Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report)

Seventy-six patients with malignant germ cell tumors of the ovary received vincristine, dactinomycin, and cyclophosphamide (VAC) postoperatively. Fifty-four were treated after removal of all gross disease. The majority of these remain disease-free. Indeed, only 15 (28%) have failed, including 11 of 24 with pure endodermal sinus tumor, 3 of 11 (27%) with mixed germ cell tumor containing endodermal sinus elements, and only 1 of 20 with immature teratoma grade 2 or 3, a patient seen initially with recurrent disease. Postoperative VAC therapy, however, did not appear to be effective in patients with unresectable or incompletely resected germ cell tumors of the ovary. Fifteen of 22 patients (68%) with incompletely resected germ cell tumors failed VAC therapy, including 4 of 7 with pure endodermal sinus tumor, 5 of 5 with mixed germ cell tumors containing endodermal sinus elements, 2 of 2 with embryonal carcinoma, and 4 of 8 with immature teratoma. In failing, patients' median time to progression was 8 months. Dose-limiting toxicity was seen in 30% of the entire group. Combined cisplatin, vinblastine and bleomycin therapy now is being tested in this group of tumors.     

Chemotherapy of extragonadal germ cell tumors

Forty-nine patients with histologically proven germ cell tumors arising in extragonadal sites were retrospectively reviewed. Included in the review were an additional seven patients with undifferentiated tumors with a pathologic appearance compatible with that of a germ cell tumor and elevated levels of serum biomarkers (beta subunit of human chorionic gonadotropin [beta-HCG] +/- alpha-fetoprotein [AFP]. Nineteen patients had a pure seminoma arising in an extragonadal site, whereas 30 patients had nonseminomatous germ cell tumors. Seven patients had primary undifferentiated tumors with elevated levels of serum biomarkers. Sixteen (84%) of the 19 patients with pure extragonadal seminomas with normal levels of serum AFP are alive and free of disease. Eighteen of these 19 patients received platinum-containing regimens and four had received prior chemotherapy that failed. Of the patients with nonseminomatous germ cell tumors, 12 (40%) of the 30 are alive and free of disease with vinblastine/bleomycin +/- cisplatin (13 patients) or CISCAII (cisplatin, cyclophosphamide, and doxorubicin) (nine patients) alternating CISCAII/VBIV (eight patients) chemotherapy. None of the seven patients with undifferentiated germ cell tumors are alive and free of disease. Three of the five patients with pure anterior mediastinal endodermal sinus tumors treated with chemotherapy remain alive and free of disease. Of the seven patients with choriocarcinomas arising in extragonadal sites, three are alive and free of disease. A classification for patients with extragonadal germ cell tumors incorporating site of origin, histology, and likelihood of being truly extragonadal is proposed. The implications of this classification are discussed.     

Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.     

Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP

During the last 6 1/2 years, serum AFP has been determined by radioimmunoassay in 387 patients with germ cell tumors of the gonads and extragonadal sites. The histological appearances of all these neoplasms were carefully reviewed. Highly elevated levels of serum AFP were noted in patients with tumors containing endodermal sinus (yolk sac) tumor elements irrespective of the location of the neoplasm or presence or absence of metastatic disease. There was good correlation between the presence and quantity of endodermal sinus (yolk sac) tumor elements within the primary tumor or its metastases and elevated levels of serum AFP. All patients with tumors composed of pure seminoma or dysgerminoma, and teratoma, had normal serum AFP levels. Slightly elevated levels of serum AFP up to 60 ng/mg (upper limit of normal 20 ng/ml) were noted in a few patients with testicular tumors composed of pure embryonal carcinoma, whereas patients with tumors composed of or containing endodermal sinus (yolk sac) tumor elements had serum AFP levels that could be measured in 100's or 1000's of ng/ml. Serum AFP was elevated only in patients with active disease. Serum AFP was determined in 81 patients with gonadal tumors of non germ cell origin and was normal in all these patients. Serum AFP is a very good tumor marker in patients with germ cell tumors composed of or containing endodermal sinus (yolk sac) tumor, irrespective of their location. Serial serum SFP determinations can be used for diagnostic purposes, for monitoring the results of treatment, and for early detection of metastases and recurrences. Serial serum AFP determination is a useful procedure in all patients with germ cell neoplasms and is highly recommended.     

Sequential combination chemotherapy for malignant germ cell tumors of the ovary

Fourteen patients with malignant ovarian germ cell tumors were treated postoperatively with a short-term, sequential regimen combining cisplatin, vincristine, methotrexate, bleomycin, dactinomycin, cyclophosphamide, etoposide, Adriamycin (Adria Laboratories, Columbus, OH), and vinblastine (POMB/ACE/PAV). Two patients had Stage I disease, Five had Stage II, five had Stage III, and two had Stage IV. The histologic diagnosis was immature teratoma in five cases (two cases were Grade 2 and three cases were Grade 3) endodermal sinus tumor in two cases, dysgerminoma in three cases, and mixed germ cell tumors in four cases. The chemotherapy regimen appeared to be highly effective against all histologic types, including advanced stages, with 12 of 14 (86%) overall sustained remissions. The median duration of treatment was 5 months. The toxicity of the regimen, which contained low total doses of cisplatin and bleomycin, was only moderate. After a median follow-up of 53+ months, 13 patients were alive without evidence of disease. The results and toxicity obtained were compared with those from other currently used regimens. Also, some comments on initial surgery and second-look surgery are given.     

The incidence of yolk sac tumor (endodermal sinus tumor) elements in germ cell tumors of the testis in adults.

The incidence of yolk sac tumor (endodermal sinus tumor) elements was studied in 147 germ cell neoplasms of the testis in adults observed over a 4 1/2-year period. Excluding 79 cases of pure seminoma, yolk sac tumor elements were found in 26 (38%) of 68 tumors; in 8 tumors the yolk sac tumor was the predominant element. Yolk sac tumor elements were found admixed with all other germ cell tumor elements. Tumors composed entirely of yolk sac tumor were not encountered. Fifteen (57%) of the 26 patients with tumors containing yolk sac tumor elements have died of their disease during the period under study, compared with 13 (31%) of the remaining 42 patients, suggesting that the prognosis of adults with testicular tumors containing yolk sac tumor elements is unfavorable. This is in contrast to the relatively good prognosis of infants and young children with testicular yolk sac tumor, and similar to the prognosis of female patients with ovarian yolk sac tumor. The results of the present study give further support to the view that yolk sac tumor (endodermal sinus tumor) is not adistinctive neoplasm of the infant's testis, but a germ cell neoplasm differentiating in the direction of yolk sac or vitelline structures, and occurring in the testis, ovary and extragonadal sites in common with other germ cell neoplasms.     

Vinblastine, bleomycin, and cisplatin in malignant germ cell tumors of the ovary

Fourteen patients with malignant ovarian germ cell tumors were treated with vinblastine, bleomycin, and cisplatin. A complete clinical response was achieved in all 14 patients; however, 1 patient had small macroscopic disease present at second-look laparotomy. One patient died of bleomycin pulmonary toxicity. The remaining 13 patients are alive and free of disease from 20 months to 8 years and 8 months after initial diagnosis. Serum alpha-fetoprotein and beta-human chorionic gonadotropin levels were monitored in all patients and were found to be reliable indicators of response to treatment and disease status. The uninvolved ovary was preserved in seven patients without compromising the response to treatment, and one patient subsequently became pregnant. Vinblastine, bleomycin, and cisplatin chemotherapy appears to be a safe, effective combination and is recommended as the primary treatment of choice in the management of patients with malignant ovarian germ cell tumors.     

Retroperitoneal germ cell tumors in childhood. A clinical and pathologic study of 11 cases

During the last 54 years at the Children's Hospital 11 children (10 female, 1 male) had been treated for an extragonadal germ cell tumor arising in the retroperitoneum. There were eight teratomas (five mature, three immature), two endodermal sinus tumors and one tumor with a mixture of both components. Abdominal pain or discomfort was the usual presenting complaint, with the average age at diagnosis being 18 months. On physical examination, each child had a palpable abdominal mass usually localized in the upper quadrants. The finding of calcification, bone or teeth, on radiologic study was most helpful in establishing a preoperative diagnosis of teratoma. The preferred treatment for children with mature and immature teratomas is complete surgical resection; decisions regarding adjuvant therapy for patients with immature tumors must be evaluated on an individual basis. The prognosis remains guarded for children with unresectable primaries or those with endodermal sinus tumor. Of three tumor-related deaths, two were due to metastatic endodermal sinus tumor and one resulted from extensive local growth by immature teratoma. Successful management of children with endodermal sinus tumor requires surgery aimed at debulking or complete resection in combination with aggressive adjuvant chemotherapy.     

Serum alpha-fetoprotein as a marker for the effect of post-operative radiation therapy and/or chemotherapy in eight cases of ovarian endodermal sinus tumour.

The clinical pathological findings of eight cases of ovarian endodermal sinus tumour (yolk sac tumour) are presented. Histological exmination in all eight cases showed a typical endodermal sinus tumour pattern, and in six of the patients other tumour elements such as dysgerminoma, choriocarcinoma, malignant teratoma, endometriosis, and a dermoid cyst were also found. Six patients had increased serum alpha-fetoprotein concentration in the post-operative period, and two patients had a normal concentration 27 and 35 days after operation, respectively. In all cases except one, a close correlation between serum alpha-fetoprotein and progression or regression of tumour was found. Serum alphafetoprotein was thus found to be a reliable parameter in post-operative radiation and/or chemotherapy (VAMBLE). In one patient who died 10 months after operation with widespread endodermal sinus tumour growth, only a small terminal increase in serum alpha-fetoprotein concentration was found. Four of the eight women are still alive with normal alpha-fetoprotein concentration, and without clinical evidence of tumour disease.     

Successful treatment of pure endodermal sinus tumors in adult men

Seven adult men with pure endodermal sinus tumors (EST) were treated with cyclical combination chemotherapy Cytoxan (cyclophosphamide; Bristol-Myers Company, Evansville, IL), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin/vinblastine and bleomycin (CISCAII/VBIV) and surgery at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1978 through 1985. Six tumors were of extragonadal origin (four anterior mediastinum, one pelvic, one prostate), and one was of gonadal origin with retroperitoneal metastasis. All patients presented with advanced local disease and a relative absence of distant metastasis. Alpha-fetoprotein (AFP) levels were elevated in six patients (median, 4,400 ng/mL; range, 2,580 to 31,200 ng/mL). Six patients achieved a complete remission (CR): one with chemotherapy alone, one with initial surgery followed by chemotherapy, and four with chemotherapy followed by consolidative surgery. The remaining patient died of progressive disease. Of the six patients who achieved a CR, five are alive with no evidence of disease (+17, +23, +34, +43, +59 months); one patient developed recurrent disease at 6 months after completion of therapy and is currently undergoing salvage chemotherapy. Of the four patients who underwent postchemotherapy surgery, three were operated on for a marker-negative stable mass; in these patients, no viable tumor was found at pathologic review. The remaining patient underwent surgery for a stable mass with a persistent elevation in AFP levels. He was found to have 95% necrosis with 5% viable tumor and remains disease free without further therapy. The observed changes in AFP levels correlated with regression and progression of tumor; a normal AFP was consistent with a CR, and elevation was consistent with residual tumor. These seven patients demonstrate that when adult men with EST are treated aggressively with combination chemotherapy and surgery, high cure rates can be achieved.     

Endodermal sinus tumor: the Stanford experience and the first reported case arising in the vulva

A review of the histology, clinical findings and results of therapy in 9 females with endodermal sinus tumor (EST) is presented. Five patients had histologically pure EST; 4 had EST mixed with other germ cell components. The site of primary tumor was the ovary in 8 of the 9 females; the remaining patient with an extraovarian primary represents the first reported case of EST arising in the vulva. The addition of combination chemotherapy has prolonged survival over historical controls treated with surgery or surgery plus irradiation. Adjuvant chemotherapy appears warranted as treatment for occult metastatic disease; postoperative radiation therapy appears useful in providing local control of primary disease. There is a suggestion of increased sensitivity of EST to combination chemotherapy as compared to other germ cell histologies with which it is commonly admixed.     

卵巢内胚窦瘤：附35例临床分析

Thirty-five patients with pure endodermal sinus tumor of the ovary treated in our hospital from 1962 to 1984 are reported. There were 8 Stage I, 13 Stage III lesions and 14 with recurrent tumor from other hospitals. All the patients were treated by surgery followed by chemotherapy including single drug or combined chemotherapy. Five of 7 patients on high-dose DDP (120 mg/M2) responded. Two of the Stage I patients survived for 33 and 39 months. One of 2 patients by AcFuCy regime was free of tumor for 82 months. Four of 6 patients with advanced tumor treated by VAC regime responded, but only one was alive without evidence of tumor for 30 months. In 21 patients treated with other combination or single drug chemotherapy before 1980, only one (Stage Ia) is alive. It is indicated that surgery combined with multi-drug chemotherapy is the best management and high-dose DDP, VAC and AcFuCy are effective in treating pure endodermal sinus tumor of the ovary. Monitoring of serum AFP levels of the patients with endodermal sinus tumor can predict the course of the disease.     

Gemcitabine in patients with relapsed or cisplatin-refractory testicular cancer.

PURPOSE: Despite generally high cure rates in patients with metastatic testicular germ cell tumors, patients with incomplete response to cisplatin-based first-line therapy or with relapsed disease after high-dose salvage chemotherapy have a very poor prognosis. This phase II study evaluates the use of gemcitabine in patients with intensively pretreated or cisplatin-refractory testicular germ cell cancers. PATIENTS AND METHODS: Thirty-five patients (median age, 33 years) were enrolled; 31 patients were fully assessable. All patients had metastatic nonseminomatous germ cell tumors; eight patients had extragonadal primary tumors. Twenty patients (63%) had lung metastases, and 12 patients (39%) had liver metastases. The median number of prior cisplatin-based chemotherapy cycles was seven; 22 patients (71%) had received high-dose chemotherapy with autologous stem-cell transplantation, and 19 patients (61%) had received treatment with paclitaxel. Seventeen patients (54%) were considered refractory or absolutely refractory to chemotherapy. RESULTS: Six of 31 assessable patients (19%) responded favorably to gemcitabine, 11 patients (35%) displayed no change, and 14 patients (45%) had disease progression. The median time to treatment failure was 4 months (range, 2 to 9+ months), and the median survival was 6 months (range, 2 to 23 months). Patients received a median of six gemcitabine applications. Ten patients (32%) required dose reductions, mainly owing to hematologic toxicity. Grade 3/4 granulocytopenia occurred in four patients (13%) and grade 3/4 thrombocytopenia in seven patients (22%). One case of severe sepsis was observed. CONCLUSION: Gemcitabine displays antitumor activity in intensively pretreated and refractory germ cell tumors. Responses were observed in approximately 20% of patients, including three of 22 patients after previous high-dose chemotherapy and one of four patients with mediastinal tumors. Gemcitabine may be a reasonable palliative option for intensively pretreated patients and should be further investigated to define its role in the risk-adapted treatment strategies for germ cell tumors.     

Serum alphafetoprotein (AFP) in diagnosis and management of endodermal sinus (yolk sac) tumor and mixed germ cell tumor of the ovary.

Serum AFP was determined serially by radioimmunoassay in 13 patients with ovarian germ cell tumors and in one patient with bilateral pure gonadoblastoma. There were 4 patients with pure dysgerminoma, one with pure endodermal sinus tumor (EST) and 8 with mixed germ cell tumors, all containing EST. The patients with dysgerminoma and gonadoblastoma had normal serum AFP at all times. All patients with tumors containing EST had raised serum AFP, although in most cases it was first determined between 1 and 3 weeks after operation and there was no evidence of metastases. Serum AFP became normal 5 to 7 weeks after operation and began to rise when disease recurred. Serum AFP determinations detected presence of recurrent disease long before it became detectable by other methods. Serum CEA was determined serially by radioimmunoassay in 8 of these patients, including 2 who dies with metastases, and was normal on all occasions.     

Combination cisplatin, vinblastine, and bleomycin chemotherapy (PVB) for malignant germ-cell tumors of the ovary

Nine women with germ-cell tumors of the ovary (three endodermal sinus tumors, four immature teratomas, and two mixed germ-cell tumors) were treated with cisplatin, vinblastine, and bleomycin (PVB) chemotherapy after cytoreductive operations. Five patients were stage I, three were stage III, and one patient had recurrent disease. All nine women are alive and without evidence of disease with a median follow-up of 31 months from diagnosis and 27 months since completion of PVB. Treatment toxicity although occasionally severe was rapidly reversible.     

Is there a role for second-look laparotomy in the management of malignant germ cell tumors of the ovary? Experience at Institut Gustave Roussy

The last two decades have seen great improvements in the management of patients with germ-cell tumors of the ovary. The initial treatment approach includes conservative surgery and cisplatin-based chemotherapy in most cases. At completion of chemotherapy, the role of second-look surgery remains questionable. We retrospectively analyzed the long-term outcome (median follow-up, 8 years) of 40 patients who received various chemotherapy regimens after primary surgery and focused on the role of second-look surgery. A second-look laparotomy was performed at completion of chemotherapy in 22 patients. Histological findings were no tumor in 13; mature teratoma in 5; immature teratoma in 1; active disease in 3. Six of the latter nine patients had persistent radiologic abnormalities after chemotherapy. All three patients with active disease had elevated serum tumor markers. Five out of the six patients with residual teratoma lesions had a teratoma component in the primary tumor. According to histological findings at second-look surgery, the number of patients without long-term evidence of disease is 12, 5, 1 and 0, respectively. Eighteen patients were not subjected to second-look surgery. One of them had clearly progressive disease and the other 17 experienced a clinical complete response at completion of chemotherapy. All patients but one are alive without evidence of disease. We conclude that second-look surgery is not necessary in patients with elevated serum tumor marker levels and in those patients with neither radiologic abnormality nor teratoma element in the primary tumor. However, we recommend a second-look procedure for the small subset of patients with a teratoma component in the primary tumor and persistent radiologic abnormalities along with normal serum tumor markers at the end of chemotherapy. © 1996 Wiley-Liss, Inc.     

Treatment of nondysgerminomatous ovarian germ cell tumors: an analysis of 69 cases.

BACKGROUND: Combination chemotherapy has dramatically improved the prognosis of patients with nondysgerminomatous ovarian germ cell tumors (NDOGCT). However, guidelines are needed for the identification of patients at risk of relapse. METHODS: The authors performed a retrospective analysis of women with NDOGCT managed during the period 1970-1994 at the Royal Marsden Hospital and other hospitals of the London Gynaecological Oncology Group. RESULTS: Sixty-nine women were included; their median follow-up was 5.7 years (minimum, 12 months). The median age was 21 years (range, 4-44 years), with a histology of immature teratoma (IT) for 17 patients, endodermal sinus tumor (EST) for 20 patients, and mixed tumors for 32 patients. Thirty-five patients (51%) had Stage I disease. Nine patients with Stage I tumors were observed without further therapy (six with IT and three with mixed tumors), and one relapsed. Seven patients received non-platinum-based chemotherapy, and four relapsed. A total of 52 patients were treated with platinum-based chemotherapy, with relapse free and overall survival rates of 87% (95% confidence interval [CI], 73-93%) and 84% (95% CI, 70-91%), respectively. Of these patients, relapse was seen in 0 of 9 IT patients, 1 of 25 patients with mixed tumors, and 6 of 18 EST patients. With alpha-fetoprotein (AFP) > 1000 kU/L, relapse was seen in 6 of 18 patients compared with 1 of 33 relapses with lower AFP levels. In multivariate analysis, including all patients who received chemotherapy, AFP >1000 kU/L (P = 0.001) and non-platinum-based chemotherapy (P = 0.005) were associated with relapse. When only patients given platinum-based treatment were considered, EST histology (P = 0.003) and AFP >1000 kU/L (P = 0.003) were associated with relapse in univariate analysis; however, these factors were linked. No malignant tumor was found at second-look surgery performed on 24 patients. Of 26 women assessable for fertility, 24 subsequently recommenced regular menstrual function, and 11 patients had pregnancies. CONCLUSIONS: Platinum-based chemotherapy has been confirmed to be effective in the management of patients with NDOGCT. Relapses were principally seen among patients with AFP >1000 kU/L or pure EST histology. Efforts to improve outcome need to focus on patients with EST, whereas less intensive management strategies may be appropriate for some patients with IT.     

Cellular localization of alpha-fetoprotein and human chorionic gonadotropin in germ cell tumors of the testis using and indirect immunoperoxidase technique.

An immunohistologic study of 21 patients with germ cell tumors of the testis with measured serum levels of chorionic gonadotropin (HCG) and alpha-feto protein (AFP) was undertaken to correlate the various types of neoplasms with the presence of these tumor markers in the tissue and serum. AFP was demonstrated in mononuclear embryonal cells within embryonal carcinoma and endodermal sinus tumor. HCG was identified within syncytiotrophoblastic giant cells, frequently in association with embryonal carcinoma, and rarely with endodermal sinus tumor and seminoma, as well as in the syncytiotropho-blastic component of choriocarcinoma. Eighteen of the 21 patients (86%) had elevated tumor markers in their serum; serum HCG alone was elevated in five (24%), AFP alone in five (24%) and both were elevated in eight (38%). There was tissue localization of HCG in 12 of the 13 patients (92%) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53%) with elevated serum AFP levels. Based on these findings, a tentative immunohistologic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma, adult type, is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma and teratoma are unlikely to be associated with either marker.     

Serum alpha1-foetoprotein levels in 153 male patients with germ cell tumours.

--alpha1-Foetoprotein (AFP) levels have been measured by radioimmunoassay in the serum of 153 male patients with gonadal and extragonadal germ cell tumours. Thirty-five patients with pure seminoma, and 34 patients with teratoma but without any postoperative evidence of residual or recurrent tumour, consistently had normal serum AFP levels (less than 25 ng/ml). Of 84 patients with active teratomas, 56 (67%) had serological evidence of AFP production. Ten patients with histological evidence of pure yolk sac (endodermal sinus) tumours all had raised levels. Teratomas containing yolk sac (elements may or may not be associated with raised serum levels. Trophoblastic (choriocarcinomatous) elements in a teratoma were not normally associated with high values. Fourteen patients with teratomas had elevated levels in the absence of histologically detectable yolk sac elements. Serum AFP levels often became elevated before clinical evidence of recurrence, so that AFP can act as an effective marker of the course of the disease and its response to therapy in many patients, but recurrent or progressive disease may be present in the absence of raised levels.     

Survival and reproductive function after treatment of malignant germ cell ovarian tumors.

PURPOSE: Germ cell ovarian tumors are curable. The possible sequelae of chemotherapy on long-term survivors are still unknown, but these patients may expect normal lives. The aim of this study was to evaluate the outcome and reproductive function in a population of women treated since 1982. MATERIALS AND METHODS: Between 1982 and 1996, 169 women with malignant germ cell ovarian tumors were seen (70 dysgerminomas, 28 endodermal sinus tumors, 24 mixed tumors, and 47 immature teratomas). Seventy-one had advanced or recurrent disease. Fertility-sparing surgery was performed in 138 (81%) women, 81 of whom received postoperative chemotherapy. RESULTS: With a median follow-up of 67 months, the survival rate was 94% for dysgerminoma, 89% for endodermal sinus tumors, 100% for mixed types, and 98% for immature teratoma. For women who were treated conservatively, the survival rate was 98%, 90%, 100%, and 100%, respectively. Two women had adnexal recurrences, and both received salvage treatment. After treatment, all but one postpubertal woman had recovery of menses within 9 months. During follow-up, 12 untreated and 20 treated patients had 55 conceptions. We recorded 40 pregnancies at term, six terminations, and nine miscarriages. Four malformations were observed: one in 14 conceptions of patients who had not received chemotherapy and three in 41 conceptions of treated patients. CONCLUSION: Irrespective of subtype and stage, conservative surgery should become the standard approach to treating most patients with malignant ovarian germ cell tumors. Fertility seems to be only marginally affected by treatments. Miscarriages are in the expected range for the general population. The malformation rate is slightly higher than in the general population, but no significant difference was seen between patients who did and did not receive chemotherapy.