Retroperitoneal Lymph Node Dissection in Testicular Cancer

Surg Oncol Clin N Am 16 (2007) 199–220

Retroperitoneal Lymph Node Dissection in Testicular Cancer Niels-Erik B. Jacobsen, MD, FRCSC, Richard S. Foster, MD, FACS*, John P. Donohue, MD, FACS Department of Urology, Indiana University, Indiana Cancer Pavilion, 535 N Barnhill Drive, Suite 420, Indianapolis, IN 46202, USA

Testicular germ cell cancer is the most common solid tumor in men aged 20 to 35 [1]. With more than 8000 new cases expected in the United States this year, the incidence of testicular cancer appears to be rising. Following radical orchiectomy, management is dictated by the histopathology of the primary tumor and its clinical stage. Available treatment options include surveillance, radiotherapy, chemotherapy, and retroperitoneal lymph node dissection (RPLND), delivered alone or in combination. With long-term survival in excess of 90% across all stages, testicular cancer has come to represent the model for successful multidisciplinary cancer care. Although improvements in the accuracy of clinical staging and the efficacy of combination chemotherapy have altered its role, RPLND remains an integral component of contemporary testis cancer staging and management. This article reviews the evolution, technique, and role of RPLND in early- and advanced-stage testis cancer.

Diagnosis and staging A germ cell tumor (GCT) of the testicle presents most commonly as a painless testicular mass. Any palpable intratesticular mass should be considered malignant, and managed accordingly. Clinical evaluation, designed to assess for the presence of contralateral and metastatic disease, consists of history and physical examination, radiologic imaging, and serum tumor marker (STM) analysis. Although a palpable testicular mass is a reliable sign of malignancy, some advocate testicular ultrasound, citing a 1% to 5% * Corresponding author. E-mail address: [email protected] (R.S. Foster). 1055-3207/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.soc.2006.10.003 surgonc.theclinics.com

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incidence of bilateral disease synchronously or metachronously [2]. Alphafetoprotein (AFP) and beta-human chorionic gonadotropin (b-HCG) are very specific markers for GCT, and one or both are elevated in approximately 80% to 90% of newly diagnosed cases [3]. Radical orchiectomy with ligation of the spermatic cord at the level of the internal inguinal ring provides effective local control in most patients. Performed through an inguinal incision, radical orchiectomy minimizes local tumor recurrence and aberrant lymphatic spread, both of which can occur following violation of the scrotal lymphatics. The orchiectomy specimen provides important histologic information that serves to guide subsequent treatment. GCTs are classified into two major groups: seminoma and nonseminoma. Nonseminomatous germ cell tumors (NSGCT) include embryonal carcinoma, teratoma, choriocarcinoma, and yolk sac tumor. Although seminoma is the most commonly identified subtype overall, 35% to 54% of cases involve tumors of mixed histology [4]. The treatment of seminoma and NSGCT are different; mixed GCTs are treated as nonseminomas, regardless of whether or not seminoma is present in the primary tumor. Once the diagnosis of testis cancer has been confirmed pathologically, a thorough clinical evaluation for metastatic disease must take place. Postorchiectomy STM levels are expected to decline commensurate with their serum half-lives (AFP 5–7 days, b-HCG 24–36 hours). Patients in whom the STM levels remain elevated are considered to harbor systemic disease and are treated with primary chemotherapy. In addition to serologic evaluation, patients diagnosed with testis cancer require imaging of the retroperitoneum, lungs, and mediastinum, because these are the most common sites of metastatic disease, in descending order. CT of the chest, abdomen, and pelvis is the most efficient modality in this regard. Generally, the use of MRI is limited to cases in which contrast CT is contra-indicated or when the patency of the inferior vena cava (IVC) or renal vessels is in question. Imaging beyond the retroperitoneum and chest is dictated by symptomatology. The 2002 American Joint Committee on Cancer’s tumor node metastases staging system and its stage grouping system for testicular cancer are presented in Tables 1 and 2 [5].

Natural history Modern multidisciplinary treatment of testicular cancer provides a cure rate greater than 85% overall, and between 48% and 92% among advanced cases, depending on risk stratification [6]. Beyond the improvements made in diagnosis and treatment, some intrinsic features of GCT contribute to an excellent prognosis. First, GCT are typically sensitive to both radiation and chemotherapy. Second, the frequent production of specific STM improves the accuracy of clinical staging, which may determine the need for adjuvant systemic therapy. Furthermore, elevated STM often represent

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Table 1 American Joint Committee on Cancer tumor node metastases staging system, 2002 Primary tumor (T) Stage

Characteristics

pTx pT0 pTis pT1

Primary tumor cannot be assessed (no radical orchiectomy has been performed) No evidence of primary tumor Intratubular germ cell neoplasia Tumor limited to testis and epididymis without vascular or lymphatic invasion Tumor may invade tunica albuginea but not tunica vaginalis Tumor limited to testis and epididymis with vascular or lymphatic invasion Or, tumor extends through tunica albuginea involving tunica vaginalis Tumor involves spermatic cord  vascular or lymphatic invasion Tumor involves scrotum  vascular or lymphatic invasion

pT2 pT3 pT4

Regional lymph nodes (N) Pathologic stage

Clinical stage

Stage

Characteristics

Stage

Characteristics

pNx

Regional lymph nodes cannot be assessed No regional lymph node metastases Metastases with a lymph node mass %2 cm and less than or equal to 5 nodes positive, none O2 cm Metastases with a lymph node mass O2 cm but!5 cm; or more than 5 nodes positive, none O5 cm; or evidence of extranodal extension Metastases with a lymph node mass O5 cm

cNx

Regional lymph nodes cannot be assessed No regional lymph node metastases

pN0 pN1

pN2

pN3

cN0 cN1

Metastases with a lymph node mass %2 cm; or multiple lymph nodes, none O2 cm

cN2

Metastases with a lymph node mass O2 cm but !5 cm; or multiple lymph nodes, any one mass O2 cm but !5 cm

cN3

Metastases with a lymph node mass O5 cm

Distant metastases (M) Stage

Characteristics

Mx M0 M1 M1a M1b

Distant metastases cannot be assessed No distant metastases Distant metastases Nonregional lymph node metastases, or pulmonary metastases Distant metastases (other than nonregional lymph nodes or lungs)

Serum tumor markers (S) Stage

AFP (ng/mL)

b-HCG (mIU/mL)

LDH

Sx S0 S1 S2 S3

Not available Normal !1000 1000–10,000 O10,000

Not available Normal !5000 5000–50,000 O50,000

Not available Normal !1.5  Normal 1.5–10.0  Normal O10.0  Normal

Abbreviation: LDH, lactate dehydrogenase. Data from American Joint Committee on Cancer. AJCC cancer staging manual. 6th edition. New York: Springer; 2002.

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Table 2 American Joint Committee on Cancer stage grouping, 2002 Stage group

Primary tumor (T)

Regional lymph nodes (N)

Distant metastases (M)

Serum tumor markers (S)

IA IB IS IIA IIB IIC IIIA IIIB

pT1 pT2-4 T any T any T any T any T any T any T any T any T any T any

N0 N0 N0 N1 N2 N3 N any N1–3 N any N1–3 N any N any

M0 M0 M0 M0 M0 M0 M1a M0 M1a M0 M1a M1b

S0 S0 S1–3 S0–1 S0–1 S0–1 S0–1 S2 S2 S3 S3 S any

IIIC

Data from American Joint Committee on Cancer. AJCC cancer staging manual. 6th edition. New York: Springer; 2002.

the first sign of distant relapse, which facilitates the timely provision of chemotherapy. Third, the metastatic spread of testicular GCT follows a predictable and systematic course, to the retroperitoneal lymph nodes first, chest second, and beyond thereafter [7]. Finally, GCT most commonly afflicts young, otherwise healthy, adults who can tolerate intensive medical or surgical therapy.

Treatment overview Following orchiectomy, treatment recommendations are based on histology of the primary tumor and clinical stage. A complete discussion of testis cancer treatment is beyond the scope of this article; however, an overview is provided to place the role of RPLND in proper context. Available management options for clinical stage I (CS I) GCT patients who have normal postorchiectomy STM levels include active surveillance, two cycles of cisplatin-based chemotherapy, or localized therapy directed toward the retroperitoneum (para-aortic external beam radiotherapy [20 Gy] for seminoma and primary RPLND for NSGCT). Patients who have elevated STM and normal radiographic imaging (CS IS) are considered to harbor systemic disease, and require full-dose chemotherapy. The standard chemotherapy protocol consists of three cycles of bleomycin, etoposide, and cisplatin. Low-volume clinical stage II disease (!3 cm retroperitoneal lymph node mass) may be treated by either RPLND or chemotherapy, alone or in combination, whereas large volume retroperitoneal disease (CS IIC), distant metastases (CS III), or persistently elevated STM necessitate chemotherapy.

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Role of retroperitoneal lymph node dissection in early-stage testis cancer RPLND serves as an important diagnostic and therapeutic modality for early-stage testis cancer (CS I, IIA, IIB). Despite technologic improvements, 20% to 37% of CS I patients remain understaged by modern CT [8–11], demonstrated by a 25% to 30% incidence of retroperitoneal lymph node metastases and a 16% to 23% incidence of retroperitoneal relapse in CS I patients undergoing primary RPLND or active surveillance, respectively [12–17]. Conversely, 23% to 40% of patients who have CS IIA who undergo RPLND are found to have no evidence of retroperitoneal disease pathologically [12,18]. Although RPLND cannot detect the roughly 10% of CS I patients who eventually develop pulmonary or biochemical recurrence, it remains the most accurate method of staging the retroperitoneum available today [19]. To this end, RPLND directs appropriate stage-specific treatment and follow-up regimens. Patients who have proven lymph node metastases can be selected for adjuvant chemotherapy on a risk-adjusted basis, whereas those with negative lymph nodes are spared the potential long-term toxicity associated with primary chemotherapy and are subjected to less intensive follow-up than is otherwise required by active surveillance protocols. Surgical and surveillance series have shown that metastatic disease, when present, is often limited to the retroperitoneum in early-stage testis cancer [12,17,19]. In this context, bilateral infrarenal RPLND, the conventional surgical approach to CS I testis cancer in North America, provides definite therapeutic benefit. Most CS I patients (70%–75%) have negative retroperitoneal lymph nodes (pN0) identified through RPLND [12–14]. Ninety percent of these patients will never develop a recurrence after surgery, and retroperitoneal relapse is exceedingly rare [13,19]. Twenty-five to thirtyfive percent of CS I patients have retroperitoneal disease documented pathologically, of which roughly three quarters are low volume (pN1) and one quarter are higher volume (pN2, pN3) [12,19]. RPLND alone cures most (66%–92%) pN1 patients and 50% of patients who have lymph node metastases larger than 2 cm [18–21]. Patients who have clinical evidence of retroperitoneal disease (clinical stage II) and normal STM can also derive therapeutic benefit from primary RPLND. The relapse rate for CS II patients confirmed to be pathologic stage II (PS II) by RPLND is 35% without adjuvant chemotherapy [18], indicating that at least 65% of CS II patients are cured by RPLND alone. An option is to administer two courses of adjuvant chemotherapy to highvolume pathologic stage II patients (pN2, pN3). With such therapy, the risk of relapse is reduced from 50% to less than 2% [21,22]. Teratoma, present in 20% to 30% of patients who have PS II disease, is resistant to chemotherapy and requires surgical resection for definitive cure [12,14,23]. Although teratoma is histologically benign, it displays a propensity for progressive local growth and compression of adjacent structures. Furthermore, it may predispose toward late retroperitoneal recurrence

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and possible malignant transformation into somatic tumors such as sarcoma, adenocarcinoma, or primitive neuroectodermal tumor, all of which are poorly responsive to cisplatin-based chemotherapy [24–28]. For these reasons, RPLND is the mainstay of therapy for retroperitoneal teratoma. Follow-up is less intense after RPLND, in comparison to surveillance or primary chemotherapy for CS I patients. The incidence of retroperitoneal recurrence is so low (!2%) after a properly performed RPLND that postoperative CT imaging of the abdomen and pelvis is not required, apart from a baseline study [12,13,19]. Five to ten percent of PS I patients relapse after RPLND, usually in the lungs or serologically (elevated STM), indicating that hematogenous dissemination has preceded lymphatic spread. Ninety percent of recurrences take place within 1 year, and most are salvaged by chemotherapy or additional surgery [12,19]. Therefore, follow-up after RPLND is narrow in focus, and consists of physical examination, chest imaging, and STM analysis performed on a frequent basis for 2 years and annually thereafter. In contrast, prolonged follow-up, including frequent CT of the abdomen and pelvis, is mandatory for CS I patients undergoing active surveillance, because up to 25% will develop a retroperitoneal recurrence. Likewise, patients managed by primary chemotherapy require long-term follow-up because retroperitoneal relapse, although uncommon (!5%), tends to occur late (beyond 2 years) in this group [29–31]. Late relapse is often chemorefractory and has a poor prognosis. Available series document a low incidence of late relapse in CS I patients after RPLND (0.3% – 0.6%) [12,32]. In contrast to late relapse after RPLND, which typically occurs in the chest and is highly curable, late relapse after chemotherapy is most common in the retroperitoneum and carries a higher mortality rate [31,33,34]. In experienced hands, RPLND is associated with minimal morbidity and negligible mortality. Of 478 primary RPLNDs performed at Indiana University between 1982 and 1992, the overall complication rate was 10.6%, almost one half of which consisted of superficial wound infections [35]. Just over 2% of patients developed a suspected small bowel obstruction (2.3%), 0.4% developed a lymphocele, and 2.3% required reoperation for ventral hernia (n ¼ 1), chylous ascites (n ¼ 1), scrotal hematoma (n ¼ 1), and small bowel obstruction (n ¼ 8). No deaths or permanent disabilities were attributed to surgery. Review of a contemporary cohort of patients undergoing primary RPLND found that the mean operative time was 132 minutes, mean blood loss was 207 mL, nasogastric decompression was required in 2.7% of cases, mean time to oral intake was 1.0 days, and mean length of hospital stay was 2.8 days [36]. The most clinically relevant long-term morbidity associated with RPLND is anejaculation as a consequence of injury to postganglionic sympathetic nerves adjacent to the great vessels. However, with modifications in both surgical technique and template of dissection, antegrade ejaculation can be preserved in up to 98% of patients [35]. Data such as these reinforce the view that primary RPLND represents a treatment option for low-stage

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testis cancer, with minimal morbidity and no long-term adverse effects. In contrast, chemotherapy predisposes to a 2.6 fold increased risk of cardiovascular disease within 10 years and a 0.5% incidence of secondary leukemia [37,38]. Role of postchemotherapy retroperitoneal lymph node dissection The standard treatment for advanced GCT of the testis (clinical stage IIC and III) is cisplatin-based chemotherapy. Approximately 70% of patients who have advanced NSGCT will obtain a complete response with primary chemotherapy, as demonstrated by a normalization of STM and a complete radiographic resolution of metastatic disease [39,40]. Because the relapse rate in this setting is less than 5%, the policy at Indiana University is to observe these patients [41]. In contrast, those with a residual radiographic mass have been shown to harbor teratoma or viable cancer in approximately 42% to 56% and 9% to 13% of cases, respectively [40,42]. Teratoma requires prompt surgical resection, based on low chemo-sensitivity, disposition for progressive local growth, risk of malignant transformation, and risk of late relapse [43,44]. Persistent, viable GCT, by definition, reflects some element of intrinsic chemo-resistance and will progress if left untreated. At present, no clinical criteria are sufficiently accurate to differentiate the 45% of patients who have only necrosis from those with teratoma or cancer [42,45,46]. Therefore, all NSGCT patients who have a demonstrable retroperitoneal mass (O1 cm) and normal STM following chemotherapy should undergo postchemotherapy RPLND (PC-RPLND). Those in whom necrosis or teratoma is found have a low risk of relapse (necrosis !5%, teratoma 7%–14%) and do not require further therapy [47–50]. In contrast, the demonstration of persistent viable GCT portends a 48% to 100% risk of subsequent relapse [51,52]. Although not universal, most centers recommend two cycles of adjuvant cisplatin-based chemotherapy because this has been shown to improve long-term, disease-free survival to 70% [51,52]. Together, surgery and chemotherapy afford an overall long-term survival rate of 70% to 80% among advanced cases of NSGCT [6,53]. Persistently elevated STM after primary chemotherapy is indicative of viable cancer. As such, salvage chemotherapy, rather than surgery, is usually recommended in this circumstance. The management of seminoma patients who have a residual retroperitoneal mass postchemotherapy is controversial, and differs from NSGCT in two regards. First, viable tumor is found in 10% of cases and residual teratoma is rare. The remaining 90% of patients have necrosis only and derive no therapeutic benefit from surgery. Second, complete surgical resection in seminoma patients often is not possible because of a severe desmoplastic reaction that obliterates the normal planes of dissection. The morbidity of PC-RPLND is much higher in the setting of seminoma than in NSGCT [54]. In light of this low therapeutic index, most centers have adopted an

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observation policy in lieu of PC-RPLND for seminoma. Investigators at Memorial Sloan Kettering recommend surgery for residual masses larger than 3 cm, based on a 27% incidence of viable tumor, in comparison to a 3% incidence among smaller masses [55,56]. Recent studies have shown that 2-18fluoro-deoxy-D-glucose positron emission tomography (FDGPET) is more accurate than CT in the prediction of residual seminoma (sensitivity: FDG-PET 80% versus CT 70%; specificity: FDG-PET 100% versus CT 74%) [57]. As such, evaluation with FDG-PET is now considered standard in seminoma patients who have a residual mass postchemotherapy. PET-positive lesions are regarded as malignant and should be resected if technically feasible. In contrast, FDG-PET has no role in the evaluation of NSGCT patients following chemotherapy, because teratoma, present in nearly one half of residual NSGCT masses, is not detected by PET. The perioperative morbidity of PC-RPLND is higher (21%–35%) than that of primary RPLND (11%) [35,58,59]. Reasons for this include a larger volume of retroperitoneal disease; an inevitable desmoplastic reaction secondary to chemotherapy, albeit less severe in cases of NSGCT; and the adverse effects of chemotherapy on renal, hematologic, and pulmonary function. Bleomycin can cause a restrictive lung defect through alveolar edema and collagen deposition, which, in turn, has been associated with a 57% incidence of postoperative pulmonary complications [60,61]. Risk factors include high inspired oxygen concentrations and intravascular fluid overload, both of which should be avoided perioperatively [62,63]. Fortunately, severe pulmonary complications are now rare. Among a contemporary cohort undergoing PC-RPLND at Indiana University, the incidence of severe pulmonary complications was 0%, compared with 8% just 1 decade earlier [64], reflecting improvements made in surgical technique, anesthetic delivery, and postoperative medical care, in addition to a reduction in cumulative bleomycin dosing. Retrograde ejaculation is no longer an unavoidable consequence of PCRPLND. Select patients (about 20%), particularly those with low-volume residual disease, may be candidates for nerve-sparing RPLND without adversely affecting survival or predisposing to retroperitoneal relapse [65]. Antegrade ejaculation is preserved in up to 77% of patients undergoing nerve-sparing PC-RPLND. It must be remembered, however, that fertility issues should never take precedence over cancer control. Evidence of viable tumor warrants full bilateral RPLND with resection of nerves en bloc if preservation proves difficult. Evolution of surgical template RPLND has been well-established in the management of testis cancer for more than 50 years. Over time, considerable modifications in the technique and template of RPLND have taken place, with the intent of minimizing morbidity while maintaining staging accuracy and therapeutic benefit. The

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foundation for these changes comes from improvements made in clinical staging and the efficacy of chemotherapy, as well as in our improved understanding of lymphatic drainage patterns and the factors responsible for seminal emission and antegrade ejaculation. The extended bilateral suprarenal RPLND, performed through a midline transabdominal approach, was described as recently as 1977 [66]. This wide template of dissection encompasses all lymphatic tissue between the ureters, from the bifurcation of the common iliac arteries up to and including the suprarenal region and diaphragmatic crura. Although this procedure was historically quite morbid, the rationale for its use came from the inaccuracy of clinical staging and the suboptimal efficacy of chemotherapy available at the time. With improved radiologic technology and the advent of effective cisplatin-based chemotherapy, it became difficult to justify such radical surgery in many patients. The first modification was elimination of the suprarenal or suprahilar component. The basis for this came from surgical mapping studies, which demonstrated that suprahilar lymphatic metastases were distinctly uncommon in cases of low-stage NSGCT [67,68]. Rather, the primary landing zone for right-sided tumors is the infrarenal interaortocaval region, whereas that for the left is the lateral, infrarenal para-aortic region, both of which represent the sites of embryologic testicular origin [67–69]. Suprarenal lymphatic metastases, when present, are found most commonly in the retrocrural space; however, they are rare in the absence of bulky retroperitoneal disease (CS IIB, IIC) [70]. As subsequent series confirmed that bilateral infrarenal RPLND provided equivalent efficacy with shorter operative time and less perioperative morbidity, it became the standard surgical template for early-stage testis cancer [67,71]. Loss of antegrade ejaculation, the most consistent long-term complication of RPLND, is almost inevitable with full bilateral RPLND, and represents the impetus for the next template modification [72,73]. Previous surgical series had demonstrated that the predominance of retroperitoneal metastases in low-volume PS II disease is unilateral and confined to the infrarenal zone of primary spread [67–69]. Recognizing that the postganglionic sympathetic nerves critical to antegrade ejaculation join the hypogastric plexus in the para-aortic tissue just below the inferior mesenteric artery (IMA), it was proposed that contralateral dissection below the IMA be omitted [74–76]. Dubbed the modified unilateral RPLND, this template has since been shown to preserve ejaculation in up to 90% of patients, without compromising cure [71]. Although most centers now consider the modified unilateral template to be the standard surgical approach for early-stage testis cancer, intraoperative evidence of high-volume metastatic disease in the primary setting is an absolute indication for bilateral dissection. In the postchemotherapy setting, full bilateral RPLND remains the standard of care; however, the modified template is appropriate in select patients who have small residual radiographic masses. At Indiana University, a modified template PC-RPLND is performed on patients who have low-volume

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retroperitoneal disease (less than 3–5 cm), both pre- and postchemotherapy, confined to the primary landing zone of the affected testicle. Of 100 modified PC-RPLNDs performed at this center, three patients relapsed, all outside the limits of the full bilateral template, providing a 2-year progression-free survival of 95% [77]. Ten to forty percent of patients who undergo a modified template RPLND will develop retrograde ejaculation secondary to sympathetic denervation of the seminal vesicles, vas deferens, and bladder neck. The sympathetic nerves that mediate seminal emission and antegrade ejaculation arise from the T12 to L3 nerve roots of the spinal cord. Postganglionic fibers leave the paravertebral sympathetic chain, converge toward the midline forming the hypogastric plexus below the IMA, and travel thereafter to the pelvis. Donohue and Jewett [74,75] simultaneously developed a technique involving prospective identification and preservation of postganglionic sympathetic nerves as they travel behind the IVC and anterior to the aorta. Although the nerve-sparing procedure is used most often in the primary setting, it may be appropriate in select patients undergoing PC-RPLND for low-volume disease. With this technique, antegrade ejaculation is preserved in more than 95% of patients undergoing primary RPLND and up to 77% undergoing PC-RPLND [71]. Furthermore, nerve sparing has not been shown to increase the risk of in-field recurrence in either setting.

Technique of retroperitoneal lymph node dissection RPLND is not one standard procedure, but rather a composite of multiple techniques and templates, each with its own appropriate indications for use. Performance of RPLND requires a detailed knowledge of retroperitoneal and vascular anatomy, and a firm understanding of the natural history of testis cancer. Furthermore, the surgeon must be cognizant of anatomic variations and intraoperative findings that may direct necessary technical modifications. Full bilateral RPLND is presented first, after which the salient features of modified templates and nerve-sparing procedures are discussed. Preoperative preparation Imaging of the chest, abdomen, and pelvis, and STM analysis (postorchiectomy or postchemotherapy) should be performed within 1 month of RPLND in all patients. Those undergoing PC-RPLND also require an evaluation of hematologic and serum chemistries to ensure normalization of blood counts, electrolytes, and renal and hepatic function, postchemotherapy. In most cases, PC-RPLND is delayed for at least 4 to 6 weeks from the conclusion of chemotherapy to allow appropriate time for physical and hematologic recuperation. Preoperative pulmonary function testing was, at one time, performed routinely in patients who had had prior

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bleomycin exposure. In fact, bleomycin-related pulmonary toxicity is rare in good-risk patients who receive 3 cycles (9 weeks) of BEP. Current indications for pulmonary evaluation at Indiana University include prolonged administration of bleomycin (R10 weeks), age greater than 40 years, advanced disease, renal insufficiency, and signs or symptoms of pulmonary compromise. Approach Although RPLND was performed traditionally through an extraperitoneal thoracoabdominal approach, most centers, including the authors’, now prefer the midline transabdominal approach. Purported advantages to the thoracoabdominal approach include superior access to the upper abdomen and the ability to perform simultaneous resection of thoracic disease. Although this is indeed true, involvement of the suprahilar lymph nodes is distinctly uncommon in the absence of bulky infrarenal disease; therefore, this region is not routinely dissected. Furthermore, in the authors’ experience, the morbidity of a thoracoabdominal RPLND tends to be greater than that of a midline transabdominal RPLND, with respect to analgesic requirements and pulmonary complications. Although patients who have both thoracic and retroperitoneal disease amenable to surgery typically undergo staged procedures at the authors’ institution, simultaneous resection may also be appropriate. The thoracoabdominal approach may be used in cases of high-volume upper abdominal disease or retrocrural tumor; however, the midline approach is usually sufficient even in these circumstances. Technique RPLND is fundamentally a three-step procedure: 1. Delineation of the appropriate template of dissection 2. Complete mobilization of the IVC, aorta, renal vessels, and relevant neural structures 3. Resection of the lymphatics and tumor from the posterior body wall The borders of a full bilateral RPLND template include the crura of the diaphragm superiorly, the bifurcation of the common iliac arteries inferiorly, and the ureters laterally (Fig. 1). The ‘‘split and roll’’ technique, popularized by Donohue, facilitates vascular mobilization and resection of the regional nodal packets (left peri-aortic, interaortocaval, right paracaval, and interiliac). A midline abdominal incision is made from the xiphoid process to the mid-lower abdomen. The length of incision varies according to the site and volume of disease, and the individual body habitus. The falciform ligament is divided between silk ties, after which a complete laparotomy is performed to determine the appropriate surgical template. Cases in which a unilateral modified template is considered must be converted to a full bilateral RPLND if disease is detected outside the confines of the ipsilateral

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Fig. 1. Bilateral RPLND template.

primary landing zone. Full bilateral RPLND begins with an incision of the posterior peritoneum from the foramen of Winslow, distally around the cecum, extending cephalad to the ligament of Treitz. The inferior mesenteric vein is divided between silk ties at the superior extent of this incision. The right colon and small bowel are then reflected off the retroperitoneum and placed within a bowel bag on the patient’s chest. The right gonadal vein serves as an important anatomic landmark during mobilization of the root of the small bowel and should remain with the retroperitoneum. The duodenum and pancreas are mobilized superiorly, thereby exposing the left renal vein, which corresponds to the superior extent of dissection. A self-retaining retractor is then placed to facilitate retraction of the abdominal wall and gastrointestinal contents. Care must be taken to not compress the superior mesenteric artery during retraction. Also, the bowel should be inspected periodically to ensure that venous return is maintained. With the right side of the retroperitoneum exposed, the first split maneuver is performed over the left renal vein, using a right-angled clamp with cautery or Metzenbaum scissors. Prior to division, large lymphatic vessels crossing anterior to the renal vein should be controlled with silk ties or surgical clips. By rolling the lymphatic tissue off the renal vein, the anterior surface of the aorta is exposed. The lymphatic tissue overlying the aorta is then split at the 12 o’clock position, beginning just inferior to the left renal vein

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and terminating at the bifurcation of the common iliac arteries bilaterally. The IMA, which is identified during the course of this dissection, usually is divided between silk ties, allowing retraction of the left mesocolon and, in turn, exposure of the retroperitoneum on the left side. Although sacrifice of the IMA generally is well-tolerated in young, healthy adults, older patients with inadequate collateral blood supply from the marginal artery of Drummond may develop colonic ischemia. As such, the authors tend to preserve the IMA in patients older than 50, if possible. If this is not feasible, the viability of the left colon should be assessed at the completion of the procedure. Once the lymphatic tissue is split over the aorta and iliac arteries, it is rolled medially and laterally, thereby exposing the paired lumbar arteries. In most cases there exist three such vessels, bilaterally, which must be divided between silk ties. Small gonadal arteries, found exiting the lateral aspect of the aorta just below the crossing of the left renal vein, should also be ligated to avoid unnecessary bleeding. Superiorly, the left gonadal vein is divided at its origin. A lumbar vein, which commonly drains into the left renal vein, is likewise divided, facilitating identification and dissection of the left renal artery away from lymphatic tissue. The next split maneuver is performed over the IVC, beginning at the level of the renal veins and ending at the bifurcation of the common iliac veins. The right gonadal vein, which typically drains into the IVC but occasionally enters the right renal vein, is identified and divided. Similar to the aortic split, lymphatic tissue is rolled medially and laterally away from the IVC and iliac veins. Typically, three lumbar veins are found on the medial aspect of the IVC; however, the lateral lumbar veins are unpredictable. All lumbar veins are divided in a sequential manner as they are identified. Once completely mobilized, the IVC and left renal vein are retracted anteriorly to allow dissection of the right renal artery from lymphatic tissue in the interaortocaval region. The right crus of the diaphragm is visible posteriorly. With the great vessels now effectively subtracted from the lymphatic tissue, attention is turned to the ureters, which represent the lateral borders of dissection. The gonadal veins are divided and tagged as they cross anterior to the ureters. The ureters are then mobilized laterally, which facilitates dissection between the perinephric fat and the paracaval or para-aortic lymph node packets. At this point, the only remaining lymphatic attachments are those on the body wall posteriorly. Individually, the left periaortic, interaortocaval, right paracaval, and interiliac lymphatic tissue is harvested from the body wall using electrocautery. Large lymphatics draining into the cisterna chyli medial to the right crus of the diaphragm should be ligated with surgical clips. Lumbar arteries and veins must be controlled with clips, ties, or cautery as they enter the posterior body wall medial to the sympathetic chain. The gonadal vein ipsilateral to the primary tumor, along with adherent lymphatics, are mobilized toward the internal inguinal ring and resected en bloc with the stump of the spermatic cord. With the procedure now complete, the retroperitoneum is irrigated thoroughly and inspected to ensure

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adequate hemostasis has been achieved. The bowel is then removed from the bowel bag, inspected in its entirety, and returned to its normal anatomic position. The posterior retroperitoneum is reapproximated over top of the great vessels, using 3-0 chromic suture. Abdominal wall closure is then performed. Modified unilateral template retroperitoneal lymph node dissection The modified unilateral template differs from the full bilateral template in that contralateral dissection is avoided to prevent injury to the contralateral postganglionic sympathetic nerves as they coalesce inferior to the IMA. Modified template RPLND is appropriate in patients who have CS I, or low-volume CS II, testis cancer limited to the ipsilateral primary landing zone. The modified template may also be applied to selected PC-RPLND in patients who have low-volume retroperitoneal disease, both pre- and postchemotherapy, limited to the ipsilateral primary landing zone. In either setting, if intraoperative findings raise suspicion for disease outside this template, a full bilateral RPLND should be undertaken. Resection margins should never be compromised in an attempt to preserve antegrade ejaculation. The modified template of dissection, as illustrated in Figs. 2 and 3, encompasses the ipsilateral lymph node packet. On the right, this includes

Fig. 2. Right modified template.

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Fig. 3. Left modified template.

the paracaval and interaortocaval lymph nodes, whereas the left modified template includes the periaortic lymph nodes. Right modified RPLND begins with an incision in the posterior peritoneum from the cecum to the ligament of Treitz. The colon and small bowel need not be reflected onto the chest, but rather the root of the small bowel is mobilized off the retroperitoneum and retracted laterally and superiorly, providing adequate visualization of the right side of the retroperitoneum. The most straightforward approach to performing a left modified RPLND is to incise the posterior peritoneum along the left lateral white line of Toldt, and reflect the left colon medially off the retroperitoneum. Division of the splenocolic ligament permits further medial mobilization of the left mesocolon. The bowel is retracted medially and cephalad, such that the entire left retroperitoneum is exposed. Mobilization of the great vessels and resection of lymphatic tissue then proceeds in a manner identical to bilateral RPLND, but within the confines of the ipsilateral modified template. Nerve-sparing technique for retroperitoneal lymph node dissection Although generally reserved for patients who have CS I or low-volume CS II disease undergoing primary RPLND, nerve-sparing techniques may be used in carefully selected patients undergoing PC-RPLND, if technically feasible. Nerve sparing has no bearing on the type of exposure or template

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to be used, and may be performed during a modified or a bilateral RPLND. Only those technical points specific to right and left nerve sparing are discussed. Nerve-sparing procedures involve the prospective identification and preservation of the sympathetic chain or chains, postganglionic sympathetic nerve fibers, and hypogastric plexus. To do so requires an intimate knowledge of retroperitoneal neuroanatomy and common variations (Fig. 4). The sympathetic chains course parallel to the great vessels, and are found bilaterally within a groove bound by the psoas muscle and vertebral column. The right chain is located directly posterior to the IVC, whereas the left chain is found posterolateral to the aorta. Typically, three or four postganglionic nerves arising from the sympathetic ganglia of L1 to L4 can be identified. These efferent fibers may coalesce into larger trunks as they course obliquely to join the hypogastric plexus inferior to the IMA on the anterior aspect of the aortic bifurcation. Nerves on the right side emerge posterior to the medial wall of the IVC as they travel through the interaortocaval space toward the hypogastric plexus. Although a lymphatic split maneuver performed on the aorta can damage postganglionic fibers, a split performed on the IVC will not. Therefore, a right-sided, nerve-sparing RPLND begins with an anterior split performed along the midline of the IVC, from the left renal vein to the right common iliac vein. As tissue is rolled medially off the IVC, the nerve fibers are visualized as they cross superior to the medial lumbar veins. The nerves are then isolated with vessel loops and dissected free from lymphatic tissue, using sharp and blunt techniques. Division of the

Fig. 4. Retroperitoneal sympathetic nerves. SNS, sympathetic nervous system.

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lumbar veins between silk ties facilitates elevation of the IVC and, in turn, proximal dissection of the nerve trunks to the sympathetic chain in continuity. With the nerves placed on gentle rightward traction, the anterior lymphatic split is performed along the midline of the aorta, proceeding from the level of the left renal vein to the bifurcation of the right common iliac artery. Care must be taken not to damage the ipsilateral sympathetic nerves as they cross anterior to the aorta below the IMA. Similarly, dissection lateral to the origin of the IMA should be avoided, because this may damage contralateral nerves. The lymphatic tissue is then rolled medially off the aorta, thereby exposing the underlying medial lumbar arteries, which are divided between silk ties. The interaortocaval lymph nodes may be harvested in two packets anterior and posterior to the sympathetic nerves, or they may be split anteriorly over the nerve fibers and removed en bloc as one specimen. Resection of the paracaval lymph nodes then follows in the manner described for bilateral RPLND. It is important to avoid damaging the right sympathetic chain posterior to the IVC during this time. Left-sided, nerve-sparing RPLND begins with exposure of the lumbar sympathetic chain posterolateral to the aorta. The left colon is reflected medially and the ureter is reflected laterally. Usually, with elevation of the left mesocolon, the postganglionic nerves are visualized in the preaortic fibrofatty tissue. Often, identification of the nerves is facilitated through delicate blunt dissection anterolateral to the aorta, using a Kittner dissector. If not, the efferent fibers can be found at their origin from the left sympathetic chain and traced inferiorly. The nerves are isolated individually with vessel loops and dissected free from the periaortic lymphatic tissue as they course toward the hypogastric plexus. With the nerves placed on gentle lateral retraction, the anterior lymphatic split can then be performed along the midline of the aorta, from the left renal vein to the bifurcation of the left common iliac artery. Damage to the contralateral sympathetic fibers is avoided by not dissecting medial to the origin of the IMA. Next, the periaortic lymphatic tissue is rolled laterally off the aorta, thereby exposing the lumbar arteries, which are divided between silk ties. Finally, the periaortic lymph nodes are harvested off the posterior body wall, all the while protecting the left sympathetic chain and postganglionic fibers as they travel anterior to the aortic bifurcation. Postoperative care Contemporary management of primary or PC-RPLND patients is fairly simple. Small bowel ileus is uncommon (2%–3%); therefore, nasogastric decompression is seldom required, and oral intake is begun usually the morning of postoperative day one [35]. Intravenous hydration is continued for approximately 2 to 3 days, at which time most patients are able to tolerate a regular diet or maintain adequate hydration by mouth. Previously, intravenous fluids and supplemental oxygen were restricted after PC-RPLND

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because of the perceived risk of inducing severe pulmonary edema in patients who had had prior bleomycin exposure. With clinical experience and improved surgical technique, blood loss, operative time, and pulmonary reserve have been optimized such that the administration of intravenous fluids is no longer restricted postoperatively. However, morbid obesity, prior salvage chemotherapy, and extensive surgical dissection remain risk factors for postoperative pulmonary complications. In these patients, judicious fluid replacement and accurate monitoring of fluid status is appropriate. Intraperitoneal drains are not used routinely because the overall rate of postoperative chylous ascites is only 1.1% [78]. Risk factors for the development of chylous ascites include high volume of resection, suprahilar dissection, and vena cava resection. Typically, it is only in these situations that prophylactic intraperitoneal drainage is used. The drain may be removed safely when the output is less than 100 mL over a 24-hour period. Management options for chylous ascites, should it occur, include dietary modifications (low-fat diet, medium-chain triglycerides, total parenteral nutrition), somatostatin, long-term peritoneal drainage (4–6 weeks), peritoneovenous shunting, and reoperation [78]. Intermittent paracentesis, although diagnostic, is seldom curative and therefore not recommended. Summary RPLND is an integral component of contemporary testis cancer management across all stages. For patients who have early-stage disease, primary RPLND remains the most accurate method of staging the retroperitoneum, directing stage-specific treatment and follow-up strategies to a degree of specificity currently not possible with radiographic imaging. The retroperitoneum is effectively eliminated as a source of relapse among CS I patients following RPLND and, furthermore, these patients are spared the potential long-term toxicity of primary chemotherapy. Two thirds of CS II patients are cured by primary RPLND alone, and those who are not are rescued uniformly by chemotherapy. RPLND is also an important tool in the postchemotherapy setting for those patients who have advanced NSGCT who demonstrate a persistent radiographic abnormality within the retroperitoneum. Roughly 50% of such masses contain teratoma or cancer, both of which are resistant to chemotherapy to varying degrees. Without prompt surgical resection, teratoma and viable cancer predispose toward local growth, systemic relapse, and poor prognosis. At the present time, no clinical criteria are sufficiently accurate to predict the histology of residual masses; therefore, PC-RPLND is recommended for all residual postchemotherapy masses larger than 1 cm. Modifications in the technique and template of RPLND have greatly reduced its morbidity, without compromising cure. Nerve-sparing techniques preserve antegrade ejaculation in more than 95% of patients undergoing

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primary RPLND, and up to 77% of select patients undergoing PC-RPLND. The sole remaining long-term morbidity of primary RPLND is small bowel obstruction, at a rate of 2%. Although the overall complication rate of PC-RPLND is higher than that of primary RPLND, it remains low when performed at centers with expertise in testis cancer management. References [1] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56(2): 106–30. [2] Coogan CL, Foster RS, Simmons GR, et al. Bilateral testicular tumors: management and outcome in 21 patients. Cancer 1998;83(3):547–52. [3] Albers P, Albrecth W, Algaba F, et al. Guidelines on testicular cancer. Eur Urol 2005;48(6): 885–94. [4] Reuter VE. Anatomy and pathology of testis cancer. In: Vogelzang NJ, Scardino PT, Shipley WU, editors. Comprehensive textbook of genitourinary oncology. 3rd edition. Philadelphia: Lippincott Williams and Wilkins; 2006. p. 573–85. [5] American Joint Committee on Cancer: AJCC cancer staging manual. 6th edition. New York: Springer; 2002. [6] International Germ Cell Cancer Collaborative Group. International germ cell consensus classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 1997;15(2):594–603. [7] Whitmore WF Jr. Surgical treatment of clinical stage I nonseminomatous germ cell tumors of the testis. Cancer Treat Rep 1982;66(1):5–10. [8] Hilton S, Herr HW, Teitcher JB, et al. CT detection of retroperitoneal lymph node metastases in patients with clinical stage I testicular nonseminomatous germ cell cancer: assessment of size and distribution criteria. AJR Am J Roentgenol 1997;169(2):521–5. [9] Leibovitch L, Foster RS, Kopecky KK, et al. Improved accuracy of computerized tomography based clinical staging in low stage nonseminomatous germ cell cancer using size criteria of retroperitoneal lymph nodes. J Urol 1995;154(5):1759–63. [10] Carlsson-Farrelly E, Boquist L, Ljungberg B. Accuracy of clinical staging in non-seminomatous testicular cancer a single centre experience of retroperitoneal lymph node dissection. Scand J Urol Nephrol 1995;29(4):501–6. [11] Fernandez EB, Moul JW, Foley JP, et al. Retroperitoneal imaging with third and fourth generation computed axial tomography in clinical stage I nonseminomatous germ cell tumors. Urology 1994;44(4):548–52. [12] Stephenson AJ, Bosl GJ, Motzer RJ, et al. Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J Clin Oncol 2005;23(12):2781–8. [13] Albers P, Siener R, Kliesch S, et al. Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group Trial. J Clin Oncol 2003;21(8):1505–12. [14] Donohue JP, Thornhill JA, Foster RS, et al. Retroperitoneal lymphadenectomy for clinical stage A testis cancer (1965 to 1989): modifications of technique and impact on ejaculation. J Urol 1993;149(2):237–43. [15] Klepp O, Olsson AM, Henrikson H, et al. Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. J Clin Oncol 1990;8(3):509–18. [16] Sturgeon JF, Jewett MA, Alison RE, et al. Surveillance after orchidectomy for patients with clinical stage I nonseminomatous testis tumors. J Clin Oncol 1992;10(4):564–8. [17] Sogani PC, Perrotti M, Herr HW, et al. Clinical stage I testis cancer: long-term outcome of patients on surveillance. J Urol 1998;159(3):855–8.

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