Purpose of This PDQ Summary
General Information
Stage Information
Early Stage Ovarian Low Malignant Potential Tumors

Current Clinical Trials

Advanced Stage Ovarian Low Malignant Potential Tumors

Current Clinical Trials

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Changes to This Summary (12/21/2007)
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Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of ovarian low malignant potential tumors. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board ¹.

Information about the following is included in this summary:

• Epidemiology and diagnosis.
• Staging.
• Treatment options by cancer stage.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system ² in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version ³, written in less technical language, and in Spanish ⁴.

General Information

Tumors of low malignant potential (i.e., borderline tumors) account for 15% of all epithelial ovarian cancers. Nearly 75% of these tumors are stage I at the time of diagnosis. These tumors must be recognized because their prognosis and treatment is clearly different from the frankly malignant invasive carcinomas.

A review of 22 series (953 patients) with a mean follow-up of 7 years revealed a survival rate of 92% for patients with advanced-stage tumors, if patients with so-called invasive implants were excluded. The cause of death was determined to be benign complications of disease (e.g., small bowel obstruction), complications of therapy, and only rarely (0.7%), malignant transformation.[1] In one series, the 5-, 10-, 15-, and 20-year survival rates of patients with low malignant potential tumors (all stages), as demonstrated by clinical life table analysis, were 97%, 95%, 92%, and 89%, respectively.[2] In this series, mortality was stage dependent: 0.7%, 4.2%, and 26.8% of patients with stages I, II, and III, respectively, died of disease.[2] Another large study showed early stage, serous histology, and younger age to be associated with a more favorable prognosis.[3] In contrast to the excellent survival rates for early stage disease reported above, the Federation Internationale de Gynecologie et d’Obstetrique Annual Report (#21) included 529 patients with stage I tumors with a 5-year actuarial survival rate of 89.1%. Similarly, good survival was found in a large prospective study.[4] Nonetheless, these survival rates are clearly in contrast with the 30% survival rate for invasive tumors (all stages).

The less common endometrioid tumor of low malignant potential should not be regarded as malignant because it seldom, if ever, metastasizes. Malignant transformation can, however, occur and may be associated with a similar tumor outside of the ovary; such tumors are the result of either a second primary or rupture of the primary endometrial tumor.[5]

References

1. Kurman RJ, Trimble CL: The behavior of serous tumors of low malignant potential: are they ever malignant? Int J Gynecol Pathol 12 (2): 120-7, 1993.  [PUBMED Abstract]
   
   
2. Leake JF, Currie JL, Rosenshein NB, et al.: Long-term follow-up of serous ovarian tumors of low malignant potential. Gynecol Oncol 47 (2): 150-8, 1992.  [PUBMED Abstract]
   
   
3. Kaern J, Tropé CG, Abeler VM: A retrospective study of 370 borderline tumors of the ovary treated at the Norwegian Radium Hospital from 1970 to 1982. A review of clinicopathologic features and treatment modalities. Cancer 71 (5): 1810-20, 1993.  [PUBMED Abstract]
   
   
4. Zanetta G, Rota S, Chiari S, et al.: Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study. J Clin Oncol 19 (10): 2658-64, 2001.  [PUBMED Abstract]
   
   
5. Norris HJ: Proliferative endometrioid tumors and endometrioid tumors of low malignant potential of the ovary. Int J Gynecol Pathol 12 (2): 134-40, 1993.  [PUBMED Abstract]
   
   

Stage Information

The Federation Internationale de Gynecologie et d’Obstetrique and the American Joint Committee on Cancer have designated staging.[1,2]

Stage I

Stage I ovarian cancer is limited to the ovaries.

• Stage IA: Tumor limited to one ovary; capsule intact, no tumor on ovarian surface. No malignant cells in ascites or peritoneal washings.*
• Stage IB: Tumor limited to both ovaries; capsules intact, no tumor on ovarian surface. No malignant cells in ascites or peritoneal washings.*
• Stage IC: Tumor limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings.[1]

* [Note: The term, malignant ascites, is not classified. The presence of ascites does not affect staging unless malignant cells are present.]

Stage II

Stage II ovarian cancer is tumor involving one or both ovaries with pelvic extension and/or implants.

• Stage IIA: Extension and/or implants on the uterus and/or fallopian tubes. No malignant cells in ascites or peritoneal washings.
• Stage IIB: Extension to and/or implants on other pelvic tissues. No malignant cells in ascites or peritoneal washings.
• Stage IIC: Pelvic extension and/or implants (stage IIA or stage IIB) with malignant cells in ascites or peritoneal washings.

Different criteria for allotting cases to stage IC and stage IIC have an impact on diagnosis. To assess this impact, of value would be to know if rupture of the capsule was (1) spontaneous or (2) caused by the surgeon; and, if the source of malignant cells detected was (1) peritoneal washings or (2) ascites.

Stage III

Stage III ovarian cancer is tumor involving one or both ovaries with microscopically confirmed peritoneal implants outside the pelvis. Superficial liver metastasis equals stage III. Tumor is limited to the true pelvis but with histologically verified malignant extension to small bowel or omentum.

• Stage IIIA: Microscopic peritoneal metastasis beyond pelvis (no macroscopic tumor).
• Stage IIIB: Macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension.
• Stage IIIC: Peritoneal metastasis beyond pelvis more than 2 cm in greatest dimension and/or regional lymph node metastasis.

Stage IV

Stage IV ovarian cancer is tumor involving one or both ovaries with distant metastasis. If pleural effusion is present, positive cytologic test results must exist to designate a case to stage IV. Parenchymal liver metastasis equals stage IV.

Ovarian low malignant potential tumors almost never reach stage IV.

References

1. Shepherd JH: Revised FIGO staging for gynaecological cancer. Br J Obstet Gynaecol 96 (8): 889-92, 1989.  [PUBMED Abstract]
   
   
2. Ovary. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 275-284. 
   
   

Early Stage Ovarian Low Malignant Potential Tumors

The value of complete staging has not been demonstrated for early stage cases, but the opposite ovary should be carefully evaluated for evidence of bilateral disease. Although the impact of surgical staging on therapeutic management is not defined, in a study, 7 of 27 patients with presumed localized disease were upstaged following complete surgical staging.[1] In two other studies, 16% and 18% of patients with presumed localized tumors of low malignant potential were upstaged as a result of a staging laparotomy.[2,3] In one of these studies, the yield for serous tumors was 30.8% compared with 0% for mucinous tumors.[4] In another study, patients with localized intraperitoneal disease and negative lymph nodes had a low incidence of recurrence (5%), whereas patients with localized intraperitoneal disease and positive lymph nodes had a statistically significantly higher incidence of recurrence (50%).[5]

In early stage disease (stage I or II), no additional treatment is indicated for a completely resected tumor of low malignant potential.[6] When a patient wishes to retain childbearing potential, a unilateral salpingo-oophorectomy is adequate therapy.[7,8] In the presence of bilateral ovarian cystic neoplasms, or a single ovary, a partial oophorectomy can be employed when fertility is desired by the patient.[9] Some physicians stress the importance of limiting ovarian cystectomy to stage IA patients in whom the margins of the cystectomy specimens are free of tumor.[4] In a large series, the relapse rate was higher with more conservative surgery (cystectomy > unilateral oophorectomy > TAH, BSO); differences, however, were not statistically significant, and survival was nearly 100% for all groups.[5,10] When childbearing is not a consideration, a total abdominal hysterectomy and bilateral salpingo-oophorectomy is appropriate therapy. Once a woman has completed her family, most, but not all,[4] physicians favor removal of remaining ovarian tissue as it is at risk of recurrence of a borderline tumor, or even rarely, a carcinoma.[2,7]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I borderline ovarian surface epithelial-stromal tumor ⁵ and stage II borderline ovarian surface epithelial-stromal tumor ⁶. 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 ⁷.

References

1. Yazigi R, Sandstad J, Munoz AK: Primary staging in ovarian tumors of low malignant potential. Gynecol Oncol 31 (3): 402-8, 1988.  [PUBMED Abstract]
   
   
2. Snider DD, Stuart GC, Nation JG, et al.: Evaluation of surgical staging in stage I low malignant potential ovarian tumors. Gynecol Oncol 40 (2): 129-32, 1991.  [PUBMED Abstract]
   
   
3. Leake JF, Rader JS, Woodruff JD, et al.: Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential. Gynecol Oncol 42 (2): 124-30, 1991.  [PUBMED Abstract]
   
   
4. Piura B, Dgani R, Blickstein I, et al.: Epithelial ovarian tumors of borderline malignancy: a study of 50 cases. Int J Gynecol Cancer 2 (4): 189-197, 1992.  [PUBMED Abstract]
   
   
5. Leake JF, Currie JL, Rosenshein NB, et al.: Long-term follow-up of serous ovarian tumors of low malignant potential. Gynecol Oncol 47 (2): 150-8, 1992.  [PUBMED Abstract]
   
   
6. Tropé C, Kaern J, Vergote IB, et al.: Are borderline tumors of the ovary overtreated both surgically and systemically? A review of four prospective randomized trials including 253 patients with borderline tumors. Gynecol Oncol 51 (2): 236-43, 1993.  [PUBMED Abstract]
   
   
7. Kaern J, Tropé CG, Abeler VM: A retrospective study of 370 borderline tumors of the ovary treated at the Norwegian Radium Hospital from 1970 to 1982. A review of clinicopathologic features and treatment modalities. Cancer 71 (5): 1810-20, 1993.  [PUBMED Abstract]
   
   
8. Lim-Tan SK, Cajigas HE, Scully RE: Ovarian cystectomy for serous borderline tumors: a follow-up study of 35 cases. Obstet Gynecol 72 (5): 775-81, 1988.  [PUBMED Abstract]
   
   
9. Rice LW, Berkowitz RS, Mark SD, et al.: Epithelial ovarian tumors of borderline malignancy. Gynecol Oncol 39 (2): 195-8, 1990.  [PUBMED Abstract]
   
   
10. Casey AC, Bell DA, Lage JM, et al.: Epithelial ovarian tumors of borderline malignancy: long-term follow-up. Gynecol Oncol 50 (3): 316-22, 1993.  [PUBMED Abstract]
    
    

Advanced Stage Ovarian Low Malignant Potential Tumors

Patients with advanced disease should undergo a total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, node sampling, and aggressive cytoreductive surgery. Patients with stage III or IV disease with no gross residual tumor have had a 100% survival rate in some series regardless of the follow-up duration.[1,2] The 7-year survival rate of patients with gross residual disease was only 69% in a large series [3] and appears to be inversely proportional to the length of follow-up.[3]

For patients with more advanced-stage disease and microscopic or gross residual disease, chemotherapy and/or radiation therapy are not indicated. Scant evidence exists that postoperative chemotherapy or radiation therapy alters the course of this disease in any beneficial way.[1,3-6] In a study of 364 patients without residual tumor, adjuvant therapy had no effect on disease-free or corrected survival when stratified for disease stage.[7] Patients without residual tumor who received no adjuvant treatment had a survival rate equal to or greater than the treated groups. Currently, no controlled studies have compared postoperative treatment with no treatment.

In a review of 150 patients with borderline ovarian tumors, the survival of patients with a residual tumor of less than 2 cm was significantly better than survival for those with a residual tumor from 2 to 5 cm and more than 5 cm.[8] Whether invasive implants imply a worse prognosis remains an unsettled question. Some investigators have correlated invasive implants with poor prognosis, [9] while others have not.[2,10] Some studies have suggested that it may be possible to use DNA ploidy of the tumors to identify those patients who will develop aggressive disease.[11,12] A study could not correlate DNA ploidy of the primary serous tumor with survival but found that aneuploid invasive implants were associated with a poor prognosis.[13] Currently, no evidence indicates that treatment of patients with aneuploid tumors would have an impact on survival. No significant association was found between p53 and HER-2/neu overexpression and tumor recurrence or survival.[14]

In the face of clinical progression, further tumor reductive surgery followed by chemotherapy is certainly indicated. If the symptom-free interval is long, using chemotherapy after a secondary cytoreductive procedure is not advisable. If, on the other hand, the disease symptomatically recurs rapidly, chemotherapy may be beneficial. Reports have surgically documented the efficacy of chemotherapy on some patients with microscopic or gross residual disease.[15,16] A Gynecologic Oncology Group study used melphalan chemotherapy for patients with progressive disease and used cisplatin for melphalan failures.[17]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III borderline ovarian surface epithelial-stromal tumor ⁸ and stage IV borderline ovarian surface epithelial-stromal tumor ⁹. 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 ⁷.

References

1. Barnhill D, Heller P, Brzozowski P, et al.: Epithelial ovarian carcinoma of low malignant potential. Obstet Gynecol 65 (1): 53-9, 1985.  [PUBMED Abstract]
   
   
2. Bostwick DG, Tazelaar HD, Ballon SC, et al.: Ovarian epithelial tumors of borderline malignancy. A clinical and pathologic study of 109 cases. Cancer 58 (9): 2052-65, 1986.  [PUBMED Abstract]
   
   
3. Leake JF, Currie JL, Rosenshein NB, et al.: Long-term follow-up of serous ovarian tumors of low malignant potential. Gynecol Oncol 47 (2): 150-8, 1992.  [PUBMED Abstract]
   
   
4. Casey AC, Bell DA, Lage JM, et al.: Epithelial ovarian tumors of borderline malignancy: long-term follow-up. Gynecol Oncol 50 (3): 316-22, 1993.  [PUBMED Abstract]
   
   
5. Tumors of the ovary: neoplasms derived from coelomic epithelium. In: Morrow CP, Curtin JP: Synopsis of Gynecologic Oncology. 5th ed. New York, NY: Churchill Livingstone, 1998, pp 233-281. 
   
   
6. Sutton GP, Bundy BN, Omura GA, et al.: Stage III ovarian tumors of low malignant potential treated with cisplatin combination therapy (a Gynecologic Oncology Group study). Gynecol Oncol 41 (3): 230-3, 1991.  [PUBMED Abstract]
   
   
7. Kaern J, Tropé CG, Abeler VM: A retrospective study of 370 borderline tumors of the ovary treated at the Norwegian Radium Hospital from 1970 to 1982. A review of clinicopathologic features and treatment modalities. Cancer 71 (5): 1810-20, 1993.  [PUBMED Abstract]
   
   
8. Tamakoshi K, Kikkawa F, Nakashima N, et al.: Clinical behavior of borderline ovarian tumors: a study of 150 cases. J Surg Oncol 64 (2): 147-52, 1997.  [PUBMED Abstract]
   
   
9. Bell DA, Scully RE: Serous borderline tumors of the peritoneum. Am J Surg Pathol 14 (3): 230-9, 1990.  [PUBMED Abstract]
   
   
10. Michael H, Roth LM: Invasive and noninvasive implants in ovarian serous tumors of low malignant potential. Cancer 57 (6): 1240-7, 1986.  [PUBMED Abstract]
    
    
11. Friedlander ML, Hedley DW, Swanson C, et al.: Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer. J Clin Oncol 6 (2): 282-90, 1988.  [PUBMED Abstract]
    
    
12. Kaern J, Trope C, Kjorstad KE, et al.: Cellular DNA content as a new prognostic tool in patients with borderline tumors of the ovary. Gynecol Oncol 38 (3): 452-7, 1990.  [PUBMED Abstract]
    
    
13. de Nictolis M, Montironi R, Tommasoni S, et al.: Serous borderline tumors of the ovary. A clinicopathologic, immunohistochemical, and quantitative study of 44 cases. Cancer 70 (1): 152-60, 1992.  [PUBMED Abstract]
    
    
14. Eltabbakh GH, Belinson JL, Kennedy AW, et al.: p53 and HER-2/neu overexpression in ovarian borderline tumors. Gynecol Oncol 65 (2): 218-24, 1997.  [PUBMED Abstract]
    
    
15. Fort MG, Pierce VK, Saigo PE, et al.: Evidence for the efficacy of adjuvant therapy in epithelial ovarian tumors of low malignant potential. Gynecol Oncol 32 (3): 269-72, 1989.  [PUBMED Abstract]
    
    
16. Gershenson DM, Silva EG: Serous ovarian tumors of low malignant potential with peritoneal implants. Cancer 65 (3): 578-85, 1990.  [PUBMED Abstract]
    
    
17. Barnhill DR, Kurman RJ, Brady MF, et al.: Preliminary analysis of the behavior of stage I ovarian serous tumors of low malignant potential: a Gynecologic Oncology Group study. J Clin Oncol 13 (11): 2752-6, 1995.  [PUBMED Abstract]
    
    

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