Evolution of retroperitoneal lymphadenectomy (RPLND) in the management of non-seminomatous testicular cancer (NSGCT)

Urologic Oncology: Seminars and Original Investigations 21 (2003) 129 –132

Review article

Evolution of retroperitoneal lymphadenectomy (RPLND) in the management of non-seminomatous testicular cancer (NSGCT) John P. Donohue, M.D.* Department of Urology, Indiana University Medical Center, 535 North Barnhill Drive, Ste. 420, Indianapolis, IN 46202, USA Received 9 December 2001; received in revised form 7 July 2002; accepted 7 July 2002

Abstract The metastatic lymphatic drainage of testis cancer to the retroperitoneum was noted clinically about a century ago. Beginning with extraperitoneal approaches, RPLND was attempted. The first cure after RPLND of node positive disease was in 1905 by Cuneo in Paris. Transperitoneal approaches failed due to infection until post World War II experience at Walter Reed Army Hospital. Thoracoabdominal approaches became popular several decades later. But Improved exposure and vascular management strategies led to increased usage of the transabdominal approach once again. The advent of platinum based combination chemotherapy has had a major impact on both the timing of and the technical requirements of RPLND. Owing to our early involvement in this area, we have accumulated the largest database available on this disease. Our experience with over 2500 RPLNDs in the last 3 decades is divided between low stage (I and II) and high stage (III, postchemotherapy) disease. The former has been “down-regulated” to modified templates and prospective nerve sparing techniques to preserve ejaculation. The latter has been “up-regulated” to include a spectrum of surgical needs including hepatic, vascular, gut and mediastinal resections. Despite these extended requirements, outcomes are good (⬎80% survival) postchemotherapy. The evolutionary change of RPLND reflects an optimal paradigm of surgical-medical oncologic interaction. © 2003 Elsevier Science Inc. All rights reserved. Keywords: History/evolution; Retroperitoneal lymphadenectomy (for testis cancer)

1. Introduction The relationship between the testis and the retroperitoneal space was apparently noted by several surgeons in the 1800s. Kocher, Potts and Von Bergman [1] are said to have attempted resection of retroperitoneal masses in young men with testis tumors, each unsuccessfully. The prevailing treatment for testicular tumors was orchidectomy alone. The concept of a high ligation of the inguinal cord as a rational, safer approach to orchidectomy for testis tumor was already understood [2]. Patient survival for “Teratoma Testis” with orchidectomy alone was 20% [1]. At the turn of the century, interest in the problem of * Corresponding author. Tel.: ⫹1-317-274-1777; fax: ⫹1-317-2740174. Note: No effort has been made to discuss the “pros and cons” of RPLND itself related to other options in each clinical stage of NSGCT, nor has there been any focus on technical details or “how to” in the various RPLND procedures. Rather, the focus of this brief discussion has been the evolving nature of the procedure as stimulated by changes in medicine and laboratory research in the past century.

retroperitoneal lymphatics, especially as related to men with testis tumors, greatly increased. Cadaveric laboratory dissections of retroperitoneal lymphatics, with special reference to testicular drainage, were published independently by Most [3], Cuneo [4], Jamison and Dobson [5]. Both Cuneo [4] and Chevassu [6] saw relevance of incorporating resection of retroperitoneal nodal masses as part of the treatment of testicular cancer, as did a colleague, Villar [7], all between 1900 –1910 [6,7]. An independent effort at a transabdominal RPLND by Roberts in Philadelphia failed owing to postoperative peritonitis [8].

2. Discussion 2.1. Early clinical reports of RPLND (extraperitoneal) Between 1905 and 1914, RPLND was done, by report, 41 times in France, 4 in England and once in Italy. Outcomes available at the time of Hinman’s review of these

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J.P. Donohue / Urologic Oncology: Seminars and Original Investigations 21 (2003) 129 –132

reports indicate that 14 of these cases were node positive and 7 were reported as survivors, suggesting the therapeutic potential of RPLND in pathologic stage II NSGCT [9]. A positive report from a case by Cuneo in Paris, August 1905, describes removal of four lymph nodes, one positive for testis “teratoma” (i.e. cancer), with the patient remaining cancer free long term. This may be the first successful outcome of RPLND for clinical stage II NSGCT. Hinman’s review also included 32 cases of testis cancer (NSGCT) treated by RPLND at Johns Hopkins University and outcomes were known in 24, pathology confirmed in 18 by Bloodgood. Of these 18, 9 had embryonal cell and 9 had teratocarcinoma. Of the following 24 cases, 20 were dead and 4 were alive. These four long-term survivors were node positive, 2 with embryonal cell and 2 with teratocarcinoma. Again, this sparked interest in RPLND as a procedure of value in managing pathologic Stage II NSGCT. Hinman went on to describe an extended lumbar incision for extraperitoneal RPLND [10], which became a practical standard approach until the mid 1900s. 2.2. Mid-century; post world war II A resurgence of interest in testicular cancer came about by way of military medicine. Young males in the armed forces who had testis cancer were referred to the Walter Reed Army Hospital, where for the first time, large numbers could be studied and treatments compared. Lewis [11], Patton [12] and Van Busksirk [13] reported what then were exceptionally large experiences with seminoma and non seminoma (NSGCT). While the majority with NSGCT had orchidectomy and radiotherapy (4000 rads), a smaller cohort was managed with orchidectomy and transabdominal RPLND. Interestingly, of 127 non seminomas treated with radiotherapy after orchidectomy, none survived if judged to have positive nodes clinically. But of 40 node positive non seminomas managed with RPLND after orchidectomy, 19/ 40 (47%) N ⫹ cases survived [12]. This report gave new impetus to RPLND as a more effective option in the management of clinical stages I and II NSGCT. Several other surgeons, working in conjunction with cancer centers, were able to gather considerable experience with transabdominal RPLND. Foremost among these were Stanbitz [14] and Whitmore [15], each of whom clearly demonstrated a therapeutic impact of RPLND alone with survival figures exceeding 60% for node positive cases. Thoracoabdominal approaches for RPLND were introduced owing to the success of esophageal surgeons in exposing the gastroesophageal and upper abdominal anatomy. Cooper et al. [16] were the first to apply this approach for RPLND for testicular cancer. Skinner [17] and Fraley [18] extended this approach with significant series of their own as did Richie [19]. Again, each demonstrated a major therapeutic impact with RPLND alone. Lymphography was to have an indirect effect on the practice of RPLND in the late 1960s. Cannulation of funic-

ular (spermatic cord) lymphatics and injection of lipiodol dye (lymphangiography or LAG) demonstrated rapid crossover (Rt.3 Lt. and Lt.3 Rt.) of dye in the paraaortic area. Still more interesting was the rapid ascent of dye into the suprarenal hilar and cysternal areas. Reports by Chiappa and Galli [20], Busch and Sayegh [21] and Wahlquist, et al. [22] raised the question for clinicians regarding the need for better accounting of nodes bilaterally and in the renal hilar and suprahilar areas in RPLND for clinical stage I and II NSGCT. Retrospective and prospective nodal distribution studies were undertaken in response to these provocative lymphography reports. Nodal distribution studies, as a clinical response to lymphography reports, provided a reassuring statistical basis for what would become modified templates of dissection for clinical stage I (NSGCT). Ray and Whitmore’s retrospective study of infrahilar paraaortic nodal disease [23] showed a predilection for unilaterality in the pattern of pathologic stage II NSGCT metastases, although paraaortic crossover did occur especially in multiple node positive disease. The Indiana study extended the analysis to include suprarenal hilar and complete bilateral dissection [24]. Again, the preponderance of early disease was localized to an ipsilateral zone of primary spread that was infrahilar. Suprarenal hilar involvement was occasionally present only in locally advanced stage II-B or II-C disease. This work was confirmed by Weissbach et al. [25], who provided the added insight that solitary (n-1) metastases invariably were unilateral and paraaortic, but not suprahilar. Therefore, this solidified opinion that modified templates of dissection were indeed appropriate for clinical low stage NSGCT. This promised to reduce both operative time and morbidity but also the postoperative complication of anejaculation so commonly seen with bilateral paraaortic dissections. Indeed, this complication was a major challenge to RPLND surgeons worldwide: could adequate RPLND be done with preservation of ejaculation postoperatively? Nerve sparing concepts were stimulated not only by RPLND distribution data and morbidity study, but also by the pioneering work of Walsh et al. [26,27], in the area of prostatectomy. Study of the venous anatomy of the prostate by Walsh and Donker [26] led to more accurate intraoperative definition of the neurovascular bundles posterolaterally permitting their preservation in the context of a total prostatectomy for cancer. This clinical breakthrough promoted the joining of functional preservation with ablative cancer surgery in a safe, reproducible manner [27]. Noteworthy, this step forward was based on sound, thorough anatomic study. In the area of the retroperitoneum, early leaders in the area of nerve sparing for preservation of ejaculation were Naraijan and Lange, Weissbach, Pizzocaro, Richie and Jewett and Collesseli [28,25,29,30,31,32]. The latter two [31,32], reported elegant prospective dissection of the postganglionic fibers of the paraaortic lumbar sympathetic nerves. The Indiana group did the same and reported a large

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clinical experience with adequate long-term follow-up to confirm its safety and efficacy [33,34]. Indeed, the one long-term morbidity of RPLND (anejaculation) had been virtually eliminated without compromise of survival or local recurrence. This permitted RPLND to hold a place in the management of low stage NSGCT despite the growing popularity of other alternatives (i.e. surveillance or primary chemotherapy), which the advent of effective chemotherapy allowed clinicians to consider as alternative management options. Post chemotherapy RPLND has become the ultimate evolutionary step in RPLND surgery. Successful platinum based combination chemotherapy truly revolutionized the management of all stages of testis cancer [35,36,37]. As noted earlier, successful rescue of advanced NSGCT (e.g. disseminated or distant relapse of low stage disease) gave the clinician several valid options in managing low stage disease at presentation, with the presumption of rescue at relapse using platinum based chemotherapy. More amazing and dramatic evidence of the profound impact of chemotherapy on the surgery of testis cancer has continued to accrue in the last two decades. Previously inoperable, very advanced cases were rendered operable thus opening an entirely new field of “Post Chemotherapy Surgery” for disseminated testicular cancer in partial remission. Such residual retroperitoneal, pelvic, mediastinal, hepatic or pulmonary masses often required extensive technical demands. In retrospect, the earlier studies on exposure techniques for extended RPLND with attendant vascular mobilization and control [38] now paid dividends when dissecting retroperitoneal masses that often involved the great vessels and extended into renal hilar and suprahilar areas. The full spectrum of these technical demands is impressive and has been duly reported [39,40,41,43], all of which confirm the full flowering of RPLND as an extensive, effective surgical procedure. To this date, RPLND and chemotherapy have evolved as an optimal paradigm of surgical and medical oncology interaction. 2.3. Futu␮re prospect RPLND, as an open procedure, has fully evolved, ranging today from nerve sparing modified templates for low stage disease to extensive, aggressive extirpation for high stage post chemotherapy residual disease—all of this in the last (20th) century. With improved instrumentation and optics, closed or semi-closed laparoscopic techniques are being actively investigated and may find a place in staging low stage NSGCT. Until laparoscopic RPLND can be demonstrated a “stand alone” procedure (without needing postoperative adjuvant chemotherapy in node positive cases), it will suffer in comparison to open RPLND, (which is a “stand alone” therapeutic procedure) on a cost/risk benefit basis. It is doubtful that a compelling case can be made for its routine use simply on the basis that laparoscopic RPLND is tech-

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nically feasible. It must be acknowledged that “cold cutting”, as we have known it for several centuries, is changing across the spectrum of all open surgical procedures. The application of different forms of thermal energy via extracorporeal sources, coupled with advances in real time imaging, holds great appeal for the future cancer surgeon. Our great vessels are efficient heat exchangers, with the potential to protect themselves from adjacent thermal insults. One can envision focused forms of high energy delivered to paraaortic nodal disease, well imaged and magnified in real time. Vectors can be “painted” across a paraaortic mass with uniform delivery of heat exceeding 60°C producing a necrotic effect without destroying adjacent structures. While this has been done to prostatic tissue using high energy focused ultrasound via transrectal probes [42], the extension of this technology to other structures, such as retroperitoneal masses, is merely conjectural at this point. It seems likely, closed and focused thermal energies will be explored as an alternative to classic open RPLND as we know it today. Having said this, however, the saying “We have come a long way, Baby” applies to RPLND over the past century! One trusts these gains will remain utilized and only very thoughtfully exchanged over time as newer, better techniques continue to evolve. References [1] Kober GM. Teratoma testis, 114 Cases. Am J Med Sci 1899;CX-VII: 535. [2] Stimson JC. A new operation for teratoma testis. Med Rec NY 1897;III:623. [3] Most. Uber die lymphgefa¨ sse und lymphdru¨ ssen des hodens. Arch. f. Anat. u. Entweckingsgesh: 1899;113. [4] Cuneo B. Note sur les lymphatiques du testicule. Bull. et Mem. Soc. Anat. de Paris, 1901;76:105. [5] Jamison JK, Dobson JF. The lymphatics of the testicle. Lancet, London 1910;493: Feb. 19. [6] Chevassu M. Deux cas d’epitheliome du testicule traite par castration et l’ablation des ganglions lumboaortique. Bull. et Mem. Soc. de Chir. Paris 1910;36:236. [7] Villar F. Methode rationelle pour practiquer la castration das cas de tumeurs du testicule. Ann. Soc. de med du Gard 1902;i:183. [8] Roberts D. Elective transperitoneal RPLND. Ann Surg 1901;36:539. [9] Hinman F. The operative treatment of tumors of the testicle. JAMA 1914;58:2009. [10] Hinman F. The radical operation for teratoma testis. SGO 1919;28: 495. [11] Lewis L. Management of testicular cancers at Walter Reed Army Hospital. J Urol 1948;59:763. [12] Patton JF, Hewitt CB, Mallis N. Diagnosis and treatment of tumors of the testis. JAMA 1959;116:2194. [13] Van Burskirk KE, Young JG. Retroperitoneal lymphadenectomy for testis cancer. Military Med. 1959;133:575. [14] Stanbitz WJ, Magoos I. Transabdominal retroperitoneal lymphadenectomy in the management of non seminomatous testicular cancer. J Urol 1973;100:350. [15] Whitmore WF. Retroperitoneal lymphadenectomy for testicular cancer. Contemp Surg 1975;6:17. [16] Cooper JF, Leadbetter WF, Chute R. The thoracoabdominal approach for retroperitoneal gland dissection: its application to testis tumors. Surg Gynecol Obstet 1950;90:486.

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