Advanced Germ Cell Tumors Research Articles

20 Pazopanib in patients (pts) with advanced germ cell tumors (GCT): Results from an open-label, single-group, phase 2 trial (Pazotest-01)

20 Pazopanib in patients (pts) with advanced germ cell tumors (GCT): Results from an open-label, single-group, phase 2 trial (Pazotest-01)

25 Impact of bleomycin (BLM) administration on the development of pulmonary toxicity in advanced germ cell tumours (GCT) receiving first-line chemotherapy (CT): A meta-analysis of randomized studies

25 Impact of bleomycin (BLM) administration on the development of pulmonary toxicity in advanced germ cell tumours (GCT) receiving first-line chemotherapy (CT): A meta-analysis of randomized studies

22 Second-line combination chemotherapy with cisplatin, gemcitabine and paclitaxel for the treatment of advanced germ cell tumours

22 Second-line combination chemotherapy with cisplatin, gemcitabine and paclitaxel for the treatment of advanced germ cell tumours

Postchemotherapy residual tumour resection in complex metastatic sites of advanced testicular germ cell tumours

Postchemotherapy residual tumour resection (PC-RTR) is an integral part of the multimodal therapy for advanced testicular germ cell tumours. Depending on the extent and localisation of the residual mass, PC-RTR may necessitate a multidisciplinary procedure (which should be planned preoperatively), to resolve even complex situations in an oncologically sound manner, with lower treatment-related morbidity The aim of article is to report on the interdisciplinary management of complex residual masses. Of atotal of 162patients who underwent PC-RTR, 24 (17.8 %) patients underwent, in addition to abilateral postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND), complex adjunctive resections including the abdominal aorta, the inferior vena cava, or the thoracic/lumbar spine, and the neighbouring vessels (n= 15). We performed aretrospective analysis of treatment-associated complications according to the Clavien-Dindo classification and of progression-free, cancer-specific and overall survival. Median patient age was 24.5 (18-52) years. All patients had an intermediate or poor prognosis according to the International Germ Cell Cancer Collaboration Group (IGCCCG). Median tumour diameter at the time of surgery was 18.6 (9.0-35) cm. In 5patients 1-2metastatic lumbar vertebral bodies were completely resected, stabilised and replaced by means of a cage. In 6 patients resection of the abdominal aorta/inferior vena cava with vascular prosthesis replacement was required owing to infiltration. In 2 patients the common iliac artery or vein was resected and replaced. In addition, retrocrural lymph nodes had to be resected in 5patients and 3patients required adjunctive nephrectomy. In another 4 patients the Whipple procedure was required owing to infiltration into the pancreas and/or duodenum. The median operating time was 7.8 (6-15) h, the median blood loss was around 1,450 (900-3,400) ml, and 2 Clavien-Dindo grade IVa complications occurred. Pathohistology revealed teratoma/vital cancer in 16/24patients and scarring/necrosis in 8 patients. After amedian follow-up of 2.5years, 1patient developed recurrent disease and 1 patient died of the disease. Postchemotherapy, a few patients with advanced nonseminomas (NS) need complex residual tumour resection in an interdisciplinary setting, with a good functional and oncological outcome. Even the involvement of vascular vertebral structures does not constitute a contraindication for complete resection.

Impact of bleomycin (BLM) administration on the development of pulmonary toxicity in advanced germ cell tumors (GCT) receiving first-line chemotherapy (CT): A meta-analysis of randomized studies.

482 Background: Little is known about the impact of BLM administration on the development of pulmonary toxicity (PT) in patients (pts) with advanced GCT. This information is critical to further enhance the successful delivery of effective and safe CT in these pts. Methods: Literature was searched for randomized trials of 1st-line CT ( ≥ 3 cycles) for GCT. Descriptive statistics were used to summarize data, dichotomized by BLM-containing vs non containing CT. Univariable and multivariable analyses by random effect models evaluated the predictive role of BLM administration on the development of all grade and G3-4 PT, adjusted for the length of follow-up (FUP, continuous), time-frame of treatment ( ≤ 1997 versus > 1997) % of pts with lung metastases (LM), % of primary mediastinal GCT (PMGCT), IGCCCG risk group. Results: 53 arms of 26 phase II and III trials totalling 6,498 pts were selected: 40 with BLM (n = 5,093) and 13 without BLM (n = 1,405). Median % of pts with LM was 44% (range 22-84%) and 31% (19-79%) in BLM-containing and non containing arms (Wilcoxon test p = 0.505). Median % of PMGCT was 15% (range 0-48%) and 2% (0-13%), respectively (p = 0.146). Median BLM total dose and No. of administrations were 360mg (range 120-375) and 12 (2-24). Median FUP was 52 and 53 months, respectively. The pooled probability of all grade PT was 11.7% (95% CI: 8.4-16.0%) and 1.7% (95% CI: 0.7-4.2%) in BLM-containing and non containing arms. Univariably, BLM administration was associated with the incidence of both all grade (odds ratio [OR]: 7.57, 95%CI: 2.84-20.18, Wald test p < 0.001) and G3-4 PT (OR: 5.19, 95%CI: 1.57-17.16, p = 0.007). Multivariably, BLM administration was significantly associated with the incidence of all grade PT (OR: 4.14, 95%CI: 1.36-12.59, p = 0.012) and trended to significance for G3-4 toxicity (OR: 2.24, 95%CI: 0.91-5.51, p = 0.080). Conclusions: In this meta-analysis, BLM administration was significantly associated with the development of PT in pts with GCT. The quantification of the magnitude of incidence of PT provided here might be useful to optimize the delivery of non-PEB CT in the 1st-line setting.

Pazopanib in patients (pts) with advanced germ cell tumors (GCT): Results from an open-label, single-group, phase 2 trial (Pazotest-01).

481 Background: Therapeutic options for pts with chemoresistant GCT are limited and prognosis is poor. Pazopanib (PZP) is a potent and selective tyrosine kinase inhibitor (TKI) with distinct antiangiogenic activity. Methods: Pazotest-01 enrolled pts who were given PZP 800 mg/day orally until disease progression (PD) or unacceptable toxicity. Eligibility included failure of ≥ 2 platinum-based regimens, including high-dose chemotherapy (HDCT). Baseline serum tumor markers (STM), a computed tomography and a FDG-PET were repeated after 4 wks of PZP and q8 weeks thereafter. The primary endpoint was PFS (H0: 3-month PFS ≤ 10%, H1: ≥ 25%, α = 5%/β = 20%). PD was defined as rising STM, an increase in tumour size, or the appearance of new lesions. An enrolment of 43 pts was planned from a single center (NCT01743482). Results: From 05/2013 to 07/2015, 32 pts were enrolled (27 [84.4%] with nonseminoma, including 5 [15.6%] with malignant transformation, and 5 seminomas). 5 (15.6%) had primary mediastinal nonseminoma (PMNSGCT). 3 had failed two prior regimens, 15 (46.9%) three, and 14 (43.7%) > 3 regimens, including HDCT in 15 (46.9%). 20 (62.5%) had liver, bone, or brain metastases. 29 pts had elevated STM: 18 of them (62.1%) had a STM decline (mean: -53.5%). 1 PR, 19 SD (64.5% clinical benefit) and 12 PD were obtained according to RECIST v1.1. 8 pts (25%) had a densitometric and 10 (29%) a metabolic partial response. The kinetics of response was predictable in all pts: best response was seen within 4wks of starting PZP, neither PR nor STM decline occurred > 4wks. Median follow up was 15.7 months. Median PFS was 2.73 months, 3-month PFS was 28% (95%CI: 13.3-44.8). 4 pts (12.5%) were progression-free at > 5 months FUP (including 1 PMNSGCT). Median OS was 4.9 months. 4 cases (12.5%) of G3 AST/ALT increase, and 1 case of G3 diarrhea and vomiting each have been observed. 7 pts (21.9%) had G2 asthenia. Conclusions: PZP is endowed with potent anti-tumor activity in extensively pretreated patients with GCT. PZP was well tolerated, and the combination with paclitaxel is a rational next step to improve the response duration. The primary endpoint is pending confirmation in the full sample-size, and mature results will be presented. Clinical trial information: NCT01743482.

Actionable targets in patients with cisplatin-resistant advanced germ cell tumors.

473 Background: Approximately 30% of patients with advanced germ cell tumor (aGCT) will progress after first-line chemotherapy. Nearly half of these patients will die of progressive GCT. We describe potentially actionable mutations in a cohort of patients with platinum-resistant aGCT through targeted sequencing. Methods: 76 patients with cisplatin-resistant (CR) disease were sequenced using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay that examines 341 cancer-related genes. Patients were categorized as CR if they met any of the following criteria: 1) incomplete response to first-line cisplatin-based chemotherapy; 2) nonteratomatous tumor progression after standard chemotherapy; 3) nonteratomatous GCT identified at postchemo surgery. We grouped all somatic mutations into core signal transduction pathways or canonical cell functions to identify potential precise targets for therapy. Results: The majority of patients had nonseminoma histology (n = 64, 84%). International Germ Cell Cancer Collaborative Group risk was good, intermediate, and poor in 34%, 13%, and 53% of patients. 17 patients died of disease. In total, 51 potentially actionable alterations were identified in 36/76 (47%) patients. In the TP53 pathway, 7 MDM2 amplifications and 4 MYCN amplifications that may sensitize to nutlin-3 inhibitors were identified. Within the receptor tyrosine kinase pathway, 3 KIT mutations, 1 KDR amplification, and 1 MET amplification were seen that may sensitize to tyrosine kinase inhibitors. Eleven KRAS mutations, 3 NRAS mutations, 3 BRAF mutations, and 2 RAC1 mutations were see among the RAS pathway with preclinical data suggesting efficacy towards respective inhibitors. Actionable targets were also among the PI3-K, WNT, and cell cycle pathways. Potential targets with chromatin modifying or tumor suppressor functions were also seen. Conclusions: We describe actionable alterations that may guide treatment selection in a significant proportion of patients with CR aGCT. Targeted sequencing of these patients may allow us to enrich future clinical trials with patients whose tumors harbor alterations in the drug target of interest.

Comprehensive genomic profiling (CGP) of advanced nonseminomatous testicular germ cell tumors (NSGCT) to reveal clinically relevant genomic alterations (CRGA) to guide targeted therapy.

477 Background: NSGCT, the most common solid malignancy in U.S. men ages 18-35, has a > 95% 5-year survival due to exquisite chemosensitivity; however, chemoresistant recurrences still contribute to 400 NSGCT deaths/year. We queried CGP results of the largest collection to date of recurrent NSGCT (n = 28) to identify targeted therapy options for this subset of high risk patients. Methods: DNA was extracted from 28 FFPE NSGCT clinical specimens. Hybridization captured libraries of 236 (FoundationOne, n = 20) or 305 (FoundationOne, n = 8) genes, plus select introns frequently rearranged in cancer were sequenced to high ( > 605x), uniform coverage. All classes of genomic alterations (GA; base subs, in/dels, rearrangements, and copy number alterations) were evaluated. CRGA were defined as GA associated with on-label targeted therapies and targeted therapies in mechanism-driven clinical trials. CGP coverage data was used to assess for chromosome 12p arm amplifications. Results: 28 samples (29% primary, 71% metastasis) from patients (avg 33.7 y) with recurrent NSGCT of predominant pattern of yolk sac tumor (43%), embryonal carcinoma (18%), choriocarcinoma (18%), or unspecified/mixed (21%) were profiled. 57% of NSGCT had chromosome 12p amplification ( > 6 copies). 89% had at least one GA not localized to chromosome 12p, including CRGA of CRKL (11%), MCL1 (11%), MDM2 (11%), GNAS (11%), KRAS (SV 7%), AURKA (7%), KIT (7%). CRGA in each of: AKT1, AKT2, BRAF, ERBB2, NF1, PIK3R2, PDGFRA, STK11 were identified in a single case. To date, we are aware of one patient in whom treatment with everolimus was initiated on the basis of the CGP results (inactivating point mutations in STK11 and PIK3R2) and who experienced marker stabilization lasting 5 months suggesting a biologic effect of this therapy. Conclusions: GA not accounted for by 12p amplification are present at a higher frequency than previously reported in recurrent or treatment-resistant NSGCT. The prevalence of CRGA and clinical response to targeted therapy in one such patient support the utility of CGP to identify additional therapeutic options for high risk NSGCT and warrants additional study.

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

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.

Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: a study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party.

Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel.

Irinotecan and nedaplatin as salvage therapy for patients with advanced germ cell tumors following intensive treatment with cisplatin-based combination chemotherapies.

To analyze the clinical outcomes of the irinotecan plus nedaplatin (IN) regimen in patients with advanced germ cell tumors (GCTs) refractory to cisplatin-based combination chemotherapies. This study included a total of 20 consecutive advanced GCT patients who were categorized into intermediate- or poor-risk GCT groups according to the International Germ Cell Consensus Classification, and were judged to show refractory or relapsed disease after bleomycin, etoposide and cisplatin and cisplatin, ifosfamide and paclitaxel therapies. All 20 patients subsequently received IN therapy (irinotecan 100 mg/m(2) on days 1 and 15; nedaplatin 100 mg/m(2) on day 1) every 4 weeks. Following a median of 3 cycles of IN, 9 patients (45 %) achieved normalization of serum tumor markers. In addition, surgical resection of the residual tumors following IN was performed in 5 patients, of whom 4 were pathologically diagnosed with no viable cancer cells. At a median follow-up of 9 months, 11 patients (55 %) were alive, including 7 (35 %) with no evidence of disease, whereas the remaining 9 (45 %) died of disease progression. The median duration of overall survival after the introduction of IN to these 20 patients was 13.4 months. Severe hematological toxicities were observed in all patients, but were manageable. Although fatal treatment-related interstitial pneumonia occurred in 1 patient, other non-hematological toxicities were generally tolerable. Considering the markedly unfavorable characteristics of the included patients with advanced GCT who were intensively treated with cisplatin-based combination chemotherapies, IN could be regarded as having promising therapeutic activity with an acceptable toxicity profile.

The impact of time of performance of delayed orchiectomy on survival of patients with advanced germ cell tumors of testicles

Aim: To investigate the impact of time of performance of delayed orchiectomy on overall survival of patients with advanced germ cell tumors of testicle who didn’t undergo surgery before starting of treatment. Materials and methods: From 1986 to 2010 in the department of clinical pharmacology and chemotherapy 71 (4,8%) of 1486 patients underwent delayed orchiectomy. During the first course of chemotherapy (1st group) 39 (55%) patients underwent surgery, 21 (29,6%) patients - during 2nd -4th courses (2nd group), after the ending of chemotherapy – 11 (15,5%) patients (3rd group). Results: Final histological investigation of the specimens revealed viable germ cell tumor in 25 (64,1%) patients in the 1st group, in 10 (47,7%) patients in the 2nd group and no viable tumor in the 3rd group. Conclusion: Performance of orchiectomy simultaneously with the removal of the other sites of the tumor after chemotherapy doesn’t impair survival.

Association of genomic alterations with cisplatin resistance (cisR) in advanced germ cell tumors (aGCT).

4510 Background: 20% of patients (pts) with aGCT progress after initial chemotherapy (chemo), displaying at least partial cisR. We sought to characterize the genetic alterations in aGCT and identif...

Impact of response to induction chemotherapy (CT) and prior paclitaxel (TXL)-based CT on the outcome of salvage high-dose chemotherapy (HDCT) for relapsed germ-cell tumors (GCT) in the modern era: An EBMT Solid Tumors Working Party study.

4535 Background: The prognostic impact of response to induction CT preceding salvage HDCT courses, and prior TXL-therapy for advanced GCT is unknown. This knowledge can inform trial design, stratif...

Clinical outcomes and histological findings of patients with advanced metastatic germ cell tumors undergoing post-chemotherapy resection of retroperitoneal lymph nodes and residual extraretroperitoneal masses.

To assess clinical outcomes of patients with advanced germ cell tumor undergoing post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection. Between 1998 and 2013, 175 retroperitoneal lymph node dissections for advanced metastatic germ cell tumors were carried out at Kyoto Prefectural University of Medicine, Kyoto, Japan. Of patients receiving retroperitoneal lymph node dissections, 156 underwent post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection as first surgery after completion of chemotherapy. Of these 156 patients, 47 underwent both post-chemotherapy retroperitoneal lymph node dissection and extraretroperitoneal mass resection. The histological findings were necrosis in 59.6%, teratoma in 31.4% and viable cancer in 9.0% at retroperitoneal lymph node. At extraretroperitoneal mass resection, necrosis was present in 59.6%, teratoma in 31.9% and viable cancer in 8.5%. Overall histological discordance between retroperitoneal lymph node and extraretroperitoneal mass was found in 31.9%. Five-year disease-free survival stratified by retroperitoneal lymph node histology in 156 patients was 91.3% for necrosis, 78.7% for teratoma and 63.5% for viable cancer (log-rank, P = 0.009). Antegrade ejaculation was preserved in 80.9%. In the worst histology of post-chemotherapy retroperitoneal lymph node dissection or extraretroperitoneal mass resection in 156 patients, 5-year disease-free survival was 93.2% for necrosis, 79.0% for teratoma and 63.4% for viable cancer (log-rank, P < 0.001). Independent prognostic factors for disease-free survival were presence of viable cancer in retroperitoneal lymph node histology and salvage chemotherapy. The presence of viable cancer at the retroperitoneal lymph node is an independent predictor of disease recurrence. In approximately one-third of cases, there is a histological discordance between retroperitoneal lymph node and extraretroperitoneal mass. Resection of residual retroperitoneal lymph node and extraretroperitoneal masses remains an important procedure in the management of advanced germ cell tumors.

603 Complications and adjunctive surgical procedures of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced germ cell tumours – single center experience

603 Complications and adjunctive surgical procedures of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced germ cell tumours – single center experience

601 Complicated postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced testicular germ cell tumours – is it worth the efforts?

601 Complicated postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced testicular germ cell tumours – is it worth the efforts?

600 Prognostic factors of antegrade ejaculation in nerve-sparing post-chemotherapy resection of retroperitoneal lymph node dissection for advanced germ cell tumors

600 Prognostic factors of antegrade ejaculation in nerve-sparing post-chemotherapy resection of retroperitoneal lymph node dissection for advanced germ cell tumors

Importance of continuous sequential chemotherapy and multimodal treatment for advanced testicular cancer: a high-volume Japanese center experience.

Patients with “difficult-to-treat” advanced testicular cancer can require multiple therapies. We retrospectively assessed our patients with advanced germ cell tumors (GCTs) and characterized the clinical efficacy, outcomes, and factors affecting overall survival (OS).Two hundred fifty-three patients with advanced GCTs were treated at Kyoto Prefectural University of Medicine, Kyoto, Japan, from June 1998 to September 2013. Of 253 patients, 142 patients had salvage chemotherapy.As first-line therapy, bleomycin, etoposide, and cisplatin, and etoposide and cisplatin therapies were performed in 234 cases (92.5%). As second-line therapy, etoposide, ifosfamide, and cisplatin/vinblastine, ifosfamide, and cisplatin, and paclitaxel, ifosfamide, and cisplatin/paclitaxel, ifosfamide, and nedaplatin therapies were carried out in 44 and 59 cases, respectively. Furthermore, 111, 72, 44, and 28 cases had third, fourth, fifth, and sixth-or-later-line chemotherapy, respectively. Five-year OS rate stratified by chemotherapy line was 95.5% in the first line, 89.4% in the second line, 82.1% in the third line, 45.1% in the fourth line, and 58.9% in the fifth or after line. A statistical significant difference was found when comparing fourth-or-after-line versus first to third-line therapy. Additional procedures were performed, including retroperitoneal lymph node dissection (RPLND) (n = 168), extra-RPLN resection (n = 114), and external beam radiotherapy/stereotactic radiotherapy (n = 78).Multivariate analysis showed that factors predicting better outcomes were in serum tumor marker (STM) normalization, RPLND, and extra-RPLN resection.Good outcomes were obtained in patients who completed chemotherapy up to third line. After fourth-line chemotherapy, approximately 50% of “difficult-to-treat” patients could be cured with normalization of STM levels and residual mass resection. Continuous or sequential chemotherapy with multimodality therapy is important for patients with “difficult-to-treat” advanced GCTs. Effective chemotherapy after third line should be developed.

Complicated postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced testicular germ cell tumours: Is it worth the efforts?

382 Background: PC-RPLND is performed in patients with residual masses following chemotherapy for advanced testicular cancer. Complicated PC-RPLND is defined by redo, salvage or desperation procedures including the necessity to resect major adjacent vascular, skeletal or intestinal structures. We report on our single centre experience of complicated (group A) versus uncomplicated PC-RPLND (group B). Methods: A total of 138 patients underwent PC-RPLND and 24 (14.8%) patients underwent complicated RPLND: resection of major retroperitoneal vessels n=15 (9.3%), skeletal and pancreaticoduodenal structures in 5 (3.1%) and 4 (2.5%) patients, respectively. We performed a retrospective analysis of treatment-associated complications (Clavien-Dindo classification). Progression-free, cancer-specific and overall survival was calculated. Results: There were significant differences between group A and B concerning tumour diameter (5.9 vs 18.6cm, p = 0.03), intermediate/poor IGCCCG risk (39.9% vs 83.4%, p=0.02), seminomatous primary (7.9% vs 20.8%, p=0.03). Pathohistology of the residual masses was significantly different between group A and B: vital cancer was identified in 6 (4.3%) and 8/24 (33.3%, p=0.02) pts, resp., whereas teratoma was identified in 37 (26.8%) and 14/24 (58.3%, p=0.01), resp. In addition 3 pts in group B demonstrated malignant somatic transformation. After a median follow-up of 32 months for group B, 3 patients with MTS experienced recurrences, 1 patient died of the disease. The remainder survived event-free. In group A, median follow-up was 37 months and DOD was observed in 2 pts, 8 pts (5.8%) experienced recurrences. Frequency of complications grade I-IIIb did not differ significantly between group A and B with vascular or skeletal surgery (6.2 vs 13.3%), however, it increased significantly to 65% in pancreatic surgery (p &lt; 0.001). Conclusions: Few patients with advanced NS need complex surgery in an interdisciplinary setting with good functional and oncological outcome. Despite an increased risk of short-term complications complicated PC-RPLND results in long-term survival &gt; 90% and it is justified if performed at specialized centres.