Urologic Oncology: Seminars and Original Investigations
Volume 30, Issue 1 , Pages 60-63, January 2012

Primary vs. post-chemotherapy retroperitoneal lymph node dissection (RPLND) in patients with presence of teratoma at orchiectomy

Division of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 20015, USA

Received 2 October 2009; received in revised form 7 December 2009; accepted 7 December 2009. published online 02 March 2010.

Article Outline

Abstract 

Objective

The presence of teratoma in the primary orchiectomy specimen creates controversies for subsequent management. Although predominant teratoma is less likely to metastasize, teratoma in the retroperitoneum may be less amenable to chemotherapy. In order to elucidate the issues about teratoma in the primary tumor, we reviewed differences between primary retroperitoneal lymph node dissection (P-RPLND) vs. post-chemotherapy RPLND (PC-RPLND) in patients with teratoma at orchiectomy.

Materials and methods

Patients who had undergone RPLND at our institution from 2001 to 2008 were identified, and clinical charts reviewed. Eighty-three patients with teratoma at orchiectomy were identified and perioperative data were obtained.

Results

Of the 83 patients with teratoma at orchiectomy who underwent RPLND, 44 (53%) and 39 (47%) underwent primary and PC-RPLND, respectively. Median follow-up was 1.4 years. Of the 83 patients with primary teratoma at orchiectomy, there were 7 (8%) patients with pure teratoma and 76 (92%) patients with mixed histology. Of the patients with mixed histology, 72 (87%) patients had embryonal carcinoma and 36 (43%) had LVI. There were 19 (43%) positive lymph nodes for P-RPLND, of which 13 (30%) contained teratoma. For the PC-RPLND group, 30 (77%) of lymph nodes were positive, of which 28 (72%) contained teratoma. There were 3 (4%) recurrences overall, all of which recurred in the PC-RPLND group. There were 11 (13%) perioperative complications total. There were no deaths in either group.

Conclusions

Patients with teratoma at orchiectomy were associated with other high risk features and are at significant risk for metastatic disease. Patients with post-chemotherapy retroperitoneal findings are at significant risk for viable GCT and/or teratoma and should undergo PC-RPLND.

Keywords:  Retroperitoneal lymph node dissection , Testicular cancer , Teratoma

 

Back to Article Outline

1. Introduction 

Carcinoma of the testis more often has a favorable prognosis with the development of effective multimodal therapy and a rate of cure from approximately 60% in the 1970s to 98% in 2000 for a majority of cases. Physician and patient preference often dictate course of treatment options or surveillance, depending on risk factors and clinical stage. Retroperitoneal lymph node dissection (RPLND) remains an integral component in the treatment and cure for testicular cancer. This is especially true for patients with retroperitoneal disease and/or high risk features [1], [2]. In addition, the morbidity with RPLND is minimal when performed at dedicated tertiary centers [1], [2], [3]. Although surveillance and primary chemotherapy have been advocated as treatment options, there are inherent risks associated with radiation exposure through repeat computer tomography (CT) scans and the added morbidity of chemotherapy induced cardiopulmonary toxicities and secondary malignancies [4], [5], [6], [7], [8], [9]. The National Comprehensive Cancer Network (NCCN) guidelines for surveillance after primary chemotherapy for CS IA-B NSGCT include 6 to 7 abdominal CT scans over 5 years, with a CT scan as clinically indicated after 5 years [10]. Tarin et al. noted the relative risk of a secondary malignancy with surveillance compared with a single scan after RPLND to be approximately 15-fold [5]. This is in contrast to the post-RPLND NCCN guideline, which recommends one postoperative baseline abdominal CT scan. These results should be included when discussing management options with patients.

Teratoma is known to be resistant to chemotherapy and can undergo malignant transformation [11], [12], [13], [14]. Prior studies have confirmed that teratoma may be present in the retroperitoneum, even in the absence of teratoma at orchiectomy. In addition, post-chemotherapy retroperitoneal masses in non-seminomatous patients with high risk features are often teratoma in up to 70% at RPLND [1], [15]. We sought to discern treatment outcomes in patients with teratoma at orchiectomy managed with primary (P-RPLND) vs. post-chemotherapy RPLND (PC-RPLND).

Back to Article Outline

2. Materials and methods 

All patients undergoing RPLND through Brigham and Women's Hospital and Dana Farber Cancer Center from 2001 to 2008 were candidates for inclusion in this study. All patients with orchiectomy specimens greater than 5% teratoma were identified and perioperative data were obtained. We included patients managed with primary chemotherapy in order to compare primary RPLND patients with a known group of patients who have a greater likelihood of harboring teratoma in the retroperitoneum (PC-RPLND). Follow-up was conducted by chart review. These data were extracted from the Brigham and Women's Hospital RPLND computerized database and analyzed accordingly. This project was approved by the Institutional Review Board (IRB) at Brigham and Women's Hospital.

At our institution, all patients are evaluated in a multidisciplinary clinic and are counseled regarding the options of active surveillance, surgery, and/or chemotherapy as previously described [1]. All cases were preoperatively staged with tumor markers (AFP, HCG, and LDH), CT of the abdomen-pelvis, and CT of the chest or chest X-ray. All orchiectomy and RPLND specimens were reviewed and reports confirmed by pathologists at Brigham and Women's Hospital. Clinical and pathologic stage were defined according to NCCN guidelines [10]. Primary chemotherapy patients with clinical stage I (CS I) underwent 2 cycles of a cisplatin-based chemotherapy, all others underwent 3 to 4 cycles depending on the extent of retroperitoneal clinical stage II (CS II) disease.

All P-RPLND patients underwent a modified template, nerve sparing procedure. All PC-RPLND underwent bilateral template and nerve sparing when deemed appropriate without compromising oncologic efficacy. Patients with retroperitoneal disease identified via CT of the abdomen and pelvis after primary chemotherapy underwent RPLND. Patients with high risk features who underwent primary chemotherapy with no retroperitoneal disease were counseled on the risk for retroperitoneal relapse and were offered RPLND.

Data were entered into a computerized database and analyzed. Differences between P-RPLND and PC-RPLND patients based on continuous variables were compared using the Student's t-test. All factors were considered simultaneously. No model selection algorithm was utilized.

Back to Article Outline

3. Results 

A total of 83 patients with teratoma at orchiectomy who underwent RPLND at Brigham and Women's Hospital and Dana Farber Cancer Center between 2001 and 2008 were identified. Of the 83 patients with primary teratoma at orchiectomy, there were 7 (8%) patients with pure teratoma and 76 (92%) patients with mixed histology. Of the patients with mixed histology, 72 (87%) patients had embryonal carcinoma and 36 (43%) had LVI. There were no patients with pure teratoma at orchiectomy with combined LVI. A summary of pathology at orchiectomy can be found in Table 1. There were no perioperative deaths.

Table 1. Patient demographic data for the 83 patients with teratoma at orchiectomy who underwent either primary (P-RPLND) or post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND)
CharacteristicP-RPLND (n=44)PC-RPLND (n = 39)
Age, median (years)28.528.6
Orchiectomy
Pure teratoma4(9%)3(8%)
Mixed histology40(91%)36(92%)
Teratoma44(100%)39(100%)
Average percent teratoma42%39%
Embryonal carcinoma38(86%)34(87%)
Yolk Sac19(43%)19(49%)
Seminoma10(23%)7(18%)
Choriocarcinoma4(9%)2(5%)
LVI17(39%)19(49%)
F/U, median(years)1.51.4

Forty-four (53%) patients underwent P-RPLND and 39 (47%) patients underwent PC-RPLND, with a majority receiving bleomycin, etoposide, and cisplatin. Comparisons between these 2 groups are summarized in Table 1. The average percent embryonal carcinoma between P-RPLND vs. PC-RPLND was 44% vs. 46%, respectively.

Clinical stage I (CS I) was noted in 28 (64%) and 7 (18%) of the P-RPLND and PC-RPLND cases, respectively (P < 0.001). Regarding clinical stage II (CS II), there were 16 (36%) and 32 (82%) cases, respectively (P < 0.001). P-RPLND and PC-RPLND had 25 (57%) and 9 (23%) pathologic stage I (PS I) cases, respectively (P = 0.03). Regarding pathologic stage II (PS II) disease, there were 19 (43%) and 30 (77%) cases, respectively (Table 2, P = 0.03). Of these, 13 (30%) and 28 (72%) had metastatic teratoma found during RPLND (P = 0.04). Metastatic embryonal tumor was found in 8 (18%) and 3 (8%) patients with positive lymph nodes (P = 0.01). Low volume disease (pN1) was found in 7 (16%) and 14 (36%) patients with positive lymph nodes for P-RPLND and PC-RPLND, respectively. Overall, there were 3 (4%) recurrences after RPLND, all of which recurred in the PC-RPLND group.

Table 2. Clinical, pathologic, and recurrence data
P-RPLND (n=44)PC-RPLND (n=39)Pvalue
CS I28(64%)7(18%)<0.001
CS II16(36%)32(82%)<0.001
PS I25(57%)9(23%)0.03
PS II19(43%)30(77%)0.03
Teratoma13(30%)28(72%)<0.001
Total recurrence03(8%)0.09

All recurrences were identified by CT scan. The average time to recurrence was 0.4 years. Of the recurrences, none underwent adjuvant chemotherapy. One patient had recurrent mass at the hilum of a solitary right kidney, a retrocrural mass, and a left upper lobe metastasis. He underwent repeat RPLND and thoracotomy with wedge resection of the pulmonary metastasis. A second patient had a 2.8 cm mesenteric mass detected on postoperative imaging, which is being managed conservatively. The third patient underwent resection of metastatic teratoma to the left subclavicular region compressing the thoracic duct. He later had resection of a recurrent pelvic retroperitoneal mass and underwent a third RPLND for recurrent retrocaval and left para-aortic teratoma. For the P-RPLND patients, 3 underwent adjuvant chemotherapy in light of positive pathology immediately after RPLND.

Operative data were analyzed and compared between the P-RPLND vs. PC-RPLND groups. The P-RPLND group had less blood loss (170 vs. 471 cc, P = 0.07) and less OR time (180 vs. 228 minutes, P = 0.01) compared witih the PC-RPLND group. Hospital stay was similar for P-RPLND vs. PC-RPLND (4 vs. 4.5 days, P = 0.1). There were 3 (7%) perioperative complications in the P-RPLND group: 1 ileus, 1 postoperative pain, and 1 due to chylous ascites/pain. The PC-RPLND group had 8 (21%) perioperative complications: 3 ileus, 3 postoperative pain, 1 chylous ascites/pain, and 1 DVT. There were no deaths in either group (Table 3).

Table 3. Perioperative data
P-RPLND (n=44)PC-RPLND (n=39)Pvalue
Operative time (min)179.8227.50.01
EBL(cc)1704710.07
Length of stay(days)44.50.1
Complications3(7%)8(21%)0.1

Back to Article Outline

4. Discussion 

RPLND remains an important therapy in the management of testis cancer. The safety and minimal morbidity of the procedure have been well described [16], [17], [18]. RPLND not only eradicates viable tumor but eliminates teratoma, which may be present in 20% to 30% of patients with pathologic stage II (PSII) disease. Teratoma predominant tumor at orchiectomy is less likely to metastasize [19], however, teratoma in the retroperitoneum may be less amenable to chemotherapy. Teratoma is resistant to chemotherapy and also carries a risk of malignant transformation in 6% to 14% of cases [11], [12], [13], [14]. These findings suggest the importance of eliminating the risk of viable tumor and/or teratoma with a meticulous RPLND.

In patients with CS II NSGCT, RPLND cannot be safely omitted after induction chemotherapy as the incidence of viable retroperitoneal disease in the form of teratoma or viable malignancy have been found to be present in up to is 20% of these patients [2]. Unfortunately, Stephenson et al. did not report orchiectomy histology in their analysis [2]. Beck et al. performed a retrospective review of 644 PC-RPLND patients to observe the incidence of teratoma in retroperitoneum after chemotherapy [20]. They found the incidence of teratoma at PC-RPLND to be 86% vs. 48% in patients with and without teratoma at orchiectomy. In our PC-RPLND cohort, 30 (77%) patients had positive pathology at RPLND of which 28 (72%) of these contained teratoma. There were 19 (43%) positive lymph nodes for P-RPLND of which 13 (30%) contained teratoma. Complete orchiectomy histology was not analyzed in either of the aforementioned studies, however, our percentage of teratoma identified at primary and PC-RPLND compares quite well. Of note, all 3 recurrences occurred in the PC-RPLND group, while only 3 (7%) P-RPLND patients underwent chemotherapy in light of positive RPLND pathology.

Inci et al. found 71% of PC-RPLND patients with teratoma at orchiectomy had positive pathology [15]. In our study, 77% of PC-RPLND patients had positive lymph nodes, which is comparable to prior series. Positive lymph nodes were identified in 19 (43%) P-RPLND patients, of which only 3 (7%) P-RPLND patients went on to receive chemotherapy in light of positive pathology found at RPLND. Thus, 41 (93%) P-RPLND were cured and spared chemotherapy in the majority.

There are inherent risks associated with chemotherapy and radiation exposure from follow-up imaging. A recent study illustrated that the risk of secondary malignancy or cardiovascular disease as a result of chemotherapy for testicular cancer was up to 1.9-fold greater compared with patients who had undergone surgery [8]. Haugnes et al. noted the effect on pulmonary function by large cisplatin doses or by combined chemotherapy and pulmonary surgery to be 2- to 4-fold the effect of smoking [9]. Surgical management with RPLND avoids the need for a more rigorous follow-up regimen with CT imaging used for surveillance in primary chemotherapy, which becomes important as a risk for secondary malignancy [4], [5]. Brenner and Hall note that 1.5% to 2.0% of all cancers in the United States may be attributable to ionizing radiation from CT scans [4]. Tarin et al. noted the relative risk of a secondary malignancy with surveillance compared to a single scan after RPLND to be approximately 15-fold [5]. This magnitude of risk is inversely proportional with patient age and should be discussed with the patient during counseling of treatment options.

The surgical and medical management of high risk testicular cancer has been well described with disease-free survival for CSI-CSII approaching 100% [21]. Two factors that have been shown to lead to high rates of retroperitoneal metastasis after orchiectomy are embryonal carcinoma predominance (ECP) and presence of lymphovascular invasion (LVI). In our series, 76 (92%) of patients had mixed histology. Of the patients with mixed histology, 72 (87%) patients had embryonal carcinoma and 36 (43%) had LVI. These high risk features combined with teratoma may have placed these patients at an even greater risk for metastatic disease. There were few cases of pure teratoma present, and we could not comment on any significant differences from the cohort.

Our P-RPLND cohort illustrates the natural history of the inherent risk of retroperitoneal disease and chemoresistant teratoma in patients with teratoma at orchiectomy. Although a majority of our patients had mixed histology, compared with prior studies [2], [20], our 30% finding of teratoma in the retroperitoneum after P-RPLND combined with no retroperitoneal recurrence bodes well for P-RPLND being not only an accurate staging modality but curative therapy. We feel that patients with a teratoma component at orchiectomy are at increased risk for teratoma in the retroperitoneum and should be counseled accordingly to the risks and benefits of undergoing RPLND vs. chemotherapy.

Back to Article Outline

5. Conclusions 

Patients with teratoma at orchiectomy were associated with other high risk features and are at significant risk for metastatic disease. Patients with post-chemotherapy retroperitoneal findings are at significant risk for viable GCT and/or teratoma and should undergo PC-RPLND. Patients managed with P-RPLND can be spared chemotherapy in the majority of cases and decrease the risk of radiation exposure.

Back to Article Outline

References 

  1. Williams SB , McDermott DW , Winston D , et al.  Retroperitoneal lymph node dissection in patients with high risk testicular cancer . J Urol . 2009;181:2097–2102
  2. Stephenson AJ , Bosl GJ , Motzer RJ , et al.  Nonrandomized comparison of primary chemotherapy and retroperitoneal lymph node dissection for clinical stage IIA and IIB nonseminomatous germ cell testicular cancer . J Clin Oncol . 2007;25:5597–5602
  3. Beck S , Peterson MD , Bihrle R , et al.  Short term morbidity of primary retroperitoneal lymph node dissection in a contemporary group of patients . J Urol . 2007;178:504–506
  4. Brenner DJ , Hall EJ . Computed tomography—an increasing source of radiation exposure . NEJM . 2007;357:2277–2284
  5. Tarin TV , Sonn G , Shinghal R . Estimating the risk of cancer associated with imaging related radiation during surveillance for stage I testicular cancer using computerized tomography . J Urol . 2009;181:627–632
  6. Richardi L , Scelo G , Boffetta P , et al.  Second malignancies among survivors of germ-cell testicular cancer: A pooled analysis between 13 cancer registries . Int J Cancer . 2006;120:623–631
  7. Howard R , Gilbert E , Lynch CF , et al.  Risk of leukemia among survivors of testicular cancer: A population-based study of 42,722 Patients . AEP . 2008;18:416–421
  8. van den Belt-Dusebout AW , de Wit R , Gietema JA , et al.  Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer . J Clin Oncol . 2007;25:4370–4378
  9. Haugnes HS , Aass N , Fossa SD , et al.  Pulmonary function in long-term survivors of testicular cancer . J Clin Oncol . 2009;27:2779–2786
  10. NCCN Clinical Practice Guidelines in Oncology . 2010; V. 1 www.nccn.org
  11. Motzer RJ , Amsterdam A , Prieto V , et al.  Teratoma with malignant transformation: Diverse malignant histologies arising in men with germ cell tumors . J Urol . 1998;159:133–138
  12. Little JS , Foster RS , Ulbright TM , et al.  Unusual neoplasms detected in testis cancer patients undergoing post-chemotherapy retroperitoneal lymphadenectomy . J Urol . 1994;152:1144–1149
  13. Comiter CV , Kibel AS , Richie JP , et al.  Prognostic features of teratomas with malignant transformation: A clinicopathological study of 21 cases . J Urol . 1998;159:859
  14. Lutke Holzik MF , Hoekstra HJ , Mulder NH , et al.  Non-germ cell malignancy in residual or recurrent mass after chemotherapy for nonseminomatous testicular germ cell tumor . Ann Surg Oncol . 2003;10:131–135
  15. Inci K , Dogan HS , Akdogan B , et al.  Presence of teratoma in orchiectomy specimen increases the need for post-chemotherapy RPLND . Urol Oncol . 2009; in press
  16. Richie JP . Clinical stage 1 testicular cancer: The role of modified retroperitoneal lymphadenectomy . J Urol . 1990;144:1160–1163
  17. Donohue JP , Foster RS , Rowland RG , et al.  Nerve-sparing retroperitoneal lymphadenectomy with preservation of ejaculation . J Urol . 1990;144(2 Pt 1):287–291
  18. Donohue JP , Foster RS . Retroperitoneal lymphadenectomy in staging and treatment (The development of nerve-sparing techniques) . Urol Clin North Am . 1998;25:461–468
  19. Leibovitch I , Foster RS , Ulbright TM , et al.  Adult primary pure teratoma of the testis (The Indiana experience) . Cancer . 1995;75:2244–2250
  20. Beck SD , Foster RS , Bihrle R , et al.  Teratoma in the orchiectomy specimen and volume of metastasis are predictors of retroperitoneal teratoma in post-chemotherapy nonseminomatous testis cancer . J Urol . 2002;168:1402–1404
  21. Einhorn LH . Testicular cancer as a model for a curable neoplasm: The Richard and Hinda Rosenthal Foundation Award Lecture . Cancer Res . 1981;41:3275–3280

 No reprints will be available.

PII: S1078-1439(09)00406-2

doi:10.1016/j.urolonc.2009.12.006

Urologic Oncology: Seminars and Original Investigations
Volume 30, Issue 1 , Pages 60-63, January 2012

Article Tools