Seminomatous Germ Cell Tumors Research Articles

Onco-testicular sperm extraction: testicular sperm extraction in azoospermic and very severely oligozoospermic cancer patients

An increased risk of testicular cancer in men with infertility and poor semen quality has been reported. In view of the high cure rates for testicular germ cell tumours, increasing clinical importance is being placed on the protection of fertility. High-dose cytostatic therapy may be expected to cause long-term infertility. Thus, the standard procedure for fertility protection is the cryopreservation of ejaculated spermatozoa or testicular tissue before therapy. Four male patients with azoospermia and two patients with very severe oligozoospermia underwent onco-testicular sperm extraction (TESE). We attempted onco-TESE in patients with azoospermia and very severe oligozoospermia after orchiectomy. Of the patients with testicular germ cell tumours, four had spermatozoa in their testicular tissues. Sertoli cell-only syndrome was found in one patient, and one patient showed maturation arrest without the detection of spermatozoa. Three of six showed seminomatous germ cell tumour, two of six had nonseminomatous germ cell tumour and one patient showed no malignancy. Two patients achieved clinical pregnancy. Fertility challenges in men with cancer are the most straightforward because of the relative ease of obtaining and cryopreserving sperm. Testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic and very severely oligozoospermic cancer patients.

Glial cell line–derived neurotrophic factor promotes invasive behaviour in testicular seminoma cells

The glial cell line-derived neurotrophic factor (GDNF) has multiple functions that promote cell survival, proliferation and migration in different cell types. The experimental over-expression of GDNF in mouse testis leads to infertility and promotes seminomatous germ cell tumours in older animals, which suggests that deregulation of the GDNF pathway may be implicated in germ cell carcinogenesis. GDNF activates downstream pathways upon binding to its specific co-receptor GDNF family receptor-a 1 (GFRA1). This complex then interacts with Ret and other co-receptors to activate several intracellular signalling cascades. To explore the involvement of the GDNF pathway in the onset and progression of testicular germ cell tumours, we analysed GFRA1 and Ret expression patterns in seminoma samples. We demonstrated, via immunohistochemistry, that GFRA1, but not Ret, is over-expressed in in situ carcinoma (CIS) and in intratubular and invasive seminoma cells compared with normal human germ cells. Functional analysis of the GDNF biological activity was performed on TCam-2 seminoma cell line. Reverse transcription-PCR (RT-PCR) and immunohistochemical analyses demonstrate that TCam-2 cells express both GFRA1 and Ret mRNA, but only GFRA1 was detected at the protein level. In TCam-2 cells, although GDNF is not mitogenic, it is able to induce migration, as demonstrated by a Boyden chamber assay, possibly through the Src and MEK pathways. Moreover, GDNF promotes invasive behaviour, an effect dependent on pericellular protease activity, possibly through the activity of matrix metalloproteinases. GFRA1 over-expression in CIS and seminoma cells, along with the functional analyses in TCam-2 cells, suggests an involvement of the GDNF pathway in the progression of testicular germ cell cancer.

917 NOVEL PREDICTORS OF BENIGN PATHOLOGY IN STAGE IA OR IB PATIENTS WITH NON-SEMINOMATOUS TESTICULAR GERM CELL MALIGNANCY UNDERGOING PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION

INTRODUCTION AND OBJECTIVES: There is no consensus on the optimal treatment for Stage I testicular non seminomatous germ cell tumors (T NSGCT), partly due to the inaccuracy of clinical staging methods. Prior reports have demonstrated that the presence of embyronal carcinoma (EC), lymphovascular invasion (LVI), and absence of yolk sac tumor (YST) in the orchiectomy specimen are important risk factors predicting occult metastatic disease. We assessed whether a novel combination of the above factors could predict the presence of benign retroperitoneal pathology. METHODS: We reviewed an institutional database of patients with T NSGCT and included all patients with Stage IA or IB NSGCT who underwent primary RPLND. Logistic regression analysis was used to compare patients with benign pathology versus germ cell tumor (GCT). A combination of significant pathologic factors was used as internal validation to predict the presence of benign or GCT pathology. Significance was determined at p 0.05. No financial funding was obtained. RESULTS: Among 55 patients with Stage IA or IB NSGCT managed with primary RPLND, 44(80%) had benign pathology and 11 (20%) had occult GCT in the retroperitoneum. No specimens revealed retroperitoneal teratoma in this cohort. Predictors of benign pathology were higher preorchiectomy alpha fetoprotein levels (p 0.03), larger percentage of YST (p 0.02), lower embryonal carcinoma to YST (E/Y) ratio (p 0.001), presence of teratoma and absence of LVI in the primary orchiectomy specimen (both p 0.01). Multivariate analysis demonstrated an E/Y ratio 4 to be a strong predictor of benign pathology in the retroperitoneum, with an area under the receiver operating curve of 0.71 0.08 (p 0.04), and a sensitivity and specificity of 37% (16/43) and 100% (12/12), respectively. In combination with absence of LVI, an E/Y ratio 4 had a 100%(10/10) positive predictive value for benign pathology on internal validation. Conversely, presence of LVI and an E/Y ratio of 4 revealed a 64% (7/11) predictive value for GCT. CONCLUSIONS: In our cohort, patients with Stage IA or IB NSGCT who had benign pathology on the primary RPLND had a significantly higher proportion of YST to EC in the preorchiectomy specimen. An E/Y cutoff value of 4 appears to be discriminatory for predicting benign pathology. Emphasis on the proportion of YST in the primary orchiectomy specimen in addition to other previously established risk factors may allow for improved risk stratification.

922 LONG-TERM FOLLOW UP USING TESTICULAR SPARING SURGERY FOR LEYDIG CELL TUMOR

You have accessJournal of UrologyPenis/Testis/Urethra: Benign & Malignant Disease III1 Apr 2012922 LONG-TERM FOLLOW UP USING TESTICULAR SPARING SURGERY FOR LEYDIG CELL TUMOR Giorgio Bozzini, Stefano Picozzi, Franco Gadda, Renzo Colombo, Ottavio De Cobelli, Giorgio Pizzocaro, Luca Carmignani, and Joan Palou Giorgio BozziniGiorgio Bozzini San Donato Milanese, Italy More articles by this author , Stefano PicozziStefano Picozzi San Donato Milanese, Italy More articles by this author , Franco GaddaFranco Gadda Milan, Italy More articles by this author , Renzo ColomboRenzo Colombo Milan, Italy More articles by this author , Ottavio De CobelliOttavio De Cobelli Milan, Italy More articles by this author , Giorgio PizzocaroGiorgio Pizzocaro Milan, Italy More articles by this author , Luca CarmignaniLuca Carmignani San Donato Milanese, Italy More articles by this author , and Joan PalouJoan Palou Barcellona, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We performed a long-term evaluation of conservative surgical treatment of benign Leydig cell Tumor. METHODS A multicenter retrospective clinical study was performed at 6 European centers. Case files of all patients diagnosed with Leydig cell Tumor and treated with conservative surgery were examined. Patients underwent physical examination, hormone and tumour marker assays, scrotal and abdominal ultrasound, chest x-ray and endocrinological examination. RESULTS From 1987 to 2006, 22 patients with Leydig cell tumor underwent conservative surgery. Patient mean age was 35 years (range 5 to 61). Mean follow up was 95.78 months (range 77 to 120). No local recurrence or metastasis was observed. Patients presented either with a palpable testicular nodule (3 patients, 13.7%) or a nodule diagnosed by ultrasound (15 patients, 68.2%), gynecomstia (2 patients, 9.1%), precocious pseudopuberty (1 patient, 4.5%) or scrotal pain (1 patient, 4.5%). Three patients were monorchid after contralateral orchiectomy for inguinal hernia repair (1 patients, 28 years before surgery) and non seminomatous germ cell tumor (2 patients, 1 month and 6 years before surgery). Diagnosis after frozen section examination was Leydig cell tumor in 20 of 22 cases (91% ). Mean histological size of the nodule was 1.11 cm (range 0.5 to 2.5 cm.). Preoperative FSH and LH levels were high in 4 patients. Tumor markers were normal before and after surgery. Follow up was conducted for all patients every 3 to 6 months with physical examination, tumor markers, scrotal and abdominal ultrasound, chest x-ray. 6 patients underwent CT scan. No local recurrence or metastasis were observed. 100% of patients are still alive with a 100% free disease survival. CONCLUSIONS When diagnosed early Leydig cell tumors present a favorable follow up even its potential metastatic behaviour. In selected cases with motivated patients sparing surgery proved to be a feasible and safe choice. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e375-e376 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giorgio Bozzini San Donato Milanese, Italy More articles by this author Stefano Picozzi San Donato Milanese, Italy More articles by this author Franco Gadda Milan, Italy More articles by this author Renzo Colombo Milan, Italy More articles by this author Ottavio De Cobelli Milan, Italy More articles by this author Giorgio Pizzocaro Milan, Italy More articles by this author Luca Carmignani San Donato Milanese, Italy More articles by this author Joan Palou Barcellona, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Current Update of Management of Clinical Stage I Non Seminomatous Germ Cell Tumors of Testis

The management of patients with testicular germ cell tumors (GCT) has evolved significantly over the past 30years with cure rates approaching nearly 100% for low-stage disease and more than 80% for advanced disease. Controversy surrounds about ideal management of clinical stage I non seminomatous germ cell tumors (CS I NSGCT) of the testis due to multiple treatment options available with more or less equal efficacy. Nerve-sparing retroperitoneal lymph node dissection (RPLND), adjuvant chemotherapy with two cycles of bleomycin, etoposide, and cisplatin , or surveillance have all achieved long-term survival in nearly 100% of patients with clinical stage I NSGCT. Retroperitoneal lymph node dissection is still favoured as the therapy of choice for clinical stage I non-seminomatous germ cell tumors in many centres, but as risk factors for the primary tumor have become better understood, surveillance and risk-adapted therapy, including surveillance for low-risk patients and adjuvant chemotherapy for the high-risk group, is now being considered a therapeutic option. The objective of this study is to review current developments in the management of CS I NSGCT testis with emphasis on risk stratification and treatment recommendations.

Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

IntroductionDevelopment of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically.Case presentationWe report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation.ConclusionThe presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma). In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

Socio-economic inequalities in testicular cancer survival within two clinical studies

Background: Testicular cancer is the most common cancer in men under 35 years of age, and has the highest survival for adult male malignancies. Despite the fact that survival is very high, there is evidence that survival differs between socio-economic groups. Methods: We analysed survival patterns for 1606 testicular cancer patients diagnosed during 1984–2001 and recruited to one of two clinical studies. The first was a surveillance study to determine relapse-free survival after orchidectomy in 865 patients with stage I nonseminomatous germ-cell testicular cancer diagnosed during 1984–1991 (TE04). The second study was a trial in which 1174 men with stage I seminomatous germ-cell tumours were randomised to receive radiotherapy or one injection of carboplatin between 1996 and 2001 (TE19). The number of men available for analysis from these two studies was 578 and 1028, respectively. We followed these patients up for their vital status, and assigned them an ecological measure of deprivation. Crude and relative survival were estimated at 5 and 10 years by socio-economic deprivation. Results: No significant socio-economic gradient was seen: 1.3% (95% CI −0.3% to 3.1%) at 5 years and 2.1% (95% CI −0.5% to 4.7%) at 10 years. Conclusion: We conclude that, given equal treatment at a given stage of disease, survival from testicular cancer does not depend on socio-economic status. This suggests that the socio-economic gradient in testicular cancer survival in the general population is more likely to be attributable to health care system factors than to personal or socio-economic factors in the men themselves.

Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: confirmation of OCT3/4 specificity for germ cell tumours

Background:OCT3/4 (POU5F1) is an established diagnostic immunohistochemical marker for specific histological variants of human malignant germ cell tumours (GCTs), including the seminomatous types and the stem cell component of non-seminomas, known as embryonal carcinoma. OCT3/4 is crucial for the regulation of pluripotency and the self-renewal of normal embryonic stem- and germ cells. Detection of expression of this transcription factor is complicated by the existence of multiple pseudogenes and isoforms. Various claims have been made about OCT3/4 expression in non-GCTs, possibly related to using nonspecific detection methods. False-positive findings undermine the applicability of OCT3/4 as a specific diagnostic tool in a clinical setting. In addition, false-positive findings could result in misinterpretation of pluripotency regulation in solid somatic cancers and their stem cells. Of the three identified isoforms – OCT4A, OCT4B and OCT4B1 – only OCT4A proved to regulate pluripotency. Up until now, no convincing nuclear OCT4A protein expression has been shown in somatic cancers or tissues.Methods:This study investigates expression of the various OCT3/4 isoforms in GCTs (both differentiated and undifferentiated) and somatic (non-germ cell) cancers, including representative cell lines and xenografts.Results:Using specific methods, OCT4A and OCT4B1 are shown to be preferentially expressed in undifferentiated GCTs. The OCT4B variant shows no difference in expression between GCTs (either differentiated or undifferentiated) and somatic cancers. In spite of the presence of OCT4A mRNA in somatic cancer-derived cell lines, no OCT3/4 protein is detected. Significant positive correlations between all isoforms of OCT3/4 were identified in both tumours with and without a known stem cell component, possibly indicating synergistic roles of these isoforms.Conclusion:This study confirms that OCT4A protein only appears in seminomatous GCTs, embryonal carcinoma and representative cell lines. Furthermore, it emphasises that in order to correctly assess the presence of functional OCT3/4, both isoform specific mRNA and protein detection are required.

Peritoneal Relapse of Testicular Seminomatous Germ Cell Tumor Treated Successfully With Salvage Chemotherapy and Autologous Stem Cell Transplantation

Introduction Peritoneal metastasis from testicular germ cell tumor (GCT) is uncommonly reported in the medical literature. Testicular tumors spread via lymphatic channels that parallel testicular blood vessels to retroperitoneal lymph nodes as well as hematogenously, most commonly to the lungs, and, in patients with advanced aggressive tumors, to the brain, bone, and liver. Less common disease sites, including the eritoneum, kidney, and spleen, are more frequently observed at the ime of relapse in previously treated patients. Other unusual metastatic ites include the adrenals, inferior vena cava, muscle, stomach, prostate, ericardium, and ureter. This case report describes a patient with peritoneal relapse of a testicular seminomatous GCT.

Salvage Chemotherapy With High-Dose Carboplatin and Etoposide With Peripheral Blood Stem Cell Transplant in Patients With Relapsed Pure Seminoma

To evaluate rates of complete remission and overall survival for patients with relapsed pure seminoma treated with high-dose carboplatin and etoposide followed by peripheral blood stem cell transplant. Forty-eight consecutive patients with relapsed pure seminoma who were treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant between May 1996 and June 2006 were retrospectively reviewed. Upon relapse (first, second, or third relapse) patients were given HDCT with carboplatin 700 mg/m(2) and etoposide 750 mg/m(2) for 3 consecutive days followed by infusion of peripheral blood stem cells. Here, we review both response and survival. Thirty-eight (79%) of 48 patients obtained a complete response (CR) with overall survival of 75%. Median follow-up of all patients was 45.6 months. Twenty-two (92%) of 24 patients in first relapse achieved CR and are still alive and continuously disease-free. Sixteen (67%) of 24 patients had HDCT as third- or fourth-line therapy with 67% CR and overall survival of 64%. There were 3 treatment-related deaths, all of which occurred as third- or fourth-line therapy. HDCT results in high rates of both CR and overall survival in patients with first or later relapsed pure seminoma germ cell tumors.

Metastatic adenocarcinoma in a young male, 12 years after treatment of primary non seminomatous germ cell tumor

A man aged 32 years presented with metastatic adenocarcinomatous deposits, 12 years after his initial diagnosis and treatment of immature teratoma of the testis. He was treated for his metastasis with local radiotherapy, failing which he underwent excision of the tumor and palliative chemotherapy. This case is presented for its rarity of occurrence, unique presenting features and difficulty in management.

Comparing the perioperative management of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in patients with pure seminomatous and nonseminomatous germ cell tumors (NSGCT).

230 Background: PC-RPLND is a potentially complicated intervention. By the time the rate of complications and adjunctive surgery increased. Only few data are available concerning PC-RPLND in patients with advanced seminomas and residual retroperitoneal tumour lesions. We examined the intra and postoperative complications as well as the frequency of adjunctive surgeries in patients with seminoma and compared the data to a cohort of patients with NSGCT who underwent PC-RPLND. Methods: In our multicenter retrospective analyses 408 patients underwent PC-RPLND between 1989 and 2010. 47 patients with advanced seminomas and 327 patients with NSGCT. The surgical approach was preferred via a midline incision or a thoracoabdominal approach due to the location of the residual tumour. In one center a laparoscopic approach was preferred. Results: Of the 47 patients with seminoma a total number of 18 adjunctive surgeries were performed in 11 patients (8 nephrectomies, 3 inferior v.cava resections, 3 resections of the abdominal aorta, 2 resections of the colon, one nerv and 2 hepatic resections/biopsies). There was only one major intraoperative complication, injury of the v. cava and two postoperative complications, (prolonged intestinal paralyses). There were no significant differences adjunctive surgeries and postoperative complications (p=0.48 and p=0.133). There were significantly less intraoperative complications in favour of seminomas (p=0.006). Conclusions: PCRLND in seminomas and NSGCT is a demanding surgical intervention. In contrast to other series we did not find significant differences in the two patient groups concerning adjunctive surgeries and postoperative complications. The indication for PCLND in patients with seminoma is limited, but if necessary it can be performed safely in experienced centers. No significant financial relationships to disclose.

Testis: Germ cell tumors

Two main entities may be distinguished within testicular germ-cell tumours: seminomas and non seminomatous germ-cell tumours (NSGCT). Seminomas are composed of neoplastic germ cells. Non seminomatous germ-cell tumours present multiple histologic subtypes with neoplastic 1embryonic tissues (embryonal carcinoma, immature and mature teratoma), or 2extraembryonic tissus (yolk sac tumour and choriocarcimoma), which are usually associated and are therefore called mixed germ cell tumours (the most frequent being teratocarcinoma). There may been combined tumours of seminomatous and non seminomatous components. Intratubular germ cell neoplasia (ITGCN), also called carcinoma in-situ, appears as a precursor lesion of invasive tumours (common precursor for both seminomas and NSGCT), but it can also be observed in patients without development of a testicular germ-cell tumour (GCT). In adults, most testicular germ cell tumours are associated with ITGCN surrounding the invasive cancer.

Linfadenectomía retroperitoneal laparoscópica primaria para el tumor testicular de células germinales no seminomatoso en estadio clínico I

Introduction this report is intended to retrospectively assess cancer control and morbidity of primary laparoscopic reproperitoneal lymphadenectomy (L-RPLND) in patients with clinical Stage I non seminomatous germ cell tumour (NSGCT). Materials and methods one hundred and sixty-four patients with clinical Stage I NSGCT underwent primary diagnostic LRPLND between 1993 and 2006. Patients were operated unilaterally limiting the dissection to templates. Kaplan Meier curves were generated estimating time to recurrence. Results of the 164 patients, 82 (48%) had embryonal components and 35 (20%) lymphovascular invasion in the orchiectomy specimen. The median (IQR) age, operative time, length of hospital stay, blood loss and number of lymph nodes retrieved was 28 years (24-33), 135 minutes. (120- 180), 48 hours (24-48), 50 cc (20-100) and 14 (10-18) nodes, respectively. All patients had negative serum markers preoperatively. Presence of lymph node metastasis was identified in 32 (19.5%) patients. Follow-up was available in 15 of these. Fourteen received adjuvant chemotherapy and 2 of them had recurrence at 3 and 64 months. Absence of lymph node metastasis was diagnosed in 132 (80.5%) patients. Follow-up was available in 80 of these. Among them 7 recurred (5 retroperitoneum, 2 lung), one of them 33 months after L-RPLND. Median follow-up for patients without recurrence was 14 months (IQR:4-35). The cumulative 3-year recurrence free rate was 82% (95%CI: 64-91). Seventeen (10%) of 164 patients had intra or perioperative complications. Conclusions this is the largest series of L-RPLND performed in a single institution. Both morbidity and oncologic safety of this technique needs to be prospectively evaluated in randomized trials.

Primary laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ-cell testis tumor

IntroductionThis report is intended to retrospectively assess cancer control and morbidity of primary laparoscopic reproperitoneal lymphadenectomy (L-RPLND) in patients with clinical Stage I non seminomatous germ cell tumour (NSGCT). Material and methodsOne hundred and sixty-four patients with clinical Stage I NSGCT underwent primary diagnostic LRPLND between 1993 and 2006. Patients were operated unilaterally limiting the dissection to templates. Kaplan Meier curves were generated estimating time to recurrence. ResultsOf the 164 patients, 82 (48%) had embryonal components and 35 (20%) lymphovascular invasion in the orchiectomy specimen. The median (IQR) age, operative time, length of hospital stay, blood loss and number of lymph nodes retrieved was 28 years (24–33), 135 minutes. (120–180), 48 hours (24–48), 50 cc (20–100) and 14 (10–18) nodes, respectively. All patients had negative serum markers preoperatively.Presence of lymph node metastasis was identified in 32 (19.5%) patients. Follow-up was available in 15 of these. Fourteen received adjuvant chemotherapy and 2 of them had recurrence at 3 and 64 months. Absence of lymph node metastasis was diagnosed in 132 (80.5%) patients. Follow-up was available in 80 of these. Among them 7 recurred (5 retroperitoneum, 2 lung), one of them 33 months after L-RPLND. Median follow-up for patients without recurrence was 14 months (IQR:4–35). The cumulative 3-year recurrence free rate was 82% (95%CI: 64–91). Seventeen (10%) of 164 patients had intra or perioperative complications.

Successful 2-year-long remission following repeated salvage surgery in a patient with chemotherapy-resistant metastatic non seminomatous germ cell tumor: an additional report to Int J Clin Oncol 2007; 12:485–487

Successful 2-year-long remission following repeated salvage surgery in a patient with chemotherapy-resistant metastatic non seminomatous germ cell tumor: an additional report to Int J Clin Oncol 2007; 12:485–487

Management options for stage 1 nonseminomatous germ cell tumors of the testis

Management of clinical stage I non seminomatous germ cell tumor includes surveillance, primary chemotherapy and retroperitoneal lymph node dissection. Stratifying clinical stage I disease to high-and low-risk groups for harboring micrometastic retroperitoneal disease (pathologic stage B) is based on pathologic characteristics of the primary tumor. The presence of embryonal dominant histology and lymphovascular invasion (high-risk group) predicts for a 50% incidence of retroperitoneal disease. Low-risk group, the absence of either factor, predicts a 20% chance of retroperitoneal disease. Irrespective of risk classification, all treatment modalities have equal survival rates of 99% to 100%, and differ only in their unique short and long-term modalities. The mode of treatment in clinical stage I disease should remain patient driven and is guided by the perceived morbidities of each therapy.

7162 Post-chemotherapy residual masses

Objective: To describe the clinical characteristics and treatment results obtained with the application of a homogeneous treatment protocol in 1490 patients with germ-cell tumours (GCT) registered in the 55 hospitals belonging to the Spanish Germ-Cell Cancer Group (GG) during the period between January 1994 and April 2001.Methods: In general, surveillance was the common policy for stage I patients without local poor prognosis factors, whereas they received adjuvant chemotherapy in case those factor were present. Chemotherapy schedules used in advanced cases were cisplatin and etoposide (EP) for seminoma and BEP or BOMP-EPI in non-seminoma, according to whether the patient was in the good or poor prognosis IGCCCG (International Germ-Cell Cancer Collaborative Group) group. Excision of residual masses was mandatory in non-seminomatous germ-cell tumour (NSGCT).Results: Initial local symptomatology was increased testis size in 90% of cases. Sonography was an excellent diagnostic tool to suggest tumour. Non-seminoma (64.2%) was more frequent than seminoma (35.8%). Approximately 10% had the antecedent of cryptorchidism. Non-seminoma patients were 7 years younger than seminoma. Right testis was involved predominantly. Pre-orchidectomy tumour markers were elevated in 21% of seminoma (βHGC) and 79% in non-seminoma (αFP and/or βHGC). Scrotum violation occurred in only 1.8%. There were significant differences among stage I and the IGCCCG prognosis groups related to a longer interval between the first symptom and orchiectomy. Eighteen percent of non-seminomatous germ-cell tumour belonged to the poor prognosis IGCCCG group. With a median follow-up to 33 months, this series has achieved a 3 year overall survival of 98% for seminoma and 94% for non-seminoma. Only 10% of excised residual masses present after chemotherapy contained malignant cells.Conclusion: Spanish GCT have a similar clinical pattern to that described in the other occidental countries except for a slight increased proportion of non-seminoma upon seminoma. Co-operative groups as GG are unique structures to obtain quick and wide experience on the treatment of testis tumours, contributing to achieve a high cure rate.

Very unusual solitary metastasis of testicular seminoma to the skull

We present a rare presentation of testicular seminoma. A 60‐year‐old man presented with a solitary subcutaneous metastasis to the skull, 4 years after radical orchidectomy and adjuvant prophylatic radiotherapy for stage T1 seminomatous germ cell tumour. The patient was treated with surgical excision of the solitary metastasis, adjuvant radiation therapy and chemotherapy. He has been followed up for two and a half years with no further recurrence.

A phase II trial of high-dose chemotherapy (HDCT) supported by haematopoietic stem cell transplantation (HSCT) in patients (pts) with disseminated germ-cell tumors (GCTs) failing chemotherapy and with adverse prognostic factors: The TAXIF II protocol

5028 Background: HDCT using the etoposide-carboplatin ± ifosfamide regimen is able to circumvent resistance in GCT pts, even when used as third-line or later therapy (Lotz, Ann Onco.l 2005 / Einhorn, N Eng J Med. 2007). Pts whose relapses occur more than 4 w after CDDP-based CT are probably the best candidates for HDCT. Epirubicine (E) and paclitaxel (P) possess interesting activity in GCTs. Thiotepa (TTP) and P can be safely combined at HD with good efficacy. The ICE regimen is a well-known worldwide used regimen. Methods: Non-resistant/refractory GCTs pts failing CT and with adverse prognostic factors were planned to receive 2 cycles combining (mg/m2) E (100) and P (250), given on day 1 and 14 supported by filgrastim (F), followed by 3 consecutive HDCTs [1 course combining a 3-d combination of P (360) + TTP (720), followed by 2 ICE regimens (IFM, 12 g/m2, CBDCA, AUC 20, VP16, 1,500 mg/m2), given on 5 days with HSCT and F]. Inclusion criterias were mainly: radiologically and/or biologically mesurable disease, seminomatous GCT in relapse after 2 lines of CT (BEP/VeIP), non-seminomatous GCT in relapse after 1 or 2 lines of CT or in PR after 1 line of CT, primary mediastinal GCT in first relapse. Resistant / refractory pts were excluded. PBSC were collected after the first ± the second courses of EP (aim: 9x10E6 CD34+/kg BW). We report herein on the preliminary results of this multicentric study. Results: From 09/04 to 12/07, 45 pre-treated (BEP ± VeIP) pts with gonadal (89%) or extra-gonadal T (11%) were treated in second-line (27%), 3rd-line (44 %) or more (29 %). Thirty-five pts received 1 HDCT, 29 two HDCTs and 21 pts could receive the whole protocol. At the time of analysis (12/08), the final overall response rate was 47%, 10 pts were in continuous CR (median time, 8 m; range, 1–18), and 37 pts (82%) were alive at a median F/U of 9 m (range, 1–26). The 1-y survival rate was 90%. The 1-y PFS rate was 62%. One pt died of multi-organ failure and 7 died of disease progression. Conclusions: This HDCT program preceded by 2 semi-intensive cycles of E-P is highly effective in non-resistant/refractory pts with disseminated GCTS failing CT and with adverse prognostic factors. No significant financial relationships to disclose.