Date Published: April 5, 2018
Author(s): Timothy A. Masterson, Clint Cary.
The surgical management of both early and advanced stage germ cell tumors of the testis remains a complex process of surgical decision making to maximize oncologic control while minimizing morbidity. Over the past 5 decades, the evolution of the surgical template for retroperitoneal lymphadenectomy (RPLND) has resulted in important modifications to achieve these goals. In this review, we will characterize the historical motivating factors that led to the modified template, outline patient and clinical factors in selecting these approaches in both early and advanced stage disease, and briefly discuss future horizons for their implementation.
Few topics generate more discussion and consideration than the extent and laterality of the surgical template when managing the retroperitoneum (RP) in germ cell tumor (GCT) patients. The implications of limiting the surgical template inappropriately leave patients at risk for RP relapses. Conversely, extending the template beyond necessary boundaries increases the risk of surgical complications and long-term side effects. Several modifications have been incorporated that allow for an optimization between functional and oncologic outcomes. Understanding the historical rationale for these alterations and the clinical scenarios in which implementation of a limited dissection can be safely integrated is imperative. For the purposes of this review, our goal is to highlight the motivating factors and clinical experience that led to changes in the surgical boundaries for retroperitoneal lymph node dissection (RPLND).
Prior to effective chemotherapy for metastatic GCT, wide surgical resection of retroperitoneal (RP) disease was necessary to provide patients their only chance for durable, cancer-free survival. Additionally, cross-sectional imaging was unavailable and staging of disease limited. Accordingly, the burden of disease in this era was great; therefore, suprahilar and bilateral retroperitoneal dissections were routinely performed. With the development of curative, platinum-based chemotherapy regimens  along with the introduction of cross-sectional imaging of the abdomen with computed tomography  and discovery of serum tumor markers (STM) , the management of testicular cancer patients shifted. Surgery was associated with significant morbidity, with the loss of ejaculatory function representing the most pressing issue for young men and their fertility, occurring in roughly 90% of patients undergoing bilateral template dissections. Surveillance protocols were implemented for patients without detectable metastatic disease (CSI) to avoid this morbidity, utilizing chemotherapy in those that relapsed or failed observation. Limitations of surveillance protocols included the inaccuracies of clinical staging in roughly 30% of patients  and the greater burden of surveillance imaging and salvage treatments at the time of relapse.
Several institutions have assessed oncologic and functional outcomes with modifications in the surgical template over time. While significant variability exists among groups as to the type of modifications made to the template, outcomes regarding RP relapse rate, and recovery of ejaculatory function are uniformly reported. In one of the earliest studies out of Italy, Pizzocaro et al. reported on 61 CSI patients, of which 10 experienced relapse in the absence of adjuvant therapy. None of these occurred in the RP and 87% reported preservation of antegrade ejaculation with template modification alone . Similar findings were seen in a cohort of 85 CSI patients from Brigham & Women’s Hospital in Boston, again with no RP recurrences identified and 94% recovering antegrade ejaculation . Donohue et al. from Indiana published their experience with unilateral template modifications, this time with ipsilateral nerve-sparing . In this series of 75 patients published in 1990, 73 of which were CSI and 2 patients had low-volume CSIIa disease. One RP recurrence was reported and later salvaged. When assessing survival outcomes across all studies, cancer specific and overall survival approaches 100%.
Early experience in using full bilateral templates following cisplatin-based chemotherapy was reported by Donohue et al. in 1982 . Given the uncertainties of frozen section pathologic evaluation in the postchemotherapy setting and bulky disease with what is now considered suboptimal chemotherapy, the authors supported the use of complete bilateral RPLND. Since that time, several centers have investigated the oncologic safety of modified unilateral templates in appropriately selected individuals in contemporary series. In 2007, Beck et al. evaluated 100 patients who underwent a modified dissection with a median follow-up of 31.9 months . Patient selection criteria were: nonseminomatous GCT’s with normal serum tumors markers after cisplatin-based chemotherapy and tumors limited to the primary landing zone both before and after chemotherapy. There were 4 recurrences during follow-up, all of which were outside the boundaries of a full bilateral template. This study was recently updated with 10-year follow-up data with an additional 3 patients demonstrating a recurrence . Again, no recurrences were within the bounds of a full bilateral template with the majority of recurrences being in the chest. An additional series of 102 patients from the Austrian group also evaluated the safety of template surgery in the postchemotherapy setting . The inclusion criteria in this series were normal serum tumor markers after first-line cisplatin-based chemotherapy with stage II disease. All patients underwent template surgery based on the location of the primary tumor. There was 1 recurrence in the RP within the boundary of a full bilateral template for a recurrence rate of 0.9% at a median follow-up of 8.5 years. The majority (73%) of these patients demonstrated a complete response to chemotherapy with residual masses <1 cm. Heidenreich et al. described the German experience in 98 patients who underwent a modified template RPLND . The inclusion criteria in this series were similar to the prior studies and also limited the residual mass to ≤5 cm in diameter. One patient developed a RP recurrence in this series for a 1% recurrence rate at 3 years of follow-up. These studies in combination demonstrate a risk of RP recurrence of 0.6% in approximately 300 patients. Historical comparisons for bilateral RPLND are associated with loss of seminal emission and ejaculation in the majority of patients. With the incorporation of unilateral templates, preservation of antegrade ejaculation was attributable to the exclusion of any dissection or disruption of the contralateral efferent, postganglionic sympathetic nerve fibers as they course to the hypogastric plexus. Donohue reported ejaculatory rates of 90% with modified, unilateral templates without any compromise in oncologic efficacy . Similar rates of preservation were reported from the Italian group among 61 CSI patients . In the only prospective trial assessing functional and oncologic outcomes among patients undergoing either a unilateral template compared to the standard bilateral template, the modified template was associated with a twofold improvement in ejaculatory rates without any greater risk of in field relapse . With further modifications to include ipsilateral nerve-sparing within the surgical template, rates of ejaculatory preservation were improved. Jewett et al. demonstrated feasibility in a series of 30 patients, with 18 of 20 patients in whom successful nerve-sparing was accomplished ultimately recovering function . The Indiana group published their experience combining unilateral template modifications with ipsilateral nerve-sparing in 1990. In this cohort of 75 early-staged patients, 100% were able to achieve successful antegrade ejaculation . In a more contemporary series of 135 men undergoing nerve-sparing primary RPLND at Indiana, 134 achieve normal function, and nearly 75% were able to conceive . The majority of the current data supports the oncologic safety of modified template surgery in strictly defined cohorts. Efforts to determine the safety in other patient populations such as poor-risk disease and late relapse offer areas of potential study. These studies would require meticulous design to ensure patient safety. For example, patients with a late relapse 10 years following their primary tumor with a small solitary recurrence in the ipsilateral landing zone could be reasonable to apply modified template principles. The assumption here would be that the disease has declared itself to the ipsilateral landing zone of the primary tumor and there has been a 10-year lag time to monitor the contralateral side with no recurrence. With more than 35 years of experience, several studies have confirmed the safety of modified templates for RPLND both in the primary and postchemotherapy setting. Benefits include limiting the morbidity of surgery, without compromising the therapeutic impact among appropriately selected patients. Expansion of its use within other patient populations warrants exploration but must be integrated in a thoughtful manner to ensure patient outcomes are not compromised. Source: http://doi.org/10.1155/2018/6783147