Key points
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Through a better understanding of lymphatic dissemination in testicular germ cell tumors, modifications in the boundaries of dissection have improved the long-term morbidity of retroperitoneal lymphadenectomy (RPLND) without compromising oncologic outcomes.
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Through the use of modified unilateral templates and nerve-sparing techniques, preservation of antegrade ejaculation can be expected in nearly all patients undergoing primary RPLND.
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Nerve-sparing primary RPLND offers the most accurate way to identify micrometastatic disease that is present in 26% to 30% of early-stage nonseminoma patients, while proving therapeutic in 80% to 90% of men and avoiding any long-term morbidity.
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Similar success rates for ejaculatory preservation are possible after postchemotherapy RPLND when it is feasible to incorporate either or both of these techniques.
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Nerve-sparing postchemotherapy RPLND offers the potential to reduce the morbidity of necessary surgery in a patient population in which limited therapeutic options exist for residual disease after chemotherapy.
Introduction
During the past 40 years, there has been a dramatic improvement in survival rates for men diagnosed with testicular cancer. Most important among these improvements are the incorporation of cisplatin-based chemotherapy, better cross-sectional imaging and serologic markers for diagnosis and staging, and a better understanding of the nodal distribution with tailoring of surgical templates. With these improvements in survival, the focus has been directed at minimizing the morbidity of therapy in men who have anticipated life expectancies of 30 to 50 years beyond curative treatment. In the setting of advanced or metastatic disease, many of the associated toxicities and side effects of systemic chemotherapy and surgery are necessary and unavoidable. However, in early-stage disease, the associated efficacy and side-effect profiles of the 3 primary options of surgery, chemotherapy, and surveillance can be scrutinized and compared with each other.
Historically, surgical intervention served as the best opportunity for a durable cure in the absence of effective chemotherapy. At select centers, surgical templates involved bilateral dissections of retroperitoneal (RP) nodal tissues surrounding the aorta and vena cava, extending caudally to include the interiliac and cranially to the suprahilar regions. However, significant morbidity was reported. After several publications elucidating the regional spread of disease based on laterality of the primary lesion, a better understanding of the nodal distribution in low-stage and high-stage disease allowed for more thoughtful assessments of the surgical boundaries of dissection. Through this, downscaling of the template could be performed without jeopardizing the accuracy of staging or therapeutic efficacy in early-stage disease. Additionally, with the advent of more effective chemotherapy, interest in reducing surgical morbidity became more relevant. One of the major issues surrounding RP lymph node dissection (RPLND) at the time was loss of seminal emission and bladder neck closure resulting in anejaculation and secondary infertility. It was recognized that, through ipsilateral or contralateral preservation of postganglionic sympathetic lumbar nerves coursing through the RP, ejaculatory function could be preserved.
Initial strategies involved the exclusion of nodal dissections contralaterally. Eventually, prospective identification of ipsilateral (or bilateral) postganglionic nerves was introduced. This article describes the anatomic and physiologic basis for, indications and technical aspects of, and functional and oncologic outcomes reported after nerve-sparing RPLND in early and advanced stage testicular cancer. Discussions regarding the indications for surgery in lieu of chemotherapy or observations in early-stage nonseminoma are beyond the scope of this article.
Introduction
During the past 40 years, there has been a dramatic improvement in survival rates for men diagnosed with testicular cancer. Most important among these improvements are the incorporation of cisplatin-based chemotherapy, better cross-sectional imaging and serologic markers for diagnosis and staging, and a better understanding of the nodal distribution with tailoring of surgical templates. With these improvements in survival, the focus has been directed at minimizing the morbidity of therapy in men who have anticipated life expectancies of 30 to 50 years beyond curative treatment. In the setting of advanced or metastatic disease, many of the associated toxicities and side effects of systemic chemotherapy and surgery are necessary and unavoidable. However, in early-stage disease, the associated efficacy and side-effect profiles of the 3 primary options of surgery, chemotherapy, and surveillance can be scrutinized and compared with each other.
Historically, surgical intervention served as the best opportunity for a durable cure in the absence of effective chemotherapy. At select centers, surgical templates involved bilateral dissections of retroperitoneal (RP) nodal tissues surrounding the aorta and vena cava, extending caudally to include the interiliac and cranially to the suprahilar regions. However, significant morbidity was reported. After several publications elucidating the regional spread of disease based on laterality of the primary lesion, a better understanding of the nodal distribution in low-stage and high-stage disease allowed for more thoughtful assessments of the surgical boundaries of dissection. Through this, downscaling of the template could be performed without jeopardizing the accuracy of staging or therapeutic efficacy in early-stage disease. Additionally, with the advent of more effective chemotherapy, interest in reducing surgical morbidity became more relevant. One of the major issues surrounding RP lymph node dissection (RPLND) at the time was loss of seminal emission and bladder neck closure resulting in anejaculation and secondary infertility. It was recognized that, through ipsilateral or contralateral preservation of postganglionic sympathetic lumbar nerves coursing through the RP, ejaculatory function could be preserved.
Initial strategies involved the exclusion of nodal dissections contralaterally. Eventually, prospective identification of ipsilateral (or bilateral) postganglionic nerves was introduced. This article describes the anatomic and physiologic basis for, indications and technical aspects of, and functional and oncologic outcomes reported after nerve-sparing RPLND in early and advanced stage testicular cancer. Discussions regarding the indications for surgery in lieu of chemotherapy or observations in early-stage nonseminoma are beyond the scope of this article.
Anatomy and physiology of ejaculation
An improved understanding of the anatomy and physiology of ejaculation has allowed men to maintain normal antegrade ejaculation following nerve-sparing RPLND. The ability to obtain an erection is controlled through the parasympathetic pathway. This arises in S2 to S4 of the sacral spinal cord and sends preganglionic fibers in the pelvic nerves to the pelvic plexus. The pelvic plexus branches to form the cavernous nerves that innervate the penis. Stimulation of the pelvic plexus and cavernous nerves induces erections. The course of these nerve fibers is not at risk during an RPLND.
The process of ejaculation involves 3 main sequential events: (1) tightening of the bladder neck, (2) seminal emission, and (3) expulsion of semen by rhythmic contraction of the ischiocavernosus and bulbocavernosus muscles. This process involves both the sympathetic and somatic nervous pathways. The sympathetic pathway originates in the preganglionic fibers from thoracic (T) 10 to lumbar (L) 2 vertebrae, which synapses in the sympathetic chain of ganglia, then exits as postganglionic fibers from L1 to L4 and coalesces near the bifurcation of the aorta into the superior hypogastric plexus. The right and left sympathetic chains course on either side of the vertebral column ( Fig. 1 ). The right sympathetic chain lies posterior to the inferior vena cava (IVC; see Fig. 1 A), whereas the left chain lies posterior lateral to the abdominal aorta (see Fig. 1 B). Prospective identification and preservation of the postganglionic fibers exiting the sympathetic chain is the objective of the nerve-sparing RPLND. The L2 and L3 postganglionic fibers are usually fused and take a more anterior course along the aorta, whereas L1 usually originates near the renal hilum and, therefore, takes a more caudal and oblique course (see Fig. 1 C; Fig. 2 ). Intraoperative electrostimulation of the postganglionic sympathetic fibers results in intraoperative ejaculation. On electrostimulation of these nerve fibers, emission begins with bladder neck closure, contraction of the seminal vesicles, and emission of semen from the prostatic ejaculatory ducts into the prostatic urethra, which can be directly visualized with suprapubic ultrasound and urethroscopy. These efforts have consistently shown the L3 postganglionic fiber to be of most importance in preserving seminal emission. The pudendal nerve then sends impulses to the ischiocavernosus and bulbocavernosus muscles to produce rhythmic contractions for ejaculation of the seminal emission. The anatomy and physiology of the ejaculatory process was characterized during the 1980s. However, the importance of the sympathetic chain of ganglia and superior hypogastric plexus were recognized as early as the 1950s during sympathectomies for various medical conditions.
Patient selection for nerve-sparing techniques
Although there remains some debate regarding indications for and template of RPLND, there is little controversy regarding the importance of strict adherence to the tenets of this surgery. Although some surgeons may view the remarkable chemosensitivity of germ cell tumors as a safety net for challenging resections, this characteristic should not be a prime consideration once the decision has been made to proceed to RPLND. The strongest argument for primary RPLND in clinical stage I patients is that chemotherapy can be avoided in 90% of patients with pathologic stage I disease and 50% to 70% of patients with pathologic stage II disease. Postchemotherapy RPLND is performed because residual teratoma is not chemosensitive and residual viable malignancy is rarely cured with salvage chemotherapy alone. Thus, the rationale for resection is that chemotherapy can be avoided or is unlikely to deliver a durable cure. Finally, the surgeon must consider the substantial financial burden that assisted reproductive technologies can place on young couples that desire fertility after a non–nerve-sparing RPLND. This is particularly germane in the cases of primary RPLND, a surgery that is rarely absolutely indicated.
Principal to any surgical modification or restriction to the boundaries of dissection is ensuring that no compromise is made in oncologic outcomes. A feature unique among solid malignancies, testicular cancer remains curable in most patients with marker-negative, low-volume RP nodal involvement. Therefore, inappropriate deviations from strict surgical principles subject patients to the potential of an unnecessary risk of relapse. A recent report demonstrated that intact lumbar vessels, as well as presence of ipsilateral gonadal vessels at reoperative RPLND, are associated with infield recurrences. Similarly, a previous series reported retroaortic and/or retrocaval recurrence in approximately half of patients undergoing reoperative RPLND.
Although the optimal template that offers the greatest balance between oncologic control and minimization of morbidity in the setting of low-volume nodal metastasis remains controversial, the importance of sparing postganglionic sympathetic nerves for preservation of ejaculatory function is not. Depending on the philosophy of the operating surgeon, reduction of the surgical template in early-stage disease allows for nerve sparing through the exclusion of dissection around the contralateral postganglionic nerve fibers in early-stage patients. Given the ability of current imaging modalities to accurately stage disease preoperatively, the need for expansion of unilateral modified templates in clinical stage I and IIa patients are now uncommon. However, conversion of unilateral templates to bilateral dissections should be performed in the presence of any radiographic or palpable disease outside the primary landing zone. In appropriately selected patients, RP recurrences should be rare after either unilateral modified template or bilateral nerve-sparing RPLND if properly performed.
Preservation of ejaculatory function with unilateral modified templates in early series were approximately 75%. In more contemporary reports, these rates exceed 95%. Therefore, the decision to perform ipsilateral, prospective nerve sparing in the setting of a unilateral template is at the discretion of the operating surgeon and patient.
In centers where bilateral modified templates are performed routinely in all patients, nerve-sparing RPLND should be considered the standard of care for those individuals wishing to preserve ejaculatory function and/or fertility. In these cases, the incorporation of unilateral or bilateral nerve preservation is based on technical feasibility. Exclusions of ipsilateral or contralateral prospective nerve sparing would include any circumstance in which complete eradication of nodal disease would be compromised. Therefore, surgeon experience and intraoperative judgment are of the utmost importance to avoid RP recurrences.
In the postchemotherapy setting, similar arguments can be made with regard to the appropriate incorporation of unilateral, modified templates and/or nerve-sparing approaches in patients indicated for surgery. Patient selection is of the greatest importance, and safe utilization of these templates in the postchemotherapy setting is imperative. Patients may be considered for modified, unilateral templates in the postchemotherapy setting if they meet the following criteria:
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Well-defined lesions less than or equal to 5 cm confined to the primary landing zone of the primary tumor on both prechemotherapy and postchemotherapy imaging
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Normal postchemotherapy serum tumor markers
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International Germ Cell Cancer Collaborative Group classification of low or intermediate risk of disease.
The standard of care remains a full bilateral, infrahilar template dissection to remove all residual macroscopic disease after chemotherapy. Therefore, when a modified, unilateral-template postchemotherapy RPLND is considered, strict adherence to these criteria is required to avoid relapses.
Technique
Preoperative imaging should occur within 4 to 6 weeks of surgery. When reviewing images, the surgeon should note of the size and location of masses, vascular anatomy, and renal or ureteral anatomy. Serum tumor markers should be checked within 2 weeks of surgery. Blood products should be reserved at the discretion of the surgeon. The anesthesia provider should be made aware of prior receipt of bleomycin if applicable. With few exceptions, the template of dissection to be used should be decided preoperatively. The boundaries of the templates can be found in Fig. 3 .
Related posts:
Epidemiology and Diagnosis of Testis Cancer
Intratubular Germ Cell Neoplasia of the Testis, Bilateral Testicular Cancer, and Aberrant Histologies
Management of Low-Stage Testicular Seminoma
Chemotherapy for Good-Risk Nonseminomatous Germ Cell Tumors
Desperation Postchemotherapy Retroperitoneal Lymph Node Dissection for Metastatic Germ Cell Tumors
Late Relapse of Testicular Germ Cell Tumors
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