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Childhood Extracranial Germ Cell Tumors Treatment (PDQ®)

Health Professional Version
Last Modified: 01/27/2014

Treatment of Malignant Gonadal GCTs

Childhood Malignant Testicular GCTs
        Testicular GCTs in young boys
        Testicular GCTs in adolescents and young adult males
        Current Clinical Trials
Childhood Malignant Ovarian GCT
        Standard treatment options
        Treatment options under clinical evaluation for stages I through III
        Current Clinical Trials



Childhood Malignant Testicular GCTs

Testicular GCTs in young boys

Testicular germ cell tumors (GCTs) in children occur almost exclusively in boys younger than 4 years.[1,2] The initial approach to evaluate a testicular mass in a young boy is important because a transscrotal biopsy can risk inguinal node metastasis.[3,4] Radical inguinal orchiectomy with initial high ligation of the spermatic cord is the procedure of choice.[5] Retroperitoneal dissection of lymph nodes is not beneficial in the staging of testicular GCTs in young boys. Computed tomography or magnetic resonance imaging evaluation, with the additional information provided by elevated tumor markers, appears adequate for staging.[3,4] Therefore, there is no reason to risk the potential morbidity (e.g., impotence and retrograde ejaculation) related to lymph node dissection.[6,7]

A Children’s Cancer Group (CCG)/Pediatric Oncology Group (POG) clinical trial evaluated surgery followed by observation for boys aged 10 years or younger with stage I testicular tumors. This treatment strategy resulted in a 6-year event-free survival (EFS) of 82%; those boys who developed recurrent disease were salvaged with four cycles of standard-dose cisplatin, etoposide, and bleomycin (PEB), with a 6-year survival of 100%.[3,4] Boys younger than 10 years with stage II tumors were treated after diagnosis with four cycles of PEB.[8] Boys and adolescents (age not limited to 10 years or younger) with stage III and IV testicular tumors were treated with surgical resection followed by four cycles of standard or high-dose (HD)-PEB therapy. The 6-year survival outcome for males younger than 15 years with stage III and IV tumors was 100%, with 6-year EFS of 100% and 94%, respectively.[9] The use of HD-PEB therapy did not improve the outcome for these boys but did cause increased incidence of ototoxicity. Excellent outcomes for boys with testicular GCTs using surgery and observation for stage I tumors and carboplatin, etoposide, and bleomycin (JEB) and other cisplatin-containing chemotherapy regimens for stage II, III, and IV tumors have also been reported by European investigators.[6,10] Thus, surgery followed by standard-dose platinum-based chemotherapy is the recommended approach for stages II, III, and IV testicular GCTs in children younger than 15 years.

Standard treatment options

Surgery: The role of surgery at diagnosis for GCTs is age- and site-dependent and must be individualized. Primary resection is appropriate when feasible without undue risk of damage to adjacent structures; otherwise, an appropriate strategy is biopsy for diagnosis followed by subsequent excision in selected patients who have residual masses following chemotherapy.

Stage I

  • Surgery and close follow-up observation are indicated to document that a normalization of the tumor markers occurs after resection.[10,3]

Stages II through IV

  • Surgery and treatment with four to six cycles of standard PEB. These patients have an overall survival (OS) outcome greater than 90% with this regimen, suggesting that a reduction in therapy could be considered.[8,9]

  • Surgery and treatment with six cycles of JEB.[10]

Treatment options under clinical evaluation for stages I through IV in patients younger than 15 years

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

  • A United Kingdom CCG trial is studying reducing the total JEB cycles.

Testicular GCTs in adolescents and young adult males

Because the biology of testicular GCTs among adolescents and young adult males is different from that of testicular tumors arising in infants and young boys, the treatment guidelines described above for young boys may not be strictly applicable to adolescent males. In particular, the use of retroperitoneal lymph node dissection may play a crucial role both in early stage testicular GCT [11] and for residual disease after chemotherapy for the treatment of metastatic GCT.[12,13] In this age group, the presence of a sarcomatous component in the primary testis GCT does not alter the prognosis, but if a sarcomatous component is found in a metastatic lesion, survival is likely to be compromised.[14]

(Refer to the PDQ summary on Testicular Cancer Treatment for more information.)

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with childhood malignant testicular germ cell tumor and childhood malignant ovarian germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Childhood Malignant Ovarian GCT

Most ovarian neoplasms in children and adolescents are of germ cell origin.[1] Ovarian GCTs are very rare in young girls, but the incidence begins to increase in children aged approximately 8 or 9 years, and continues to rise throughout adulthood.[1] Childhood malignant ovarian GCTs can be divided into dysgerminomas (seminomatous) and nonseminomatous malignant GCTs (i.e., immature teratomas, yolk sac carcinomas, mixed GCTs, choriocarcinoma, and embryonal carcinomas). (For information on childhood mature and immature teratomas arising in the ovary, see the Nonsacrococcygeal Teratomas in Children section of this summary. Refer to the PDQ summary on Ovarian Germ Cell Tumors Treatment for more information.)

For stage I ovarian dysgerminomas and immature teratomas, cure can usually be achieved by unilateral salpingo-oophorectomy, conserving the uterus and opposite ovary, and close follow-up observation.[10,15-18] Chemotherapy can be given if tumor markers do not normalize or if tumors recur.

While advanced-stage ovarian dysgerminomas similar to testicular seminomas are highly curable with surgery and radiation therapy, the effects on growth, fertility, and risk of treatment-induced second malignancy in these young patients [19,20] make chemotherapy a more attractive adjunct to surgery.[21,22] Complete tumor resection is the goal for advanced dysgerminomas; platinum-based chemotherapy can be given preoperatively to facilitate resection or postoperatively (after debulking surgery) to avoid mutilating surgical procedures.[18] This approach results in a high rate of cure and the maintenance of menstrual function and fertility in most patients with dysgerminomas.[21,23]

For ovarian malignant GCTs other than dysgerminomas or immature teratomas, treatment generally involves surgical resection and adjuvant chemotherapy.[24,25] Platinum-based chemotherapy regimens such as PEB or JEB have been used successfully in children,[8-10,15] and PEB is a common regimen in young women with ovarian GCTs.[26,27] This approach results in a high rate of cure and the maintenance of menstrual function and fertility in most patients with nondysgerminomas.[25,28] A few small studies have suggested that observation after surgery may be an option, but only as part of a clinical trial with strict adherence to surgical guidelines.[10,28]

A multidisciplinary approach is essential for treatment of ovarian GCTs. Various surgical subspecialties and the pediatric oncologist must be involved in clinical decisions. The reproductive surgical approach for pediatric GCTs is often guided by the hope that function can be preserved. In a completed pediatric intergroup trial, pediatric patients with ovarian GCTs (stages I-IV) had excellent survival with PEB and conservative surgery, rather than the strict guidelines proposed originally in the study.[29] The role of laparoscopy in children with ovarian GCTs has not been well studied.

Standard treatment options

Surgery: The role for surgery at diagnosis is age- and site-dependent and must be individualized. Primary resection is appropriate when feasible without undue risk of damage to adjacent structures; otherwise, an appropriate strategy is biopsy for diagnosis followed by subsequent surgery in selected patients who have residual masses following chemotherapy.

Stages I through IV

  • Surgery and treatment with four to six cycles of standard PEB, with the exception of patients with stage I ovarian GCTs for whom observation is currently being evaluated. These patients have an OS outcome greater than 90% with this regimen, suggesting that a reduction in therapy could be considered.[8,9,29]

  • Surgery and treatment with six cycles of JEB.[10,29]

Treatment options under clinical evaluation for stages I through III

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

  • A United Kingdom CCG trial is studying the reduction of total JEB cycles.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with childhood malignant ovarian germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References
  1. Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649. Also available online. Last accessed March 12, 2014. 

  2. Walsh TJ, Grady RW, Porter MP, et al.: Incidence of testicular germ cell cancers in U.S. children: SEER program experience 1973 to 2000. Urology 68 (2): 402-5; discussion 405, 2006.  [PUBMED Abstract]

  3. Schlatter M, Rescorla F, Giller R, et al.: Excellent outcome in patients with stage I germ cell tumors of the testes: a study of the Children's Cancer Group/Pediatric Oncology Group. J Pediatr Surg 38 (3): 319-24; discussion 319-24, 2003.  [PUBMED Abstract]

  4. Canning DA: Excellent outcome in patients with stage I germ cell tumors of the testes: a study of the Children's Cancer Group/Pediatric Oncology Group [Editorial Comment on Schlatter]. J Urol 174 (1): 310, 2005. 

  5. Rescorla FJ: Pediatric germ cell tumors. Semin Surg Oncol 16 (2): 144-58, 1999.  [PUBMED Abstract]

  6. Haas RJ, Schmidt P, Göbel U, et al.: Treatment of malignant testicular tumors in childhood: results of the German National Study 1982-1992. Med Pediatr Oncol 23 (5): 400-5, 1994.  [PUBMED Abstract]

  7. Pinkerton CR: Malignant germ cell tumours in childhood. Eur J Cancer 33 (6): 895-901; discussion 901-2, 1997.  [PUBMED Abstract]

  8. Rogers PC, Olson TA, Cullen JW, et al.: Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891. J Clin Oncol 22 (17): 3563-9, 2004.  [PUBMED Abstract]

  9. Cushing B, Giller R, Cullen JW, et al.: Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study--Pediatric Oncology Group 9049 and Children's Cancer Group 8882. J Clin Oncol 22 (13): 2691-700, 2004.  [PUBMED Abstract]

  10. Mann JR, Raafat F, Robinson K, et al.: The United Kingdom Children's Cancer Study Group's second germ cell tumor study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity. J Clin Oncol 18 (22): 3809-18, 2000.  [PUBMED Abstract]

  11. de Wit R, Fizazi K: Controversies in the management of clinical stage I testis cancer. J Clin Oncol 24 (35): 5482-92, 2006.  [PUBMED Abstract]

  12. Carver BS, Shayegan B, Serio A, et al.: Long-term clinical outcome after postchemotherapy retroperitoneal lymph node dissection in men with residual teratoma. J Clin Oncol 25 (9): 1033-7, 2007.  [PUBMED Abstract]

  13. Carver BS, Shayegan B, Eggener S, et al.: Incidence of metastatic nonseminomatous germ cell tumor outside the boundaries of a modified postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol 25 (28): 4365-9, 2007.  [PUBMED Abstract]

  14. Guo CC, Punar M, Contreras AL, et al.: Testicular germ cell tumors with sarcomatous components: an analysis of 33 cases. Am J Surg Pathol 33 (8): 1173-8, 2009.  [PUBMED Abstract]

  15. Baranzelli MC, Bouffet E, Quintana E, et al.: Non-seminomatous ovarian germ cell tumours in children. Eur J Cancer 36 (3): 376-83, 2000.  [PUBMED Abstract]

  16. Dark GG, Bower M, Newlands ES, et al.: Surveillance policy for stage I ovarian germ cell tumors. J Clin Oncol 15 (2): 620-4, 1997.  [PUBMED Abstract]

  17. Marina NM, Cushing B, Giller R, et al.: Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study. J Clin Oncol 17 (7): 2137-43, 1999.  [PUBMED Abstract]

  18. Gershenson DM: Chemotherapy of ovarian germ cell tumors and sex cord stromal tumors. Semin Surg Oncol 10 (4): 290-8, 1994 Jul-Aug.  [PUBMED Abstract]

  19. Teinturier C, Gelez J, Flamant F, et al.: Pure dysgerminoma of the ovary in childhood: treatment results and sequelae. Med Pediatr Oncol 23 (1): 1-7, 1994.  [PUBMED Abstract]

  20. Mitchell MF, Gershenson DM, Soeters RP, et al.: The long-term effects of radiation therapy on patients with ovarian dysgerminoma. Cancer 67 (4): 1084-90, 1991.  [PUBMED Abstract]

  21. Brewer M, Gershenson DM, Herzog CE, et al.: Outcome and reproductive function after chemotherapy for ovarian dysgerminoma. J Clin Oncol 17 (9): 2670-75, 1999.  [PUBMED Abstract]

  22. Williams SD, Blessing JA, Hatch KD, et al.: Chemotherapy of advanced dysgerminoma: trials of the Gynecologic Oncology Group. J Clin Oncol 9 (11): 1950-5, 1991.  [PUBMED Abstract]

  23. Gershenson DM: Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors. J Clin Oncol 6 (2): 270-5, 1988.  [PUBMED Abstract]

  24. Gershenson DM, Morris M, Cangir A, et al.: Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin. J Clin Oncol 8 (4): 715-20, 1990.  [PUBMED Abstract]

  25. Mitchell PL, Al-Nasiri N, A'Hern R, et al.: Treatment of nondysgerminomatous ovarian germ cell tumors: an analysis of 69 cases. Cancer 85 (10): 2232-44, 1999.  [PUBMED Abstract]

  26. Williams SD: Ovarian germ cell tumors: an update. Semin Oncol 25 (3): 407-13, 1998.  [PUBMED Abstract]

  27. Williams S, Blessing JA, Liao SY, et al.: Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group. J Clin Oncol 12 (4): 701-6, 1994.  [PUBMED Abstract]

  28. Palenzuela G, Martin E, Meunier A, et al.: Comprehensive staging allows for excellent outcome in patients with localized malignant germ cell tumor of the ovary. Ann Surg 248 (5): 836-41, 2008.  [PUBMED Abstract]

  29. Billmire D, Vinocur C, Rescorla F, et al.: Outcome and staging evaluation in malignant germ cell tumors of the ovary in children and adolescents: an intergroup study. J Pediatr Surg 39 (3): 424-9; discussion 424-9, 2004.  [PUBMED Abstract]