abstract

What's known on the subject? and What does the study add?

  • Bladder cancer (BC) is a public health problem throughout the world, and now radical cystectomy (RC) has been introduced as a standard treatment for BC invading muscle and some BCs not invading muscle. Pelvic lymph node dissection (PLND) is considered an integral part of RC for its prognostic and therapeutic significance, but the extent of the PLND has not been precisely defined.
  • Computed tomography is considered one of the most preferable methods to assess the BC stage preoperatively because of its high sensitivity and specificity. However, there are few articles referring to CT as an aid in deciding the extent of lymphadenectomy during RC.
  • In the present study, we prospectively studied the clinical value of preoperative CT staging of primary tumours in deciding the extent of PLND during laparoscopic RC in the management of BC. The preliminary findings suggested that all patients with higher preoperative CT stage should be given super-extended PLND during RC. For those with lower CT stage, careful and thorough clearance of all lymphatic and adipose tissues within the true pelvis could be more helpful than super-extended PLND.

Objective

  • To study prospectively the clinical value of preoperative spiral computed tomography (CT) staging of primary tumours in deciding the extent of pelvic lymph node dissection (PLND) during laparoscopic radical cystectomy (RC) in the management of bladder cancer (BC).

Patients and Methods

  • Between January 2010 and December 2011, a total of 63 patients with urothelial BC received laparoscopic RC, super-extended PLND and ileac conduit.
  • The super-extended PLND removed all lymphatic tissues in the boundaries at the level of the inferior mesenteric origin from the aorta (cephalad), the pelvic floor (distally), the genitofemoral nerve (laterally) and the sacral promontory (posteriorly).
  • All of the operations were performed by one experienced surgeon, and all harvested lymph nodes were submitted separately.
  • CT was used to evaluate the preoperative CT stage (CTx) of each primary bladder tumour.

Results

  • All patients were divided into five categories according to their CTx stages: three at CT1, seven at CT2a, 38 at CT2b, seven at CT3b, and eight at CT4a.
  • All 63 procedures were completed successfully without any conversion to open surgery. The mean estimated blood loss was 450 mL, and 14 patients (22.2%) had postoperative lymphatic leakage.
  • Each case was pathologically confirmed as transitional cell carcinoma with negative margins at the urethral and ureteric stumps.
  • None of the patients with a low CTx stage (CT1–CT2a) had positive lymph nodes above the level of the common iliac artery bifurcation.
  • There was no jump lymph node metastasis, and no positive lymph node was detected above the level of aortic bifurcation in all cases.

Conclusion

  • Based on the preoperative CT staging, urological surgeons can determine the boundaries of PLND to reduce intraoperative injury and postoperative complications in patients with BC, especially those at the lower CTx stages (CT1 and CT2a).
Abbreviations
BC

bladder cancer

PLND

pelvic lymph node dissection

RC

radical cystectomy

Introduction

Bladder cancer (BC) is a public health problem throughout the world, and most of the cases are presented as urothelial cell carcinoma [1-3]. Recently, radical cystectomy (RC) has been introduced as a standard treatment for BC invading muscle (muscle-invasive BC [MIBC]) and some BCs not invading muscle (non-muscle-invasive BC [NMIBC]), such as multiple recurrent high-grade tumours, high-grade T1 tumours and high-grade tumours with concurrent carcinoma in situ [4-6]. The standard of RC is radical cystoprostatectomy for men and anterior exenteration (including bladder, urethra, uterus and ventral vaginal wall) for women [3]. Currently, pelvic lymph node dissection (PLND) is considered as an integral part of RC for its prognostic and therapeutic significance, but the extent of the PLND has not been precisely defined [4]. Laparoscopic RC with PLND is advised to be a good option for treating BC because of its minimal invasion, reduced blood loss and rapid recovery [4, 7-9].

However, due to the lack of standardization of PLND during RC, the exact extent and the number of lymph nodes to achieve clearance has not yet been defined. Numerous studies have recently advocated super-extended PLND, which involves dissection and removal of lymph nodes to the inferior mesenteric origin from the aorta [10, 11]. Considering the longer operating duration and the higher blood loss, there is still some controversy about whether super-extended PLND should be performed for all patients who undergo RC, especially those with BC at a low clinical stage.

Although the diagnosis and clinical stage of BC are mainly established by cystoscopic examination of the bladder and biopsy [3-5], CT is considered one of the most preferable methods for assessing the BC stage before surgery because of its high sensitivity and specificity [12]. However, to our knowledge, there are few articles referring to CT as an aid in deciding the extent of lymphadenectomy during RC. In the present study, we initiated a prospective single-institution study of laparoscopic RC associated with super-extended PLND in 63 patients with BC from January 2010 to March 2012, and attempted to establish an evaluation system for determining the surgical extent based on preoperative primary tumour stage (T stage) by CT.

Patients and Methods

Between January 2010 and March 2012, all Chinese patients with BC admitted to the Department of Urology of Xiangya Hospital, Central South University (Changsha, China), were considered for enrolment. Each had their complete history taken and underwent routine haematological and biochemical examination, cystoscopy, and chest, abdomen and pelvic multidetector row CT scans. Exclusion criteria were patients with poor cardiopulmonary function, distant metastases, pelvic or abdominal wall invasion, radiation therapy or chemotherapy before surgery. Finally, after consenting to the nature, purpose and potential risks of the present study, a total of 51 male patients and 12 female patients aged 35–78 years were included. The mean body mass index of all 63 patients was ≈23.1 kg/m2 (Table 1). Each participant signed an informed consent form and the study was approved by the Institutional Ethics Committee of Xiangya Hospital.

Table 1. Demographic, intraoperative and postoperative data of all patients.
  1. BMI, body mass index.
No. patients63
Mean (range) age, years57 (35–78)
No (%) of males51 (80.9)
Mean (range) BMI, kg/m223.1 (18.7–29.5)
Surgical technique [n (%)] 
Laparoscopic63 (100)
Laparoscopic converted to open surgery0 (0)
Mean (range) lymph nodes retrieved at each anatomical site 
Para-aortal, paracaval, interaortocaval2.1 (1–4)
Bilateral common iliac3.5 (2–7)
Presacral1.0 (0–3)
Bilateral internal iliac7.1 (2–12)
Bilateral external iliac2.0 (1–4)
Bilateral obturator10.2 (4–18)
Mean (range) minimum total operation duration250 (230–310)
Mean (range) minimum time for super-extended PLND100 (85–130)
Mean (range) estimated blood loss, mL450 (200–1300)
Complications [n (%)]21 (33.3)
Bowel obstruction [n (%)]3 (4.8)
Lymphatic leakage [n (%)]14 (22.2)
Leakage of urine [n (%)]4 (6.3)

All patients were asked to drink water 2 h before CT examination to ensure their bladder was filled with urine during CT scanning. A standardized method was used to evaluate the preoperative CT T stage (CTx) of BC as follows. The imaging diagnostic criterion for stage CT1 were defined as the high-density linear shadow remaining continuous and confined to the submucosa around the primary tumour. Stage CT2a was diagnosed as an interrupted submucosal high-density linear shadow invading the inner half of muscle wall. At the CT2b stage the primary tumour invades the outer half of muscle wall, and makes the contours of bladder wall uneven or stiff. Stage CT3a was not defined because microscopic invasion of the perivesical tissue by the primary tumour could not be distinguished on CT scans. Stage CT3b was defined as the extension of high-density cord-like or mass shadow, enhanced similarly to the primary tumour, to the perivesical fat tissue. Tumours invading the adjacent organs but not the pelvic or abdominal wall were considered as stage CT4a. All the final CTx stage diagnoses were made by two experienced abdominal/genitourinary radiologists from Xiangya Hospital.

All patients received laparoscopic super-extended PLND before cystectomy under general anaesthesia in the Trendelenburg tilt position. The boundaries of lymphadenectomy were based on visible anatomical landmarks as follows: the level of the inferior mesenteric origin from the aorta (cephalad), the pelvic floor (distally), the genitofemoral nerve (laterally) and the sacral promontory (posteriorly). All lymphatic and adipose tissues in this region, including para-aortal, paracaval, interaortocaval, bilateral common iliac, bilateral internal iliac, bilateral external iliac, bilateral obturator and presacral nodes, were harvested carefully and thoroughly. All harvested lymphoid tissues were submitted in at least 10 separate specimen packets.

After super-extended PLND, cystectomy was also performed intracorporeally. The resected bladder was then removed through a new small longitudinal incision (about 8 cm long) above the umbilicus, followed by a Bricker ileal conduit. All postoperative follow-ups and treatments were carried out in a standardized manner.

The pathological examinations of each specimen (including resected bladder and corresponding harvested lymphatic tissue) were performed by experienced genitourinary pathologists. The region of lymph node metastasis (LN+) was divided into three different levels as introduced by Leissner et al. [10]: level I (from the pelvic floor to the level of the common iliac artery bifurcation), including bilateral internal iliac, external iliac and obturator lymph nodes; level II (from the level of the common iliac artery bifurcation to the level of aortic bifurcation), including bilateral common iliac and presacral lymph nodes; and level III (from the level of aortic bifurcation to the level of the inferior mesenteric origin from the aorta), including para-aortal, paracaval and interaortocaval lymph nodes.

The statistical software package SPSS13.0 (SPSS Inc, Chicago, IL, USA) was used for all analyses. The rates of lymph node metastases at the defined CTx stages are shown as percentages, and the comparison among stages was analysed using Fisher's exact test. P < 0.05 was considered to indicate statistical significance in all tests.

Results

All 63 patients were included in the final analysis, and all of them were managed successfully by super-extended PLND and RC under laparoscopy without conversion to open surgery. The demographic, intraoperative and postoperative data of all 63 patients are given in Table 1. The median total operation duration was 250 min, and the median estimated blood loss was about 450 mL. The median operation duration for super-extended PLND was 100 min and the mean (range) number of lymph nodes retrieved was 25.9 (14–43). Postoperative complications occurred in 21 patients (33.3%), including three cases with bowel obstruction (4.8%), 14 with lymphatic leakage (22.2%) and four with leakage of urine (6.3%).

All the preoperative classifications of CTx stage were defined based on the uniform standards as mentioned earlier: three were defined as CT1, seven as CT2a, 38 as CT2b, seven as CT3b, and eight as CT4a (Table 2).

Table 2. Patients [n (%)] with lymph node metastases (LN+) in each CTx category at levels I–III.
CTxNo. of patientsLN+ in level ILN+ in level I + IILN+ in level I + II + III
  1. The n (%) of patients with LN+ in each level is based on the number of patients in the specific CTx group.
CT130 (0)0 (0)0 (0)
CT2a70 (0)0 (0)0 (0)
CT2b3810 (26.3)2 (5.3)0 (0)
CT3b73 (42.9)0 (0)0 (0)
CT4a83 (37.5)1 (12.5)0 (0)
Total6316 (25.4)3 (4.8)0 (0)

After surgery, all 63 cases were pathologically confirmed as urothelial cell carcinoma with negative margins at the urethral and ureteric stumps. A total of 25.4% of patients (n = 16) had positive lymph nodes (three patients with lymph node metastases at levels I and II, and the remaining 13 cases with positive nodes only at level I). No patients with a low CTx stage (CT1–CT2a) had positive lymph nodes. There was no jump lymph node metastasis, and no positive lymph node was detected at level III. The percentage of LN+ at stages CT2b–CT4a was significantly higher than that at stages CT1–CT2a. But there was no statistically significant difference in the percentages of LN+ among CT2b–CT4a stages (P > 0.05). All data are given in Table 2.

Discussion

The prognosis and survival of patients with bladder cancer are related to several factors, including pathological T stage (T), pathological grade and tumour diameter. RC, which has been routinely performed for more than 60 years, is considered the standard of care for BC, especially MIBC [3, 4]. More and more researchers have realized that lymph node metastasis is one of the most important dependent variables [10, 13-15]. As a result, RC associated with PLND has been gradually accepted by urologists and oncologists as a standard treatment for BC, especially for MIBC. As an attractive minimally invasive alternative to the conventional open operation, laparoscopic RC with PLND for treating BC is recommend by some authors [11, 16].

Accurate preoperative clinical staging plays an important role in guiding the treatment plan and predicting prognosis for patients with BC [17-19]. Shariat et al. [18] indicated that the clinical T stage diagnosed by predictive tools could give a preoperative estimate of the nodal metastasis and thereby help to decide the extent of lymph node dissection during RC. CT is now considered one of the most valuable predictive tools for the diagnosis and staging of BC [4, 12, 20]. In the present study, preoperative CTx of each primary tumour was evaluated according to a consistent protocol.

Pelvic lymph node dissection, as an indispensable part of RC, can help not only to determine the precise clinical stage of BC but also to improve their expected survival rates [21, 22]. However, the exact boundaries and templates of PLND remain controversial, and there are at least four templates of PLND described in the literature, including limited, standard, extended and super-extened PLND [10, 11, 23, 24]. Currently, super-exteneded PLND with RC is advocated by many professionals, and it has been pointed out that super-extened PLND with RC could provide both diagnostic and therapeutic benefits [10, 11]. We therefore suggest that super-extended PLND should be carried out as a routine surgical treatment for patients with BC with higher-stage CTx tumours (CT2b–CT4a).

However, compared with the standard and extended PLND, the super-extended PLND could have a longer operation duration and a higher chance of damaging blood and lymphatic vessels. It was reported that a super-extended PLND takes up to 60 min longer than a lymphadenectomy that cranially ends at the level of the iliac arteries [10]. Shao et al. [11] also reported that lymphatic leakage occurred in 39.5% of patients in their study. In the present study, the lymphatic leakage was also the most postoperative complication, and its incidence rate was ≈ 22.2% (n = 14). As a result, from our own experience, the more important goal for urological surgeons is to remove all lymphatic and adipose tissue within the true pelvis carefully and thoroughly for those cases with a lower CTx stage BC (CT1–CT2a) instead of super-extended PLND.

The foremost limitation of the present study is the lack of long-term follow-up and the fact it was not a randomized controlled study. Therefore, we cannot compare the operative outcome between super-extened PLND and standard PLND during RC in patients with lower-stage BC (CT1-CT2a). We await further studies with larger cohorts and long-term follow-up evaluation to determine which surgical approach is more suitable for patients with BC with lower-CTx tumours. Moreover, the result of the present study could potentially be limited by the number of patients included in the analysis. We suggest that a further large clinical multicentre trial for laparoscopic PLND with RC based on preoperative clinical CTx staging in patients with BC is necessary.

In conclusion, the preliminary findings of the present study suggest that all patients with higher preoperative CTx stage (CT2b–CT4a) should be given super-extended PLND during RC. For those patients with a lower CTx stage (CT1–CT2a), careful and thorough clearance of all lymphatic and adipose tissues within the true pelvis could be more helpful than super-extended PLND.

Conflict of Interest

None declared.

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