Pelvic Lymphadenectomy

89
Pelvic Lymphadenectomy

Marc D. Manganiello¹ & Andrew A. Wagner²

¹ Tufts School of Medicine, Lahey Hospital and Medical Center, Boston, MA, USA

² Beth Israel Deaconess Medical Center, Boston, MA, USA

Introduction

Pelvic lymphadenectomy is the most accurate method of diagnosing lymph node involvement in patients with genitourinary malignancies. In practice, this is most commonly seen in patients with prostate and bladder cancer, but may also be performed in patients with penile or urethral cancers. Histologic confirmation of metastatic disease within the pelvic lymph nodes provides significant prognostic data and potentially therapeutic benefit. Additionally, this information may help guide the decision for future, adjuvant therapy [1, 2]. Minimally invasive pelvic lymphadenectomy (laparoscopic or robotic) offers a nodal yield similar to that from open surgery, but with improved convalescence [3]. Herein we describe the anatomy, procedure, and complications of minimally invasive pelvic lymph node dissection. Our procedure section specifically describes the robotic approach, but an identical dissection can be performed laparoscopically with similar benefits in visualization during the procedure and recovery afterwards.

Accepted templates for pelvic lymph node dissection

There are varying definitions describing the extent of a pelvic lymph node dissection. Herein we describe the technique for each. The “limited template” (LT), also known as the standard template, lymph node dissection involves the nodes of the obturator fossa between the obturator nerve and external iliac vein. The lateral border of the dissection is the pelvic sidewall and medial border is the bladder. The tissue removed includes from the node of Cloquet to the bifurcation of the iliac vein proximally. The LT is commonly performed for low‐ and intermediate‐risk prostate cancer. The “extended template” (ET) includes all the nodes in the LT, in addition to the nodes surrounding the external iliac artery back to the level of the common iliac artery at the level of the ureter crossing into the deep pelvis. The dissection also includes the tissue laterally from the external iliac artery to the genitofemoral nerve. Also included is tissue surrounding and deep to obturator nerve. The ET often includes the nodes in the presacral area. A “super extended template” (SET) includes the nodes of the LT and ET in addition to the nodes around the proximal common iliac artery and veins bilaterally up to the bifurcation of the aorta and the periaortic nodes up to the inferior mesenteric artery.

Prostate cancer

Lymph node metastases in prostate cancer are reported to range from 4% to 6% in patients undergoing lymphadenectomy [4]. Nodal spread is associated with higher Gleason score, higher pT stage, older age, and higher incidence of positive surgical margin [5]. In addition, the number of positive lymph nodes found at surgery impacts overall survival. Patients with 1 or 2 positive nodes were found to have a clinical recurrence‐free survival (no physical, radiographic, or symptomatic evidence of recurrence) of 70% and 73% at 10 years, whereas those with greater than 5 positive nodes were found to have a clinical recurrence‐free survival of 49% at 10 years. This study did not compare prostate specific antigen (PSA), only recurrence between these groups. Overall survival between these two groups at 10 years was 74% versus 49% [6]. Touijer et al. reported a 78% overall 5‐year progression‐free probability for all prostate cancer risk groups, but noted a 49% 3‐year progression‐free probability in lymph node‐positive patients. All of these patients experienced a clinical recurrence within 5 years [7].

Lymph node imaging

Imaging has been consistently unreliable in diagnosing nodal metastases, particularly in patients with low‐risk disease. The size criteria to identify possible lymph node involvement vary from 0.5 cm to 2 cm, although a lymph node with a short axis of 1 cm or greater is generally considered clinically abnormal. Computed tomography (CT) and conventional magnetic resonance imaging (MRI) have both demonstrated poor sensitivity for detecting nodal disease; one meta‐analysis reported a pooled sensitivity of 0.42 and 0.39, respectively [8]. Evaluation of fluoromethylcholine positron emission tomography (PET)/CT for detection of lymph node metastases demonstrated a sensitivity and specificity of 73.2% and 87.6%, respectively. Neither the sensitivity nor the specificity is adequate enough to recommend PET/CT for routine use [9]. High‐resolution MRI with magnetic nanoparticles has been shown to improve the sensitivity of detection of lymph node metastases, but has not yet been adopted as a recommended imaging option as availability of this technology is limited [10, 11]. Although current imaging modalities may not be ideal, significantly elevated preoperative PSA or high‐risk biopsy pathology should prompt preoperative imaging. The American Urological Association (AUA) recommends preoperative imaging to evaluate for nodal disease in patients with clinically localized prostate cancer and a PSA greater than 20 ng/ml, locally advanced disease, or a Gleason score greater than or equal to 8 [12] (Table 89.1). The National Comprehensive Cancer Network (NCCN) recommends preoperative imaging with bone scan and pelvic CT or MRI if patients are cT1 and PSA greater than 20 ng/ml, cT2 and PSA greater than 10 ng/ml, locally advanced disease, symptomatic disease, or cT1–2 with a nomogram probability of lymph node involvement greater than 10% [13].

Table 89.1 American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN) criteria for preoperative imaging to evaluate for metastatic disease.

American Urological Association	National Comprehensive Cancer Network
Clinically localized disease and PSA >20 ng/ml	T1 and PSA >20 ng/ml
Locally advanced disease	T2 and PSA >10 ng/ml
Gleason Score 8, 9, or 10	Locally advanced or symptomatic disease
	Probability of lymph node positivity >10%

Who should undergo pelvic lymphadenectomy?

In an attempt to determine the need for pelvic lymphadenectomy, several nomograms exist to risk stratify patients prior to surgery. The Partin tables incorporate preoperative PSA, clinical stage, and biopsy Gleason score to predict the possibility of lymph node involvement, in addition to other adverse pathologic features (such as organ‐confined disease, extraprostatic extension, and seminal vesical involvement). These tables were recently updated and confirmed the increased possibility of pT3 and N1 disease in patients with a PSA level >10 ng/ml. The Partin tables recommend that a pelvic lymphadenectomy be performed if the predicted probability of positive nodal disease is greater than or equal to 4%. This value gave the optimal ratio of appropriate to inappropriate lymphadenectomy [14].

Researchers from Memorial Sloan Kettering Cancer Center and several other institutions published a nomogram using similar variables of pretreatment PSA, clinical stage, and biopsy Gleason score. The negative predictive value of this nomogram was 0.99 when the predicted chance of lymph node involvement was less than 3%, thus obviating the need for lymphadenectomy in this subset of patients [15].

Briganti et al. recommended that patients with low‐risk prostate cancer (Gleason 6, PSA <10 ng/ml, cT1c or cT2a) not routinely undergo pelvic lymphadenectomy as the chance of positive lymph nodes in these patients is less than 5% (Table 89.2). Intermediate‐risk prostate cancer (Gleason 7, PSA between 10 and 20 ng/ml, or cT2b) carries a risk of positive lymph nodes between 3.7 and 20.1%, therefore, Briganti suggests lymphadenectomy should be performed if the nomogram risk is 5% or greater. All high‐risk prostate cancer patients (Gleason 8–10, PSA >20 ng/ml, or cT2c) should undergo a pelvic lymph node dissection, as estimated risk is 15–40% for discovering positive lymph nodes [16].

Table 89.2 European Association of Urology (EAU) and Briganti et al. recommendations for performing pelvic lymphadenectomy.

EAU/Briganti – risk	Probability of positive lymph node	PLND?
Low (Gleason 6, PSA < 10, cT1c, cT2a)	Less than 5%	No
Intermediate (Gleason 7, 10 < PSA < 20, cT2b)	Greater than 5%	Yes
High (Gleason 8–10, PSA >20, cT2c)	15–40%	All high‐risk patients should undergo PLND

PLND, pelvic lymph node dissection.

The European Association of Urology (EAU) guidelines for pelvic lymphadenectomy are based on a nomogram using a cohort of patients who underwent open prostatectomy and extended pelvic lymph node dissection template (ET). The EAU recommendation is to perform lymphadenectomy in patients who have a predicted positive nodal risk greater than 5% (based on findings by Briganti et al.). Using this cutoff for low‐risk individuals, unnecessary pelvic lymph node dissection would be avoided in 65% of patients. This has been externally validated in a cohort of patients undergoing a robot‐assisted radical prostatectomy, assuming that an adequate extended lymph node dissection is performed (i.e. at least 15 lymph nodes removed). Of note, in this study, there was no anatomic standardization of the pelvic lymph node dissection. Tissue within the obturator fossa and along the external iliac vein was removed in all patients. However, tissue along the internal and common iliac vessels was removed based on the individual surgeon’s clinical judgment [16, 17].

Finally, the NCCN recommends performing a pelvic lymphadenectomy in patients with low‐ and intermediate‐risk prostate cancer whose nomogram predicts a greater than 2% chance of positive lymph nodes (Table 89.3). All high‐risk patients should undergo an extended template lymphadenectomy if surgery is performed [13].

Table 89.3 National Comprehensive Cancer Network (NCCN) recommendations for performing pelvic lymphadenectomy.

NCCN – risk	Probability of positive lymph node	PLND?
Low	If >2%	Yes
Intermediate	If >2%	Yes
High		All patients

Rationale for extended pelvic lymphadenectomy template in prostate cancer

Lymphatic drainage from the prostate follows a fairly predictable pattern, with low chance of skip lesions. Drainage occurs first to the pelvic nodes in the external iliac, obturator, internal iliac, and presacral lymph node packets. Lymph drainage may then ascend to the common iliac and retroperitoneal lymph nodes; however, this is generally seen only in patients with high‐risk prostate cancer [18]. Pelvic lymph node mapping in prostate cancer has demonstrated that the most common location for a positive lymph node was the internal iliac region (35%), followed by the external iliac region (26%), the obturator fossa (25%), presacral region (9%), common iliac region (3%), and the aortic bifurcation (1%) [19]. There has been some controversy over the extent of lymph node dissection given the technical difficulties and the potential for further and possibly unnecessary complications. Early reports of extended lymphadenectomy published complication rates of 12–24% and included lymphocele, lymphedema, and thromboembolic events. This led to development of the limited dissection template or the obturator fossa packet [20]. Clark et al. prospectively randomized 123 patients undergoing radical retropubic prostatectomy to an extended lymph node dissection on one side and a limited lymph node dissection on the opposite side. The majority of these patients were T1c (72%) and Gleason 6 (68%). Positive lymph node metastases were similarly found between the extended (3.3%) and the limited (2.4%) groups (P = 0.15). In patients with complications attributed to the lymph node dissection (i.e. lymphocele, lower extremity edema, deep venous thrombosis, pelvic abscess, ureteral injury) the complication occurred 75% of the time on the side of the extended node dissection. Although this finding was not clinically significant (P = 0.08), the authors concluded that an extended lymph node dissection does not yield a higher rate of positive lymph nodes and that there may be a trend toward higher complications with an extended pelvic lymph node dissection [21]. On the other hand, Eden et al. describe a series of 374 men who had a pelvic lymph node dissection during laparoscopic radical prostatectomy. Of these, 253 men had a standard lymph node dissection, while 121 men underwent an extended template. The operative time for an extended template was significantly longer by a median of 26.5 minutes (180 vs. 206.5 minutes, P < 0.001). Although there were more complications (i.e. bowel injury, neurovascular injury, lymphocele) with an extended template as compared to a standard template (8.3% vs. 3.6%), this was not found to be statistically significant (P = 0.10). Importantly, in patients undergoing an extended pelvic lymph node template versus a standard template, there was a significantly higher total lymph node yield (17.5 vs. 6.1, P = 0.002) as well as a higher rate of detection of lymph nodes harboring metastatic disease (9.6% vs. 0.8%, P = 0.01) [22].

The important distinction comes in patients with intermediate‐ and high‐risk disease. A significant amount of nodal disease may occur outside of the ST, thus the importance of extending the template to include the common iliac, internal iliac, and presacral regions. Several studies demonstrate that almost 60% of patients harbored positive lymph nodes along the internal iliac vessels; in fact, this was the only site of lymphatic spread in 12–25% of patients undergoing prostatectomy [19, 23]. By extending the template of dissection, more lymph nodes are removed and the accuracy of staging improves. Briganti et al. demonstrated that the number of nodes removed is directly proportional to the probability and ability of detecting lymph node involvement. For each lymph node removed, the probability of accurately predicting lymph node involvement in a patient with prostate cancer increases by 6%. If fewer than 10 nodes are removed, there is less than 10% probability of finding lymph node involvement if it actually exists. In contrast, as the number of nodes removed increases from 10 to 30, the probability of detecting positive lymph nodes increases substantially. This plateaus when 28 lymph nodes are removed, resulting in a 90% ability to accurately predict whether or not lymph node involvement is present [24]. Maccio et al. have recommended submitting the entire pelvic lymph node specimen, including fatty tissue, for pathological evaluation, not just examining visually enlarged or palpable nodes. Incidence of nodal metastasis was significantly higher when all fatty tissue removed at the time of dissection was histologically evaluated. This minimized pathologic diagnostic bias and helped to determine the presence of micrometastatic disease [5].

In addition to improving the accuracy of disease staging, an extended lymph node dissection may improve survival. Abdollah et al. found that in pN1 patients with prostate cancer, cancer‐free survival rates increased as the number of lymph nodes removed increased. For example, at 10 years after surgery, the cancer‐free survival for a patient with 8 lymph nodes removed was 74.7%; this improved to 96.0% when 36 lymph nodes were removed. In general, survival rates were significantly higher in pN1 patients with more than 14 lymph nodes removed compared to patients with less than 14 lymph nodes removed [25]. Extended lymph node dissection may also improve the survival in pN0 patients as well. Joslyn et al. reported that when greater than 10 lymph nodes were removed, node‐negative patients were found to have a 15% decreased risk of prostate cancer death [26].

Bladder cancer

The standard of care for muscle invasive urothelial cell carcinoma of the bladder is radical cystectomy with bilateral pelvic lymph node dissection. Positive lymph node status and pathologic stage are associated with a worse overall prognosis and survival. Approximately 25% of patients undergoing radical cystectomy are found to have lymph node metastases [27]. These patients have a reported 5‐year recurrence‐free survival of 33% and overall survival of 26% [28]. An aggressive surgical approach has consistently demonstrated both a diagnostic and therapeutic advantage [29, 30].

Preoperative imaging

Initial metastatic workup for patients with muscle invasive urothelial carcinoma includes cross‐sectional, contrast‐enhanced imaging with either CT or MRI. Sensitivity and specificity of these imaging studies are suboptimal, similar to lymph node detection in prostate cancer [31, 32]. Roughly 25% of individuals whose preoperative imaging studies were negative for lymph node involvement were found to have lymph node involvement on final pathology [27]. PET/CT has been evaluated as a potential modality; however, the false‐negative rate was 33% and it has not been found to be helpful in evaluating patients with primary bladder cancer. Thus it is currently not a recommended imaging option [33].