Nerve Sparing Retroperitoneal Lymphadenectomy After Primary Chemotherapy for Metastatic Testicular Carcinoma

0022-534 7/94/1522-0428$03.00/0 Tm: JOURNAL OF UROLOGY Copyright© 1994 by AMERICAN UROLOGICAL AssocIATION,

Vol. 152, 428-430, August 1994

Printed in U.S.A

INc.

NERVE SPARING RETROPERITONEAL LYMPHADENECTOMY AFTER PRIMARY CHEMOTHERAPY FOR METASTATIC TESTICULAR CARCINOMA GREGORY R. WAHLE, RICHARDS. FOSTER, RICHARD BIHRLE, RANDALL G. ROWLAND, RICHARD M. BENNETT AND JOHN P. DONOHUE From the Department of Urology, Indiana University Medical Center, Indianapolis, Indiana

ABSTRACT

Initial success with nerve sparing retroperitoneal lymph node dissections in patients with low stage nonseminomatous germ cell tumors of the testis has led to the application of these techniques to a select group of 40 patients treated after chemotherapy at our institution between March 1988 and November 1991. A minimum 1-year followup was available for 38 patients. There have been no abdominal relapses, and 34 of the 38 patients report normal ejaculation postoperatively. Nerve sparing techniques are applicable to select patients undergoing retroperitoneal lymph node dissection after primary chemotherapy for metastatic disease without increasing the chance of local recurrence. Emission and ejaculation are preserved in the majority of patients. KEY WORDS: testicular neoplasms; infertility, male; lymph node excision; drug therapy

Retroperitoneal lymph node dissection is a vital component in the staging and treatment of testicular carcinoma. Extensive experience at our institution 1 and others2 has led to the routine application of nerve sparing techniques to node dissection procedures in patients with low stage disease, which has resulted in nearly eliminating the morbidity of postoperative ejaculatory dysfunction in these patients. In light of the success of these procedures in patients with low stage testicular carcinoma, we began to apply these nerve sparing principles to select patients undergoing retroperitoneal lymph node dissection for relatively small volumes of residual retroperitoneal disease after receiving primary chemotherapy for metastatic cancer. We report the results of our experience with 38 patients who underwent nerve sparing post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS

Between March 1988 and November 1991, 296 patients underwent retroperitoneal lymphadenectomy at our institution after having received primary chemotherapy for either bulky retroperitoneal disease or clinical stage C testicular carcinoma at initial presentation. Of these patients 40 underwent some form of nerve sparing procedure, the selection based on the relatively small and predominantly unilateral initial retroperitoneal lymphadenopathy, and residual disease after chemotherapy. A minimum 12-month followup is available for 38 patients. Presenting data. Of the patients 21 had left testis primaries, while the remaining 17 had right tumors. A total of 19 patients presented with stage C disease, while 19 had bulky retroperitoneal disease only at presentation. All patients underwent primary therapy with multiagent platinum-based chemotherapeutic regimens initially and 3 had subsequent salvage courses before retroperitoneal dissection. Two patients failed initial platinum, etoposide and bleomycin regimens, and salvage therapy with platinum, vinblastine and ifosfamide, and they received high dose carboplatin plus etoposide with autologous bone marrow transfer before eventual retroperitoneal lymph node dissection. A total of 37 patients had normal markers before retroperitoneal lymph node dissection, while 1 had stable low grade elevation of 13-human Accepted for publication January 7, 1994.

chorionic gonadotropin at 38 mIU/ml. after autologous bone marrow transplantation. Orchiectomy pathological findings. Seven patients had orchiectomy specimens showing embryonal carcinoma as the only cell type and 4 had only teratoma or teratocarcinoma in the specimens. One patient had seminoma only. A total of 25 patients had mixed germ cell tumors, with 20 of these containing embryonal cell elements, 18 teratoma, 8 yolk sac tumor, 9 seminoma and 3 choriocarcinoma. Two patients had orchiectomy specimens that were described only as having mixed germ cell tumors. One patient who presented with bulky retroperitoneal adenopathy received chemotherapy before orchiectomy, which was subsequently performed at retroperitoneal lymph node dissection. The histology of the orchiectomy specimen showed atrophy. Preoperative computerized tomography (CT). Seven patients had less than 2 cm. of residual retroperitoneal disease after chemotherapy, 25 had 2 to 6 cm. of residual adenopathy and 6 had greater than 6 cm. of disease before retroperitoneal lymph node dissection, with the largest linear dimension being 9 cm. Retroperitoneal lymph node dissection procedures. Of the 38 patients 31 underwent full bilateral dissections, including 1 who underwent left suprahilar dissection as well. The other 7 patients underwent a unilateral procedure, including 3 left template dissections, 2 right template procedures, and 2 right dissections modified according to the location and volume of the disease. Two patients were approached through thoracoabdominal transperitoneal incisions, while the remaining 36 were explored through a midline laparotomy. Two patients underwent concomitant pulmonary resections for residual pulmonary disease and 2 required nephrectomy for complete excision of the disease. Lumbar roots spared. Three patients were noted on dictated operative summaries to have had all postganglionic lumbar sympathetic roots dissected and preserved during retroperitoneal lymph node dissection, while 12 had all right and 8 had all left roots spared. One patient had all left and 3 right roots spared, 1 had all right roots and 3 left roots spared, 2 had all left and 2 right roots (L2 and L3) spared, and 1 had 3 right (Ll to L3) and 1 left (Ll) roots preserved. In 10 patients 1 to 3 roots on either side were spared during retroperitoneal lymph node dissection (table 1). Retroperitoneal lymph node dissection pathological findings. A total of 23 patients (60%) had teratoma in the retro-

428

429

NERVE-SPARING RETROPERITONEAL LYMPHADENECTO\\IIY AFTER CHEMOTHERAPY Ti'-llLE 1.

Pt.-Age

Lumbar roots spared

Lymph Node Dissection

AB-33 BB-34 CB-22 PB-36 RB-35 WB-27 CC-25 TC-21 BD-22 CD-24

Bilat. retroperitoneal Bilat. retroperitoneal Bilat. retroperitoneal Bilat. retroperitoneal Bilat. retroperitoneal Lt. template Bilat. retroperitoneal Bilat. retroperitoneal Bilat. retroperitoneal Rt. template

CD-24 HG-29 KG-20 SG-27 RH-29 SH-27 CJ-22 JL--36

Bilat. retroperitoneal Bilat. retroperitoneal (including lt. nephrectomy) Bilat. retroperitoneal Bilat. retroperitoneal Bilat. retroperitoneal Bilat. retroperitoneal Lt. template Rt. template

LL--30 NM-34

Bilat. retroperitoneal Lt. template

RM-27

Bilat. retroperitoneal (including lt. nephrectomy) Bilat. retroperitoneal Bilat. retroperitoneal Rt. modified dissection

CN-32 GN-31 R0-24 R0-20 SP-23 TP-25 DR-33 RR-35

Bilat. retroperitoneal Bilat. retroperitoneal Bilat. retroperitoneal (including It. suprahilar dissection) Bilat. retroperitoneal Bilat. retroperitoneal

CS-34 DS-28 ES-30 ES-24 TS-33

Bilat. Bilat. Bilat. Bilat. Bilat.

DT-31 PT-42 RT-32 JW-24

retroperitoneal retroperitoneal retroperitoneal retroperitoneal retroperitoneal

Bilat. retroperitoneal Bilat. retroperitoneal Bilat. retroperitoneal Rt. modified dissection

Roots Spared

Ejaculation

2 lt. All rt. Lt. L3, L4 All rt. All Rt. L2, L3 All It. All rt. Rt. Ll, L2 All lt., rt. L2, L3 All rt. All rt.

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

All lt. All Lower lt. All All rt. All lt., rt. L2 to L4 All rt. Rt. Ll to L3, lt. L1 Rt. L2 to L4

Yes No Yes Yes Yes Yes

No Yes

Yes Yes Yes

Rt. L2 to L4 Rt. Ll, L2 All It., rt. L2, L3 All lt. All rt. Rt. L3

Yes Yes Yes

All It. All rt., It. L2 to L4 All rt. All It. All rt. All rt. All lt.

Yes Yes

All rt. All lt. Lower rt. All It.

Yes Yes No

Yes Yes No Yes Yes (21-mo. delay) Yes Yes Yes Yes

peritoneal lymph node dissection specimen, including 1 with elevation of {3-human chorionic gonadotropin preoperatively, while 12 (32%) had necrosis. Two patients (5%) had choriocarcinoma in the specimen and l (3%) had ganglioneuroma as the predominant histological finding from retroperitoneal lymph node dissection. One patient from the teratoma group also had a small area of atypical leiomyoma in the specimen. RESULTS

Followup data. All 38 patients had no evidence of disease at the most recent followup. Mean followup was 34 months (range 12 to 57 months). One patient had a pulmonary relapse treated with salvage chemotherapy and subsequent pulmonary resection, with pathological study of the lung specimen showing necrosis only. In 1 patient a marker-normal mediastinal relapse was treated with surgical resection and pathological examination revealed teratoma. A new contralateral left testis mass developed in 1 patient who was treated with radical orchiectomy and the pathological result was embryonal cell carcinoma. Although the post-orchiectomy markers were normal, abdominal CT obtained elsewhere was read as showing a small retroperitoneal mass in the interaortocaval area. He received 2 courses of platinum, etoposide and ifosfamide. Retrospective interpretation of this CT by radiologists at our facility reported that the tissue believed to be interaortocaval tumor was actually nonopaci-

fied bowel lying in the region of the previous resection. Repeat CT at our facility was normal. Two patients, 26 and 47 months after retroperitoneal lymph node dissection with normal markers, are being followed for small areas of residual pulmonary densities that have been stable on serial chest radiographs and are presumed to be areas of necrosis. Postoperative complications. One patient had a superficial wound infection with fascial dehiscence of a portion of the incision within 1 week postoperatively requiring exploration and closure. Two patients had partial small bowel obstructions 6 weeks and 14 months, respectively, after hospital discharge and they underwent exploration and lysis of adhesions. Symptomatic lymphoceles developed postoperatively in 2 patients who were treated with percutaneous drainage procedures. One patient experienced transient partial left femoral neurapraxia that was believed to be related to the self-retaining retractor used during surgery. Status of ejaculation. Of the 38 patients 34 report normal ejaculation after retroperitoneal lymph node dissection, with l experiencing a delay of 21 months before return. Of the 4 patients who report absence of ejaculatory function postoperatively l had all roots spared, 2 had all right roots spared and 1 had only a single root (right L3) preserved during retroperitoneal lymph node dissection. One of the 3 patients with all right roots spared suffered an intraoperative injury to the right sympathetic chain during the procedure. Fertility. Of the 34 patients who ejaculated 9 report 10 pregnancies, with 6 partners completing uneventful term pregnancies and giving birth to 7 healthy children without complication. There were 4 miscarriages reported among the partners of 3 patients (1 was attributed to cervical incompetence in the wife). Post-retroperitoneal lymph node dissection semen analysis data are available in 9 patients (table 2). Mean ejaculate volume is 3.2 ml. and 3 of the 9 analyses, obtained at 21, 28 and 37 months postoperatively, showed persistent azoospermia. DISCUSSION

The methods of surgical treatment of testicular carcinoma continue to evolve in an effort to improve efficacy and decrease morbidity. Initial studies of patterns of nodal metastasis from nonseminomatous germ cell tumors of the testes led to limitations of standard bilateral and suprahilar retroperitoneal dissections to template procedures without sacrificing efficacy of treatment. 3 , 4 These modifications in dissection borders limited postoperative ejaculatory dysfunction. 5 Recent advances and review of previous findings in anatomical knowledge and surgical technique have led to the ability to define and surgically preserve the retroperiton.eal neurovascular structures responsible for emission and antegrade ejaculation. 6 - 8 At our institution, patients with clinical stage A nonseminomatous testicular carcinoma who undergo retroperitoneal lymph node dissections routinely have procedures that spare the postga_nglionic lumbar sympathetic roots. Postoperative ejaculatory dysfunction has been virtually eliminated in these patients. In light of the success of these nerve sparing procedures in patients with low stage disease, we began to apply nerve sparing techniques to select patients with relatively

TABLE 2.

Pt. AB PB RB JL CN RO DS DT RT

Mos. Postop. Specimen Obtained 28 21 18

21 33 24 21 23 37

Semen analyses Vol. (ml.)

Count (million/ml.)

1.8 1.7 3.0 5.0 2.0 2.5 4.0 1.0 8.0

0 0 93 93 78.2 45.4 142 29 0.7

430

NERVE-SPARING RETROPERITONEAL LYMPHADENECTOMY AFTER CHEMOTHERAPY

small volumes of residual retroperitoneal disease after receiving primary chemotherapy for metastatic cancer. It should be stressed that our patients represent a select group among the many patients treated at our facility for residual disease after chemotherapy. During the 44 months of this series, a total of 256 patients underwent full bilateral post-chemotherapy retroperitoneal lymph node dissection without the use of a nerve sparing technique. Our 40 patients, therefore, represent only 13.5% of the total population of post-chemotherapy retroperitoneal lymph node dissection patients during the period of our initial experience. These 40 patients were chosen on the basis of the relatively small and predominantly unilateral distribution of the initial retroperitoneal adenopathy and residual disease after chemotherapy (see figure). The fact that only 2 of the 40 patients (5%) had persistent germ cell elements in the retroperitoneal lymph node dissection specimens also reflects the selection bias in the series. Of 38 patients 34 report normal ejaculatory function postoperatively. Although others have noted delay in return of ejaculation after retroperitoneal lymph node dissection, 9 • 10 only 1 patient in our series reported a delay of 21 months before return. Of the 4 anejaculatory patients 1 had only a single root spared and 1 had an intraoperative sympathetic chain injury that might explain anejaculation. All 4 patients in our series who report absence of ejaculation postoperatively initially presented with left primaries and eventually underwent full bilateral dissection. This observation raises the possibility that patients undergoing a full left clean out are more prone to "downstream" sympathetic fiber injury, in the preaortic area below the inferior mesenteric artery or in the hypogastric plexus, despite adequate preservation of right lumbar roots in the interaortocaval region. The adverse effects of testicular carcinoma and chemotherapy on semen parameters are well documented. 11 • 12 Multiagent chemotherapy for metastatic testicular carcinoma results in severe oligospermia in nearly all patients within the first 2 to 3 years after treatment but only 25% remain persistently azoospermic. 13 All of our patients were requested to obtain semen analyses at our expense but only 9 complied. Three patients are persistently azoospermic, 2 of whom received salvage chemotherapy and 1 of whom underwent high dose carboplatin therapy with autologous bone marrow transplantation. Although our results suggest that the application of nerve sparing techniques in select patients does not appear to increase the risk of treatment failure, the subfertility associated with testicular malignancy and the risk of persistent azoospermia associated with combination chemotherapy must be con-

Patient S. H. Preoperative abdominal CT shows 2 X 5 cm. residual periaortic adenopathy after primary chemotherapy.

sidered when selecting patients for possible nerve sparing postchemotherapy retroperitoneal lymph node dissection in an attempt to preserve ejaculatory function. We are encouraged that despite a mean followup of almost 3 years we have not noted an abdominal relapse in these patients and we believe that our efforts to preserve ejaculatory function have not compromised the efficacy of the procedures. The fact that 6 of our patients have been able to father 7 healthy children gives us additional encouragement and strengthens our belief that the careful application of nerve sparing techniques to patients undergoing retroperitoneal lymph node dissection after primary chemotherapy for metastatic disease improves the means of surgical treatment of testicular carcinoma by further decreasing its morbidity. REFERENCES

1. Donohue, J. P., Foster, R. S., Rowland, R. G., Bihrle, R., Jones,

2.

3. 4. 5.

J. and Geier, G.: Nerve-sparing retroperitoneal lymphadenectomy with preservation of ejaculation. J. Urol., 144: 287, 1990. Jewett, M.A. S., Kong, Y.-S. P., Goldberg, S. D., Sturgeon, J. F. G., Thomas, G. M., Alison, R. E. and Gospodarowicz, M. K.: Retroperitoneal lymphadenectomy for testis tumor with nerve sparing for ejaculation. J. Urol., 139: 1220, 1988. Donohue, J. P., Zachary, J. M. and Maynard, B. R.: Distribution of nodal metastases in nonseminomatous testis cancer. J. Urol., 128: 315, 1982. Pizzocaro, G., Salvioni, R., and Zanoni, F.: Unilateral lymphadenectomy in intraoperative stage I nonseminomatous germinal testis cancer. J. Urol., 134: 485, 1985. Foster, R. S. and Donohue, J. P.: Surgical treatment of clinical stage A nonseminomatous testis cancer. Sem. Oncol., 19: 166, 1992.

6. Whitelaw, G. P. and Smithwick, R. H.: Some secondary effects of sympathectomy with particular reference to disturbance of sexual function. New Engl. J. Med., 245: 121, 1951. 7. Colleselli, K., Poisel, S., Schachtner, W. and Bartsch, G.: Nervepreserving bilateral retroperitoneal lymphadenectomy: anatomical study and operative approach. J. Urol., 144: 293, 1990. 8. Jones, D.R., Norman, A. R., Horwich, A. and Hendry, W. F.: Ejaculatory dysfunction after retroperitoneal lymphadenectomy. Eur. Urol., 23: 169, 1993. 9. Narayan, P., Lange, P. H. and Fraley, E. E.: Ejaculation and fertility after extended retroperitoneal lymph node dissection for testicular cancer. J. Urol., 127: 685, 1982. 10. Leiter, E. and Brendler, H.: Loss of ejaculation following bilateral retroperitoneal lymphadenectomy. J. Urol., 98: 375, 1967. 11. Brenner, J., Vugrin, D. and Whitmore, W. F., Jr.: Effect of treatment on fertility and sexual function in males with metastatic nonseminomatous germ cell tumors of testis. Amer. J. Clin. Oncol., 8: 178, 1985. 12. Drasga, R. E., Einhorn, L. H., Williams, S. P., Patel, D. N. and Stevens, E. E.: Fertility after chemotherapy for testicular cancer. J. Clin. Oncol., 1: 179, 1983. 13. Boyer, M. and Raghaven, D.: Toxicity of treatment of germ cell tumors. Sem. Oncol., 19: 128, 1992. EDITORIAL COMMENT The authors are to be congratulated on an extension of nerve sparing techniques to select patients who undergo retroperitoneal lymph node dissection after primary chemotherapy for metastatic testicular cancer. I would emphasize that this is a select series with only 40 of 296 patients (14%) who were candidates for this nerve sparing approach. The followup is relatively short, with a range of 12 to 57 months. Only 9 patients have undergone semen analyses and 3 of them were azoospermic. Importantly, there has been no retroperitoneal relapse. Nerve sparing retroperitoneal lymphadenectomy after chemotherapy can be performed in select circumstances. However, one must balance the risks of recurrence, or the possibility of leaving behind residual teratoma or cancer against the relatively modest number of patients who will regain spermatogenesis after chemotherapy. Accordingly, this approach should be used judiciously. Jerome P. Richie Division of Urology Brigham and Women's Hospital Boston, Massachusetts