Ovarian Low Malignant Potential Tumors

Summary Type: Treatment
Summary Audience: Health professionals
Summary Language: English
Summary Description: Expert-reviewed information summary about the treatment of ovarian low-malignant potential tumors.

Ovarian Low Malignant Potential Tumors

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 FIGO 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,

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.

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.

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.

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.

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.

Treatment Option Overview

The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.

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 2 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 1 of these studies, the yield for serous tumors was 30.8% (4/13) compared with 0% (0/12) for mucinous tumors.⁴ In yet 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/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,

¹ Yazigi R, Sandstad J, Munoz AK: Primary staging in ovarian tumors of low malignant potential. Gynecol Oncol 31 (3): 402-8, 1988.

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.

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.

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.

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.

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.

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.

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.

⁹ Rice LW, Berkowitz RS, Mark SD, et al.: Epithelial ovarian tumors of borderline malignancy. Gynecol Oncol 39 (2): 195-8, 1990.

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.

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 II/III 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 series³ 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.^1,3,4,5,6 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 <2 cm was significantly better than survival for those with a residual tumor from 2 to 5 cm and >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,

¹ Barnhill D, Heller P, Brzozowski P, et al.: Epithelial ovarian carcinoma of low malignant potential. Obstet Gynecol 65 (1): 53-9, 1985.

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.

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.

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.

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.

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.

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.

⁹ Bell DA, Scully RE: Serous borderline tumors of the peritoneum. Am J Surg Pathol 14 (3): 230-9, 1990.

¹⁰ Michael H, Roth LM: Invasive and noninvasive implants in ovarian serous tumors of low malignant potential. Cancer 57 (6): 1240-7, 1986.

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.

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.

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.

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.

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.

¹⁶ Gershenson DM, Silva EG: Serous ovarian tumors of low malignant potential with peritoneal implants. Cancer 65 (3): 578-85, 1990.

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.

Changes to This Summary (06/16/2005)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

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