Extended lymphadenectomy in robot-assisted radical cystectomy

Bladder lymphatic drainage

An anatomical understanding of the lymphatic drainage of the bladder and the definition of appropriate boundaries is crucial to performing an appropriate extended lymphadenectomy in RARC. ^, The bladder lymphatic drainage can be separated into six different levels: (1) the visceral lymphatic plexus, found within the bladder wall, from the submucosal layer to the bladder muscle layers; (2) the intercalated lymph nodes, found within the perivesical fat and separated into anterior, lateral, and posterior groups; (3) the pelvic collecting trunks, which are medially located lymph nodes draining into the external iliac and hypogastric lymph nodes; (4) the regional pelvic lymph nodes, thought to be the first level of metastasis and including the obturator, the internal and external iliac nodes, and sacral lymph node groups; (5) the lymphatic trunks, which bridge from the regional pelvic lymph nodes to the common iliac lymph nodes; and (6) the common iliac lymph nodes, surrounding the common iliac vessels and thought to be the second level of metastases before the aortocaval lymph nodes.

Lymphadenectomy template in RARC and evidence

The standard template for a lymphadenectomy in a context of RARC for bladder cancer comprises the regional pelvic lymph nodes, which represent the first levels of nodal metastasis. However, when we refer to extended lymphadenectomy, it includes internal, external, and common iliac artery stations. A modified template of extended dissection during laparoscopic and robotic radical cystectomy is based on patient age, associated comorbidities, and clinical stage.

Radical cystectomy series have confirmed that the obturator and external iliac lymph nodes are the two most common sites of lymph node metastasis in the setting of muscle-invasive bladder cancer, reporting nodal metastases were involved in 74% and 65% of cases, respectively. Furthermore, Smith et al. demonstrated lymph node involvement in 19% of patients to the common iliac packets. This was one of the first anatomical lymph node mapping studies in this setting that underlined the importance of performing an extended lymph node dissection and a removal of all potentially affected lymph nodes.

It has been shown that a super extended lymphadenectomy, including removal of the lymphatic tissue distal to the inferior mesenteric artery, can be performed safely. ^, Furthermore, there is pathologic evidence to suggest that the lymph node region extending from the aortic bifurcation to the level of the inferior mesenteric artery may be a common site of nodal metastasis, even though it has been demonstrated not to improve cancer-specific survival (CSS).

The specific distribution of nodal metastases was prospectively evaluated in a multicenter study in which an extended lymphadenectomy was performed in all patients with bladder cancer. This mapping study demonstrated that positive lymph nodes were most commonly found in the obturator spaces and adjacent to the iliac vessels. Interestingly, 16% of lymph node metastases also included nodes above the aortic bifurcation, while 8% of nodal metastases involved the presacral region. Among patients with nodal metastases located within the limits of a “standard” dissection (below the bifurcation of the common iliac vessels), a significant proportion of patients also had nodal involvement at the level of the common iliac vessels and above the aortic bifurcation (57% and 31%, respectively). The authors noted, had the dissection been limited to the obturator spaces, 74% of all positive lymph nodes would have been left behind and nearly 7% of the patients in this cohort would have been misclassified as node negative. The significance of an extended lymphadenectomy was also corroborated in a study that found 33% of patients with unexpected microscopic nodal involvement at the time of cystectomy to have metastases to the common iliac lymph nodes. A stage-specific lymph node metastasis mapping study was recently reported by Vazina et al. A total of 176 patients underwent an extended lymphadenectomy with radical cystectomy, in which 43 (24.4%) had pathologic lymph node involvement. Although the most common sites of nodal metastases were the external iliac and hypogastric/obturator regions, 5.1% had presacral nodal involvement and 9% had disease above the common iliac bifurcation. Importantly, 33% of patients with involvement of the common iliac lymph nodes also had involvement of the presacral region, supporting the importance of removing these nodes as well. Interestingly, a “skip metastasis” occurred in only one patient with positive lymph nodes at or above the common iliac bifurcation without involvement of the more distal pelvic lymphatics. Collectively, these studies support the application of a more extended lymphadenectomy with a cephalad extent of dissection that includes common iliac and paracaval lymph nodes, as well as removal of the presacral nodal packet.

The need for a bilateral lymph node dissection has also been questioned, particularly in patients with a unilateral bladder tumor. ^, In the mapping study by Leissner et al., bilateral lymph node metastases were commonly seen even if the primary cancer was limited to the right or left hemisphere of the bladder wall. Mills et al. evaluated lymph node metastases in 83 patients with bladder cancer following radical cystectomy and found that 41% of patients with a unilateral bladder tumor had contralateral nodal involvement. In a mapping study of 200 patients undergoing an extended lymphadenectomy, 24% of patients were found to have node-positive disease and 39% of these cases had bilateral involvement. These data suggest that a bilateral lymphadenectomy is important to remove all potential sites for nodal metastases at the time of cystectomy. In addition, in view of the diversity and potential for bilateral spread of nodal metastases, the concept of a sentinel node lymphadenectomy, as in penile cancer, is difficult to apply and not transferable to bladder cancer treated with radical cystectomy. On the contrary, Roth et al. published a series of 40 patients with cystectomy and unilateral bladder cancer who preoperatively underwent flexible cystoscopy-guided injection of radioactive technetium into the contralateral bladder wall. A total of 228 radioactive lymph nodes were detected, 85% and 15% on the ipsilateral and contralateral side, respectively. Although lymphatic drainage to the contralateral side was found in a high proportion of patients (40%), it was found to involve just the external iliac, obturator fossa, and common iliac region (i.e., none in the internal iliac region). Thus, when bladder tumors are strictly unilateral, contralateral pelvic lymph node dissection can be limited to these areas.

Zehnder et al. compared oncologic outcomes at two cystectomy centers where two different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage. Nine hundred fifty-nine patients affected by a pT2 and pT3 bladder cancer were analyzed, with similar 5-year recurrence-free survival for pT2pN0-2 (57% vs. 67%) and pT3 N0-2 (32% vs. 34%) disease ( P = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the two institutions (38%). The authors conclude that extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Similarly, Gschwend et al. and Moschini et al. showed, in a series of 401 and 903 patients, that the extended lymph node dissection failed to show a significant advantage over limited lymph node dissection in recurrence free survival, CSS, and overall survival. ^, Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.