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ORIGINAL ARTICLE
Year : 2016  |  Volume : 32  |  Issue : 1  |  Page : 40-44
 

Outcomes following retroperitoneal lymph node dissection in postchemotherapy residual masses in advanced testicular germ cell tumors


Department of Urology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication4-Jan-2016

Correspondence Address:
Prabhjot Singh
Department of Urology, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi -110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-1591.173102

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   Abstract 

Introduction: We aimed to study the outcomes of retroperitoneal lymph node dissection (RPLND) in postchemotherapy residual masses in advanced testicular germ cell tumor (GCT) in the Indian population.
Patients and Methods: We retrospectively analyzed 35 patients who underwent postchemotherapy RPLND at our institute after primary (29 patients) or salvage (6 patients) chemotherapy over a period of 9 years (June 2003 to July 2012).
Results: The mean age of our patients was 26.8 years. 18 (51.42%) presented with primary tumor in the right testis and 3 (8.51%) had bilateral tumors. Mixed GCT was the most common histology among 19 (54.3%) patients. 14 (40%) patients had the residual mass in para-aortic location, which was the most common site. 14 (40%) patients required an adjunctive procedure, most commonly nephrectomy which was required in 9 out of 14 (25.7%). We recorded 25 complications, mostly Clavien-Dindo grade II. Histopathology of residual mass was necrosis in 17 (48.57%), teratoma in 12 (34.28%), and viable tumor in 6 (17.14%) patients.
Conclusion: Nearly half of the patients had either teratoma or viable tumor, thus justifying the surgical resection of postchemotherapy residual mass. Although nearly half of the patients had complications, they were adequately managed and there was no mortality. Thus, postchemotherapy RPLND can be a useful procedure in multimodality approach to GCT in carefully selected patients.


Keywords: Postchemotherapy, retroperitoneal lymph node dissection (RPLND), testicular tumor


How to cite this article:
Singh P, Yadav S, Mahapatra S, Seth A. Outcomes following retroperitoneal lymph node dissection in postchemotherapy residual masses in advanced testicular germ cell tumors. Indian J Urol 2016;32:40-4

How to cite this URL:
Singh P, Yadav S, Mahapatra S, Seth A. Outcomes following retroperitoneal lymph node dissection in postchemotherapy residual masses in advanced testicular germ cell tumors. Indian J Urol [serial online] 2016 [cited 2019 Nov 17];32:40-4. Available from: http://www.indianjurol.com/text.asp?2016/32/1/40/173102



   Introduction Top


Testicular tumors are rare and account for 1-1.5% of all the tumors affecting men but are the commonest tumors in 15-35 years of age.[1] Ninety to ninety five percent of testicular tumors are germ cell tumors (GCTs), 52-56% of which are seminomas.[2],[3] With the current multimodality approach, GCTs are considered as one of the most curable solid neoplasms with &> 90% survival rates.[4]

Chemotherapy is the usual first-line treatment for stage IIA-IIB GCTs with bulky disease or stage IIC-III disease after high inguinal orchidectomy. Postchemotherapy, 60-80% of seminomatous [5],[6] and 30% of nonseminomatous GCTs (NSGCTs) have residual masses, most commonly in the retroperitoneum.[7] Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is indicated in patients with normal serum markers with radiologically identifiable disease in the retroperitoneum [especially in NSGCT &> 1 cm and seminoma &> 3 cm with fluorodeoxyglucose (FDG) uptake]. Various studies show that postchemotherapy residual masses comprise necrosis in 50%, viable tumor in 15%, and teratoma in 35% of cases with NSGCT [8] and viable tumor in 10% and necrosis in 90% of patients with seminoma.[5],[6] Thus, there is a significant rate of nontherapeutic exploration. In the absence of established imaging or nomogram parameters that can accurately predict the histology of residual masses, there is no option but to surgically resect them.

Thus, PC-RPLND is both diagnostic by providing definite histology and therapeutic by achieving local control. This is especially true for NSGCT because a teratoma may be present in the retroperitoneal mass that is chemoresistant and has potential for local growth, invasion, and transformation. Further, postchemotherapy residual masses can be considered chemotherapy resistant and they are better served by surgery. With growing experience of such surgical procedures refinement in surgical technique and better understanding of the anatomy, the morbidity rates are decreasing, further supporting its widespread role and incorporation into a therapeutic protocol.

We present a tertiary care center experience of the role and postoperative outcomes of RPLND in patients with retroperitoneal residual masses after primary or salvage chemotherapy.


   Patients and Methods Top


From June 2003 to July 2012, a total of 70 patients underwent RPLND for GCT, of whom 45 had received chemotherapy. Patients who had residual, resectable retroperitoneal masses after chemotherapy, normal postchemotherapy tumor markers [alpha-fetoprotein and beta-human chorionic gonadotropin (beta-HCG)] and no previous RPLND were included in this study. Patients who underwent primary RPLND, had inadequate follow-up or incomplete data were excluded. Out of 45 patients, 35 met these inclusion criteria.

All patients underwent detailed physical examination, contrast-enhanced computed tomography (CECT) of the chest and abdomen, and tumor marker assessment preoperatively and clinical stage was assigned according to the American Joint Committee on Cancer (AJCC) staging system [9] and the International Germ Cell Cancer Collaborative Group (IGCCCG) Tumor Risk Categorization.[10] The mean age of our patient group was 26.8 years (16-50 years) with primary testicular tumor on the right side in 18 (51.4%) patients and bilateral tumor in three (8.5%) patients. Cryptorchidism was present in five (14.2%) patients. Mixed GCT was the most prevalent histology of primary tumor present in 19 (54.5%) patients. Thirteen (37.1%) patients had teratoma in the primary tumor, either alone (in 6 patients - 17.1%) or as a component of mixed GCT (in 7 patients - 20%). Seminoma was present in four (11.4%) patients, all of whom had undescended testes. Characteristics of primary tumor are summarized in [Table 1].
Table 1: Characteristics of primary testicular tumor

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The most common site of retroperitoneal mass was the paraaortic region (14 patients - 40%) and the mean size of retroperitoneal mass was 8.8 cm (range 2.2 cm-20.4 cm) before chemotherapy and 5.4 cm (range 1.2 cm-14.6 cm) postchemotherapy. Characteristics of retroperitoneal mass are summarized in [Table 2].
Table 2: Characteristics of retroperitoneal mass

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Chemotherapy

All patients received cisplatin-based chemotherapy either as induction (29 patients) or salvage therapy (six patients). Twenty-two (62.8%) patients received four cycles of BEP (bleomycin, etopside, cisplatin), five (14.2%) patients received three cycles of BEP, and two (5.7%) patients received four cycles of EP (etopside and cisplatin) as induction therapy. Salvage chemotherapy was given to six patients, five (14.2%) received four cycles of VIP (vinblastin, ifosfamide, cisplatin), and one (2.8%) received four cycles of TIP (paclitaxel, ifosfamide, cisplatin). Two patients were given radiotherapy in addition to four cycles of BEP as induction therapy.

RPLND template

RPLND was performed by abdominal or thoracoabdominal approach in standard bilateral infrahilar template and nerve sparing was done whenever possible. Standard template extended from renal vessels superiorly to bifurcation of common iliac vessels inferiorly and up to ureters laterally and anterior spinal ligament and psoas muscle fascia posteriorly. Split and roll technique was used to dissect the lymph node packet. In patients with small volume residual disease and minimal desmoplastic reaction, nerve-sparing technique with preservation of sympathetic chains, postganglionic fibers, and hypogastric plexus was performed. Postoperative complications were graded according to Clavien-Dindo classification.[11]

Follow-up

Postoperatively, all patients were scheduled for regular follow-up every 3 months with physical examination, serum tumor markers, chest x-ray, and CECT of the abdomen and pelvis for the first 2 years and then every 6 months for the next 2 years and then annually. The median follow-up was of 33 months (range 9 months-60 months) and data were censored on January 1, 2014.


   Results Top


All our patients underwent PC-RPLND by an open approach; an abdominal incision was used in 32 (91.4%) and thoracoabdominal incision in three (8.5%) patients. Standard template RPLND (as described) was performed in all the patients with three patients requiring extension of template in suprahilar area for residual masses. Nerve sparing was possible in seven patients (20%) (unilateral sparing in five and bilateral sparing in two) with low volume stage IIA/B disease. Fourteen patients (40%) required 15 adjunctive procedures, the most common being nephrectomy in nine (25.7%) patients, which was more common on the left side (six patients). Adjunctive procedures were more common in patients with larger retroperitoneal masses (&>5 cm) (9 out of 12 patients with &> 5 cm residual mass), patients who presented with stage III disease (six out of 10 patients) or have received salvage chemotherapy (four out of six patients) or had fibrosis as the final histology (six out of six patients).

Thirteen patients had 25 complications (37.1% complication rate). Most of the surgical complications were of Clavien grade I or II (the most common being blood transfusion in 28.5% patients) and required conservative management. Only two (5.7%) patients required surgical intervention for Clavien grade III complications. One patient who developed adhesive intestinal obstruction in the immediate postoperative period was re-explored on postoperative day 12 after a failed trial of conservative management. Intraoperatively, there was a band at terminal ileum with twisting of the small bowel requiring adhesiolysis and detorsion. The postoperative recovery was smooth. Another patient developed paralytic ileus after drain removal on postoperative day 5 and ultrasonography of the patient revealed a 19 cm × 10 cm localized collection in the right paracolic gutter extending into the pelvis that turned out to be of serous nature on diagnostic tapping. Ultrasound-guided percutaneous drain was placed under local anesthesia and the ileus resolved after 2 days. The drain was removed after 5 days when serial abdominal ultrasounds documented no residual collection. Complications were more common in patients with larger postchemotherapy masses (&>5 cm) and fibrosis as the final histology. Surgical procedures and complications are summarized in [Table 3] and [Table 4], respectively.
Table 3: Characteristics of surgical procedures

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Table 4: Surgical complications

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The histopathology of RPLND specimen was fibrosis or necrosis in 17 (48.5%) patients, teratoma in 12 (34.2%) patients, and viable tumor in six (17.1%) patients. On retrospect, among these six cases with viable tumor, two had lung metastasis and three were at high risk according to the IGCCCG risk classification, and the clinical stage was of either stage IIC (three cases) or stage III (three cases). Four of these patients had received salvage chemotherapy and the retroperitoneal mass size was &>5 cm in three patients.

The median follow-up was of 33 months (ranging 9-60 months). Antegrade ejaculation was preserved in five out of 28 (17.8%) patients with standard RPLND and in five out of seven (71.4%) patients with nerve-sparing procedure. Seven (20%) patients had recurrence over a median follow-up of 33 months. Three patients had recurrence in the retroperitoneum; bilateral complete RPLND was performed in two patients and extended RPLND in one. Three patients had distant recurrence, one had bony recurrence, and the other two had pulmonary recurrence. One patient had simultaneous recurrence in the retroperitoneum and lungs. Out of these four patients with retroperitoneal recurrence, the histopathology of the resected residual mass was viable tumor in two, teratoma in one, and necrosis in one patient. Of all the seven patients with recurrences, four were given salvage chemotherapy. Five of these seven patients with recurrences succumbed to their disease and two were alive with stable disease at the last follow-up.


   Discussion Top


Surgical resection of residual retroperitoneal lymph node mass represents an integral part of the multimodality treatment for patients with advanced testicular cancer undergoing systemic chemotherapy.[12],[13] The objective is to remove persistent retroperitoneal lymph nodes that may have mature teratoma in about 40-50% or viable tumor in 10-20% of cases.[12],[13],[14]

In our series, out of 35 patients, 26 presented with advanced disease (stage IIC in 16 and stage III in 10) and 11 patients were in the poor risk category according to the IGCCC Tumor Risk Categorization. The postchemotherapy mean retroperitoneal tumor size was 5.4 cm (range 1.2 cm-14.6 cm). Bulky retroperitoneal mass necessitated bilateral classical RPLND in 32 patients with extended dissection in three cases. Unilateral or modified templates were not used. Nerve sparing was possible in seven patients. Fourteen patients required adjunctive procedures and the complication rate was 37.1%. At a median follow-up of 33 months, there were seven recurrences and the estimated 5-year survival was 83.7%.

Nerve sparing may be used in PC-RPLND although the rates of antegrade ejaculation are lower than that for primary RPLND as complete resection of the often large, adherent mass supersedes ejaculatory concerns. In our series, nerve-sparing procedure was possible in seven patients with low volume IIA/IIB disease with preservation of antegrade ejaculation in five (71.4%) patients without any disease recurrence with a median follow-up of 42 months. In 28 patients who had undergone bilateral standard template RPLND, antegrade ejaculation was preserved in only five (17.8%) patients. This compares favorably with 79-89% antegrade ejaculation rates and 98% 5-year relapse free survival rates reported in the literature.[15],[16] The small number of nerve-sparing procedures in our series was attributed to the advanced stage of presentation and bulky retroperitoneal disease.

In PC-RPLND, 20-25% of the patients require adjunctive procedures for completeness of the resection, nephrectomy being the most common amongst them.[12],[17] In our series, 14 (40%) patients underwent adjunctive procedure and among them, nine (25.7%) underwent nephrectomy. Four patients required resection of adjacent structures and two required separation of the ureter from the desmoplastic mass (ureterolysis). Of those who underwent adjunctive nephrectomy, four patients received salvage chemotherapy, three had advanced stage (III) disease, and two had bulky retroperitoneal disease (retroperitoneal tumor size &> 10 cm). The higher proportion of patients with adverse features in our PC-RPLND series may explain the higher rate of adjunctive nephrectomy unlike the usual 25% reported in the literature.[17] In our series, histopathological analysis of the nephrectomy specimen revealed residual disease in six (66.6%) patients, justifying the need for adjunctive nephrectomy in these patients.

The complication rates for postchemotherapy surgery are higher than that for primary RPLND.[18] In our series, the complication rate was 37.1% that compares well with the reported rates of 20-35% in various series.[18],[19] Most of the complications were of Clavien grade I and II, which included blood transfusion, postoperative fever, superficial wound infection, and paralytic ileus. The higher complication rate in our series is attributed to the advanced stage of presentation, bulky retroperitoneal disease, and high number of patients with salvage chemotherapy with severe desmoplastic reaction, all of which are known risk factors. Luz et al. observed that patients with fibrosis in the residual mass had more complications and ended up undergoing nonnerve-sparing procedures.[20] We also have similar observation. These findings pose a dilemma when offering PC-RPLND in residual masses as almost half of the patients will have necrosis and nontherapeutic resections with higher complications.

We observed seven recurrences including three retroperitoneal, three distant, and one combined. Among these 7 patients with recurrence all belonged to the IGCCC high risk category and 4 patients had a viable tumor in residual mass and received postoperative chemotherapy. Fox et al. noted that if viable GCT was present in the retroperitoneal mass and is entirely resected, two additional cycles of adjuvant chemotherapy confer a disease-free survival of 70%.[21] In our series among the seven patients with recurrences (local or distant), five died due to disseminated neoplasia and two were alive with stable disease till the last follow-up.

The estimated 5-year overall survival of PC-RPLND after induction and salvage chemotherapy has been reported as 85-95% and 44-61%, respectively.[10],[12],[21],[22] In our series, the median follow-up was of 33 months. The estimated 5-year overall survival rate after PC-RPLND in our series was 83.75% and approaches the results of previously reported series.


   Conclusion Top


PC-RPLND is a relatively safe procedure in experienced hands with an acceptable morbidity rate. Half of the residual masses have teratoma or viable tumor, thereby, justifying surgical resection. Complete removal of post-chemotherapy residual mass remains the standard of care and allows improved oncologic and functional outcomes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Flechon A, Rivoire M, Droz JP. Management of advanced germ-cell tumors of the testis. Nat Clin Pract Urol 2008;5:262-76.  Back to cited text no. 1
    
2.
Powels TB, Bhardwa J, Shamash J, Mandalia S, Oliver T. The changing presentation of germ cell tumors of testes between 1983 and 2002. BJU Int 2005;95:1197-200.  Back to cited text no. 2
    
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McGlynn KA, Devesa SS, Graubard BI, Castle PE. Increasing incidence of testicular germ cell tumors among black men in United States. J Clin Oncol 2005;23:5757-61.  Back to cited text no. 3
    
4.
Sheinfeld J, Herr HW. Role of surgery in management of germ cell tumor. Semin Oncol 1998;25:203-9.  Back to cited text no. 4
    
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Flechon A, Bompas E, Biron P, Droz JP. Management of post-chemotherapy residual masses in advanced seminoma. J Urol 2002;168:1975-9.  Back to cited text no. 5
    
6.
De Santis, Becherer A, Bokemeyer C, Stoiber F, Oechsle K, Sellner F, et al. 2-18 fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: An update of the prospective multicentric SEMPET trial. J Clin Oncol 2004;22:1034-9.  Back to cited text no. 6
    
7.
Donohue JP, Leviovitch I, Foster RS, Baniel J, Tognoni P. Integration of surgery and systemic therapy: Results and principles of integration. Semin Urol Oncol 1998;16:65-71.  Back to cited text no. 7
    
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Sim HG, Lange PH, Lin DW. Role of post-chemotherapy surgery in germ cell tumors. Urol Clin North Am 2007;34:199-217; abstract ix.  Back to cited text no. 8
    
9.
From AJCC. Testis. In: Edge SE, Byrd DR, Compton CC, editors. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010. p. 469-73.  Back to cited text no. 9
    
10.
International Germ Cell Consensus Classification: A prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 1997;15:594-603.  Back to cited text no. 10
[PUBMED]    
11.
Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Shulick BD, et al. The Clavien-Dindo classification of surgical complications: Five-year experience. Ann Surg 2009;250:187-96.  Back to cited text no. 11
    
12.
Schmoll HJ, Souchon R, Krege S, Albers P, Beyer J, Kollmannsberger C, et al.; European Germ Cell Cancer Consensus Group. European consensus on diagnosis and treatment of germ cell cancer: A report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004;15:1377-99.  Back to cited text no. 12
    
13.
Albers P, Albrecht W, Algaba F, Bokemeyer C, Cohn-Cedermark G, Horwich A, et al. Guidelines on testicular cancer. Eur Urol 2005;48:885-94.  Back to cited text no. 13
    
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Beck SD, Foster RS. Long-term outcome of retroperitoneal lymph node dissection in the management of testis cancer. World J Urol 2006;24:267-72.  Back to cited text no. 14
    
15.
Jacobsen KD, Ous S, Waehre H, Trasti H, Stenwig AE, Lien HH, et al. Ejaculation in testicular cancer patients after post-chemotherapy retroperitoneal lymph node dissection. Br J Cancer 1999;80:249-55.  Back to cited text no. 15
    
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Pettus JA, Carver BS, Masterson T, Stasi J, Sheinfeld J. Preservation of ejaculation in patients undergoing nerve-sparing postchemotherapy retroperitoneal lymph node dissection for metastatic testicular cancer. Urology 2009;73:328-32.  Back to cited text no. 16
    
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Nash PA, Leibovitch I, Foster RS, Bihrle R, Rowland RG, Donohue JP. En bloc nephrectomy in patients undergoing post-chemotherapy retroperitoneal lymph node dissection for nonseminomatous testis cancer: Indications, implications and outcomes. J Urol 1998;159:707-10.  Back to cited text no. 17
    
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Baniel J, Sella A. Complications of retroperitoneal lymph node dissection in testicular cancer: Primary and post-chemotherapy. Semin Surg Oncol 1999;17:263-7.  Back to cited text no. 18
    
19.
Baniel J, Foster RS, Rowland RG, Bihrle R, Donohue JP. Complications of post-chemotherapy retroperitoneal lymph node dissection. J Urol 1995;153:976-80.  Back to cited text no. 19
    
20.
Luz MA, Kotb AF, Aldousari S, Brimo F, Tanguay S, Kassouf W, et al. Retroperitoneal lymph node dissection for residual masses after chemotherapy in nonseminomatous germ cell testicular tumor. World J Surg Oncol 2010;8: 97.  Back to cited text no. 20
    
21.
Fox EP, Weathers TD, Williams SD, Loehrer PJ, Ulbright TM, Donohue JP, et al. Outcome analysis for patients with persistent nonteratomatous germ cell tumor in postchemotherapy retroperitoneal lymph node dissections. J Clin Oncol 1993;11:1294-9.  Back to cited text no. 21
    
22.
Steyerberg EW, Keizer HJ, Fosså SD, Sleijfer DT, Toner GC, Schraffordt Koops H, et al. Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic nonseminomatous germ cell tumor: Multivariate analysis of individual patient data from six study groups. J Clin Oncol 1995;13:1177-87.  Back to cited text no. 22
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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