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For inconclusive testicular tumors with negative tumor markers, frozen section examination (FSE) during inguinal exploration is recommended. However, FSE is time-consuming and therefore often not requested. Furthermore, the exact diagnostic benefit remains poorly defined. We performed a systematic review and meta-analysis summarizing 12 published studies and our own series of FSE in patients with inconclusive testicular tumors, resulting in a cohort of 1052 FSEs. FSE showed sensitivity of 99% and specificity of 96% with a positive predictive value of 98% and a negative predictive value of 97%. Most importantly, one-third of all testicular tumors investigated were correctly identified as being suitable for testis-sparing surgery and orchiectomy could be avoided. For patients with inconclusive testicular tumors, FSE is useful for deciding whether testis-sparing surgery is an option or whether radical orchiectomy should be performed. Thus, these patients should be optimally treated in institutions where FSE is available. PATIENT SUMMARY: We found that intraoperative examination of a frozen section is useful in deciding on whether the entire or only parts of the testicle can be removed. We conclude that frozen section examination should be offered to men with small testicular lesions and negative tumor markers.

Die Mehrzahl der Manner mit metastasiertem Hodenkrebs wird durch eine primare Chemotherapie geheilt. Nur selten spricht die Erkrankung auf die primare Behandlung ungenugend an oder tritt nach zunachst erfolgreicher Behandlung zu einem spateren Zeitpunkt erneut auf. Die dann erforderliche Salvage-Chemotherapie kann bei vielen Betroffenen immer noch zu einer langfristigen Kontrolle und dauerhaften Heilung der Erkrankung fuhren. Allerdings ist die Salvage-Chemotherapie komplizierter und nebenwirkungsreicher als die primare Behandlung und sollte ausschlieslich an Einrichtungen durchgefuhrt werden, die sich auf die Therapie dieser Patienten spezialisiert haben. Bei der konventionell dosierten Salvage-Chemotherapie kommen verschiedene konventionell dosierte Kombinationen von Cisplatin, Ifosfamid und entweder Vinblastin, Etoposid oder Paclitaxel zum Einsatz, ohne dass eine Uberlegenheit eines bestimmten Schemas gezeigt worden ware. Die trotz allem unbefriedigenden Ergebnisse der konventionell dosierten Salvage-Chemotherapie fuhrten schon fruh zum breiten Einsatz einer hoch dosierten Salvage-Chemotherapie mit autologer Stammzellreinfusion, die in der Regel nach Stammzellmobilisation mit 2–3 Zyklen hoch dosiertem Carboplatin und Etoposid durchgefuhrt wird. Eine ganzlich andere Strategie wird dagegen bei den seltenen Spatrezidiven verfolgt, die mindestens 2 Jahre nach der letzten Cisplatin-haltigen Chemotherapie oder sogar noch spater auftreten. Diese Spatrezidive sind haufig refraktar gegenuber Chemotherapie und konnen meist nur durch eine vollstandige operative Resektion geheilt werden. Nur in Fallen, in denen die vollstandige operative Resektion nicht moglich ist, sollte eine medikamentose Chemotherapie mit einem Salvage-Regime ggf. dosisintensiviert erfolgen. Eine vollstandige operative Resektion benotigen auch diejenigen Patienten, die nach einer Salvage-Chemotherapie noch radiologische Residuen aufweisen. Da die Rate an vitalem undifferenziertem Tumor oder Teratom nach Salvage-Chemotherapie hoher ist als nach primarer Behandlung, mussen Patienten mit Tumorresiduen nach Salvage-Chemotherapie obligat eine Residualtumorresektion aller radiologisch nachweisbaren Residuen erhalten. Patienten mit mehrfachen Rezidiven oder Patienten mit Rezidiven nach Hochdosis-Chemotherapie werden nur selten geheilt. Durch den gut abgestimmten Einsatz von palliativer Chemotherapie, palliativen Tumorresektionen und gelegentlich auch palliativer Bestrahlung konnen jedoch oft trotz fehlender Heilungsaussicht Lebenszeit erheblich verlangert oder Symptome gelindert werden.

BACKGROUND MiR-371a-3p predicts the presence of a macroscopic non-teratomatous germ cell tumour (GCT). We hypothesised that miR-371a-3p can also detect recurrence during active surveillance (AS) of stage I GCT. METHODS We prospectively collected serum samples of 33 men. Relative expression of serum miR-371a-3p levels was determined at each follow-up visit using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS Recurrence was detected using standard follow-up investigations in 10/33 patients (30%) after a median of 7 months. Directly after orchiectomy, miR-371a-3p levels were not elevated in any of the 15 patients with available post-orchiectomy samples. However, all ten recurring patients exhibited increasing miR-371a-3p levels during follow-up, while miR-371a-3p levels remained non-elevated in all but one patient without recurrence. MiR-371a-3p detected recurrences at a median of 2 months (range 0-5) earlier than standard follow-up investigations. CONCLUSIONS MiR-371a-3p levels immediately post orchiectomy are not predictive for recurrences and unfortunately cannot support decision-making for AS vs. adjuvant treatment. However, miR-371a-3p detects recurrences reliably and earlier than standard follow-up investigations. If this can be confirmed in larger cohorts, monitoring miR-371a-3p could replace surveillance imaging in seminomatous GCT and reduce the amount of imaging in non-seminomatous GCT. Earlier detection of disease recurrence may also reduce the overall treatment burden.

Purpose Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumor, and currently, there are no published treatment recommendations. Methods We performed a systematic literature review and synthesized clinical presentation, clinicopathological factors associated with metastatic disease, treatment options, and outcomes in men with MTVT. Results We included 170 publications providing data on 275 patients. Metastatic disease occurred in 84/275 (31%) men with malignant MTVT: Most common sites included retroperitoneal lymph nodes (LNs) (40/84, 48%), lungs (30/84, 36%), and inguinal LNs (23/84, 27%). Invasion of the spermatic cord or scrotum was the only risk factor for local recurrence [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.36–7.57]. Metastatic disease was associated with age ≥ 42 years (OR 3.02, 95% CI 1.33–6.86), tumor size ≥ 49 mm (OR 6.17, 95% CI 1.84–20.74), presence of necrosis (OR 8.31, 95% CI 1.58–43.62), high mitotic index (OR 13.36, 95% CI 1.53–116.51) or angiolymphatic invasion (OR 3.75, 95% CI 1.02–13.80), and local recurrence (OR 4.35, 95% CI 2.00–9.44). Complete remission in the metastatic setting was observed in five patients, most of whom were treated with multimodal therapy. Median survival in patients with metastatic disease was 18 months (IQR 7–43). Conclusion Malignant MTVT is a rare but aggressive disease. Since local recurrence is a risk factor for metastatic progression, we recommend aggressive local treatment. Survival and response to any treatment in the metastatic setting are limited.

Purpose:Leydig cell tumors are rare but they are the most common nongerm cell testicular tumors. Only limited evidence exists for reliably differentiating between benign and malignant Leydig cell t...

Background Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this study was to summarize evidence on SCTs’ clinical presentation, clinicopathological risk factors for malignancy, treatment options, and oncological outcomes. Materials and Methods Data sources included Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and Web of Science. Published case reports, case series, and cohorts were included. Data on clinicopathological variables, treatment of local or metastatic disease, site of metastasis, or survival were extracted from each study considered in this paper, and associations between clinicopathological variables and metastatic disease were analyzed. Whenever feasible, data on individual patients were collected. Results Of the 435 patients included, only one ( Conclusion Our findings suggest that few local recurrences result after TSS, and no adjuvant therapy can be regarded as a standard of care. Several risk factors are predictive of metastatic disease. Surgery leads to remission in metastatic disease, whereas systemic treatment alone does not result in long-term remission. Implications for Practice Testicular Sertoli cell tumors usually present without metastatic disease and show low local recurrence rates after testis-sparing surgery; no adjuvant therapy option can be regarded as a standard of care. Patients with risk factors should undergo staging investigations. Those with metastatic disease have poor prognoses, and metastasectomy may be offered in selected cases.

Purpose Testicular granulosa cell tumors (tGrCT) are rare sex cord-stromal tumors. This review aims to synthesize the available evidence regarding the clinical presentation and clinicopathological characteristics, treatment and outcomes. Methods We conducted a systematic literature search using the most important research databases. Whenever feasible, we extracted the data on individual patient level. Results From 7863 identified records, we included 88 publications describing 239 patients with tGrCT. The majority of the cases were diagnosed with juvenile tGrCT (166/239, 69%), while 73/239 (31%) patients were diagnosed with adult tGrCT. Mean age at diagnosis was 1.5 years (± 5 SD) for juvenile tGrCT, and 42 years (± 19 SD) for adult tGrCT. Information on primary treatment was available in 231/239 (97%), of which 202/231 (87%) were treated with a radical orchiectomy and 20/231 (9%) received testis sparing surgery (TSS). Local recurrence after TSS was observed in 1/20 (5%) cases. Metastatic disease was never observed in men with juvenile tGrCT but in 7/73 (10%) men with adult tGrCT. In 5/7 men with metastatic tGrCT, metastases were diagnosed at initial staging, while 2/7 patients developed metastases after 72 and 121 months of follow-up, respectively. Primary site of metastasis is represented by the retroperitoneal lymph nodes, but other sites including lungs, liver, bone and inguinal lymph nodes can also be affected. In comparison with non-metastatic adult tGrCT, men with metastatic adult tGrCT had significantly larger primary tumors (70 vs 24 mm, p 0.001), and were more likely to present with angiolymphatic invasion (57% vs 4%, p 0.002) or gynecomastia (29% vs 3%, p 0.019). In five out of seven men with metastatic disease, resection of metastases or platinum-based chemotherapy led to complete remission. Conclusion Juvenile tGrCT represent a benign entity whereas adult tGCTs have metastatic potential. Tumor size, presence of angiolymphatic invasion or gynecomastia represent risk factors for metastatic disease. The published literature supports the use of testis sparing surgery but there is only limited experience with adjuvant therapies. In the metastatic setting, the reviewed literature suggests that aggressive surgical and systemic treatment might cure patients.

Background To validate the utility of the chemokine ligand 12 (CXCL12) as prognostic marker in patients with localized and metastatic germ cell tumors (GCT). Methods CXCL12 expression was analyzed on a tissue microarray consisting of 750 tissue cores of different histological tumor components, Germ cell neoplasia in situ (GCNIS) and adjacent normal tissue of 263 testicular cancer patients using a semi-quantitative score. The association between CXCL12 expression and recurrence-free survival (RFS) as well as overall survival (OS) was assessed using Kaplan-Meier curves with log-rank tests. Results CXCL12 expression was absent in all seminomas but was found in 52 of 99 (52.5%) non-seminomas. Follow-up was available for 260 patients of which 36 (13.8%) recurred. In patients with stage 1 non-seminoma GCT, CXCL12 expression was not associated with higher risk of disease recurrence (p = 0.270). In contrast, post chemotherapy RFS of patients with metastatic non-seminoma and positive CXCL12 expression was significantly shorter compared to CXCL12 negative patients (p = 0.003). OS differences were not statistically different between patients with CXCL12 positive or negative tumors for either localized or metastatic disease. Conclusions CXCL12 is almost exclusively expressed in non-seminoma. Pure seminoma, GCNIS and adjacent normal testicular tissue are CXCL12 negative. Our analysis suggests that patients with metastatic disease and a CXCL12-positive non-seminoma are at higher risk for disease recurrence after first-line chemotherapy and might thus be candidates for more intensive treatment and/or closer follow-up.

Because spermatocytic tumors of the testis are rare, only limited evidence exists regarding the malignant potential and the optimal management of localized and metastatic disease. We performed a systematic review through MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science to identify reports including patients with testicular spermatocytic tumors. From originally 7863 studies, we extracted data of 146 patients of which 99% were treated with radical orchiectomy. Metastases in patients with initially localised disease were diagnosed in 7% of patients and detected after a median follow-up of 5.5 months (range 2–21 months). Patients with aggressive histology (sarcoma or anaplastic subtype) were more likely to have metastatic disease (6/124 (5%) vs 9/22 (41%), p

To investigate whether the use of pre-orchiectomy instead of pre-chemotherapy tumor marker (TM) levels has an impact on the International Germ Cell Consensus Classification (IGCCCG) risk group assignment in patients with metastatic germ cell tumors (GCT). Demographic and clinical information of all patients treated for primary metastatic testicular non-seminomatous GCT in our tertiary care academic center were extracted from medical charts. IGCCCG risk group assignment was correctly performed with pre-chemotherapy marker levels and additionally with pre-orchiectomy marker levels. Agreement between pre-chemotherapy and pre-orchiectomy risk group assignments was assessed using Cohen’s kappa. Our cohort consisted of 83 patients. The use of pre-orchiectomy TMs resulted in an IGCCCG risk group upstaging in 12 patients (16%, 8 patients from good to intermediate risk and 4 patients from intermediate to poor risk) and a downstaging in 1 patient (1.2%, from intermediate- to good-risk). The agreement between pre-orchiectomy and pre-chemotherapy IGCCCG risk groups resulted in a Cohen’s kappa of 0.888 (p

BACKGROUND The prognostic utility of systemic inflammatory markers has so far not been investigated in patients with metastatic testicular germ cell tumours (GCTs). METHODS International Germ Cell Cancer Cooperative Group (IGCCCG) risk groups and blood-based systemic inflammatory markers (haemoglobin, leukocytes, platelets (P), neutrophils (N), lymphocytes (L), C-reactive protein (CRP) and albumin) of 146 patients undergoing first-line chemotherapy for GCT were retrieved. In addition, N to L ratio (NLR), P to L ratio and the systemic immune-inflammation index (SII=N × P/L) were calculated. The prognostic ability of these markers for overall survival (OS) were assessed using regression analyses and Kaplan-Meier curves with log-rank tests. RESULTS In univariate Cox regression, low haemoglobin and albumin as well as high leukocytes, N, NLR, SII and CRP were associated with a shorter OS. In multivariable Cox regression analyses, high leukocyte (hazard ratio (HR) 1.274 (95% confidence interval (CI) 1.057-1.535); P=0.011) and N count (1.470 (1.092-1.980); P=0.011), higher NLR (84.5 (2.2-3193.4); P=0.017) and SII (12.15 (1.17-126.26); P=0.037) remained independent prognostic predictors for OS besides the IGCCCG risk groups. CONCLUSIONS Systemic inflammatory markers might have prognostic utility for patients with metastatic GCT. The planned IGCCCG update could be an opportunity to test these markers in a larger data set.

Background The International Germ Cell Cancer Collaborative Group (IGCCCG) has been the reference classification for assessing prognosis in men with advanced non-seminomatous germ-cell tumors (NSGCT) for more than 20 years and it relied on 5202 cases treated between 1975 and 1990. Methods An international consortium (30 centers/groups) contributed data on 9530 advanced NSGCT patients treated with cisplatin/etoposide based first line chemotherapy between 1990 and 2013 in prospective cohorts or clinical trials. Updated 5-year progression-free (PFS) and overall survival (OS) rates were calculated. A subset of 4874 patients with complete information on components of IGCCCG, age and lung metastases were split into training (3536) and validation sets (1338). Prognostic factors for PFS were identified in the training set (alpha=0.05) by Cox model, including (transformed) continuous factors and interactions. Results Compared to the 1997 IGCCCG figures, the contemporary 5-year PFS was unchanged for good and intermediate, but significantly improved for poor risk patients; whereas 5-year OS was substantially better for all risk groups (Table). The subgroup with complete data was unbiased. Besides traditional IGCCCG components, we identified older age and lung metastases as negative determinants of PFS. A nomogram including AFP, HCG (both continuous), LDH>2.5xnormal, mediastinal primary, non-pulmonary visceral metastases, age (linear) and lung metastases, with several interactions was built. Its c-index was 0.745 in the training set compared to 0.701 for the 1997 IGCCCG. Table . 903O 5-year PFS IGCCCG 1997 5-year PFS contemporary 5-year OS IGCCCG 1997 5-year OS contemporary Good 89 (87 – 91%) 90 (89 - 91%) 91 (89 - 93%) 96 (95 - 97%) Intermediate 75 (71 – 79%) 78 (76 - 80%) 79 (75 - 83%) 89 (88 - 91%) Poor 41 (35 – 47%) 54 (52 - 56%) 48 (42 - 54%) 67 (65 - 69%) Conclusions In this modern series, PFS improved for poor risk patients, while OS improved in all IGCCCG risk groups. A new prognostic model including older age and presence of lung metastases as additional negative factors is proposed. Independent validation and comparison to the IGCCCG 1997 are being conducted and will tell if the model can identify patient subgroups who may require intensified treatment. Legal entity responsible for the study The International Germ Cell Cancer Collaborative Group (IGCCCG). Funding Swiss Cancer Foundation. Disclosure S. Gillessen: Advisory / Consultancy: AAA International, Active Biotech, Amgen, Astellas Pharma, Bayer, Bristol-Myers Squibb, CellSearch, Clovis, CureVac, Dendreon, ESSA Pharmaceuticals, Ferring, Innocrin Pharmaceuticals, Janssen Cilag, MaxiVAX SA, Millennium, Nectar, Novartis, Orion, Pfizer,; Licensing / Royalties: Co-inventor on patent application (WO 2009138392 A1) for a method for biomarker discover (granted in China, Europe, Japan and the US). R. de Wit: Honoraria (self): Merck, Sanofi, Bayer, Janssen, Roche and Clovis. R.A. Huddart: Honoraria (self): Janssen; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Bristol-Myers Squibb; Research grant / Funding (self): CRUK; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar. All other authors have declared no conflicts of interest.

510 Background: Clin. stage I (CSI) non-seminoma (NS) is disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant (adjuv) chemotherapy with BEP after which relapses are rare. Little is known about the outcome of patients (pts) relapsing after such treatment. Methods: Data from 51 pts with CSI NS and relapse after adjuv BEP from 18 centers/11 countries was collected and retrospectively analyzed. Primary endpoints were OS and PFS calculated from start of treatment of relapse. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results: 23 pts received one cycle adjuv BEP and 28 pts two. Median time to relapse was 13 months, with the earliest relapse two months after start of adjuv BEP and the latest relapse recorded after 26 years. According to IGCCCG, 84% of pts classified as good prognosis at relapse. With a median follow up of 50 months 5y PFS was 64% (95% CI 52-80%) and 5y OS 79% (95% CI 68-92%). Treatment upon relapse was diverse, the majority of pts received combination- chemotherapy and surgery. 10 pts (20%) had pure mature teratoma at relapse treated with surgery alone. None of these pts experienced a second relapse. If teratoma relapses were excluded, 5y PFS dropped to 58% (44-77%) and 5y OS to 76% (63-92%). Relapses later than three years after adjuv therapy occured in 15/51 pts. (29%) and were associated with a statistically significant higher risk of death from germ-cell cancer (p=0.02). 15/51 pts (29%) experienced a subsequent relapse. Excluding pts with teratoma only, subsequent relapses occured in 15 of the remaining 41 pts (37%). At last follow-up, 41/51 (80%) pts were alive and disease-free, 8/51 (16%) had died from progressive disease and one pt each had died from therapy-related or other causes. Conclusions: Outcome of pts with relapse after adjuv BEP seems to be better compared to pts with relapse after metastatic disease, but worse compared to de novo metastatic pts. There is a substantial rate of late and subsequent relapses. Pts and care-takers need to be informed about this and therapy intensification at first relapse might be considered. However, considering the low rate of relapses, OS in general for CSI NS pts receiving adjuv BEP is excellent.

In 2015, an estimated number of 8430 new cases of germ cell tumour (GCT) will be diagnosed in the USA.1 Although GCTs show a high sensitivity to cisplatin-based chemotherapy, 10%–15% of patients fail first-line chemotherapy and 3%–5% of all patients with GCT will eventually die of their disease.2 Despite a response rate above 95% to cisplatin-based chemotherapy, the search for new treatment strategies remains worthwhile in accordance to reduce treatment toxicity and offer therapeutic options in non-responding patients.3–5 Various tumours have been described to express L1 cell adhesion molecule (L1-CAM) including lung carcinoma, gliomas, melanoma, renal, ovarian, endometrial and colon carcinoma.6 L1-CAM is associated with tumour cell dissemination via the regulation of prometastatic MMP-2 and MMP-9 in solid and non-solid tumours7 as well as in brain metastases.8 L1-CAM is involved in epithelial-to-mesenchymal transition.9 In various malignancies, there is evidence showing that the expression of L1-CAM is associated with a subset of highly aggressive tumours with adverse clinical outcome and might serve as a therapeutic target.10 We aimed to investigate the expression of L1-CAM in the different GCT subtypes. The construction of the tissue micro array (TMA) was described before.9 L1-CAM immunohistochemistry (IHC) was performed …

4521 Background: Residual disease is a frequent finding after chemo for metastatic seminoma. Watchful waiting is recommended for residual lesions < 3 cm or lesions ≥3 cm with negative PET. Data on the optimal management of PET positive residual lesions is lacking. Methods: A retrospective analysis within the G3 Group identified 91 patients (pts) from 9 countries with metastatic seminoma and residual PET positive lesions after chemo. Pts with elevated AFP ( > 2xULN) or non-seminomatous components at diagnosis were excluded. We analyzed the post PET management chosen and its impact on relapse and survival. Results: Median follow-up was 29 (IQR 10 – 64) months. Median age at diagnosis was 41 (range 19 – 69) years. The primary tumor was gonadal in 68 pts (76%), retroperitoneal in 12 pts (13%) and mediastinal in 10 pts (11%). Prior to chemo the median size of the largest metastasis was 10 (range 1.4 – 23) cm, 67 pts (74%) had elevated LDH and 51 pts (57%) elevated HCG. Median diameter of the largest residual mass was 4.8 (range 1.1 – 14) cm mainly located in the retroperitoneum (77%), pelvis (15%), mediastinum (16%) or lung (4%). Median time from last day of chemo to PET was 7 (IQR 4 – 10) weeks. Post PET management was repeated imaging in 46 pts (51%), resection in 32 pts (35%), biopsy in 9 pts (10%) and radiotherapy in 4 pts (4%). Histology of the resected specimen was necrosis only in 25 (78%) and vital seminoma in 7 cases (22%). No biopsy revealed vital seminoma. Relapses occurred after a median of 3.7 (IQR 2.5 – 4.9) months in 16 pts (18%): 2/9 (22%) after biopsy, 12/46 (26%) on repeated imaging and 2/32 (6%) after resection (one necrosis, one < 10% vital seminoma). Site of relapse was the area of residual disease in 14 pts (88%) and additional distant relapse (one bone, one lung) in 2 pts (12%). All relapsed pts received successful salvage chemo apart from one who died from treatment and two pts who are alive with ongoing treatment. Conclusions: PET positive post chemo residual lesions in seminoma pts are false positive in about 75%. Relapses in PET positive pts occur early and can be salvaged with chemo. Further analysis is needed to identify risk factors for relapse.

Background Patients with testicular germ cell tumors (TGCT) have an increased risk for venous thromboembolism (VTE). We identified risk factors for VTE in this patient cohort and developed a clinical risk model. Methods In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich. Results Venous thromboembolic events occurred in 34 (5.2%) patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the strongest predictors of VTE (p

e15535 Background: Patients (pts) with relapsed or refractory metastatic germ cell cancer (GCC) after multiple lines of standard chemotherapy have a very poor prognosis. The mTOR inhibitor everolim...

1988 grundeten fuhrende Wissenschaftler auf den Gebieten Urologie, internistische und Radioonkologie eine Deutsche Arbeitsgruppe „Hodentumoren”. Seitdem hat die Arbeitsgruppe mehrere klinische Studien und Konferenzen initiiert mit dem Ziel, aktuelle Standards der Behandlung von Hodentumoren zu definieren. Nach einer Reihe von vorbereitenden Sitzungen der Vertreter der AUO, AIO und ARO der Deutschen Krebsgesellschaft wurde im Mai 1996 eine Konsensus-Konferenz uber Diagnose und Behandlung von Hodentumoren abgehalten. Die Standards, auf die man sich bei der Konferenz einigte, beziehen sich auf die aktuelle internationale Literatur und geben Empfehlungen fur die meisten klinischen Situationen. Behandlungsstrategien, die von diesen Standards abweichen, sollten nicht angewandt werden mit Ausnahme von gut begrundbaren Einzelfallen oder Patienten in klinischen Studien. Kein Konsens konnte gefunden werden fur nichtseminomatose Hodentumoren der Stadien I, IIA und IIB. Deshalb werden die unterschiedlichen Behandlungsstrategien fur diese Stadien in dem Beitrag wiedergegeben. Eine Nachfolgekonferenz in den kommenden Jahren ist notwendig, um zu einer moglichen Ubereinkunft fur diese Tumorstadien zu kommen und die derzeitigen Standards nach neuen klinischen Erfahrungen und Erkenntnissen zu uberarbeiten.

To provide guidance regarding follow-up procedures after initial treatment of early stage testicular seminoma (clinical stages (CS) I–II A/B) based on current published evidence complemented by expert opinion. An interdisciplinary, multinational working group consisting of urologists, medical oncologists, and radiation oncologists analyzed the published evidence regarding follow-up procedures in various stages of seminomatous and nonseminomatous testicular cancers. Focusing on radiooncological aspects, the recommendations contained herein are restricted to early stage seminoma (with radiotherapy being a standard treatment option). In particular, extent, frequency, and duration of imaging at follow-up were analyzed concerning relapse patterns, risk factors, and mode of relapse detection. Active surveillance, adjuvant carboplatin or radiotherapy are equally accepted options for CS I seminoma but they result in different relapse rates and patterns. Usually relapses occur within the first 2(–6) years. Routinely performed follow-up using computerized tomography (CT) after adjuvant treatment yield only low detection rates of recurrences. Therefore, there is no evidence to maintain routine examinations every 3–4 months. After treatment of stage IIA/B, detection rates of relapses or progression identified solely by routinely performed CT during follow-up are low. Considering lifelong cure rates of up to 99% for patients treated for seminoma CS I–IIA/B, the negative impact of unnecessary ionizing radiation exposure has to be considered. The presented recommendations for various follow-up scenarios for early stage seminoma strongly promote the restrictive use of imaging procedures that utilize ionizing radiation (especially CT), due to its potential to induce secondary malignancies.

379 Background: Testicular germ-cell cancer is curable even in the presence of metastatic disease. Yet, about 10-15% of patients become cisplatin-refractory and will eventually die of their disease. Moreover, short- and long-term side effects of cisplatin make the search for less toxic treatment strategies worthwile. Programmed Death Receptor 1 (PD-1, CD279) is one member of the extended family of T cell regulators expressed on the surface of activated T cells, B cells, and macrophages. Its ligand, PD-L1 (B7-H1, CD274), is expressed on tumor cells, T cells and other tissues. The interaction of these two molecules negatively regulates immune responses. Of major interest is that inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses in vitro and mediate clinical antitumor activity . The aim of this study was to analyze the expression of PD-L1 in testicular germ-cell tumors to evaluate its potential as predictive marker for further therapeutic strategies. Methods: Immunohistochemistry was performed in 486 Formalin Fixed Paraffin Embedded (FFPE) specimens using a monoclonal rabbit antibody (E1L3N, Cell Signaling Technology, Inc. (CST) of Danvers, MA, USA). Results: PD-L1 expression was found in 171 out of 248 (69%) seminomas, 19 out of 48 (40%) yolk sac tumors, 7 out of 46 (15%) teratomas, 2 out of 10 (20%) choriocarcinomas and 53 out of 87 (61%) embryonal carcinomas. In 20 out of 20 Intratubular germ-cell neoplasia unclassified (IGCNU) and also in 20 out of 20 normal tissue specimens no single case exhibited PD-L1 expression. Conclusions: Our study describes for the first time the frequent expression of PD-L1 in a large series of human testicular germ-cell tumors, but not on normal testis tissue or IGCNU. Based on our results, checkpoint inhibition with anti-PD1 and anti-PDL1 antibodies might represent an attractive approach in germ-cell cancer, where new active agents are urgently needed.

Combination chemotherapy containing high-dose carboplatin is a therapeutic option for patients with poor-risk germ cell tumors. Since such treatment is relatively toxic, pharmacokinetic characteristics of total and ultrafiltered platinum, representing different species of platinum complexes formed, were investigated in 29 patients in relation to toxicity. The goodness-of-fit parameters revealed that a two-compartment model with weighting (1/C2i) resulted in the best fit. The terminal half-life of total platinum > 5 days was fourfold longer than that of ultrafiltered platinum, indicating long-term retention. At stem cell rescue, an ultrafiltered concentration of < or = 0.223 microg/ml did not impair hematological recovery. Ultrafiltered but not total platinum concentrations or AUC values were significantly correlated to an increase in creatinine concentration and different types of toxicity associated with high-dose treatment. Since the fraction unbound is time dependent and highly variable among patients, measuring ultrafiltered concentrations is highly recommended as they represent the clinically relevant platinum complexes in high-dose treatment.

Aim: Characteristics, treatment and outcome of patients (pts) with brain metastases (BMet) from GCT are largely unknown due to a lack of data. We addressed these issues in a large international retrospective cohort. Methods: Data on pts diagnosed with BMet between 1990 and 2013 was retrospectively collected across 46 institutions worldwide. Data collection and analyses followed a predefined protocol and had obtained appropriate ethical approval. Univariate analysis was used to identify prognostic factors. The Kaplan Meier method was used to assess outcome. Results: Data on 523 patients were collected: 228 (44%) in pts with BMet at initial diagnosis (group A) and 295 (56%) in pts with BMet at relapse (group B), 150 (31%) pts were asymptomatic at presentation. Median age was 29 years (range 16-67 years). Median follow-up after diagnosis of BMet was 7 years. Pts from group A had a significantly better PFS (median 6.9 versus 3.6 months, HR 0.60: 95%CI; 0.49 – 0.73; P Conclusions: Conclusions: Pts with GCT and BMet can be cured. Pts with BMet at initial diagnosis and those with solitary BMet have superior outcomes compared to pts with BMet at relapse or with multiple BMet lesions. Surgery and/or radiotherapy in addition to chemotherapy as well as HDCT in pts with BMet at relapse may improve survival. Disclosure: All authors have declared no conflicts of interest.

4559 Background: About 20-30% of patients (pts) with advanced germ-cell cancer (GCC) relapse after cisplatin-based chemotherapy. This database evaluates first salvage treatment and the prognostic categories at first relapse according to the International Prognostic Factors Study Group (= IPFSG; JCO 2010). Methods: A total of 144 pts (78% nonseminoma) with relapsed or refractory GCC undergoing 1st salvage treatment with either conventional (CD-CX) or high-dose chemotherapy with autologous stem cell support (HD-CX) from 16 German centers were retrospectively analysed. Results: Subgroups according to the IPFSG prognostic categories, were: very low risk in 9/144 (6%), low risk in 26/144 (18%), intermediate risk in 78/144 (54%), high risk in 27/144 (19%), and very high risk in 4/144 pts (3%). 1st salvage treatment consisted of HD-CX in 96 (67%) and CD-CX in 48 pts (33%). Treatment response was CR/PR- in 60%, PR+/SD in 33%, and PD in 7%. After a median follow-up (mFU) of 21 months (mos) (range, 0 – 193), 53% of all pts had relapsed and 30% had died resulting in a median progression-free survival (PFS) of 7 mos (95%CI 0-16) and overall survival (OS) of 47 mos (95%CI 21-73). At subsequent relapses, 25/48 pts (52%) received HD-CX as > 2nd-salvage treatment. For the total cohort, PFS rate after 2 years was 35%, and OS rate after 5 years was 53%. Stratification according to IPFSG prognostic categories significantly correlated with PFS (p=0.001) and OS (p=0.004) after 1st salvage treatment. Even among high-risk and very high risk (n=31, mFU 12 mos) a PFS of 37 % at 2 years and an OS of 60 % at 2 years was observed, after 1st or 2nd salvage treatment, which might be due to patient selection and short follow-up. Conclusions: IPFSG prognostic categories highly correlated with observed PFS and OS after first salvage treatment in this cohort of pts with refractory or relapsed GCC. First salvage treatment with CD- or HD-CX resulted in overall 5 year-OS rates of about 50% across all prognostic categories. Even pts with high and very high risk achieved 2 year-OS rates of about 60% with salvage HD-CX at first or subsequent relapses.

e15026 Background: High-dose VIP chemotherapy plus ABSCT given as first line treatment might be a strategy in patient with advanced germ cell tumors (GCT) with poor prognosis. The objective of the trial was to investigate the addition of darbepoetin alfa to HD-VIP in order to reduce anemia/red blood cell (RBC) transfusions. Methods: This was a randomized, open-label multicenter phase 2 study conducted in 20 hospitals. Darbepoetin 2.25 mcg/kg weekly or 500 mcg Q3W s.c., started with high dose VIP (dose level 6) was applied in arm B (arm A: HD-VIP alone). The primary objective was freedom from blood transfusions (FFT). Secondary objectives included objective remission rate (ORR) after chemotherapy, 24 mos PFS and OS, median course of hemoglobin (Hb) levels during 3 HD-VIP cycles as well as drug safety. Results: Between 7/2003 and 11/2008 108 pts were allocated to the study, and 106 were included in the intention-to-treat (ITT) analysis. By March 2011 the median follow-up time after randomization was 20 mos. Localisation of primary was gonadal in 66%, retroperitoneal in 19% and mediastinal in 14%s. A favourable treatment outcome (CR/NED/PR m-) in conjunction with secondary surgery (n = 76 pts) was achieved in 58% of pts with no difference between arms A and B. Overall FFT occurred in 2 pts (4.2%) in arm A and 3 pts (5.6%) in arm B, and in 23%/15%/15% and 15%/17%/19% of pts during cycles 1-3, respectively. No differences in baseline Hb, severity of anemia, no of RBC transfusions and area under the curve of Hb levels during HD-VIP was observed. Pts assigned to darbepoetin had similar treatment toxicity compared to those assigned to HD-VIP alone. 24-mos OS in arm A was 86.3% compared to 67.8% (p=.064) in Arm B. 2-year RFS was 66.8% in arm A vs 55.5% in Arm B (p=0.45). Darbopoetin was generally well tolerated with 2 pts discontinuing treatment due to thrombosis. Since compliance to study protocol was generally poor (6 out of 55 pts never received study drug during HD-VIP) a per-protocol analysis is in preparation. Conclusions: Based on ITT analysis, the addition of darbepoetin alfa to the high dose regimen compared to HD-VIP alone does not appear to impact on FFT, ORR, and 2-year survival rate in poor prognosis GCT pts (NCT00204633).

4597 Background: Bone metastases (mets) are rare events in GCT patients (pts) and data on characteristics, risk factors, treatment and outcome in these pts are largely missing. Methods: A subgroup of 104 ptswith bone metsfrom the IPFSG database was analyzed. All patients experienced unequivocal relapse/progression after > 3 cycles of cisplatin-based chemotherapy and received conventional-dose (CDCT) or high-dose salvage chemotherapy (HDCT). Results: 104 / 1594 pts presented with bone mets (6,5%) at first relapse. Histology was pure seminoma in 26%, and non-seminoma in 74%. At initial diagnosis, 54% of pts had presented with "poor risk" according to IGCCCG. Overall response rate (ORR; CR+PR) to 1st-line chemotherapy was 89%. Median PFS after primary treatment was 3 months (range 0 - 140). Bone mets at first relapse were accompanied by abdominal, lung, mediastinal, liver and brain mets in 54%, 48%, 28%, 36%, and 14%, respectively. Tumor marker profiles were heterogeneous (elevation of AFP / ß-HCG: 51% / 37%). Salvage treatment was CDCT in 34%, and HDCT in 66% of pts. ORR to salvage chemotherapy was 68% for the total cohort, and 43% vs. 81% for CDCT vs. HDCT (p

4600 Background: The number of long term survivors after treatment for relapsed/refractory germ cell cancer (GCC) is increasing but little is known about quality of life (QOL) and late toxicities (LT). Methods: We assessed LT and QOL in GCC patients (pts), treated in a prospective, randomized, multicenter, phase III trial comparing single versus sequential high-dose chemotherapy (HDCT) (Lorch 2007). All 216 pts were asked to complete the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to HDCT, 6 weeks after and yearly thereafter. Results were analyzed according to standard methods (Fayers 2001). In addition pts were contacted at a median of 76 months (range 45-109) after HDCT to obtain information about current social and professional activities as well as LT. Results: Among 216 pts, 92/216 (42%) were alive and without evidence of disease one year after randomization. Median age of pts was 34 years (range 15-56). A median of 4 conventional-dose cisplatin-based treatment cycles had been given prior to HDCT. Questionnaires and response to the survey were evaluable in 86/92 (93%) pts overall and in 59/86 (69%) pts more than 3 years after HDCT. Values for global health status, role functioning and emotional functioning declined during the first year after HDCT, increased in the following years, but did not reach the reference values from large samples of the general population in Norway (Hjermstad 1998). Pts after sequential HDCT scored better in a number of items (e.g. emotional-, cognitive-, social-functioning, fatigue and dyspnoea) in comparison to single HDCT including high-dose cyclophosphamide. Persisting polyneuropathy was reported in 59%, ototoxicity or tinnitus in 56%, erectile dysfunction in 24%, hypertension in 23%, hypercholesterinemia in 17%, diabetes mellitus in 6%, nephrotoxicity in 6%, myocardial infraction in 2% and second cancers in 1% of pts. Overall 82 % of pts were employed, 30% exercised regularly. Conclusions: HDCT has a negative impact on QOL, including social and professional life. Most common late toxicities were ototoxicity and polyneuropathy. Sequential HDCT without cyclophosphamide seems to result in a better outcome in respect to QOL.

4507 Background: Sequential and single high-dose chemotherapy (HDCT) can both be curative in patients (pts) with relapsed or refractory germ-cell tumors (GCT). The long-term efficacy of either moda...

4513 Background: Salvage treatment in male patients (pts) with relapsed or refractory germ-cell tumors (rr-GCT) can be administered using conventional-dose (CDCT) or high-dose (HDCT) chemotherapy. ...

4579 Background: The clinical relevance of germ cell tumor (GCT)-specific mRNA in peripheral blood stem cell (PBSC) harvests of germ-cell cancer patients undergoing high dose chemotherapy (HDCT) is...

5086 Background: Early serum tumor marker decline during chemotherapy was previously shown to be prognostic for progression-free survival (PFS) and overall survival (OS) in patients with relapsed GCT in an analysis of the IT94 phase III trial, which compared conventional chemotherapy versus high dose chemotherapy (Massard C, ASCO 2008. Abstract No. 5085). The aim of this study was to validate this concept in an independent set of patients. Methods: Data on tumor site, response to first line chemotherapy, serum tumor markers at baseline and after two cycles of chemotherapy were obtained from 235 patients accrued in the IT94 trial (training set) and from 181 patients included in phase III prospective trials of high-dose chemotherapy conducted by the German GCT group (Lorch et al, J Clin Oncol. 2007) (validation set). The change from baseline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) was assessed and classified into ‘favorable marker decline‘ and ‘unfavorable marker decline‘ group, as previously described (ASCO 2008. Abstract No. 5085). Results: In both series, favourable serum AFP decline was significantly associated with a better 2-year PFS (46% vs 24%; p < 0.0001) and OS (62% vs 34%; p = 0.0013) while serum hCG decline did not affect outcome. In multivariate analysis of the IT94 trial, an unfavorable AFP decline and a mediastinal primary site were adverse prognostic factors for both PFS and OS, and this was confirmed in the validation set. Among patients from the good prognostic group (favorable AFP decline and non-mediastinal primary site), those who were treated with high-dose chemotherapy had a better PFS (2-year PFS rate: 54% vs 37%; HR = 0.62; p = 0.017), and a trend for a better OS (2-year OS rate: 68% vs. 58%; HR = 0.77; p = 0.29) as compared to patients who were treated with conventional chemotherapy. In contrast, there was no difference in outcome in patients from the poor prognostic group (unfavourable AFP decline and/or mediastinal primary site), whether they received conventional chemotherapy or high-dose chemotherapy. Conclusions: AFP decline during the first 6 weeks of salvage chemotherapy and a mediastinal primary tumor site predict for PFS and OS in patients with relapsed disseminated GCT. No significant financial relationships to disclose.

16055 Background: Addition of paclitaxel to sequential high-dose chemotherapy has been suggested to improve treatment outcome in relapsed or refractory GCT. Methods: Single institution retrospectiv...

16012 Background: In patients (pts) treated for advanced germ cell tumors (GCT), radiologic procedures (RP), including computed tomography, and serum tumormarkers (TM) are performed as routine foll...

5086 Background: The management of patients (pts) with late-relapse GCT and unresectable tumors or very high tumor markers is controversial. Methods: A total of 41 late-relapse pts were identified among a group of 216 pts with refractory or relapsed GCT who were treated in an open, prospective, randomized, multicenter phase III trial. Late relapse was defined as any relapse occurring more than 2 years after completion of initial chemotherapy for GCT. Treatment consisted of either one cycle cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE, arm A) or of three cycles of VIP plus one cycle high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2 and cyclophosphamide 6,400 mg/m2 (CEC, arm B). Each HDCT was followed by reinfusion of autologous peripheral blood progenitor cells. Results: Overall 20 pts with late-relapse GCT received sequential HDCT and 21 pts single HDCT when the study was stopped due to excess treatment-related mortality in arm B; median time to late relapse in 41 pts was 5.4 years (range 2–18 years); 8/41 (20%) pts had seminomatous GCT, 32/41 (78%) pts had nonseminomatous GCT with or without teratoma; one pt (2%) had unknown GCT histology. No non-GCT histologies were included. The retroperitonum was most commonly involved in 30/41 (73%) pts. 29 of 41 (71%) pts had unresectable, multifocal disease and 20/41 (49%) pts also had very high markers. A complete remission to chemotherapy alone was achieved in 4/41 (10%) pts, 16/41 (39%) pts achieved a partial remission with negative tumor markers. The remaining 21/41 (51%) either had a transient or no response despite HDCT. Residual tumor resections were performed in 17/41 (41%) pts. Residual tumor histology was viable cancer in 8/17 (47%) pts, teratoma in 4/17 (24%) pts and necrosis in 5/17 (25%) pts. With a minimum follow-up of 1 year and a median follow-up of 3 years the estimated Kaplan-Meier rates are 17%, 20% and 32% for event-free, progression-free and overall survival. Conclusion: Treatment outcome after HDCT was inferior in late-relapse pts compared to the group of pts who relapsed within less than 2 years. Despite an overall poor prognosis, HDCT can still result in long-term remissions in selected late-relapse GCT pts. No significant financial relationships to disclose.

Seventy-one patients with acute myeloid leukemia (AML), most of them (63/71) considered ineligible for conventional allogeneic hematopoietic stem cell transplantation (HSCT), were enrolled into a phase II study on reduced intensity myeloablative conditioning with fractionated 8 Gy total body irradiation (TBI) and fludarabine (120 mg/m2) (Blood. 2005 Nov 1;106(9):3314–21). Patients received mobilized peripheral blood stem cells (n=68) or bone marrow (n=3) from siblings (n=39) or unrelated donors (n=32). HLA-typing was performed for HLA-A, -B, -Cw (serological matching or intermediate resolution DNA typing), DRB1 and DQB1 (high resolution DNA typing). Three patients had unrelated donors with an allele mismatch in HLA DRB1 (2 with an additional mismatch in HLA Cw) and 7 patients were transplanted from unrelated donors with an antigen mismatch in HLA Cw. Thirty-six patients were transplanted in complete remission (CR) and 35 with untreated or refractory disease (non-CR). Median patient age was 51 years (range, 20–66). Sustained engraftment was attained in all evaluable patients. With a median follow-up of now 41.3 months (range, 20.4–70.4) in surviving patients, probabilities of overall survival for patients transplanted in CR and non-CR were 80% (95% CI, 66 to 94%) and 17% (95% CI, 5 – 29%) at 4 years, respectively. Relapse-free survival rates were 57% (95% CI, 39 – 75%) and 14% (95% CI, 2 – 26%). Of the 35 evaluable patients transplanted in CR, 10 patients suffered a relapse between days 68 and 868 after transplantation (cumulative incidence 29%). Five patients with late relapse (>1 year after transplantation) achieved a subsequent CR after conventional chemotherapy, blood stem cell boost and treatment with granulocyte-macrophage colony-stimulating factor, lasting 2000+, 1841+, 909+, 847+ and 480 days, respectively. Depending on donor type, relapse-free survival was similar in patients transplanted from unrelated or sibling donors. Overall survival in patients transplanted in complete remission from unrelated vs. sibling donors was 84% (95% CI, 73 – 95%) vs. 77% (95% CI, 68 – 86%). The cumulative incidence of non-relapse mortality (NRM) in CR patients was 11% at 4 years and beyond (3 patients deceased before day 100 and 1 patient 25 months after transplantation), but amounted to 37% at 4 years in non-CR patients. Nine of the 33 surviving patients (27%) have actually active chronic GvHD (5 limited and 4 extensive disease). This update confirms that allogeneic HSCT from related or unrelated donors with 8 Gy TBI/fludarabine conditioning is feasible with low NRM and preserved long-term antileukemic activity in AML patients in first or later CR.

4511 Background: Patients (pts) with relapsed or refractory GCT may be cured by HDCT. It is unknown whether single or sequential HDCT is superior. Methods: Between 11/99 and 11/04, 216 pts with relapsed or refractory GTC were treated in a prospective, randomized, multicenter phase III trial with either one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1500 mg/m2 and etoposide 1500 mg/m2 (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2200 mg/m2, etoposide 1800 mg/m2 and cyclophosphamide 6400 mg/m2 (CEC, arm B) followed by reinfusion of autologous peripheral blood progenitor cells. Primary study endpoint was the event-free survival (EFS) one year after randomization. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. An event was defined as any deviation from the planned treatment, relapse, progression or death from any cause. The planned study size was 230 pts to detect a difference of 15% with an alpha error of 5% and a power of 80%. Results: The study was stopped after recruitment of 216 pts due to excess treatment-related mortality in arm B: 111 pts were randomized in arm A and 105 pts in arm B. Due to non-GCT histologies at review 5/216 pts had to be excluded from further analysis. With a median follow-up of 36 months, 109/211 (52%) evaluable pts are still alive and 91/211 (43%) are progression-free. At one year EFS; PFS and OS are 40%, 55% and 80% in arm A as compared to 37%, 49% and 61% in arm B. Treatment-related deaths mainly due to sepsis and cardiac toxicity were less frequent in arm A (4/111 pts, 4%) as compared to arm B (15/105 pts, 14%) (p = 0.01). Severe non-hematologic organ toxicities were also less frequent in arm A. Conclusions: Treatment with sequential high-dose carboplatin and etoposide is at least as effective but less toxic than single HDCT with carboplatin, etoposide and cyclophosphamide. No significant financial relationships to disclose.

4585 Background: To identify prognostic variables in patients (pts) with metastatic germ cell tumors (GCT) and relapse or progression after first-line chemotherapy (FLC). Methods: In our database of 257 GCT pts treated with HDCT, 176/257 (67.4%) pts with first relapse or progression were identified. All patients had received platinum-based FLC. As salvage treatment all pts had received 1–3 cycles of conventional-dose salvage chemotherapy (CDCT) followed by one cycle HDCT. First, pts were retrospectively classified according to a prognostic score developed for CDCT by Fossa et al. [Br J Cancer 1999,80:1392], based on variables present at the time of relapse. Thereafter, a multivariate analysis was performed to evaluate further risk factors. Results: After a median follow up of 9 years the event-free survival (EFS) and overall survival (OS) for all 176 patients was 34% and 38%, respectively. Patients with good (n= 100/176, 57%) and poor (n = 76/176, 43%) prognosis in accordance to Fossa et al. showed an EFS of 41% and 26% (p < 0.01) and an OS of 47% and 26% (p < 0.01). Thus, in contrast to the data of Fossa et al, long-term survival could be demonstrated even in the poor prognosis subset. In the multivariate analysis, the level of elevated tumor markers alfa-fetoprotein and human chorionic gonadotrophin (p < 0.01), the presence of extrapulmonal visceral metastases (p < 0.01) and refractoriness to cisplatin (p < 0.01) adversely influenced OS after HDCT significantly. Based on these latter factors three different groups with increasingly poor OS could be identified: none factor (n = 39/176, 22%) 4 year OS of 59%, one factor (n = 78/176, 44%) 6 year OS of 42% and more than one factor (n = 59/176, 34%) 4 year OS of 17%. Conclusion: In pts with first relapse or progression after platinum-based FLC high serum tumor markers, presence of extrapulmonal visceral metastases and cisplatin refractoriness proved to be independent prognostic significance for OS after salvage HDCT. However, even in the poor prognosis subset long-term survival could be demonstrated. No significant financial relationships to disclose.