Retroperitoneal Lymph Node Dissection
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Retroperitoneal lymph node dissection (RPLND) has a diagnostic and therapeutic role in many urologic malignancies. Testicular carcinoma is the most common urologic indication for RPLND, followed by renal cell carcinoma and upper urinary tract urothelial carcinoma.
In the setting of testicular tumors, RPLND may be used as a primary treatment modality for low-volume nonseminomatous germ cell tumors (NSGCTs) localized to the retroperitoneum. In addition, RPLND may be used as a salvage therapy for residual masses following chemotherapy in NSGCTs and in seminomatous tumors that are refractory to chemoradiotherapy.
RPLND was initially a component of all radical nephrectomy procedures, as outlined by Robson. [1] RPLND subsequently evolved mainly into a staging procedure, believed to confer limited therapeutic benefit in most circumstances. In 1999, a randomized trial conducted by the European Organisation for Research and Treatment of Cancer (EORTC) evaluated whether RPLND conferred a benefit in the management of renal cell cancer. The patients studied were randomized to undergo either radical nephrectomy alone or in conjunction with RPLND. Among the patients who underwent RPLND, only 3.3% were found to have positive lymph nodes, and the addition of RPLND did not change 5-year progression-free survival or overall survival rates. [2]
However, new adjuvant therapies, as well as laparoscopic RPLND (L-RPLND), have renewed interest in the topic. One study demonstrated a nodal yield of 12.1 toward the end of their series of 50 patients with clinically node-negative renal cell carcinoma undergoing laparoscopic nephrectomy and L-RPLND. [3] In another study, a very experienced laparoscopist found laparoscopic nephrectomy with hilar lymph node dissection to be feasible and safe in patients with clinically node-positive disease. [4]
Similarly, RPLND has not had a traditional role in the management of upper urinary tract urothelial carcinoma. A provocative retrospective report recently showed that RPLND conferred a significant survival advantage in univariate analysis, although, in multivariate analysis, the improved overall survival occurred without improvement in local recurrence or disease-specific survival rates, suggesting selection bias or unexplained confounding factors. [5]
This article focuses primarily on RPLND in the setting of testicular tumors. For additional information on testicular cancer, see Medscape’s Testicular Cancer Resource Center.
The famous English surgical oncologist Bland-Sutton is credited with performing the first RPLND in the early 1900s following radical orchiectomy for NSGCTs. Pioneering work by Jamieson, Dobson, and others over the next few decades led to detailed anatomic descriptions of testicular lymphatic drainage. [6, 7, 8] Hinman et al also described a series of RPLND procedures performed via a transabdominal approach. [9] In 1950, Cooper et al published his experience with thoracoabdominal RPLND, stating that this modification provided excellent exposure of the renal pedicle. [10]
During the 1960s, the advent of lymphangiography led to more complete mapping of lymphatic drainage patterns, including to suprahilar regions and crossover to the contralateral side. [11, 12] This finding led to the implementation of bilateral retroperitoneal dissection combined with suprahilar dissection. In the 1960s, this classic technique became the standard operative procedure for patients with low-stage NSGCTs. [13] The “split-and-roll” technique popularized by Donohue requires division of the lumbar arteries and veins to allow access to the lymphatic tissue dorsal to the great vessels. [14]
The major shortcoming of bilateral retroperitoneal dissection combined with suprahilar dissection was the high incidence of postoperative ejaculatory dysfunction, ie, anejaculation or failure of seminal emission. In the 1980s, Narayan et al detailed the sympathetic neuroanatomy involved in antegrade ejaculation. [15] These studies led to the conclusion that injury to the hypogastric plexus during RPLND was the most plausible etiology for ejaculatory dysfunction.
In 1990, Richie reported his experience with modified RPLND for clinical stage I NSGCTs. [16] He theorized that, because the primary landing site for regional metastasis was located well above the aortic bifurcation, his limit of distal dissection should be at the level of the inferior mesenteric artery (IMA). By operating only on the ipsilateral side and limiting his dissection cranial to the IMA, Richie discovered that he could preserve contralateral sympathetic pathways and maintain normal ejaculatory function without compromising the overall prognosis. Using this new modified template, he was able to preserve antegrade ejaculation in 95% of these men while keeping the relapse rate comparable to that associated with standard bilateral RPLND.
Around the same time, Donohue et al created a separate modification that included identification and preservation of the lumbar postganglionic sympathetic nerves. During the dissection, only the node-bearing tissue around the postganglionic sympathetic fibers was removed. This was known as nerve-sparing RPLND. Using this technique, Donohue reported that 98% of patients experienced antegrade ejaculation, with cure rates comparable to those who underwent classic RPLND. [17]
L-RPLND was introduced into the surgical armamentarium beginning with a case report in 1992 by Rukstalis and Chodak. [18] As with the open approach, numerous refinements have been made. In 2000, Janetschek et al reported on 76 patients with a nearly 4-year median follow-up who had undergone L-RPLND for clinical stage I disease. [19] Antegrade ejaculation was preserved in 99% of these patients. Retroperitoneal recurrence occurred in one patient, who was cured with 2 cycles of chemotherapy. Of note, in contrast to experience with the open approach, all patients who underwent L-RPLND with proven pathologic stage II disease routinely received adjuvant chemotherapy.
In 2002, Peschel et al described a laparoscopic nerve-sparing approach. [20] This may allow for the performance of therapeutic ipsilateral complete template dissections and for the avoidance of adjuvant chemotherapy in patients with low-volume stage II disease. Recently, a robotic-assisted laparoscopic approach has been described. [21] A few reports have described port-site spread of the cancer and extratemplate recurrences in patients with otherwise-favorable features, which have tempered some of the enthusiasm for minimally invasive testis cancer surgery. [22, 23]
In 2012, a midline extraperitoneal approach to postchemotherapy RPLND was described. This may limit the small risk of long-term bowel complications and achieve an earlier discharge and resumption of a normal diet. [24]
Retroperitoneal lymph node dissection (RPLND) is an important component in the management of low-stage nonseminomatous germ cell tumors (NSGCTs), as well as in patients with higher-stage disease who have residual retroperitoneal masses or enlarging retroperitoneal masses (termed growing teratoma syndrome) following chemotherapy.
The management options for patients with no clinical or radiographic evidence of residual tumor after orchiectomy include surveillance, RPLND, and adjuvant chemotherapy.
The argument for surveillance is that relapse occurs in only approximately 30% of all patients with cT1N0M0 disease during surveillance and that the survival rate after salvage therapy is between 96-100%. [25, 26] Thus, 70% of patients avoid an unnecessary abdominal operation. The 30% of patients in whom relapse occurs are exposed to 4 cycles of chemotherapy, and as many as 20% may still require RPLND to manage residual masses. Postchemotherapy RPLND is usually more extensive and more difficult and often cannot be performed in a prospective nerve-sparing fashion.
The argument for initial RPLND is that, of the 30% of patients who have true pathologic stage IIA disease, at least 65% will be cured with surgery alone. In addition, most patients in whom RPLND confirms pathologic stage I disease can be reassured that the risk of distant relapse is only 5%. Finally, following open RPLND, most patients return to basic activities within 2 weeks and full activity within 4-6 weeks, with long-term small-bowel obstruction occurring in less than 1% of patients. Thus, the potential morbidity caused by RPLND is well-defined and generally limited compared with the as-yet-undefined sequelae of adjuvant chemotherapy. The decreased morbidity afforded by L-RPLND must also be weighed into decisions made by the patient and clinician, although additional study and follow-up are needed.
Currently, clinicians can use risk stratification to assist patients with clinical stage I NSGCT select therapy. [27] High-risk patients include those with embryonal carcinoma involving over 40% of the orchiectomy specimen, T stage greater than T1, and any lymphatic or vascular invasion. [28] Using this strategy, patients with all low-risk features have a 5%-20% risk of harboring microscopic retroperitoneal metastasis, and patients with one or more high-risk features have a 40%-80% risk. [29]
Stage II disease is broken down into 3 groups based on the size of retroperitoneal nodes on imaging (IIA, < 2 cm; IIB, 2-5 cm; IIC, >5 cm). The general agreement is that patients with IIC disease have significant disease burden and a high likelihood of pre-existing microscopic pulmonary or visceral metastases and should therefore be treated with initial chemotherapy, similar to the management strategy for stage III disease. To complicate matters, clinical practice diverges even further from the staging system in that many authors recommend RPLND over chemotherapy based on a 3-cm nodal cut-off value.
Up to 25% of patients with clinical stage II disease have false-positive CT scan findings and have pathologic stage I disease. By undergoing RPLND, these patients avoid 4 cycles of chemotherapy. In addition, 65-80% of patients with pathologic stage IIA disease are cured with RPLND alone. [30] In the 20% who subsequently develop pulmonary metastases, 4 cycles of chemotherapy confers a cure rate approaching 100%. If RPLND reveals pathologic stage IIB disease, relapse occurs in 65% of patients, but 2 cycles of adjuvant chemotherapy decrease this relapse rate to 2%.
Alternatively, all patients with clinical stage II disease can be given 4 cycles of chemotherapy. [31] A complete response is seen in 40-70% of patients and major abdominal surgery is initially avoided. Unfortunately, 30-60% of these patients have residual retroperitoneal masses larger than 1 cm or have tumors that are reduced by less than 90%. In these patients, salvage RPLND is indicated, and complication rates are higher; in addition, nerve sparing is often impossible. Among patients with viable germ cell tumor at the time of RPLND, salvage chemotherapy regimens are often necessary.
Patients with stage III disease, as well as those with stage IIC and stage IIB with poor prognostic factors, undergo primary chemotherapy.
The role of adjunctive RPLND in these patients is controversial. Multiple series have shown that, on average, masses that persist after chemotherapy are composed of necrosis (40%), teratoma (40%), or viable germ cell tumor (20%). [30] However, up to 33% of patients with a normal CT scan findings may have viable germ cell tumor in the retroperitoneum. [32]
Among patients with no teratoma in the primary specimen, if the volume was reduced by 90% after chemotherapy, one study found no viable tumor or teratoma on RPLND. [33] In contrast, another study reported that, among 51 patients with teratoma on RPLND, only 28% of the primary specimen had teratoma. [34] Similarly, a third study found retroperitoneal teratoma in 16% of patients with clinical stage I/IIA disease with pure embryonal carcinoma. [35]
Despite the use of variables including tumor shrinkage, size of residual mass, teratoma in primary specimen, and pretreatment markers, the false-negative rate is still 20%. Thus, unless the CT scan shows no abnormalities or the primary tumor was 100% embryonal and no residual masses are larger than 2 cm, expert opinion is that patients should undergo salvage RPLND. [36] The goal of aggressive surgical management in these patients is to prevent growing teratoma syndrome, which is characterized by a residual mass that continues to grow in the absence of viable germ cell. Because only complete surgical resection can achieve a cure in such patients, early RPLND to prevent progression to inoperable disease is crucial.
Choriocarcinoma is the only testicular tumor that spreads hematogenously. With the exception of choriocarcinoma, testicular tumors generally spread via the lymphatics. Lymph nodes of the testis extend from T1 to L4 but are concentrated in the region of the renal hilum because of their common embryologic origin with the kidney.
Stepwise spread for right-sided testicular cancer is from the testis to interaortocaval, precaval, preaortic, paracaval, right common iliac, and right external iliac lymph nodes. The most common landing site for a right-sided testicular tumor is the interaortocaval lymph nodes.
The testicular lymphatics of the left testis drain stepwise from the testis to the nodes of the paraaortic, preaortic, left common iliac, left external iliac, interaortocaval, precaval, and finally, to the paracaval nodes. The primary landing site for the left testis is the para-aortic area at the level of the left renal hilum.
Stepwise systemic spread occurs from retroperitoneal nodes to the cisterna chyli, thoracic duct, supradiaphragmatic nodes, and finally, to extranodal/distant metastasis. These include (in decreasing frequency) lung, liver, brain, bone, kidney, adrenal, and gastrointestinal tract.
For more information about the relevant anatomy, see Testes and Epididymis Anatomy and Lymphatic System Anatomy.
Contraindications to primary retroperitoneal lymph node dissection (RPLND) include (1) abnormal levels of serum tumor markers after orchiectomy (see Lab Studies), (2) pure seminoma, (3) bulky retroperitoneal lymphadenopathy (ie, clinical stage >IIB), and (4) comorbid conditions that preclude general anesthesia (rare given the high incidence in young adults).
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Jared M Whitson, MD Urologic Oncologist, Department of Urology, Kaiser-Permanente South Sacramento Medical Center
Jared M Whitson, MD is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Medical Association, American Urological Association, Endourological Society, American Society of Clinical Oncology
Disclosure: Nothing to disclose.
Maxwell Meng, MD Associate Professor-in-Residence, Department of Urology, University of California, San Francisco, School of Medicine
Maxwell Meng, MD is a member of the following medical societies: American College of Surgeons, American Urological Association, Society of Urologic Oncology
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, Society of University Urologists
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Cook Medical; Olympus.
Jong M Choe, MD, FACS †, Former Assistant Professor, Department of Surgery, Division of Urology, University of Cincinnati College of Medicine, Former Director of Continence and Urodynamic Center, Mount Vernon Urological Associates, LLC
Disclosure: Nothing to disclose.
Rajesh Prasad, MD, Staff Physician, Department of Surgery, Division of Urology, University of Cincinnati Medical Center
Disclosure: Nothing to disclose.
Dan Theodorescu, MD, PhD Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center
Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology
Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership; KromaTiD, Inc Stock Options Board membership
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