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Laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular tumors
ADULT UROLOGY
LAPAROSCOPIC RETROPERITONEAL LYMPH NODE DISSECTION FOR CLINICAL STAGE I NONSEMINOMATOUS GERM CELL TESTICULAR TUMORS JOEL B. NELSON, ROLAND N. CHEN, JAY T. BISHOFF, WILLIAM K. OH, PHILIP W. KANTOFF, ROSS C. DONEHOWER, AND LOUIS R. KAVOUSSI
ABSTRACT Objectives. To assess retrospectively whether laparoscopic retroperitoneal lymph node dissection (RPLND) in patients with clinical Stage I nonseminomatous germ cell testicular tumor (NSGCT) provides useful pathologic staging information on which subsequent management can be based. Approximately 30% of patients with clinical Stage I NSGCT will have pathologic Stage II disease. Methods. A retrospective review of 29 patients with clinical Stage I NSGCT who underwent transperitoneal laparoscopic RPLND by a single surgeon was performed. Selection criteria included the presence of embryonal carcinoma in the primary tumor or vascular invasion. A modified left (n ⫽ 18) or right (n ⫽ 11) template was used. Results. Positive retroperitoneal nodes were detected in 12 (41%) of 29 patients. Ten of these patients received immediate adjuvant platinum-based chemotherapy, and 2 patients refused chemotherapy. The nodes were negative in 17 (59%) of 29 patients; all but 2 patients (one with recurrence in the chest, the other with biochemical recurrence) have undergone observation. No evidence of disease recurrence has been found in the retroperitoneum of any patient (follow-up range 1 to 65 months). Prospectively, the dissection was limited if grossly positive nodes were encountered; therefore, the total number of nodes removed was significantly different if the nodes were positive or negative (14 ⫾ 2 and 25 ⫾ 3, respectively; P ⬍0.004). Two patients required an open conversion because of hemorrhage. Complications included lymphocele (n ⫽ 1) and flank compartment syndrome (n ⫽ 1). Conclusions. Laparoscopic RPLND is a feasible, minimally invasive surgical alternative to observation or open RPLND for Stage I NSGCT. Disease outcomes are favorable to date. Longer follow-up in a larger series is necessary to determine therapeutic efficacy. UROLOGY 54: 1064–1067, 1999. © 1999, Elsevier Science Inc.
A
fter radical orchiectomy, men with Stage I nonseminomatous germ cell testicular tumor (NSGCT) have several acceptable treatment options to pursue: surveillance, primary chemotherapy, or open retroperitoneal lymph node dissection (RPLND). Thirty percent of those who undergo surveillance can be expected to develop evidence of metastatic disease; 70% of those who From the James Buchanan Brady Urological Institute and Division of Medical Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland and Lank Center for Genitourinary Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts Reprint requests: Louis R. Kavoussi, M.D., Brady Urological Institute, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224 Submitted: April 9, 1999, accepted (with revisions): June 1, 1999
1064
© 1999, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
receive primary chemotherapy or undergo open RPLND obtain no therapeutic benefit from the intervention.1,2 Parameters to identify patients at low risk of metastatic disease, such as using volume of embryonal carcinoma, lymph node diameters in the primary landing zones, and percentage of proliferating cells, have been proposed and studied retrospectively.3 Whether such models allow a more rational assignment of treatment options in a prospective fashion is yet to be determined. Pathologic staging in clinical Stage I NSGCT has two advantages: patients with metastatic disease can be identified and treated promptly, and those without metastatic disease can be offered modified surveillance. Laparoscopic RPLND has been developed primarily as a diagnostic technique to provide pathologic staging information for clinical Stage I 0090-4295/99/$20.00 PII S0090-4295(99)00289-7
TABLE I. Demographic data Median age (yr) Race White Asian African American Primary histology (% with positive nodes) Pure embryonal Mixed with embryonal Mixed Teratoma with embryonal Teratoma Vascular invasion Primary tumor side Left Right
28 (range 19–41) 26 2 1
14 11 2 1 1 11
(50%) (46%) (0) (0) (0) (64%)
18 11
NSGCT.4 Whether laparoscopic RPLND provides therapeutic benefit is currently unknown. This retrospective study was designed to evaluate the hypothesis that laparoscopic RPLND provides useful pathologic information in patients with clinical Stage I NSGCT with minimal morbidity. MATERIAL AND METHODS PATIENT POPULATION A retrospective review of 29 patients who underwent laparoscopic RPLND by a single surgeon (L.R.K.) between January 1992 and November 1998 was performed. Demographic data are given in Table I. Inclusion criteria for laparoscopic RPLND included the presence of embryonal carcinoma in the primary tumor or vascular invasion. Exclusion criteria for laparoscopic RPLND included elevated serum levels of alpha-fetoprotein or human chorionic gonadotropin after orchiectomy, any radiographic evidence of metastatic disease (retroperitoneal lymphadenopathy by computed tomography [CT] or pulmonary metastases by chest radiograph).
SURGICAL TECHNIQUE All patients underwent laparoscopic RPLND by a transperitoneal approach using a modified template, as previously described, with minor modifications.4 In brief, after induction with general anesthesia and nasogastric tube and Foley catheter placement, patients were placed in a modified flank position and taped securely to the operating room table. Insufflation was performed through a Veress needle. Three 10-mm laparoscopic ports were placed: at the umbilicus, in the midline halfway between the umbilicus and pubic symphysis, and in the midline halfway between the xiphoid and the umbilicus. If additional retraction was needed, a 5-mm trocar was placed at the ipsilateral anterior axillary line midway between the iliac crest and the ribs. The peritoneum was incised, and the colon was mobilized away from the ipsilateral abdominal wall, exposing the spermatic and great vessels. The stump of the spermatic cord was identified by finding the nonabsorbable suture left at orchiectomy. The stump was dissected free from the internal inguinal ring and widely mobilized to the renal vein on the left or the inferior vena cava on the right. The cord was then clipped, divided, and excised along with the surrounding tissues, and sent for pathologic examination as a UROLOGY 54 (6), 1999
separate specimen. For left-sided primary tumors, the paraaortic and pre-aortic tissue medial to the ureter was excised; for right-sided primary tumors, the paracaval and precaval tissue medial to the ureter was excised. In both cases, the inter-aortocaval tissue was then mobilized and excised. All tissues were placed in an organ entrapment sack before removal. Retroaortic and retrocaval tissue was not routinely removed. If grossly positive nodes were encountered, a complete template dissection was not performed.
STATISTICAL ANALYSIS
All data are given as mean ⫾ SEM. A two-tailed, unpaired t test was used when appropriate (Jandel SigmaPlot for Windows, version 3.02). Significance was defined as P ⬍0.05.
RESULTS Laparoscopic RPLND was completed successfully in 27 of the 29 patients (93% overall completion rate). For all procedures, the mean operative time was 258 ⫾ 10 minutes (range 157 to 380). The mean estimated blood loss was 389 ⫾ 114 mL (range 75 to 3000) for the entire group. After excluding the 2 patients who required an open conversion because of hemorrhage whose mean estimated blood loss was 3000 and 1775 mL, respectively, the mean estimated blood loss was 241 ⫾ 41 mL (range 75 to 1100). The mean hospital stay was 2.6 ⫾ 0.2 days (range 1 to 5). Postoperatively, the mean time to full activity was 17 ⫾ 2 days. The median follow-up for the entire group was 16 months. Of the 29 patients, 17 (59%) had negative nodes; 15 of these 17 patients are under observation, consisting of physical examination, chest radiograph, CT scanning of the retroperitoneum, and determination of alpha-fetoprotein and beta-human chorionic gonadotropin levels every 3 months for 2 years, every 6 months for years 3 through 5, and yearly thereafter. One patient, whose procedure was converted to an open RPLND and had undergone a standard modified template dissection, developed a chest recurrence 3 months postoperatively. He was treated with platinum-based chemotherapy, and surgical excision of residual lung nodules revealed mature teratoma. The other patient with negative nodes developed an elevated beta-human chorionic gonadotropin level 5 months postoperatively, but without radiographic evidence of disease recurrence by CT scan of the chest, abdomen, or pelvis. He also was treated with platinum-based chemotherapy. No other patient with negative nodes had evidence of disease at a median follow-up of 16 months (mean 22 ⫾ 4, range 1 to 57). The other 12 patients (41%) had positive lymph nodes; 10 of these patients received adjuvant platinum-based chemotherapy (bleomycin, etoposide, cis-platinum). Two patients with positive nodes refused chemotherapy: 1 patient, a professional mu1065
sician, was concerned about sensory loss and the ototoxicity associated with chemotherapy; the other did not want to risk losing function in a transplanted kidney. Neither patient had evidence of disease at 16 and 13 months postoperatively, respectively. None of the other 10 patients with positive nodes who received chemotherapy had evidence of disease at a median follow-up of 34 months (mean 39 ⫾ 5, range 19 to 65). For the entire group, a mean of 20 ⫾ 2 nodes were excised (range 7 to 53). Prospectively, laparoscopic RPLND was limited if grossly positive nodes were encountered; therefore, the mean number of nodes removed was significantly different if the nodes were positive or negative (14 ⫾ 2 and 25 ⫾ 3, respectively; P ⬍0.004). Two patients had hemorrhage requiring open conversion and completion of a standard RPLND. The first case was our initial attempt, and the hemorrhage was caused by avulsion of the gonadal vein. The second patient developed a tear in a lumbar vein that could not be controlled laparoscopically. In both cases, blood transfusion was required. No other patient received a blood transfusion. There were two postoperative complications. One patient developed a retroperitoneal lymphocele 1 week after surgery that was drained percutaneously. One muscular patient with low body fat underwent the procedure laying on a bean-bag. Within 24 hours, he developed a compartment syndrome in his latissimus dorsi, which was treated conservatively and resolved without neurologic sequelae. Because of this complication, we no longer use the bean-bag. Instead, we use a rolled towel to stabilize patients in the modified flank position (20° from horizontal). Normal ejaculatory function was present in 28 of 29 patients at last follow-up; 1 patient developed retrograde ejaculation postoperatively. COMMENT The results of this study support the hypothesis that laparoscopic RPLND in patients with clinical Stage I NSGCT provides useful pathologic information on which subsequent treatment alternatives can be based. The technique, although technically demanding, is feasible. The perioperative morbidity is limited, and recovery is prompt. Except for 1 patient who developed retrograde ejaculation, we did not encounter any long-term side effects. The average patient undergoing an open RPLND can expect a 5 to 7-day hospital stay, limited employment and activity for 2 weeks postoperatively, and a return to full activity within 6 weeks.5 In this series of laparoscopic RPLND, both the hospital stay and time to full recovery were 1066
significantly shorter. Although the importance of surveillance is emphasized to patients with negative nodes on laparoscopic RPLND, we have reduced the standard staging follow-up evaluations6 from six to four times per year, during the period when recurrence is most likely.7 The technical demands of laparoscopic RPLND can be substantial, with a steep learning curve.8 Comparing the first half of the series with the second half, the total blood loss and operative times were nearly identical: overall operative times have been less than those previously reported.4,8 Whether the top of the learning curve has been reached is unknown, but it is clear regular performance of complex laparoscopic procedures is a prerequisite to achieving good results. Retroaortic and retrocaval tissue was not routinely removed. It is technically feasible but adds at least 1 hour to the overall operative time. Others have found all positive nodes ventral to the lumbar vessels when the node tissue packets are taken separately.8,9 We have not been able to find a report documenting positive nodes in the retroaortic or retrocaval region as the only site of metastatic disease. Only time will tell whether patients undergoing surveillance will develop recurrences specifically in this region. Unlike an open RPLND, which has both diagnostic and therapeutic benefits,10,11 at present, our data only address laparoscopic RPLND as a diagnostic maneuver. Although to date no recurrence has occurred in the retroperitoneum for those undergoing surveillance, the follow-up time has been short, and the series was relatively small. Similarly, those with positive nodes (who received a more limited dissection) have not had recurrence in the retroperitoneum after chemotherapy. In another series of 29 patients who underwent a laparoscopic RPLND, 21 had negative lymph nodes. At a mean follow-up of 16 months, none of these patients had evidence of disease.8 Longer follow-up is necessary to determine the therapeutic role of laparoscopic RPLND. Unlike the reported low psychologic stress associated with surveillance,12 many patients are uncomfortable with observation— even in the presence of low risk features.11 Likewise, because of the current toxicity and effects on fertility, we do not recommend primary chemotherapy in the absence of metastatic disease. Laparoscopic RPLND provides useful pathologic staging information on which more rational treatment can be based. Historically, the use of a limited retroperitoneal sampling for Stage I NSGCT has been condemned,11 largely because of the risks of chemoresistant-retroperitoneal recurrences.13 In one large series, no patients had recurrence in the retroperitoneum after open RPLND,14 supporting a folUROLOGY 54 (6), 1999
low-up regimen in which abdominal CT scans can be eliminated. In a subset of patients who did have recurrence “in-field,” the tumor was chemoresistant.13 Whether this refractory phenotype is acquired or inherent is unknown. Furthermore, RPLND after chemotherapy or other retroperitoneal surgery is technically challenging.15 An extension of this line of reasoning had led some to advocate a complete bilateral node dissection, including suprahilar regions, for patients with palpable, suspicious lymph nodes or for patients with markerpositive low-stage retroperitoneal involvement.11 Our incorporation of laparoscopic RPLND in the management of Stage I NSGCT is based on a different view. Systemic chemotherapy is curative in most patients with metastatic NSCGT.16,17 Even in patients undergoing a complete open RPLND, the philosophy of the primary surgeon has been to recommend chemotherapy when metastatic disease is discovered.18 The goal of laparoscopic RPLND—to identify and treat with chemotherapy those with disease and to observe those without disease— has been performed with less morbidity than open RPLND. Although the follow-up in our study was short and the number of patients treated small, our results to date support a role for laparoscopic RPLND in the management of Stage I NSGCT. CONCLUSIONS For pathologic staging, laparoscopic RPLND is a feasible, minimally invasive alternative to open RPLND. It allows discrimination of those with pathologic Stage I disease from those with pathologic Stage II disease19 and more rational assignment to surveillance or systemic chemotherapy protocols.20 REFERENCES 1. Freedman LS, Parkinson MC, Jones WG, et al: Histopathology in the prediction of relapse of patients with stage I testicular teratoma treated by orchidectomy alone. Lancet 2: 294 –298, 1987. 2. Read G, Stenning SP, Cullen MH, et al, for the Medical Research Council Testicular Tumors Working Party: Medical Research Council prospective study of surveillance for stage I testicular teratoma. J Clin Oncol 10: 1762–1768, 1992. 3. Leibovitch I, Foster RS, Kopecky KK, et al: Identification of clinical stage A nonseminomatous testis cancer patients at extremely low risk of metastatic disease: a combined approach using quantitative immunohistochemical, histopathologic, and radiographic assessment. J Clin Oncol 16: 261–268, 1998.
UROLOGY 54 (6), 1999
4. Gerber GS, Bissada NK, Hulbert JC, et al: Laparoscopic retroperitoneal lymphadenectomy: multi-institutional analysis. J Urol 152: 1188 –1192, 1994. 5. Ritchie JP: Modified retroperitoneal lymph node dissection for patients with clinical stage 1 testicular cancer. Semin Urol 216: 222–232, 1986. 6. Sarosdy M: Testicular cancer: an overview, in Crawford ED, and Das S (Eds): Current Genitourinary Cancer Surgery. Philadelphia, Lea & Febiger, 1990, pp 306 –318. 7. Rorth M, and Daugaard G: Observation and expectant management for low-stage seminoma and nonseminoma, in Vogelzang NJ, Scardino PT, Shipley WU, et al (Eds): Comprehensive Textbook of Genitourinary Oncology. Baltimore, Williams & Wilkins, 1996, vol 1, pp 1016 –1021. 8. Janetschek G, Hobisch A, Ho¨lti L, et al: Retroperitoneal lymphadenectomy for clinical stage I nonseminomatous testicular tumors: laparoscopy versus open surgery and impact of learning curve. J Urol 156: 89 –94, 1996. 9. Ho¨lti L, Hobisch A, Knapp R, et al: Where are the primary landing sites for retroperitoneal metastases from testicular tumor? J Urol 157S: 303, 1997. 10. Donohue JP, Zachary JM, and Maynard BR: Distribution of nodal metastases in nonseminomatous testis cancer. J Urol 128: 315–320, 1982. 11. Steele GS, and Ritchie JP: Current role of retroperitoneal lymph node dissection in testicular cancer. Oncology 11: 717–729, 1997. 12. Fossa SD, Jacobsen AB, Aass N, et al: How safe is surveillance in patients with histologically low-risk non-seminomatous testicular cancer in a geographically extended country with limited computerized tomographic resources? Br J Cancer 70: 1156 –1160, 1994. 13. Baniel J, Foster RS, Einhorn LH, et al: Late relapse of clinical stage I testicular cancer. J Urol 154: 1370 –1372, 1995. 14. Donohue JP, Thornhill JA, Foster RS, et al: Primary retroperitoneal lymph node dissection in clinical stage A nonseminomatous germ cell testis cancer. Review of the Indiana University experience 1965–1989. Br J Urol 71: 326 –335, 1993. 15. Waters WB, and Lindgren BW: Resection of residual or metastatic disease, in Vogelzang NJ, Scardino PT, Shipley WU, et al (Eds): Comprehensive Textbook of Genitourinary Oncology. Baltimore, Williams & Wilkins, 1996, vol 1, pp 1002–1015. 16. Einhorn LH: Testicular cancer as a model for a curable neoplasm: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res 41: 3275–3280, 1981. 17. Einhorn LH, and Donohue JP: Advanced testicular cancer: update for urologists. J Urol 160: 1964 –1969, 1998. 18. Williams SD, Stablein DM, Einhorn LH, et al: Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med 317: 1433–1438, 1987. 19. Donohue JP: Laparoscopic retroperitoneal lymphadenectomy: multi-institutional analysis (editorial comment). J Urol 152: 1191–1192, 1994. 20. Richie JP: Laparoscopic retroperitoneal lymphadenectomy: multi-institutional analysis (editorial comment). J Urol 152: 1191, 1994.
1067
LAPAROSCOPIC RETROPERITONEAL LYMPH NODE DISSECTION FOR CLINICAL STAGE I NONSEMINOMATOUS GERM CELL TESTICULAR TUMORS JOEL B. NELSON, ROLAND N. CHEN, JAY T. BISHOFF, WILLIAM K. OH, PHILIP W. KANTOFF, ROSS C. DONEHOWER, AND LOUIS R. KAVOUSSI
ABSTRACT Objectives. To assess retrospectively whether laparoscopic retroperitoneal lymph node dissection (RPLND) in patients with clinical Stage I nonseminomatous germ cell testicular tumor (NSGCT) provides useful pathologic staging information on which subsequent management can be based. Approximately 30% of patients with clinical Stage I NSGCT will have pathologic Stage II disease. Methods. A retrospective review of 29 patients with clinical Stage I NSGCT who underwent transperitoneal laparoscopic RPLND by a single surgeon was performed. Selection criteria included the presence of embryonal carcinoma in the primary tumor or vascular invasion. A modified left (n ⫽ 18) or right (n ⫽ 11) template was used. Results. Positive retroperitoneal nodes were detected in 12 (41%) of 29 patients. Ten of these patients received immediate adjuvant platinum-based chemotherapy, and 2 patients refused chemotherapy. The nodes were negative in 17 (59%) of 29 patients; all but 2 patients (one with recurrence in the chest, the other with biochemical recurrence) have undergone observation. No evidence of disease recurrence has been found in the retroperitoneum of any patient (follow-up range 1 to 65 months). Prospectively, the dissection was limited if grossly positive nodes were encountered; therefore, the total number of nodes removed was significantly different if the nodes were positive or negative (14 ⫾ 2 and 25 ⫾ 3, respectively; P ⬍0.004). Two patients required an open conversion because of hemorrhage. Complications included lymphocele (n ⫽ 1) and flank compartment syndrome (n ⫽ 1). Conclusions. Laparoscopic RPLND is a feasible, minimally invasive surgical alternative to observation or open RPLND for Stage I NSGCT. Disease outcomes are favorable to date. Longer follow-up in a larger series is necessary to determine therapeutic efficacy. UROLOGY 54: 1064–1067, 1999. © 1999, Elsevier Science Inc.
A
fter radical orchiectomy, men with Stage I nonseminomatous germ cell testicular tumor (NSGCT) have several acceptable treatment options to pursue: surveillance, primary chemotherapy, or open retroperitoneal lymph node dissection (RPLND). Thirty percent of those who undergo surveillance can be expected to develop evidence of metastatic disease; 70% of those who From the James Buchanan Brady Urological Institute and Division of Medical Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland and Lank Center for Genitourinary Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts Reprint requests: Louis R. Kavoussi, M.D., Brady Urological Institute, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224 Submitted: April 9, 1999, accepted (with revisions): June 1, 1999
1064
© 1999, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
receive primary chemotherapy or undergo open RPLND obtain no therapeutic benefit from the intervention.1,2 Parameters to identify patients at low risk of metastatic disease, such as using volume of embryonal carcinoma, lymph node diameters in the primary landing zones, and percentage of proliferating cells, have been proposed and studied retrospectively.3 Whether such models allow a more rational assignment of treatment options in a prospective fashion is yet to be determined. Pathologic staging in clinical Stage I NSGCT has two advantages: patients with metastatic disease can be identified and treated promptly, and those without metastatic disease can be offered modified surveillance. Laparoscopic RPLND has been developed primarily as a diagnostic technique to provide pathologic staging information for clinical Stage I 0090-4295/99/$20.00 PII S0090-4295(99)00289-7
TABLE I. Demographic data Median age (yr) Race White Asian African American Primary histology (% with positive nodes) Pure embryonal Mixed with embryonal Mixed Teratoma with embryonal Teratoma Vascular invasion Primary tumor side Left Right
28 (range 19–41) 26 2 1
14 11 2 1 1 11
(50%) (46%) (0) (0) (0) (64%)
18 11
NSGCT.4 Whether laparoscopic RPLND provides therapeutic benefit is currently unknown. This retrospective study was designed to evaluate the hypothesis that laparoscopic RPLND provides useful pathologic information in patients with clinical Stage I NSGCT with minimal morbidity. MATERIAL AND METHODS PATIENT POPULATION A retrospective review of 29 patients who underwent laparoscopic RPLND by a single surgeon (L.R.K.) between January 1992 and November 1998 was performed. Demographic data are given in Table I. Inclusion criteria for laparoscopic RPLND included the presence of embryonal carcinoma in the primary tumor or vascular invasion. Exclusion criteria for laparoscopic RPLND included elevated serum levels of alpha-fetoprotein or human chorionic gonadotropin after orchiectomy, any radiographic evidence of metastatic disease (retroperitoneal lymphadenopathy by computed tomography [CT] or pulmonary metastases by chest radiograph).
SURGICAL TECHNIQUE All patients underwent laparoscopic RPLND by a transperitoneal approach using a modified template, as previously described, with minor modifications.4 In brief, after induction with general anesthesia and nasogastric tube and Foley catheter placement, patients were placed in a modified flank position and taped securely to the operating room table. Insufflation was performed through a Veress needle. Three 10-mm laparoscopic ports were placed: at the umbilicus, in the midline halfway between the umbilicus and pubic symphysis, and in the midline halfway between the xiphoid and the umbilicus. If additional retraction was needed, a 5-mm trocar was placed at the ipsilateral anterior axillary line midway between the iliac crest and the ribs. The peritoneum was incised, and the colon was mobilized away from the ipsilateral abdominal wall, exposing the spermatic and great vessels. The stump of the spermatic cord was identified by finding the nonabsorbable suture left at orchiectomy. The stump was dissected free from the internal inguinal ring and widely mobilized to the renal vein on the left or the inferior vena cava on the right. The cord was then clipped, divided, and excised along with the surrounding tissues, and sent for pathologic examination as a UROLOGY 54 (6), 1999
separate specimen. For left-sided primary tumors, the paraaortic and pre-aortic tissue medial to the ureter was excised; for right-sided primary tumors, the paracaval and precaval tissue medial to the ureter was excised. In both cases, the inter-aortocaval tissue was then mobilized and excised. All tissues were placed in an organ entrapment sack before removal. Retroaortic and retrocaval tissue was not routinely removed. If grossly positive nodes were encountered, a complete template dissection was not performed.
STATISTICAL ANALYSIS
All data are given as mean ⫾ SEM. A two-tailed, unpaired t test was used when appropriate (Jandel SigmaPlot for Windows, version 3.02). Significance was defined as P ⬍0.05.
RESULTS Laparoscopic RPLND was completed successfully in 27 of the 29 patients (93% overall completion rate). For all procedures, the mean operative time was 258 ⫾ 10 minutes (range 157 to 380). The mean estimated blood loss was 389 ⫾ 114 mL (range 75 to 3000) for the entire group. After excluding the 2 patients who required an open conversion because of hemorrhage whose mean estimated blood loss was 3000 and 1775 mL, respectively, the mean estimated blood loss was 241 ⫾ 41 mL (range 75 to 1100). The mean hospital stay was 2.6 ⫾ 0.2 days (range 1 to 5). Postoperatively, the mean time to full activity was 17 ⫾ 2 days. The median follow-up for the entire group was 16 months. Of the 29 patients, 17 (59%) had negative nodes; 15 of these 17 patients are under observation, consisting of physical examination, chest radiograph, CT scanning of the retroperitoneum, and determination of alpha-fetoprotein and beta-human chorionic gonadotropin levels every 3 months for 2 years, every 6 months for years 3 through 5, and yearly thereafter. One patient, whose procedure was converted to an open RPLND and had undergone a standard modified template dissection, developed a chest recurrence 3 months postoperatively. He was treated with platinum-based chemotherapy, and surgical excision of residual lung nodules revealed mature teratoma. The other patient with negative nodes developed an elevated beta-human chorionic gonadotropin level 5 months postoperatively, but without radiographic evidence of disease recurrence by CT scan of the chest, abdomen, or pelvis. He also was treated with platinum-based chemotherapy. No other patient with negative nodes had evidence of disease at a median follow-up of 16 months (mean 22 ⫾ 4, range 1 to 57). The other 12 patients (41%) had positive lymph nodes; 10 of these patients received adjuvant platinum-based chemotherapy (bleomycin, etoposide, cis-platinum). Two patients with positive nodes refused chemotherapy: 1 patient, a professional mu1065
sician, was concerned about sensory loss and the ototoxicity associated with chemotherapy; the other did not want to risk losing function in a transplanted kidney. Neither patient had evidence of disease at 16 and 13 months postoperatively, respectively. None of the other 10 patients with positive nodes who received chemotherapy had evidence of disease at a median follow-up of 34 months (mean 39 ⫾ 5, range 19 to 65). For the entire group, a mean of 20 ⫾ 2 nodes were excised (range 7 to 53). Prospectively, laparoscopic RPLND was limited if grossly positive nodes were encountered; therefore, the mean number of nodes removed was significantly different if the nodes were positive or negative (14 ⫾ 2 and 25 ⫾ 3, respectively; P ⬍0.004). Two patients had hemorrhage requiring open conversion and completion of a standard RPLND. The first case was our initial attempt, and the hemorrhage was caused by avulsion of the gonadal vein. The second patient developed a tear in a lumbar vein that could not be controlled laparoscopically. In both cases, blood transfusion was required. No other patient received a blood transfusion. There were two postoperative complications. One patient developed a retroperitoneal lymphocele 1 week after surgery that was drained percutaneously. One muscular patient with low body fat underwent the procedure laying on a bean-bag. Within 24 hours, he developed a compartment syndrome in his latissimus dorsi, which was treated conservatively and resolved without neurologic sequelae. Because of this complication, we no longer use the bean-bag. Instead, we use a rolled towel to stabilize patients in the modified flank position (20° from horizontal). Normal ejaculatory function was present in 28 of 29 patients at last follow-up; 1 patient developed retrograde ejaculation postoperatively. COMMENT The results of this study support the hypothesis that laparoscopic RPLND in patients with clinical Stage I NSGCT provides useful pathologic information on which subsequent treatment alternatives can be based. The technique, although technically demanding, is feasible. The perioperative morbidity is limited, and recovery is prompt. Except for 1 patient who developed retrograde ejaculation, we did not encounter any long-term side effects. The average patient undergoing an open RPLND can expect a 5 to 7-day hospital stay, limited employment and activity for 2 weeks postoperatively, and a return to full activity within 6 weeks.5 In this series of laparoscopic RPLND, both the hospital stay and time to full recovery were 1066
significantly shorter. Although the importance of surveillance is emphasized to patients with negative nodes on laparoscopic RPLND, we have reduced the standard staging follow-up evaluations6 from six to four times per year, during the period when recurrence is most likely.7 The technical demands of laparoscopic RPLND can be substantial, with a steep learning curve.8 Comparing the first half of the series with the second half, the total blood loss and operative times were nearly identical: overall operative times have been less than those previously reported.4,8 Whether the top of the learning curve has been reached is unknown, but it is clear regular performance of complex laparoscopic procedures is a prerequisite to achieving good results. Retroaortic and retrocaval tissue was not routinely removed. It is technically feasible but adds at least 1 hour to the overall operative time. Others have found all positive nodes ventral to the lumbar vessels when the node tissue packets are taken separately.8,9 We have not been able to find a report documenting positive nodes in the retroaortic or retrocaval region as the only site of metastatic disease. Only time will tell whether patients undergoing surveillance will develop recurrences specifically in this region. Unlike an open RPLND, which has both diagnostic and therapeutic benefits,10,11 at present, our data only address laparoscopic RPLND as a diagnostic maneuver. Although to date no recurrence has occurred in the retroperitoneum for those undergoing surveillance, the follow-up time has been short, and the series was relatively small. Similarly, those with positive nodes (who received a more limited dissection) have not had recurrence in the retroperitoneum after chemotherapy. In another series of 29 patients who underwent a laparoscopic RPLND, 21 had negative lymph nodes. At a mean follow-up of 16 months, none of these patients had evidence of disease.8 Longer follow-up is necessary to determine the therapeutic role of laparoscopic RPLND. Unlike the reported low psychologic stress associated with surveillance,12 many patients are uncomfortable with observation— even in the presence of low risk features.11 Likewise, because of the current toxicity and effects on fertility, we do not recommend primary chemotherapy in the absence of metastatic disease. Laparoscopic RPLND provides useful pathologic staging information on which more rational treatment can be based. Historically, the use of a limited retroperitoneal sampling for Stage I NSGCT has been condemned,11 largely because of the risks of chemoresistant-retroperitoneal recurrences.13 In one large series, no patients had recurrence in the retroperitoneum after open RPLND,14 supporting a folUROLOGY 54 (6), 1999
low-up regimen in which abdominal CT scans can be eliminated. In a subset of patients who did have recurrence “in-field,” the tumor was chemoresistant.13 Whether this refractory phenotype is acquired or inherent is unknown. Furthermore, RPLND after chemotherapy or other retroperitoneal surgery is technically challenging.15 An extension of this line of reasoning had led some to advocate a complete bilateral node dissection, including suprahilar regions, for patients with palpable, suspicious lymph nodes or for patients with markerpositive low-stage retroperitoneal involvement.11 Our incorporation of laparoscopic RPLND in the management of Stage I NSGCT is based on a different view. Systemic chemotherapy is curative in most patients with metastatic NSCGT.16,17 Even in patients undergoing a complete open RPLND, the philosophy of the primary surgeon has been to recommend chemotherapy when metastatic disease is discovered.18 The goal of laparoscopic RPLND—to identify and treat with chemotherapy those with disease and to observe those without disease— has been performed with less morbidity than open RPLND. Although the follow-up in our study was short and the number of patients treated small, our results to date support a role for laparoscopic RPLND in the management of Stage I NSGCT. CONCLUSIONS For pathologic staging, laparoscopic RPLND is a feasible, minimally invasive alternative to open RPLND. It allows discrimination of those with pathologic Stage I disease from those with pathologic Stage II disease19 and more rational assignment to surveillance or systemic chemotherapy protocols.20 REFERENCES 1. Freedman LS, Parkinson MC, Jones WG, et al: Histopathology in the prediction of relapse of patients with stage I testicular teratoma treated by orchidectomy alone. Lancet 2: 294 –298, 1987. 2. Read G, Stenning SP, Cullen MH, et al, for the Medical Research Council Testicular Tumors Working Party: Medical Research Council prospective study of surveillance for stage I testicular teratoma. J Clin Oncol 10: 1762–1768, 1992. 3. Leibovitch I, Foster RS, Kopecky KK, et al: Identification of clinical stage A nonseminomatous testis cancer patients at extremely low risk of metastatic disease: a combined approach using quantitative immunohistochemical, histopathologic, and radiographic assessment. J Clin Oncol 16: 261–268, 1998.
UROLOGY 54 (6), 1999
4. Gerber GS, Bissada NK, Hulbert JC, et al: Laparoscopic retroperitoneal lymphadenectomy: multi-institutional analysis. J Urol 152: 1188 –1192, 1994. 5. Ritchie JP: Modified retroperitoneal lymph node dissection for patients with clinical stage 1 testicular cancer. Semin Urol 216: 222–232, 1986. 6. Sarosdy M: Testicular cancer: an overview, in Crawford ED, and Das S (Eds): Current Genitourinary Cancer Surgery. Philadelphia, Lea & Febiger, 1990, pp 306 –318. 7. Rorth M, and Daugaard G: Observation and expectant management for low-stage seminoma and nonseminoma, in Vogelzang NJ, Scardino PT, Shipley WU, et al (Eds): Comprehensive Textbook of Genitourinary Oncology. Baltimore, Williams & Wilkins, 1996, vol 1, pp 1016 –1021. 8. Janetschek G, Hobisch A, Ho¨lti L, et al: Retroperitoneal lymphadenectomy for clinical stage I nonseminomatous testicular tumors: laparoscopy versus open surgery and impact of learning curve. J Urol 156: 89 –94, 1996. 9. Ho¨lti L, Hobisch A, Knapp R, et al: Where are the primary landing sites for retroperitoneal metastases from testicular tumor? J Urol 157S: 303, 1997. 10. Donohue JP, Zachary JM, and Maynard BR: Distribution of nodal metastases in nonseminomatous testis cancer. J Urol 128: 315–320, 1982. 11. Steele GS, and Ritchie JP: Current role of retroperitoneal lymph node dissection in testicular cancer. Oncology 11: 717–729, 1997. 12. Fossa SD, Jacobsen AB, Aass N, et al: How safe is surveillance in patients with histologically low-risk non-seminomatous testicular cancer in a geographically extended country with limited computerized tomographic resources? Br J Cancer 70: 1156 –1160, 1994. 13. Baniel J, Foster RS, Einhorn LH, et al: Late relapse of clinical stage I testicular cancer. J Urol 154: 1370 –1372, 1995. 14. Donohue JP, Thornhill JA, Foster RS, et al: Primary retroperitoneal lymph node dissection in clinical stage A nonseminomatous germ cell testis cancer. Review of the Indiana University experience 1965–1989. Br J Urol 71: 326 –335, 1993. 15. Waters WB, and Lindgren BW: Resection of residual or metastatic disease, in Vogelzang NJ, Scardino PT, Shipley WU, et al (Eds): Comprehensive Textbook of Genitourinary Oncology. Baltimore, Williams & Wilkins, 1996, vol 1, pp 1002–1015. 16. Einhorn LH: Testicular cancer as a model for a curable neoplasm: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res 41: 3275–3280, 1981. 17. Einhorn LH, and Donohue JP: Advanced testicular cancer: update for urologists. J Urol 160: 1964 –1969, 1998. 18. Williams SD, Stablein DM, Einhorn LH, et al: Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med 317: 1433–1438, 1987. 19. Donohue JP: Laparoscopic retroperitoneal lymphadenectomy: multi-institutional analysis (editorial comment). J Urol 152: 1191–1192, 1994. 20. Richie JP: Laparoscopic retroperitoneal lymphadenectomy: multi-institutional analysis (editorial comment). J Urol 152: 1191, 1994.
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