Pure Seminoma Research Articles

Rete testis invasion by malignant germ cell tumor and/or intratubular germ cell neoplasia: what is the significance of this finding?

Pathologic stage and postsurgical treatment guidelines of malignant germ cell tumors, currently take into account angiolymphatic invasion, degree of extra testicular invasion, and serum tumor marker levels. The significance of rete testis invasion by malignant germ cell tumors or intratubular germ cell neoplasia however remains controversial. A search through the surgical pathology and expert consultation files at our institution from 2002 to 2009 was made for malignant germ cell tumors and intratubular germ cell neoplasia in orchiectomy specimens. Clinicopathologic data including rete testis status were obtained. Two hundred ninety-two orchiectomy specimens were identified. One hundred thirty-six were associated with malignant germ cell tumors. Mean patient age was 33 years (range, 14-67 years). The mean greatest tumor dimension was 4.1 cm (range, 0.8-18 cm). Fifty-six were pure seminoma (40%), 50 were nonseminomatous malignant germ cell tumors (35%), and 35 were mixed malignant germ cell tumors including a seminoma component (25%). Intratubular germ cell neoplasia was identified in 99 cases (70%). Pathologic stage at presentation was as follows: stage 1, 71 patients (50%); stage 2, 62 patients (45%); stage 3, 2 patients (1%); and indeterminate, 6 patients (4%). Seventy-eight patients had documented rete testis status: rete testis invasion, 41 (53%); no rete testis invasion, 37 (47%). Angiolymphatic invasion was present in 62 cases (44%). Follow-up information was available in 43 patients with known rete testis status. Mean follow-up duration was 43 months (range, 3-65 months). Twenty patients had rete testis invasion, and 23 patients had no rete testis invasion. Intratubular germ cell neoplasia was present in patients with rete testis invasion in 18 cases (90%), compared to only 13 cases (57%) in patients without rete testis invasion, P = .02. Serum markers were elevated in 10 patients (50%) with rete testis invasion compared to only 6 patients (26%) without rete testis invasion, P = .05. The combination of rete testis invasion and angiolymphatic invasion were present in 8 cases and were found to be associated with elevated serum tumor markers in 7 (88%) of the 8 cases, compared to the combination of no invasion of the rete testis and angiolymphatic invasion showing elevated serum tumor markers in 3 (38%) of 8 cases. However, 7 patients (35%) with rete testis invasion developed metastatic disease, and 11 patients (48%) without rete testis invasion developed metastatic disease. Rete testis status should be documented in orchiectomy specimens with malignant germ cell tumors. Intratubular germ cell neoplasia may be the only component of a malignant germ cell tumor involving the rete testis. In this series, elevated tumor markers were more likely associated with angiolymphatic invasion and positive rete testis status. Positive rete testis status does not appear to be an independent predictor of patient outcome.

Progression-free survival (PFS) as a new endpoint for designing phase II trials in patients with refractory germ cell tumors (GCT).

4583 Background: Refractory GCT patients have a poor prognosis and limited treatment options. Identification of novel active agents is a priority but may be impaired by use of response as the main endpoint in phase II trials. Improved endpoints may hasten the development of new effective agents. Methods: We retrospectively reviewed the characteristics and outcome of refractory GCT patients enrolled in 7 single-agent phase II trials conducted at MSKCC between 1990 and 2008. Study agents included: suramin, all- transretinoic acid, topotecan, pyrazoloacridine, temozolamide, ixabepilone, and sunitinib. For patients treated on more than 1 study, baseline characteristics and outcome to the first trial therapy were used. The major endpoints evaluated were response, PFS, and overall survival (OS). Results: 90 patients (M:F 87:3) were treated, including 4 patients enrolled on more than 1 study. The median age was 35 (range 17-64) and primary tumor site was testis in 65, mediastinum in 17, retroperitoneum in 4, and other in 4. 86 patients had non-seminoma and 4 had pure seminoma. Best responses were 1 (1%) partial response (ixabepilone), 15 (17%) stable disease, and 74 (82%) progressive disease. Median PFS and OS were 1.0 month (95%CI: 0.8-1.3) and 4.7 months (95%CI: 3.5-6.4), respectively. 86 patients died; of the remaining 4 patients, 1 was rendered disease-free by salvage resection of a lung nodule, 1 achieved a durable complete response to single agent paclitaxel, and the other 2 have been lost to follow-up. The 12- and 16-week PFS rates were 9% and 6% respectively. Conclusions: Patients with refractory GCT progress rapidly when treated with ineffective agents. PFS may be a useful endpoint for designing phase II trials testing novel agents in this population. A 12-week PFS endpoint (with comparison to the 9% benchmark rate reported herein) is recommended. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Lilly, Pfizer Bristol-Myers Squibb, Genentech, Lilly, Pfizer

2-18fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) for postchemotherapy seminoma residuals: A retrospective validation of the SEMPET trial.

4581 Background: The use of FDG-PET for the evaluation of postchemotherapy seminoma residuals has been recommended by several international guidelines. This is based on the prospective SEMPET trial including 56 PET studies. Our trial was designed to confirm these recommendations in a larger group of patients. Methods: Investigators from Europe and Canada were invited to contribute consecutive patient data. The eligibility criteria included: metastases of pure seminoma (testicular or extragonadal), negative tumor markers after first line or salvage platinum-containing chemotherapy (completed after 2001), CT evidence of clearly measurable residual masses ≥ 1cm in diameter after chemotherapy, a postchemotherapy FDG-PET scan evaluated by visual interpretation; and a follow-up of ≥ 24 months (unless relapse) or surgery of residual lesions. Results: By October 2009, 147 FDG-PET results from 17 institutions were contributed, of which 42 were ineligible, mostly due to insufficient follow-up (88%), 13 were rated equivocal and were not included in the final analysis. Interestingly, all patients with equivocal scans remained relapse-free. The results of the remaining 92 PET studies demonstrated 64 true negative (TN), 8 true positive (TP), 4 false negative (FN) and 16 false positive (FP). The interval between chemotherapy and PET scan was inadequate according to the current guidelines in 10/16 (63%) FP and in 2/4 (50%) FN scans. Excluding scans with inadequate timing, specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 91%, 80%, 57%, 97%, and 90%, respectively. Eight of 45 (18%) residual lesions ≥ 3cm contained viable tumor; 42/45 (93%) were correctly predicted by FDG-PET. Conclusions: These retrospective data confirm a high specificity, sensitivity, and NPV of FDG-PET for the evaluation of postchemotherapy seminoma residuals. Based on a small number of positive PET scans, the PPV was less reliable than previously reported. However, FDG-PET performed within the correct timeframe remains a valuable tool for clinical decision-making in this clinical setting, and allows to omit unnecessary surgery. No significant financial relationships to disclose.

Testicular sparing surgery for small masses

ObjectivesTo determine the proportion of benign testicular lesions among candidates for testicular sparing surgery (TSS) and to assess the safety and efficacy of this procedure. Methods and MaterialsSixteen patients underwent surgical exploration for testicular tumors with TSS intent in our center. Surgery was performed via an inguinal approach with temporary cord occlusion and frozen section (FS) analysis of the lesions. Benign findings allowed for TSS, whereas cancer prompted total orchiectomy. ResultsThe lesions measured 8–25 mm in the largest diameter. Eleven of the 16 lesions were benign (69%) and TSS was accomplished in these cases. Complete concordance was observed between the results of FS and permanent sections. Of the 5 patients with cancer, 3 had pure seminoma, and embryonal carcinoma and teratoma were found in 1 patient, each. Surveillance was applied in 4 of these patients, and chemotherapy was used in the patient with embryonal carcinoma. With an average follow-up duration of 48 months, all are alive and free of disease. All 11 patients in whom TSS was accomplished had an uneventful postoperative course, and with an average follow-up duration of 28 months, 9 have normal scrotal physical examination and ultrasound, whereas 2 patients were lost to follow-up. ConclusionsSixty-nine percent of testicular lesions under 25 mm are benign. TSS is safe and effective in patients with small benign lesions. Cancer is reliably detected by FS, and testicular exploration is not associated with local or distant recurrence in any of our patients.

Testicular seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Testicular seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Métastase cutanée d’un séminome testiculaire pur

Seminomas are germinal tumors from testicular cells in men. Cutaneous metastasis are very rare. The authors report the case of a 56-year-old male patient admitted for treatment of an enlarged left testicular mass. Physical examination revealed a cutaneous nodule on the right side of the back. Histopathologic examination of both orchiectomy materiel and cutaneous lesion revealed pure seminoma. Chest and abdomen-pelvis CT revealed a pulmonary metastatic nodules, enlarged para-aortic lymph nodes and metastatic lesions in the adrenals glands. The patient died sixmonths after diagnosis due to complications of metastatic disease despite adjuvant chemotherapy. To our knowledge, we report the first case demonstrating that seminoma may spread to skin.

1928 SMALL INCIDENTALLY DISCOVERED TESTICULAR MASSES IN INFERTILE MEN: IS ACTIVE SURVEILLANCE THE NEW STANDARD OF CARE?

You have accessJournal of UrologyInfertility: Therapy/Evaluation1 Apr 20101928 SMALL INCIDENTALLY DISCOVERED TESTICULAR MASSES IN INFERTILE MEN: IS ACTIVE SURVEILLANCE THE NEW STANDARD OF CARE? Paul Toren, Matthew Roberts, Irene Lecker, Ethan Grober, Keith Jarvi, and Kirk Lo Paul TorenPaul Toren More articles by this author , Matthew RobertsMatthew Roberts More articles by this author , Irene LeckerIrene Lecker More articles by this author , Ethan GroberEthan Grober More articles by this author , Keith JarviKeith Jarvi More articles by this author , and Kirk LoKirk Lo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1896AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES With the widespread use of scrotal ultrasound in the evaluation of male infertility, the incidence of small, incidentally detected testicular masses is increasing. Traditionally, treatment has been surgical removal due to concerns about malignancy. Ultrasound follow-up has been proposed as an alternative to surgery. We present the largest series to date of small, non-palpable, incidentally detected testes masses, and document the natural history of these lesions. METHODS We reviewed the records of patients seen at the Mount Sinai Hospital Fertility Clinic from 2001-2008. Patients with one or more testicular lesions fitting all of the following criteria were included in the study: intratesticular, hypoechoic, diameter < 1cm, non-palpable. We assessed patient age and semen parameters, the size and growth of the lesion(s) on serial ultrasounds, need for surgery, and pathologic diagnosis. RESULTS Of 4418 patients evaluated, 46 (1%) met the inclusion criteria. Mean age was 35. Thirty-nine(85%) presented with infertility. Semen analysis showed azoospermia, oligospermia, and normospermia in 15, 18, and 7 patients respectively, and was unavailable in 6 patients. Mean ultrasound follow-up interval was 253 days, and mean number of ultrasounds was 2.8. Mean lesion diameter was 4.3 mm (range 1-10mm). Thirty-eight patients had serial ultrasound follow-up only, with a mean growth of 0.5mm/yr(95% CI: -2.2 - 3.3mm/yr). Three had immediate surgery, and 5 had surgery following a period of ultrasound follow-up. Indications for surgery were interval growth in 2 and patient choice in 6. Larger size(p=0.02) and presence of vascular flow(p<0.01) were associated with intervention. One patient had radical orchiectomy for pure seminoma identified due to interval growth from 3mm to 6mm at 3 months; he remains recurrence free. The other 7 masses excised by partial orchiectomy were benign. CONCLUSIONS The vast majority of small, non-palpable testicular masses were safely followed with serial ultrasound and did not show significant growth or require surgical removal. Serial ultrasound follow-up of small, non-palpable, hypoechoic testicular masses detected incidentally during work-up for infertility appears to be a safe alternative to immediate surgical removal. Toronto, Canada© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e749 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paul Toren More articles by this author Matthew Roberts More articles by this author Irene Lecker More articles by this author Ethan Grober More articles by this author Keith Jarvi More articles by this author Kirk Lo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Small Incidentally Discovered Testicular Masses in Infertile Men—Is Active Surveillance the New Standard of Care?

The management of small, incidental testicular masses found on scrotal ultrasound is controversial. Although these neoplasms are classically treated with surgical excision, ultrasound surveillance has been proposed as an alternative to surgery. We reviewed our experience of ultrasound surveillance for small testicular masses at Mount Sinai Hospital Fertility Clinic from 2001 to 2008, offered to all patients with subcentimeter, incidentally discovered hypoechoic testicular lesions. Patient age, semen parameters, the size and growth of the lesion on serial ultrasounds, need for surgery and pathological diagnosis were collected in a database. Of 4,418 patients evaluated 46 (1%) met the study inclusion criteria. Mean age was 35 years, and 39 patients (85%) presented with infertility. Semen analysis revealed azoospermia, oligospermia and normospermia in 15, 18 and 7 patients, respectively, and was unavailable in 6. Mean ultrasound followup was 253 days and mean number of ultrasounds was 2.8. Mean lesion diameter was 4.3 mm (range 1 to 10). There were 38 patients with serial ultrasound followup only with a mean growth of 0.5 mm per year (95% CI -2.2-3.3). Three patients underwent immediate surgery and 5 underwent surgery following a period of ultrasound followup. Indications for surgery were interval growth in 2 patients and patient choice in 6. Larger size (p = 0.02) and presence of vascular flow (p <0.01) were associated with intervention. One patient underwent radical orchiectomy for pure seminoma identified due to interval growth from 3 to 6 mm at 3 months. The other 7 masses excised with partial orchiectomy were benign. Ultrasound surveillance of small (less than 1 cm) incidental testicular masses is a safe alternative to immediate surgical removal.

Expression of embryonic stem cell markers in cultured JKT‐1, a cell line derived from a human seminoma

Testicular germ cell tumours (TGCTs), the most frequent solid tumour of the young men, originate from the primitive germ cells. They share some pluripotency stem-cell markers which may help to distinguish between seminoma, the most frequent TGCTs and non-seminoma tumours, such as embryonal carcinoma, teratocarcinoma or choriocarcinoma. Due probably to the propensity of seminoma to apoptosis, only two cell lines originated from pure testicular seminoma, TCam-2 and JKT-1 have been up to now, established, maintained and proposed as representative models of human testicular seminoma. However, both seem, following recent reports, to be able to drift. Thus, the molecular signature of embryonic stem-cell markers of the JKT-1 cells cultured in our laboratory, were studied by RT-PCR, Western blot and immunofluorescence (IF). JKT-1 cells analysed after 30 passages, expressed placenta alkaline phosphatase but not alphafoetoprotein (alphaFP) nor beta-human chorionic gonadotropin. JKT-1 cells also expressed markers of pluripotency such as NANOG and OCT3/4 and more specific seminoma markers, such as AP2gamma and HIWI. However, protein expression of OCT3/4 and AP2y was weak and these JKT-1 cells expressed SOX2, a marker of embryonal carcinoma and did not express c-KIT usually expressed in most seminoma. Possible derivation through in vitro culture conditions was supported by looking at later passages (61) which showed a decrease of NANOG and HIWI protein expression. JKT-1 cells express a signature of markers which is still near from the one express by seminoma cells, allowing carcinogenetic studies. However, because of their great ability to drift as shown for TCam-2, it is recommended to verify and to precise this molecular signature before reporting functional results.

Pure seminoma in the setting of androgen insensitivity syndrome treated with surgical resection and para-aortic radiation: A case report and review of literature

Complete androgen insensitivity is a rare X-linked disorder characterized by a female phenotype in a chromosomally male individual. Malignant transformation of the un-descended testis is a rare phenomena compared to other inter-sex syndromes. This is a case of a 32-year-old female who was diagnosed with androgen insensitivity and presented to the emergency room with pelvic pain. Later the pelvic pain was found to be due to testicular masses, one of which was pure seminoma. We reviewed the literature emphasizing the biochemical and endocrinologic abnormalities leading to the syndrome, as well as the potential for malignant changes of the un-descended testes, diagnosis, and therapeutic management. We discuss the importance of early diagnosis and the consequence associated with misdiagnosis.

進行性胚細胞腫瘍治療成績の検討―ＩＧＣＣＣ分類とマーカー半減期による予後予測，救済化学療法早期導入の意義―

We retrospectively analyzed our therapeutic results of advanced male germ cell tumors in terms of efficacy and feasibility of our treatment strategy. Fifty-one new cases were treated in Saitama Cancer Center between April 1997 and August 2007. Patients age ranged from 16 to 58 (median 33). Primary site of the tumor was testis in 41 (80%) patients, retroperitoneum in 6 (12%), and mediastinum in 4 (8%). Histology of the primary germ cell tumor was pure seminoma in 14 (27%), and non-seminoma in 30 (59%). Twenty (39%), 14 (27%) and 17 (33%) were classified as good-, intermediate-, and poor-risk, retrospectively, based on The International Germ Cell Consensus Classification (IGCCC) criteria. The initial treatment for good-risk patients was BEP x 3. Intermediate- or poor-risk patients were treated by VIP from 1997 to 2000, VIPVB from 2001 to 2004, and BEP from 2005 to 2007. Second line salvage treatments were high-dose VIP or ICE from 1997 to 2000. TIP x 4 has been employed since. Marker-negative cases with residual tumors underwent surgical resection of the mass lesion. Five-year survival rate was 100%, 74%, and 76% in patients with good-, intermediate- and poor-risk characteristics, respectively. After two courses of initial chemotherapy, tumor marker decline was satisfactory in 37 patients (73%) and unsatisfactory in 14 (27%). Of these 14 patients, 12 (86%) had unsatisfactory hCG decline, 4 (29%) had unsatisfactory AFP decline, and 2 (14%) had unsatisfactory decline in both markers. Five-year overall survival was 94% in cases with satisfactory maker decline and 71% in those with unsatisfactory marker decline (p = 0.03). In this IGCCCG era, 5 year survival rates of the advanced germ cell tumors have improved by the earlier administration of second line chemotherapies based on both the prognostic factor-based staging system and the tumor marker decline in initial chemotherapy. Development of effective treatment for cases with unfavorable tumor maker decline is the most challenging issue to be addressed.

Clinicopathological Study of Regressed Testicular Tumors (Apparent Extragonadal Germ Cell Neoplasms)

Testicular germ cell tumors sometimes regress spontaneously and manifest exclusively by metastasis. We report our experience with extragonadal germ cell tumors of probable testicular origin to study the frequency of this entity, and clinical, ultrasound and histopathological correlations in a series of patients. A retrospective 16-year review of 1.2 million inhabitants in Spain revealed 17 with regressed testicular tumors treated at a total of 4 institutions. We analyzed clinical information, ultrasound features and histopathological characteristics of testicular lesions and metastasis, and highlight the main findings. A primary testicular origin was confirmed in all cases. This entity is more common than initially suspected since it accounts for 4% of consecutive germ cell tumors. Clinical manifestations varied according to metastatic site with an abdominal palpable mass (47% of cases), loin pain (35%) and transient testicular pain (29%) the most common complaints. No evidence of testicular neoplasms was found on physical examination in any case. Metastasis histology was nonseminomatous in 53% of cases, pure seminoma in 29% and mixed in 18%. The most common ultrasound features were calcifications in 65% of cases, hyperechogenic linear images in 59% and hypoechogenic nodular areas in 41%. Histological findings consisted of fibrotic areas in 100% of cases, hemosiderin deposits in 65%, seminiferous tubule atrophy in 59% and psammoma bodies in 29%. In testicular parenchyma or spermatic chord intratubular neoplasms and viable tumor foci were also noted (47% and 41% of cases, respectively). Spontaneous regression of a germ cell testicular tumor should be considered in each patient with extragonadal germ cell neoplasms. Ultrasound diagnosis of and surgical treatment for these primary testicular tumors appear critical to prevent relapse because residual disease develops in a significant proportion of cases.

7103 Baseline and on-treatment expression of HIF-1a, HIF-2a and CAIX in patients with metastatic renal cell carcinoma

Of 15 patients with malignant germ cell tumours of the mediastinum, 9 patients had pure seminomas and 6 had non-seminomas. Resection was radical in only 4 non-seminomas, 1 of which was resected after chemotherapy; radiotherapy was delivered to all seminoma patients as sole therapy (2 patients) or as part of combined modality therapy. All patients with non-seminomatous tumours underwent chemotherapy (cisplatin-based combination). Therapy was generally well tolerated, but 1 seminoma patient died of sepsis. Chemotherapy achieved a 71% complete response rate in pure seminoma patients and a 33% complete response rate in non-seminoma patients. 53% of patients are alive and free of disease beyond 36 months from start of any treatment. Pure seminoma patients survived longer than non-seminoma patients (3 and 5 year survivals were 67% and 33%, respectively). Although cisplatin-based chemotherapy is highly effective in pure seminomas and also in non-seminomas, a better therapeutic approach is needed in non-seminomas.

CDX2 Expression in Yolk Sac Component of Testicular Germ Cell Tumors

CDX2 has been detected in the majority of colorectal adenocarcinoma cases and may be useful in determining the sites of origin of tumors. In this study, the authors evaluated CDX2 expression in germ cell tumors (GCTs) by immunohistochemistry. Forty cases of testicular GCTs and 8 cases of metastatic GCTs were retrieved for study. In the 40 cases of testicular GCTs, 13 were pure seminomas and 27 mixed GCTs. Yolk sac tumor (YST) was identified by morphology and glypican 3 staining in 20 testicular mixed GCTs. Of these 20 cases, 8 cases showed 1+ positivity for CDX2. Other primitive components of GCTs were negative. For the 6 cases of metastatic mixed GCT with YST, 4 cases were positive, 2+ in 2 cases and 1+ in 2 cases. The positivity of CDX2 in GCTs warrants including YST in the differential diagnosis of adenocarcinoma of unknown origin.

Results of retroperitoneal lymph node dissection after chemotherapy in patients with pure seminoma in the orchidectomy specimen but elevated serum α‐fetoprotein

To determine the incidence of necrosis, teratoma, and active cancer in specimens at retroperitoneal lymph node dissection (RPLND) after chemotherapy in patients who presented with a pure seminoma primary tumour and an elevated serum alpha-fetoprotein (AFP) level at diagnosis who underwent surgery. A retrospective review of the Indiana University testis cancer database from 1980 to 2004 was performed to identify all patients with metastasic germ cell cancer, pure seminoma in the orchidectomy specimen, and an elevated AFP level. In all, 42 patients were identified; two with nonseminomatous germ cell cancer in the contralateral testicle were excluded. RPLND pathology in the 40 patients showed necrosis in 13 (32.5%), teratoma in 12 (30%), and cancer in 15 (37.5%). The histological subtype of the 15 cancer specimens at RPLND was pure seminoma in two, embryonal in three, yolk sac in seven, variant in one, and mixed elements in two (one with seminoma and yolk sac, and one with embryonal and variant). In all, 20 patients presented with a serum AFP level of <1000 microg/mL with nine (45%) having teratoma only in the retroperitoneum in contrast to 20 patients with an AFP level of >1000 microg/mL with three (15%) having teratoma only in the retroperitoneum (P = 0.04). The level of serum AFP did not predict for active cancer in the retroperitoneum (P = 0.5). RPLND in patients after chemotherapy who presented with pure seminoma in the orchidectomy specimen and an elevated AFP do not have a high probability of finding necrosis only in the RPLND specimen. In fact, the prevalence of persistent cancer is higher compared with the general group of patients that have RPLND after chemotherapy.

High-dose chemotherapy (HDCT) as second salvage treatment in patients with multiple relapsed or refractory germ cell tumors

5082 Background: To determine the activity of high-dose chemotherapy (HDCT) as intensification of second salvage treatment (SST) in patients with multiple relapsed germ-cell tumors (GCT). Methods: Databases in Berlin and Marburg (Germany) on patients treated with HDCT between 1989 and 2008 for germ-cell tumors were screened. Among 534 patients overall, 71/534 (13%) patients were identified as scheduled for HDCT having failed at least one previous conventional-dose first-line and first-salvage chemotherapy regimen. Forty-nine patients who had received at least cisplatin- and etoposide as first-line as well as conventional-dose cisplatin as first-salvage treatment and were diagnosed after January 1, 1990, were further analyzed. Results: Median age at SST was 32 years (range 19 to 52 years). Median follow-up for surviving patients was 4 years (range 1,7 to 8,5 years). Histology was pure seminoma in 5/49 (10%) patients and non-seminoma or mixed histologies in 44/49 (90%). The median number of cisplatin-based treatment cycles prior to SST was 7 (range 5 to 11 cycles). Three of forty-nine (6%) patients either progressed or died prior to scheduled HDCT, the remaining 46/49 (94%) received either single or sequential HDCT. The rate of favorable responses to HDCT as intensification of SST was 27/49 (55%). Ten patients are alive without progression. One additional patient is lost-to-follow at four years without progression. The projected overall survival rate at five years after initiation of SST was 17%. Conclusions: HDCT can induce long term remissions even in patients with multiple relapsed GCT. No significant financial relationships to disclose.

A risk-adapted study of cisplatin and etoposide, with or without ifosfamide, in patients with metastatic seminoma: Results of the GETUG S99 multicenter prospective study

5031 Background: Cisplatin plus etoposide-based chemotherapy is the recommended treatment and results in a high cure rate in patients (pts) with metastatic seminoma (Eur Urol 2008, 53: 478–96). Whether pts with good-prognosis and intermediate-prognosis metastatic seminoma should be treated differently or not has not been defined. Methods: From December 1999 to September 2008, pts with pure seminoma, a normal serum alpha-feto protein value, and evidence of metastases were included in this prospective study. Pts with a good prognosis according to the IGGCCG classification were treated with 4 cycles of EP (cisplatin 20 mg/m2/day and etoposide 100 mg/m2/day x 5 days, every 3 weeks). Pts with an intermediate prognosis according to the IGCCCG or MRC classifications (extra-pulmonary visceral metastases or supra-diaphragmatic metastases plus serum LDH&gt; 2 x N) (J Clin Oncol. 1997;15:594–603; Eur J Cancer. 1999;33:1347–1350) were treated with 4 cycles of VIP + G-CSF (cisplatin 20 mg/m2/day, ifosfamide 1.2 g/m2/day, and etoposide 75 mg/m2/day x 5 days, every 3 weeks + G-CSF). Toxicity was assessed using the NCI-CTC scale. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: 133 pts were included in this study. Median age was 36 years (20–66). The median follow-up is 3.6 years (0.4–9.1). 110 (83%) pts had good-prognosis metastatic seminoma and received EP. Grade 3–4 toxicity included mainly neutropenia (41%) and neutropenic fever (13%). The 3-year PFS rate in good-prognosis pts is 94% (87–97), and the OS rate is 99% (94–100). 23 (17%) pts had intermediate-prognosis disease and received VIP + G-CSF. Toxicity included grade 3–4 neutropenia (32%), neutropenic fever (18%), grade 3–4 thrombocytopenia (18%), and grade 3–4 anemia (19%). Platelet and erythrocyte transfusions were required in 32% and 36% of pts, respectively . The 3-year PFS rate is 86% (67–95), and the OS rate is 91% (72–97) in intermediate-prognosis pts. Overall, 92 pts (69%) had post-chemotherapy residual masses and 75 pts (56%) were managed with 18Flurorodeoxyglucose positron emission tomography. Conclusions: This risk-adapted chemotherapy yielded an excellent outcome with an OS rate of 97% in metastatic seminoma. No significant financial relationships to disclose.

Cisplatin-based chemotherapy for advanced seminoma: report of 52 cases treated in two institutions

We evaluated an intensified therapeutic strategy in order to optimize treatment outcomes while maintaining acceptable toxicity in patients with advanced seminoma. Fifty-two patients with advanced pure seminoma were retrospectively evaluated. Patients with low-risk advanced seminoma, according to the International Germ Cell Cancer Collaborative Group Consensus Classification criteria, had received four cycles of the BEP regimen either in the 5-day or the alternative 3-day schedule, while patients with intermediate-risk advanced seminoma had received four cycles of the IBEP regimen. Forty-two patients (80.7%) had testicular seminoma while ten patients (19.3%) presented with primary extragonadal (mediastinal or retroperitoneal) tumor. Forty-seven (90.8%) patients belonged to the low-risk group and five patients (9.2%) to the intermediate-risk group. Treatment-related toxicity was moderate, with febrile neutropenia being the most prevalent (13.5%). Twenty patients (38.5%) achieved a complete response to chemotherapy. Twenty-three from the remaining 32 patients had residual masses more than 3 cm and were submitted to surgery (2 patients), FDG-PET scan (8 patients) or surveillance (13 patients). After 69 months of follow-up there were three recurrences that were successfully treated with high-dose or salvage chemotherapy. No death by any cause was recorded. Intensified cisplatin-based chemotherapy for patients with advanced seminoma does not confer evidence of superiority over radiotherapy alone or the standard BEP regimen. Patients with low-volume abdominal disease (clinical stage IIA and IIB) can be cured by four cycles of BEP instead of radiotherapy at the cost of a substantial increase in chemotherapy exposure and the resulting toxicity.

Controversies in the management of early-stage germ cell tumors

The optimal management of clinical stage I testicular germ cell tumors remains controversial despite a cure rate of 99%. Alternatives for stage I nonseminomas include close surveillance, retroperitoneal lymph node dissection, and chemotherapy. For pure seminomas, the options are surveillance, chemotherapy, and radiation. Understanding the pros and cons of each approach may help in choosing a management plan.

Commentary on Chemotherapy as an alternative to radiotherapy in the treatment of stage IIa and IIb testicular seminoma: A Spanish germ cell cancer group study

To assess the long-term efficacy and toxicity of front-line cisplatin-based chemotherapy in patients with stage IIA or IIB testicular seminoma. Untreated patients with pure seminoma of the testis after orchiectomy, with clinical stage IIA or IIB, were considered eligible for this prospective observational study. Chemotherapy consisted of either 4 cycles of cisplatin and etoposide or 3 cycles of cisplatin, etoposide, and bleomycin. Between April 1994 and March 2003, 72 patients were entered into the study at 26 participating centers. Eighteen patients had stage IIA disease, and 54 patients had stage IIB disease. Eighty-three percent of patients achieved complete response, and 17% achieved partial response with residual mass. After a median follow-up time of 71.5 months, 6 patients with stage IIB disease experienced relapse, and 1 of these patients died as a result of seminoma. Three patients experienced non-seminoma-related deaths (2 died from a further esophageal carcinoma, and 1 died from an upper digestive hemorrhage). The estimated 5-year progression-free survival rates for patients with stage IIA or IIB disease were 100% and 87% (95% CI, 77.5% to 97%), respectively. Five-year progression-free and overall survival rates for the whole group were 90% (95% CI, 82% to 98%) and 95% (95% CI, 89% to 100%), respectively. Severe granulocytopenia and thrombocytopenia were observed in 8 and 2 patients, respectively. Mild to moderate emesis, stomatitis, and diarrhea were the most common nonhematologic effects. Chemotherapy is a highly effective and well-tolerated treatment for patients with stage IIA or IIB seminoma and represents an available alternative that could avoid some of the serious late effects associated with radiotherapy. Further studies focusing on long-term toxicities of different treatment modalities are needed.