Introduction

Lymph node status is a primary factor in determining a patient’s prognosis and future therapy for prostate cancer. Lymph node involvement (LNI) is associated with a significant increase in recurrence and mortality. ^, Pelvic lymph node dissection (PLND) remains the most accurate means of determining lymph node status. Conventional cross-sectional imaging (computed tomography [CT] and magnetic resonance imaging [MRI]) has significant limitations in detecting LNI, with newer molecular imaging modalities such as prostate-specific membrane antigen (PSMA) and fluciclovine (Axumin) showing added accuracy, but seeming to lack specificity. ^,

While some men with limited LNI may have prolonged recurrence free survival following surgery with PLND, most will require additional therapy, and the therapeutic benefit of PLND for prostate cancer remains controversial. ^, Most retrospective analyses of this are limited by stage migration and the “Will Rogers phenomenon.”

Following our description of the technique for performance of PLND, including tips for minimization of morbidity, this chapter will review the guidelines and evidence around PLND in prostate cancer.

Guidelines and pelvic lymph node dissection

Contemporary guidelines from the European Association of Urology (EAU), National Comprehensive Cancer Network (NCCN), and American Urological Association (AUA) suggest that a PLND be performed in higher risk cases for the purposes of staging and prognosis. The EAU recommends an extended PLND (ePLND) for all patients with a risk for nodal metastasis greater than 5% based on preoperative risk nomograms, including the Briganti/Gandaglia nomogram, Memorial Sloan Kettering Cancer Center (MSKCC) or Partin nomograms, or the Roach formula. These nomograms utilize several preoperative variables—age, pretreatment prostate-specific antigen (PSA), clinical tumor stage—as well as biopsy data—Gleason grade and percentage of positive cores—to predict risk of LNI. They also have been extensively validated by several studies with no significant differences in predictive ability.

The rationale for the 5% risk cutoff focuses on maximizing diagnostic accuracy and potentially the therapeutic benefit, while minimizing missed diagnoses and additional morbidity associated with PLND. As an example, the negative predictive value of a 5% cutoff in the Briganti nomogram is 98.4%, sparing ePLND in 65% of patients while only missing 1.5% of nodal involvement cases. As these stratification systems are all based on preoperative data as well as systematic template prostate biopsy, a new Briganti nomogram was created to allow for MRI-targeted biopsy information. This novel nomogram utilizes a cutoff point of 7% risk, which would avoid unnecessary PLNDs in 70% of men at the cost of missing only 1.5% of cases with nodal involvement. The 2021 NCCN guidelines also support the use of ePLND as the optimal staging modality while also providing the potential for cure for certain individuals with limited micrometastatic disease. The NCCN has a lower cutoff of 2% for risk of nodal metastasis based on preoperative nomograms. AUA guidelines have a slightly different approach, though based on the same principles of targeting higher risk patients. These state that PLND can be considered for any localized prostate cancer patients undergoing radical prostatectomy and is recommended for those with unfavorable intermediate-risk or high-risk disease. While it is not explicitly mandated, these guidelines also suggest the benefits of a more extensive PLND in sampling more nodes, resulting in improved detection of nodal metastases.

Extent of pelvic lymph node dissection

While it is widely accepted that PLND improves staging of prostate cancer through detection of lymph node metastases, the question remains as to the extent of the lymph node dissection. Understanding the lymphatic drainage of the prostate and prostate cancer is crucial to maximizing the benefits of PLND. Mattei et al. studied this in 34 patients with organ-confined prostate cancer, utilizing single-photon emission computed tomography (SPECT)/CT and SPECT/MRI after intraprostatic injection of technetium (Tc-99m) nanocolloid to map the lymphatic landing sites. The accuracy of this technique was validated by intraoperative use of a gamma probe and ultimately by a super extended PLND (sePLND). Thirty-eight percent of the lymph nodes were located in the region of the external iliac vein and obturator fossa. An additional 25% of the nodes were within the region medial and lateral to the internal iliac artery, indicating that 63% of the positive nodes were in the field of what many describe as an extended template PLND. The other lymphatic regions for the prostate include the common iliac (16%), paraaortic/paracaval (12%), and presacral (8%). Another study with a similar approach—intraprostatic injection of technetium (Tc-99m) nanocolloid followed by planar scintigraphy, SPECT/CT, and sePLND—investigated the sites of lymph node metastases for localized prostate cancer. This revealed the following distribution: internal iliac region (35%), external iliac region (26%), obturator region (25%), presacral region (9%), and common iliac region (3%). It is clear that the lymphatic drainage is quite variable and may be affected by tumor location within the prostate gland as well as malignant obstruction of the predicted channels of lymphatic flow. As a result, PLND, especially if more extensive, is beneficial for staging because it encompasses multiple channels and regions. This is supported by many studies, showing that more extensive PLND improves nodal yield and detection of nodal metastasis. ^,

One newer area of interest to minimize the morbidity of PLND is sentinel lymph node biopsy. The concept behind this approach is to identify the exact pathway of lymphatic drainage and remove the first echelon node as a means of staging the disease. Therein, an ePLND may possibly be avoided if the sentinel node does not harbor malignancy. The two most common tracers are indocyanine green, which is combined with intraoperative fluorescence, and technetium (Tc-99m) nanocolloid, which is detected with the intraoperative gamma probe. Both can be injected into the prostate to define the lymphatic channels. Some studies show promising results, with one review concluding that sentinel node biopsy (SNB) has considerable diagnostic ability with a negative predictive value of 98% and sensitivity of 95%. However, several other articles have demonstrated quite variable results, with sensitivity as low as 50%. Overall, there is currently not enough evidence to support SNB as the sole staging modality, though it may provide additional information when utilized simultaneously with ePLND.

Is pelvic lymph node dissection therapeutic?

An area of great controversy is the therapeutic utility of PLND. Theoretically, removing micrometastatic disease that has solely spread to the lymph nodes could improve cancer control by decreasing recurrence, metastasis, and even potentially mortality. At this time, however, there is a dearth of evidence to support this notion. The majority of articles on this topic are retrospective studies with inconsistent definitions of PLND and variable degrees of follow-up. This makes it challenging to draw any definitive conclusions about the oncological benefits of PLND, especially when the effects of recurrent and metastatic prostate cancer may take several years to manifest in measurable outcomes. Thus, longer follow-up of at least 10 to 15 years is needed to provide a more accurate assessment of any therapeutic potential with PLND.

Earlier studies had revealed a positive impact of PLND on biochemical recurrence (BCR), particularly in patients with low volume node-positive disease. Bader et al. showed this by performing an ePLND, including external iliac, internal iliac, and obturator regions, on patients with clinically organ-confined prostate cancer. At a median follow-up of 45 months, 39% of patients with only one positive lymph node remained free of BCR. BCR-free survival was only 14% in those with more than two positive nodes. A study by Allaf et al. also described the potential benefit of ePLND in low volume node-positive prostate cancer. For patients with less than 15% positive lymph nodes, there was a significant improvement between standard PLND (sPLND)—external iliac and obturator regions—and ePLND—which also included the hypogastric region—with respect to 5-year PSA progression-free survival. There was also a nonstatistically significant trend toward improved survival in all patients who underwent ePLND ( P = .07). A follow-up study of this same cohort of node-positive men followed for at least 10 years revealed improved metastasis-free survival with ePLND. Importantly, patients were excluded from the aforementioned studies if they received adjuvant treatment with radiation or hormone deprivation, allowing for measurement of the potential merits of surgery alone. An additional retrospective study also found that removal of a higher number of lymph nodes in pathologic node-positive patients is associated with improved 10-year cancer-specific survival.

More recent studies have failed to find an oncological benefit with PLND for prostate cancer. Fossati et al. tackled this question in a 2017 comprehensive review. First, 21 retrospective comparative studies were used to compare oncological outcomes with any form of PLND versus no PLND. There was no difference in BCR, metastasis-free survival, or cancer-specific or overall mortality in patients who underwent any form of PLND, although a significant number of these studies included limited PLND (lPLND) only (or the extent of PLND was unknown). The same authors evaluated eight articles comparing limited/sPLND and sePLND and found no significant differences in BCR.

Certainly, there is a need for randomized prospective data and a few studies have tried to address this. Lestingi et al. measured early oncological outcomes in 300 patients with intermediate- or high-risk clinically localized prostate cancer, randomized to lPLND (obturator nodes) or ePLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes). The BCR-free, metastasis free, and cancer specific survival was similar between the groups, though an exploratory subgroup analysis revealed a significant difference in BCR free survival for patients with grade group 3 to 5 prostate cancer undergoing ePLND. Another randomized prospective trial evaluated lPLND versus ePLND in 1440 patients with clinically localized prostate cancer and reported similar findings—there was no difference in BCR. A notable limitation in many of these studies is the short follow-up, which in the two aforementioned articles was 5 and 3 years, respectively.

The Will Rogers phenomenon should be factored into consideration in the interpretation of all of these studies. More extensive PLND for higher risk patients may transfer the more aggressive tumors with micrometastatic disease from a better prognostic group (N0) to a worse prognostic group (N1). Consequently, the prognostics and outcomes of both groups improve. For example, pN0 patients undergoing ePLND are more likely to truly have organ-confined prostate cancer. As a result, their oncological outcomes may appear better than pN0 patients who underwent no or only lPLND because some of those patients may, in fact, have had pN0 disease and had a truly worse prognosis. The difference in outcomes may not be related to the PLND, but rather to the improved diagnostics and accurate staging (stage migration) associated with removal of a high number of lymph nodes.

An important consideration is not just how the surgical removal of more nodes affects disease control, but also how the diagnosis of more advanced node-positive disease affects the utilization of additional therapies, as this could indirectly impact oncological outcomes. Selecting patients that would benefit from adjuvant hormone deprivation and/or radiation is dependent on accurate staging, and ePLND serves that purpose. Studies have examined this question—the benefit of adjuvant therapy in node-positive patients—and found an oncological benefit, particularly in patients with high-risk features. Touijer et al. retrospectively evaluated 1338 patients with lymph node metastases after prostatectomy and PLND who were managed with either observation, lifelong androgen deprivation therapy (ADT), or adjuvant ADT and radiotherapy (RT). Treatment with ADT and RT was associated with better overall survival (OS) and cancer-specific survival (CSS) than ADT alone or observation, and this difference was most pronounced in high-risk men. Because of the selection bias and the stratification of higher risk patients to the treatment arms, one might expect the opposite results, which provide even greater support for the use of adjuvant therapy. Another report found that adjuvant radiation in node-positive patients improves oncological outcomes more than salvage RT or observation, regardless of tumor characteristics. These findings were corroborated by a systematic review by Marra et al. Management of LNI can be tailored to the patient and tumor characteristics and the severity of the disease, and several strategies exist to improve oncological outcomes. In support of this, the EAU offers three management options for pN1 patients after prostatectomy and ePLND: observation, adjuvant ADT, or ADT and radiation.

Finally, any benefits of PLND must be weighed against the risks of the procedure itself. PLND is time-consuming and can add costs for both the patient and the facility. It is technically challenging and has the potential for intraoperative complications—vascular injury, nerve injury, and ureteral injury. There is also a significant risk of postoperative morbidity in the form of lymphocele or deep venous thrombosis (DVT). The likelihood of any of these complications during radical prostatectomy increases with the inclusion of a PLND in the procedure as well as the extent of PLND.

Anatomical extent of pelvic lymph node dissection

The extent of a PLND varies widely in the literature and among surgeons. A lPLND generally includes only the obturator nodes. A sPLND includes the obturator and external iliac nodes. An ePLND encompasses the obturator, external, and internal iliac nodes. And finally, a sePLND includes the ePLND template plus the common iliac and presacral nodes. The EUA defines an ePLND as the following: the nodes overlying the external iliac artery and vein, the nodes within the obturator fossa, and the nodes medial and lateral to the internal iliac artery. According to the NCCN, the boundaries of ePLND are the external iliac vein anteriorly, pelvic sidewall laterally, bladder wall medially, floor of the pelvis posteriorly, Cooper’s ligament distally, and internal iliac artery proximally.

(Refer to Table 16.1 for the anatomical landmarks/boundaries for each type of PLND. Figs. 16.1–16.8 demonstrate intraoperative images of the progression of steps in an ePLND. Please see Table 16.2 for key steps and Table 16.3 for special equipment required.)

Representative Image Illustrating the Initial Landmarks of an Extended Pelvic Lymph Node Dissection.

If not already visible, incision of the peritoneal lining allows identification of the ureter as a landmark for the iliac bifurcation and the cephalad boundary of this template. The obliterated umbilical artery is located and will be retracted medially. The external iliac vein can often be seen during this initial step, as it is here.

Intraoperative Photo Depicting the First Step of an Extended Pelvic Lymph Node Dissection.

The peritoneal incision is extended anteriorly to the abdominal wall and posteriorly to the ureter. The obliterated umbilical artery is traced to its origin at the internal iliac artery. The vas deferens is located and transected at this time.

Image Showing the Technique of Defining the Medial Plane of Dissection.

The next step is medialization of the bladder to locate the avascular plane between the lateral perivesical fat—the medial boundary—and the pelvic nodal packet. This plane extends from the internal iliac artery posteriorly to the pubic bone anteriorly and inferiorly to the pelvic floor. Medial retraction of the obliterated umbilical artery is critical. The obturator artery can often be seen as a branch of the internal iliac artery. The obturator vein and nerve may also be identified during this step. The dashed black line marks the medial plane of dissection.

Intraoperative Photo Demonstrating the Technique of Defining the Lateral Plane of Dissection.

The lateral plane is created by removing the tissue anterior and medial to the external iliac vein. The dashed black line marks the lateral plane of dissection. This plane is carried inferiorly and posteriorly toward the obturator nerve and vessels and the pelvic floor.

Representative Image Depicting an Approach to Identification of the Obturator Nerve and Vessels.

The lateral plane is carried inferiorly and posteriorly to release the lymphatic tissue over the external iliac vein. This will expose the lateral aspect of the pubic bone as well as the obturator nerve and vessels and the pelvic floor. The black lines outline the lymph node packet.

Clinical Photo Showing the Final Step of the Extended Pelvic Lymph Node Dissection.

At this point, the only remaining attachments for the lymph node packet are posterolaterally. The obturator nerve and vessels are isolated. The packet is retracted medially and anteriorly to complete the lymphadenectomy. The purple lines outline the lymph node packet.

Representative View of a Completed Right Extended Pelvic Lymph Node Dissection, Including All Critical Structures.

Technique of Dissection of the Retroiliac Space.

One optional addition to the extended pelvic lymph node dissection is dissection of the lymphatic tissue behind the iliac artery and vein, known as the retroiliac space or triangle of Marseilles. Medial retraction of the external iliac vessels will expose the space medial to the psoas muscle. This dissection should reveal the proximal aspect of the obturator nerve.

TABLE 16.2

Key Steps for Robotic Extended Pelvic Lymph Node Dissection

Step	Notes
1. Identify the ureter as a landmark for the iliac bifurcation and the cephalad boundary of this template.	May be more challenging in obese patients and may require lysis of adhesions between sigmoid colon and pelvic sidewall.
2. Incise the peritoneum lateral to the medial umbilical ligament (extending from abdominal wall superiorly to ureter and iliac bifurcation inferiorly).	The vas deferens can be ligated and divided during this step.
3. Define the medial plane of dissection.	Dissection along the perivesical fat, keeping the nodal packet lateral. The medial plane extends from the internal iliac artery posteriorly (at the takeoff of the obliterated umbilical artery) to the pubic bone anteriorly. The caudal boundary is the pelvic floor.
4. Separate the lymphatic tissue over the external iliac artery and vein.	Split-and-roll technique for removal of maximal lymphatic tissue posterior to the external iliac vessels along the pelvic sidewall. *It is vital to identify the proximal end of the obturator nerve and vessels during this step.
5. Dissect the distal extent of the nodal packet to the node of Cloquet.	Distal lymphatic channels are sealed with either bipolar electrocautery or clips. Note the circumflex branch of the external iliac vein coursing on the inner aspect of the pubic bone. Identification of the distal aspect of the obturator nerve during this step.
6. Carry the dissection inferiorly and posteriorly along the inner surface of the pubic bone.	Obturator nerve and vessels are identified during this step if not already seen.
7. Release the proximal attachments of the nodal packet along the internal iliac artery.	Control of the proximal lymphatics and small vessels with either bipolar electrocautery or clips.
8. Inspect the lymphadenectomy bed for adequate hemostasis.

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