Retroperitoneal Lymph Node Dissection Treatment & Management

Clinical stage I disease

Recent National Comprehensive Cancer Network Guidelines recommend surveillance (in compliant patients only), nerve-sparing retroperitoneal lymph node dissection (RPLND), or chemotherapy (IB) for patients with stage I NSGCT.^[33] For those patients who choose RPLND over surveillance, ipsilateral modified nerve-sparing RPLND can be performed. If minimal retroperitoneal disease is discovered, the surgeon may choose to perform a full ipsilateral dissection, although nerve-sparing is still likely to be performed.

The development of advanced laparoscopic techniques has provided the opportunity to perform laparoscopic RPLND (L-RPLND), both template and nerve-sparing. However, debate persists regarding whether L-RPLND is merely a diagnostic staging procedure or yields cancer control comparable to that of open RPLND in the 30% of patients with pathologic stage II disease. The nodal count possible with L-RPLND and the adherence to the template format are persistent questions. Research is ongoing as to the appropriate threshold number of nodes removed for diagnostic and therapeutic efficacy.^[34]

A review of the literature identified 333 patients who underwent L-RPLND for stage I disease.^[35] Positive nodes were found in 22% of patients, 97% of whom received adjuvant chemotherapy. Only a 0.3% incidence of retroperitoneal recurrence occurred, again with the caveat that the vast majority of patients with pathologic stage II disease received chemotherapy.

Clinical stage II disease

Patients with low-volume stage II disease who undergo primary RPLND are also candidates for ipsilateral modified nerve-sparing RPLND. Candidates for primary RPLND include patients with normal tumor marker levels, adenopathy smaller than 2 cm in diameter within the primary landing zone, and the absence of multiple enlarged lymph nodes.^[36] However, in this case, if the clinical stage is underestimated and high-volume stage II disease is detected, the surgeon should perform a full ipsilateral dissection. Once again, the sympathetic nerves can be prospectively identified and preserved.

Many patients with clinical stage IIB disease who undergo initial chemotherapy have residual retroperitoneal masses and require salvage RPLND. Recently, both Janetschek et al^[37] and Kavoussi^[38] reported series of patients in whom L-RPLND in this setting was successful. A recent review of the literature identified 117 patients who underwent L-RPLND in the setting of clinical stage II disease or postchemotherapy.^[35] Viable NSGCT was found in 6.8%, with teratoma identified in 23%. Recurrence occurred in 5.1% of patients, with the location of recurrence not reported in most instances.

Clinical stage IIc/III disease

Patients with residual masses following chemotherapy for advanced disease usually require standard RPLND with full bilateral dissection from the crura of the diaphragm to below the aortic bifurcation. Proponents of this method argue that 7-32% of patients will have tumor or teratoma outside a modified template, with decreasing percentages associated with decreased prechemotherapy clinical staging.^[39] In initial experience, Rassweiller et al found a high open conversion rate with postchemotherapy L-RPLND.^[40]

Preoperative preparation for RPLND involves obtaining informed consent and arranging a mechanical bowel preparation. Type and crossmatch for possible blood transfusion, especially in preparation for complex RPLND. In patients exposed to chemotherapy, WBC and platelet counts should be within the reference range or stabilized prior to surgery. Preoperatively evaluate patients receiving bleomycin with pulmonary function testing. Preoperatively evaluate patients with comorbid disease presentations (eg, renal insufficiency, anemia, heart conditions, liver pathology) with the appropriate consultations and/or laboratory studies.

Patients who have received bleomycin as a component of chemotherapy should probably undergo pulmonary function testing to evaluate for restrictive pulmonary fibrosis. Low inspired oxygen levels were once recommended during surgery; however, the most predictive factors for pulmonary complications include transfusion and total intravenous fluids.^[41] Therefore, fluids must be limited to the greatest degree possible during and after surgery.

From the time of its inception, RPLND has undergone many modifications and enhancements. Today, the two most popular approaches are the transabdominal and thoracoabdominal techniques. A laparoscopic alternative to the open procedure has been reported, but is limited to a few centers in the United States and Europe with significant laparoscopic experience.

The thoracoabdominal approach offers good exposure to the upper retroperitoneum and exposes the renal hilum in the center of the operating field. This procedure is useful in patients with advanced disease, who may present with a large retroperitoneal mass. This approach also allows for a complete suprahilar dissection, as well as the opportunity to easily access the retrocrural lymph nodes. Another advantage of this approach for RPLND is that it can be performed completely extraperitoneally in patients with lower-stage disease. This decreases the risks of small-bowel obstruction and ileus.

The second most common approach to RPLND is the transabdominal incision. This modification allows for faster opening and closing time. Additionally, this approach allows for good exposure to the suprahilar region, at the expense of mobilization of the pancreas and spleen. Advantages of a midline transperitoneal approach include familiarity and comfort for the surgeon and tolerable morbidity for the patient.

Currently, at the authors' institution, L-RPLND is used for select patients with low-stage disease. The procedure mimics the open operation in order to obtain similar oncologic and functional outcomes. A 4-port, transperitoneal technique is used, similar to that for laparoscopic nephrectomy. The authors perform a modified template operation with prospective nerve-sparing, adhering to the boundaries for each side outlined below. Intraoperative frozen-section analysis of the lymphatic tissue is used to determine whether the dissection is carried out to extended boundaries or an open conversion is necessary.

Right-sided modified template primary retroperitoneal lymph node dissection

The limits of dissection for the modified template RPLND on the right side include the right ureter, the renal veins, the lateral edge of the aorta, the IMA, and the ipsilateral iliac artery, where the ureter crosses. Note that the interaortocaval and retrocaval tissue is completely removed.

Left-sided modified template primary retroperitoneal lymph node dissection

The limits of dissection for the modified template RPLND on the left side include the left ureter, left renal vein, left edge of vena cava, IMA, and ipsilateral iliac artery, where the ureter crosses. Again, the interaortocaval tissue is included with the retroaortic lymphatics.

Postchemotherapy retroperitoneal lymph node dissection

Postchemotherapy RPLND typically entails full bilateral dissection of retroperitoneal lymphatics. This procedure involves removal of lymphatic tissue between both ureters, spanning from the diaphragmatic crus to the bifurcation of the common iliac arteries. The rationale for this extended region of dissection is the greater likelihood of bilateral disease with greater tumor burden. However, some patients with smaller-volume, localized disease within the primary landing site may be candidates for less-extensive RPLND.

Provide routine postoperative care. Patients should receive an appropriate amount of intravenous fluid replacements for the first 24-48 hours because of third-spacing.

Postoperative ileus is minimized with the retroperitoneal approach, and most patients are discharged within 3-6 days. If ileus is encountered, institute nasogastric suction for several days until symptoms resolve.

The pulmonary function in patients undergoing postchemotherapy RPLND should be closely monitored since they may have received bleomycin. Minimizing inspired oxygen concentration and intravenous fluids limits the risk of respiratory distress.

All patients with testicular cancer, regardless of stage, require frequent follow-up care. Many different follow-up protocols exist, and they vary depending on the clinical and pathologic stage and whether the patient is on a surveillance, post-RPLND, or post-chemotherapy protocol.

Most protocols involve history taking, physical examination (including examination of the contralateral testis), assessment of serum tumor markers, chest radiography, and abdominal imaging. After RPLND, postoperative baseline CT scanning, along with chest radiography, examinations, and assessment of serum tumor markers, is recommended every 2-3 months for the first 2 years, every 4 months for the subsequent 2 years, every 6 months for the fifth year, and yearly thereafter.

Complications of retroperitoneal lymph node dissection (RPLND) vary widely and can include injuries to major vascular structures such as the aorta and vena cava; to solid organs including the liver, kidney, and pancreas; and to smaller tubular structures such as the ureters and cisterna chyli.

Most of these injuries can be managed with primary repair and conservative management, which may include placement of a nephrostomy tube or ureteral stent, prolonged drainage of lymphatic fluid, and modified low-fat diets.

The overall complication rates of primary RPLND and postchemotherapy RPLND vary but probably lie between 1% and 5% for major complications and around 15% for minor complications (eg, wound infection, urinary tract infection, ileus).

• Chylous ascites - 1-3%
• Renovascular injury - 1-3%
• Small-bowel obstruction - 1-3%
• Spinal cord ischemia - Less than 1%

The survival rate among patients with testicular cancer who undergo retroperitoneal lymph node dissection (RPLND) has improved significantly since the early 1980s. All stages are associated with a cure rate of at least 90%. Stages I, IIA, and IIB are associated with a 98-100% cure rate. Stages IIC and III have a response rate of approximately 90% with chemotherapy and RPLND, with an 86% durable response rate.

Investigators generally agree that the presence of mediastinal primary tumor and metastasis to visceral sites indicates a poor prognostic outcome. Significantly elevated levels of the tumor serum markers are thought to be a significant independent predictor of poor outcome.

Progress in the management of testicular cancer has resulted from a multimodal treatment strategy, yielding excellent oncologic outcomes in most men with the disease. Despite the advances in chemotherapy and the ability to assess risk in patients with low clinical stage, surgical therapy, involving removal of retroperitoneal lymph nodes, continues to play a crucial role in management algorithms for low-stage to advanced cases and for all histologic subtypes, including nonseminomatous germ cell tumors (NSGCTs) and seminoma.

The surgical techniques of retroperitoneal lymph node dissection (RPLND) have evolved. In patients with low-clinical-stage NSGCT, the preservation of ejaculatory function has minimized morbidity, while oncologic efficacy has been maintained through meticulous removal of all lymphatic tissue within the desired boundaries.

Currently, the inaccuracy of clinical staging and selection of appropriate therapy in patients with low-stage NSGCT is controversial. For example, testis-confined tumors (pathologic stage I) may be indistinguishable from occult microscopic stage II/III disease; approximately 30% of retroperitoneal disease cases are not categorized as such using initial imaging studies. Conversely, 70% of patients who undergo RPLND for clinical stage I disease are overtreated.

Presently, the most useful prognostic factors in risk stratification of low-clinical-stage NSGCT include the percentage of embryonal carcinoma and presence or absence of lymphatic/vascular invasion by tumor cells in the primary tumor. In the future, oncogene markers, tumor-suppressor gene markers,^[42] flow cytometry,^{[43, 44]} and advanced imaging modalities may play an important role in more accurately predicting true stage in patients with clinical stage I disease.^[45] The prediction of a response to chemotherapy based on the expression of multidrug resistance protein 1 (MDR1) efflux pump has recently showed a trend toward significance.^[46] Should L-RPLND prove to be as accurate and useful as the traditional open RPLND approach, the reduced morbidity of L-RPLND may shift more patients toward surgical intervention, away from either initial surveillance or chemotherapy. Nevertheless, L-RPLND remains technically challenging and requires further study and refinement.

Whether robotic-assistance facilitates more widespread implementation of the laparoscopic approach remains to be determined.

Although contemporary postchemotherapy RPLND has attained a higher success rate, it still is a relatively morbid procedure. The operation is best performed via an open incision and requires wide exposure of the retroperitoneal structures. Careful and extensive removal of lymph nodes is balanced against potential injury to major vascular structures and organs such as the kidneys and ureters. In the future, methods of differentiating fibrosis and scar from viable germ cell tumor and/or teratoma after chemotherapy may spare some patients RPLND.

Further improvements in the management of testicular cancer may result from better selection of patients with low-stage and high-stage disease for adjuvant therapy. RPLND remains an integral part of all treatment approaches and has a role in staging and cure in those with low-stage disease; in addition, it can be used effectively to treat teratoma and germ cell tumor in patients with advanced disease after systemic therapy.