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.  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.  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.  Another large study showed early stage, serous histology, and younger age to be associated with a more favorable prognosis.  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.  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. 
The Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging to define ovarian low malignant potential tumors; the FIGO system is most commonly used.  
|aAdapted from FIGO Committee on Gynecologic Oncology. |
|bIn order to evaluate the impact on prognosis of the different criteria for allotting cases to stage Ic or IIc, it would be of value to know if rupture of the capsule was spontaneous, or caused by the surgeon; and if the source of malignant cells detected was peritoneal washings, or ascites.|
|I||Growth limited to the ovaries.|
|Ia||Growth limited to one ovary; no ascites present containing malignant cells. No tumor on the external surface; capsule intact.|
|Ib||Growth limited to both ovaries; no ascites present containing malignant cells. No tumor on the external surfaces; capsules intact.|
|Icb||Tumor either stage Ia or Ib, but with tumor on surface of one or both ovaries, or with capsule ruptured, or with ascites present containing malignant cells, or with positive peritoneal washings.|
|II||Growth involving one or both ovaries with pelvic extension.|
|IIa||Extension and/or metastases to the uterus and/or tubes.|
|IIb||Extension to other pelvic tissues.|
|IIcb||Tumor either stage IIa or IIb, but with tumor on surface of one or both ovaries, or with capsule(s) ruptured, or with ascites present containing malignant cells, or with positive peritoneal washings.|
|III||Tumor involving one or both ovaries with histologically confirmed peritoneal implants outside the pelvis and/or positive regional lymph nodes. Superficial liver metastases equals stage III. Tumor is limited to the true pelvis, but with histologically proven malignant extension to small bowel or omentum.|
|IIIa||Tumor grossly limited to the true pelvis, with negative nodes, but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces, or histologic proven extension to small bowel or mesentery.|
|IIIb||Tumor of one or both ovaries with histologically confirmed implants, peritoneal metastasis of abdominal peritoneal surfaces, none exceeding 2 cm in diameter; nodes are negative.|
|IIIc||Peritoneal metastasis beyond the pelvis >2 cm in diameter and/or positive regional lymph nodes.|
|IV||Growth involving one or both ovaries with distant metastases. If pleural effusion is present, there must be positive cytology to allot a case to stage IV. Parenchymal liver metastasis equals stage IV.|
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.  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.   In one of these studies, the yield for serous tumors was 30.8% compared with 0% for mucinous tumors.  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%). 
In early-stage disease (stage I or II), no additional treatment is indicated for a completely resected tumor of low malignant potential.  When a patient wishes to retain childbearing potential, a unilateral salpingo-oophorectomy is adequate therapy.   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.  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.  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.   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,  physicians favor removal of remaining ovarian tissue as it is at risk of recurrence of a borderline tumor, or even rarely, a carcinoma.  
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I borderline ovarian surface epithelial-stromal tumor and stage II borderline ovarian surface epithelial-stromal 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.
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.   The 7-year survival rate of patients with gross residual disease was only 69% in a large series  and appears to be inversely proportional to the length of follow-up. 
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.      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.  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.  Whether invasive implants imply a worse prognosis remains an unsettled question. Some investigators have correlated invasive implants with poor prognosis,  while others have not.   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.   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.  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. 
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.   A Gynecologic Oncology Group study used melphalan chemotherapy for patients with progressive disease and used cisplatin for melphalan failures. 
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III borderline ovarian surface epithelial-stromal tumor and stage IV borderline ovarian surface epithelial-stromal 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.
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