Primary peritoneal carcinomas develop from the "peritoneum, a membrane that covers the "abdominal cavity that has the same embryonic origin as the ovary. They are often discussed and classified with ovarian cancers when they affect the ovary. They can develop even after the ovaries have been removed and may appear similar to "mesothelioma.
"Clear-cell ovarian carcinomas do not typically respond well to chemotherapy and may be related to endometriosis. They represent approximately 5% of all endometrial cancers. Japanese women develop clear-cell ovarian cancer more frequently than other groups of women.
Clear-cell adenocarcinomas are histopathologically similar to other "clear cell carcinomas, with "clear cells and "hobnail cells. They represent approximately 5–10% of epithelial ovarian cancers and are associated with endometriosis in the pelvic cavity. They are typically early-stage and therefore curable by surgery, but advanced clear-cell adenocarcinomas (approximately 20%) have a poor prognosis and are often resistant to platinum chemotherapy.
Endometrioid adenocarcinomas make up approximately 15–20% of epithelial ovarian cancers. Because they are typically low-grade, endometrioid adenocarcinomas have a good prognosis. These tumors frequently co-occur with "endometriosis or endometrial cancer.
Malignant mixed müllerian tumor (carcinosarcoma)
Mixed müllerian tumors make up less than 1% of ovarian cancer. They have epithelial and mesenchymal cells visible and tend to have a poor prognosis.
Mucinous tumors include mucinous adenocarcinoma and mucinous cystadenocarcinoma.
Mucinous adenocarcinomas make up 5–10% of epithelial ovarian cancers. Histologically, they are similar to intestinal or cervical adenocarcinomas, and are often actually metastases of "appendiceal or "colon cancers. Advanced mucinous adenocarcinomas have a poor prognosis, generally worse than serous tumors, and are often resistant to platinum chemotherapy, though they are rare.
Pseudomyxoma peritonei refers to a collection of encapsulated mucous or gelatinous material in the abdominopelvic cavity, which is very rarely caused by a primary mucinous ovarian tumor. More commonly, it is associated with ovarian metastases of intestinal cancer.
Undifferentiated cancers - those where the cell type cannot be determined - make up about 10% of epithelial ovarian cancers and have a comparatively poor prognosis. When examined under the microscope, these tumors have very abnormal cells that are arranged in clumps or sheets. Usually there are recognizable clumps of serous cells inside the tumor.
Malignant Brenner tumor
Malignant Brenner tumors are rare. Histologically, they have dense fibrous stroma with areas of transitional epithelium, and some squamous differentiation. To be classified as a malignant Brenner tumor, it must have Brenner tumor foci and transitional cell carcinoma. The transitional cell carcinoma component is typically poorly differentiated and resembles urinary tract cancer.
Transitional cell carcinoma
Transitional cell carcinomas represent less than 5% of ovarian cancers. Histologically, they appear similar to "bladder carcinoma. The prognosis is intermediate - better than most epithelial cancers but worse than malignant Brenner tumors.
Sex cord-stromal tumor
"Sex cord-stromal tumor, including "estrogen-producing "granulosa cell tumor, the benign "thecoma, and virilizing "Sertoli-Leydig cell tumor or "arrhenoblastoma, accounts for 7% of ovarian cancers. They occur most frequently in women between 50 and 69 years of age, but can occur in women of any age, including young girls. They are not typically aggressive and are usually unilateral; they are therefore usually treated with surgery alone. Sex cord-stromal tumors are the main hormone-producing ovarian tumors.
Several different cells from the "mesenchyme can give rise to sex-cord or stromal tumors. These include "fibroblasts and endocrine cells. The symptoms of a sex-cord or stromal ovarian tumor can differ from other types of ovarian cancer. Common signs and symptoms include "ovarian torsion, "hemorrhage from or rupture of the tumor, an abdominal mass, and hormonal disruption. In children, "isosexual precocious pseudopuberty may occur with granulosa cell tumors since they produce estrogen. These tumors cause abnormalities in menstruation ("excessive bleeding, "infrequent menstruation, or "no menstruation) or postmenopausal bleeding. Because these tumors produce estrogen, they can cause or occur at the same time as "endometrial cancer or "breast cancer. Other sex-cord/stromal tumors present with distinct symptoms. Sertoli-Leydig cell tumors cause "virilization and "excessive hair growth due to the production of "testosterone and "androstenedione, which can also cause "Cushing's syndrome in rare cases. Also, sex-cord stromal tumors occur that do not cause a hormonal imbalance, including benign fibromas, which cause ascites and "hydrothorax. With germ cell tumors, sex cord-stromal tumors are the most common ovarian cancer diagnosed in women under 20.
Granulosa cell tumor
Granulosa cell tumors are the most common sex-cord stromal tumors, making up 70% of cases, and are divided into two histologic subtypes: adult granulosa cell tumors, which develop in women over 50, and juvenile granulosa tumors, which develop before puberty or before the age of 30. Both develop in the "ovarian follicle from a population of cells that surrounds germinal cells.
Adult granulosa cell tumor
Adult granulosa cell tumors are characterized by later onset (30+ years, 50 on average). These tumors produce high levels of estrogen, which causes its characteristic symptoms: "menometrorrhagia; "endometrial hyperplasia; "tender, "enlarged breasts; "postmenopausal bleeding; and "secondary amenorrhea. The mass of the tumor can cause other symptoms, including abdominal pain and distension, or symptoms similar to an "ectopic pregnancy if the tumor bleeds and ruptures.
Juvenile granulosa cell tumor
Sertoli-Leydig cell tumor
Sertoli-Leydig tumors are most common in women before the age of 30, and particularly common before puberty.
Sclerosing stromal tumors
Sclerosing stromal tumors typically occur in girls before puberty or women before the age of 30.
Germ cell tumor
Germ cell tumors of the ovary develop from the ovarian "germ cells. "Germ cell tumor accounts for about 30% of ovarian tumors, but only 5% of ovarian cancers, because most germ-cell tumors are "teratomas and most teratomas are benign. Malignant teratomas tend to occur in older women, when one of the germ layers in the tumor develops into a "squamous cell carcinoma. Germ-cell tumors tend to occur in young women (20s–30s) and girls, making up 70% of the ovarian cancer seen in that age group. Germ-cell tumors can include dysgerminomas, teratomas, yolk sac tumors/endodermal sinus tumors, and choriocarcinomas, when they arise in the ovary. Some germ-cell tumors have an "isochromosome 12, where one arm of chromosome 12 is deleted and replaced with a duplicate of the other. Most germ-cell cancers have a better prognosis than other subtypes and are more sensitive to chemotherapy. They are more likely to be stage I at diagnosis. Overall, they metastasize more frequently than epithelial ovarian cancers. In addition, the cancer markers used vary with tumor type: "choriocarcinomas are monitored with "beta-HCG and endodermal sinus tumors with "alpha-fetoprotein.
Germ-cell tumors are typically discovered when they become large, palpable masses. However, like sex cord tumors, they can cause ovarian torsion or hemorrhage and, in children, isosexual precocious puberty. They frequently metastasize to nearby lymph nodes, especially para-aortic and pelvic lymph nodes. The most common symptom of germ cell tumors is "subacute abdominal pain caused by the tumor bleeding, "necrotizing, or stretching the ovarian capsule. If the tumor ruptures, causes significant bleeding, or torses the ovary, it can cause "acute abdominal pain, which occurs in less than 10% of those with germ-cell tumors. They can also secrete hormones which change the "menstrual cycle. In 25% of germ-cell tumors, the cancer is discovered during a "routine examination and does not cause symptoms.
Diagnosing germ cell tumors may be difficult because the normal menstrual cycle and "puberty can cause pain and pelvic symptoms, and a young woman may even believe these symptoms to be those of pregnancy, and not seek treatment due to the stigma of "teen pregnancy. Blood tests for alpha-fetoprotein, "karyotype, human chorionic gonadotropin, and liver function are used to diagnose germ cell tumor and potential co-occurring gonadal dysgenesis. A germ cell tumor may be initially mistaken for a benign "ovarian cyst.
Dysgerminoma accounts for 35% of ovarian cancer in young women and is the most likely germ cell tumor to metastasize to the lymph nodes; nodal metastases occur in 25–30% of cases. These tumors may have mutations in "the KIT gene, a mutation known for its role in "gastrointestinal stromal tumor. "People with an XY karyotype and ovaries ("gonadal dysgenesis) or an X,0 karyotype and ovaries ("Turner syndrome) who develop a unilateral dysgerminoma are at risk for a "gonadoblastoma in the other ovary, and in this case, both ovaries are usually removed when a unilateral dysgerminoma is discovered to avoid the risk of another malignant tumor. Gonadoblastomas in people with Swyer or Turner syndrome become malignant in approximately 40% of cases. However, in general, dysgerminomas are bilateral 10–20% of the time.
They are composed of cells that cannot "differentiate further and develop directly from germ cells or from gonadoblastomas. Dysgerminomas contain "syncytiotrophoblasts in approximately 5% of cases, and can therefore cause elevated hCG levels. On gross appearance, dysgerminomas are typically pink to tan-colored, have multiple lobes, and are solid. Microscopically, they appear identical to "seminomas and very close to "embryonic primordial germ cells, having large, polyhedral, rounded "clear cells. The nuclei are uniform and round or square with prominent "nucleoli and the "cytoplasm has high levels of "glycogen. Inflammation is another prominent histologic feature of dysgerminomas.
Choriocarcinoma can occur as a primary ovarian tumor developing from a germ cell, though it is usually a gestational disease that metastasizes to the ovary. Primary ovarian choriocarcinoma has a poor prognosis and can occur without a pregnancy. They produce high levels of hCG and can cause "early puberty in children or "menometrorrhagia (irregular, heavy menstruation) after menarche.
Immature (solid) teratoma
Immature, or solid, teratomas are the most common type of ovarian germ cell tumor, making up 40–50% of cases. Teratomas are characterized by the presence of disorganized tissues arising from all three embryonic "germ layers: "ectoderm, "mesoderm, and "endoderm; immature teratomas also have undifferentiated "stem cells that make them more malignant than mature teratomas (dermoid cysts). The different tissues are visible on gross pathology and often include bone, cartilage, hair, "mucus, or "sebum, but these tissues are not visible from the outside, which appears to be a solid mass with lobes and cysts. Histologically, they have large amounts of "neuroectoderm organized into sheets and tubules along with "glia; the amount of neural tissue determines the histologic grade. Immature teratomas usually only affect one ovary (10% co-occur with dermoid cysts) and usually metastasize throughout the peritoneum. They can also cause mature teratoma implants to grow throughout the abdomen in a disease called "growing teratoma syndrome; these are usually benign but will continue to grow during chemotherapy, and often necessitate further surgery. Unlike mature teratomas, immature teratomas form many "adhesions, making them less likely to cause ovarian torsion. There is no specific marker for immature teratomas, but "carcinoembryonic antigen (CEA), CA-125, CA19-9, or AFP can sometimes indicate an immature teratoma.
Stage I teratomas make up the majority (75%) of cases and have the best prognosis, with 98% of patients surviving 5 years; if a Stage I tumor is also grade 1, it can be treated with unilateral surgery only. Stage II though IV tumors make up the remaining quarter of cases and have a worse prognosis, with 73–88% of patients surviving 5 years.
Mature teratoma (dermoid cyst)
Mature teratomas, or dermoid cysts, are rare tumors consisting of mostly benign tissue that develop after menopause. The tumors consist of disorganized tissue with nodules of malignant tissue, which can be of various types. The most common malignancy is "squamous cell carcinoma, but "adenocarcinoma, "basal-cell carcinoma, "carcinoid tumor, "neuroectodermal tumor, "malignant melanoma, "sarcoma, "sebaceous tumor, and "struma ovarii can also be part of the dermoid cyst. They are treated with surgery and adjuvant platinum chemotherapy or radiation.
Yolk sac tumor/endodermal sinus tumor
"Yolk sac tumors, formerly called endodermal sinus tumors, make up approximately 10–20% of ovarian germ cell malignancies, and have the worst prognosis of all ovarian germ cell tumors. They occur both before menarche (in one-third of cases) and after menarche (the remaining two-thirds of cases). Half of people with yolk sac tumors are diagnosed in stage I. Typically, they are unilateral until metastasis, which occurs within the peritoneal cavity and via the bloodstream to the lungs. Yolk sac tumors grow quickly and recur easily, and are not easily treatable once they have recurred. Stage I yolk sac tumors are highly treatable, with a 5-year disease free survival rate of 93%, but stage II-IV tumors are less treatable, with survival rates of 64–91%.
Their gross appearance is solid, friable, and yellow, with necrotic and hemorrhagic areas. They also often contain cysts that can degenerate or rupture. Histologically, yolk sac tumors are characterized by the presence of "Schiller-Duval bodies (which are pathognomonic for yolk sac tumors) and a reticular pattern. Yolk sac tumors commonly secrete "alpha-fetoprotein and can be "immunohistochemically stained for its presence; the level of alpha-fetoprotein in the blood is a useful marker of recurrence.
Embryonal carcinomas, a rare tumor type usually found in mixed tumors, develop directly from germ cells but are not terminally differentiated; in rare cases they may develop in dysgenetic gonads. They can develop further into a variety of other neoplasms, including choriocarcinoma, yolk sac tumor, and teratoma. They occur in younger people, with an average age at diagnosis of 14, and secrete both alpha-fetoprotein (in 75% of cases) and hCG.
Histologically, embryonal carcinoma appears similar to the "embryonic disc, made up of epithelial, "anaplastic cells in disorganized sheets, with gland-like spaces and papillary structures.
Polyembryomas, the most immature form of teratoma and very rare ovarian tumors, are histologically characterized by having several "embryo-like bodies with structures resembling a germ disk, "yolk sac, and "amniotic sac. "Syncytiotrophoblast giant cells also occur in polyembryomas.
Squamous cell carcinoma
Primary ovarian squamous cell carcinomas are rare and have a poor prognosis when advanced. More typically, ovarian squamous cell carcinomas are cervical metastases, areas of differentiation in an endometrioid tumor, or derived from a mature teratoma.
Mixed tumors contain elements of more than one of the above classes of tumor histology. To be classed as a mixed tumor, the minor type must make up more than 10% of the tumor. Though mixed carcinomas can have any combination of cell types, mixed ovarian cancers are typically serous/endometrioid or clear cell/endometrioid. Mixed germ cell tumors make up approximately 25–30% of all germ cell ovarian cancers, with combinations of dysgerminoma, yolk sac tumor, and/or immature teratoma. The prognosis and treatment vary based on the component cell types.
Secondary ovarian cancer
Ovarian cancer can also be a secondary cancer, the result of "metastasis from a primary cancer elsewhere in the body. About 7% of ovarian cancers are due to metastases, while the rest are primary cancers.["citation needed] Common primary cancers are "breast cancer, "colon cancer, "appendiceal cancer, and "stomach cancer (primary gastric cancers that metastasize to the ovary are called "Krukenberg tumors). Krukenberg tumors have signet ring cells and mucinous cells. Endometrial cancer and lymphomas can also metastasize to the ovary.
Low malignant potential tumors
Low malignant potential ovarian tumors, also called borderline tumors, have some benign and some malignant features. LMP tumors make up approximately 10%-15% of all ovarian tumors. They develop earlier than epithelial ovarian cancer, around the age of 40–49. They typically do not have extensive invasion; 10% of LMP tumors have areas of stromal microinvasion (<3mm, <5% of tumor). LMP tumors have other abnormal features, including increased mitosis, "changes in cell size or nucleus size, "abnormal nuclei, cell stratification, and small projections on cells (papillary projections). Serous and/or mucinous characteristics can be seen on histological examination, and serous histology makes up the overwhelming majority of advanced LMP tumors. More than 80% of LMP tumors are Stage I; 15% are stage II and III and less than 5% are stage IV. Implants of LMP tumors are often non-invasive.
Ovarian cancer is staged using the "FIGO staging system and uses information obtained after surgery, which can include a total "abdominal hysterectomy via "midline laparotomy, "removal of (usually) both ovaries and Fallopian tubes, "(usually) the omentum, "pelvic (peritoneal) washings, assessment of "retroperitoneal lymph nodes (including the pelvic and "para-aortic lymph nodes), "appendectomy in suspected mucinous tumors, and pelvic/peritoneal biopsies for "cytopathology. Around 30% of ovarian cancers that appear confined to the ovary have metastasized microscopically, which is why even stage-I cancers must be staged completely. 22% of cancers presumed to be stage I are observed to have lymphatic metastases. The AJCC stage is the same as the FIGO stage. The AJCC staging system describes the extent of the primary tumor (T), the absence or presence of "metastasis to nearby "lymph nodes (N), and the absence or presence of distant metastasis (M). The most common stage at diagnosis is stage IIIc, with over 70% of diagnoses.
|I||Cancer is completely limited to the ovary|
|IA||involves one ovary, capsule intact, no tumor on ovarian surface, negative washings|
|IB||involves both ovaries; capsule intact; no tumor on ovarian surface; negative washings|
|IC||tumor involves one or both ovaries|
|IC2||capsule has ruptured or tumor on ovarian surface|
|IC3||positive ascites or washings|
|II||pelvic extension of the tumor (must be confined to the pelvis) or primary peritoneal tumor, involves one or both ovaries|
|IIA||tumor found on uterus or fallopian tubes|
|IIB||tumor elsewhere in the pelvis|
|III||cancer found outside the pelvis or in the retroperitoneal lymph nodes, involves one or both ovaries|
|IIIA||metastasis in retroperitoneal lymph nodes or microscopic extrapelvic metastasis|
|IIIA1||metastasis in retroperitoneal lymph nodes|
|IIIA1(i)||the metastasis is less than 10 mm in diameter|
|IIIA1(ii)||the metastasis is greater than 10 mm in diameter|
|IIIA2||microscopic metastasis in the peritoneum, regardless of retroperitoneal lymph node status|
|IIIB||metastasis in the peritoneum less than or equal to 2 cm in diameter, regardless of retroperitoneal lymph node status; or metastasis to liver or spleen capsule|
|IIIC||metastasis in the peritoneum greater than 2 cm in diameter, regardless of retroperitoneal lymph node status; or metastasis to liver or spleen capsule|
|IV||distant metastasis (i.e. outside of the peritoneum)|
|IVA||pleural effusion containing cancer cells|
|IVB||metastasis to distant organs (including the parenchyma of the spleen or liver), or metastasis to the inguinal and extra-abdominal lymph nodes|
The AJCC/TNM staging system indicates where the tumor has developed, spread to lymph nodes, and metastasis.
|Tx||Cannot be assessed|
|T1||Tumor limited to ovary/ovaries|
|T1a||One ovary with intact capsule, no surface tumor, and negative ascites/peritoneal washings|
|T1b||Both ovaries with intact capsules, no surface tumor, and negative ascites/peritoneal washings|
|T1c||One or both ovaries with ruptured capsule or capsules, surface tumor, positive ascites/peritoneal washings|
|T2||Tumor is in ovaries and pelvis (extension or implantation)|
|T2a||Expansion to uterus or Fallopian tubes, negative ascites/peritoneal washings|
|T2b||Expansion in other pelvic tissues, negative ascites/peritoneal washings|
|T2c||Expansion to any pelvic tissue, positive ascites/peritoneal washings|
|T3||Tumor is in ovaries and has metastasized outside the pelvis to the peritoneum (including the liver capsule)|
|T3b||Macroscopic metastasis less than 2 cm diameter|
|T3c||Macroscopic metastasis greater than 2 cm diameter|
|N||Regional lymph node metastasis|
|Nx||Cannot be assessed|
|M1||Metastasis present (excluding liver capsule, including liver parenchyma and cytologically confirmed pleural effusion)|
The AJCC/TNM stages can be correlated with the FIGO stages:
In addition to being staged, like all cancers, ovarian cancer is also graded. The histologic grade of a tumor measures how abnormal or malignant its cells look under the microscope. The four grades indicate the likelihood of the cancer to spread and the higher the grade, the more likely for this to occur. Grade 0 is used to describe noninvasive tumors. Grade 0 cancers are also referred to as borderline tumors. Grade 1 tumors have well differentiated cells (look very similar to the normal tissue) and are the ones with the best prognosis. Grade 2 tumors are also called moderately well-differentiated and they are made up of cells that resemble the normal tissue. Grade 3 tumors have the worst prognosis and their cells are abnormal, referred to as poorly differentiated.
Metastasis in ovarian cancer is very common in the abdomen, and occurs via exfoliation, where cancer cells burst through the ovarian capsule and are able to move freely throughout the peritoneal cavity. Ovarian cancer metastases usually grow on the surface of organs rather than the inside; they are also common on the omentum and the peritoneal lining. Cancer cells can also travel through the "lymphatic system and metastasize to lymph nodes connected to the ovaries via blood vessels; i.e. the lymph nodes along the "infundibulopelvic ligament, the "broad ligament, and the "round ligament. The most commonly affected groups include the "paraaortic, hypogastric, "external iliac, obturator, and "inguinal lymph nodes. Usually, ovarian cancer does not metastasize to the liver, lung, brain, or kidneys unless it is recurrent disease; this differentiates ovarian cancer from many other forms of cancer.
The only "screening recommended for all women is an annual pelvic examination. This is not very effective in detecting early ovarian cancer because it is usually only palpable in advanced stages. Ovarian cancer screening is of high clinical interest because the disease is not typically detectable at its early stages, when it is the most curable. Screening is not recommended using "CA-125 measurements, "HE4 levels, ultrasound, or adnexal palpation in women who are at average risk. "Screening for any type of cancer must be accurate and reliable—it needs to accurately detect the disease and it must not give false positive results in people who do not have cancer.
Ovarian cancer has low prevalence, even in the high-risk group of women from the ages of 50 to 60 (about one in 2000), and screening of women with average risk is more likely to give ambiguous results than detect a problem which requires treatment. Because ambiguous results are more likely than detection of a treatable problem, and because the usual response to ambiguous results is invasive interventions, in women of average risk, the potential harms of having screening without an indication outweigh the potential benefits. The purpose of screening is to diagnose ovarian cancer at an early stage, when it is more likely to be treated successfully.
Screening with "transvaginal ultrasound, pelvic examination, and CA-125 levels can be used instead of preventative surgery in women who have BRCA1 or BRCA2 mutations. This strategy has shown some success.
People with strong genetic risk for ovarian cancer may consider the surgical removal of their ovaries as a preventative measure. This is often done after completion of childbearing years. This reduces the chances of developing both breast cancer (by around 50%) and ovarian cancer (by about 96%) in people at high risk. Women with BRCA gene mutations usually also have their Fallopian tubes removed at the same time (salpingo-oophorectomy), since they also have an increased risk of "Fallopian tube cancer. However, these statistics may overestimate the risk reduction because of how they have been studied.
People with a significant family history for ovarian cancer are often referred to a "genetic counselor to see if they should be tested for BRCA mutations.
Treatment usually involves "chemotherapy and surgery, and sometimes "radiotherapy, regardless of the subtype of ovarian cancer. Surgical treatment may be sufficient for well-differentiated malignant tumors and confined to the ovary. Addition of chemotherapy may be required for more aggressive tumors confined to the ovary. For patients with advanced disease, a combination of surgical reduction with a combination chemotherapy regimen is standard. Borderline tumors, even following spread outside of the ovary, are managed well with surgery, and chemotherapy is not seen as useful. Second-look surgery and "maintenance chemotherapy have not been shown to provide benefit.
"Surgery is the preferred treatment and is frequently necessary to obtain a tissue specimen for differential "diagnosis via its histology. The type of surgery depends upon how widespread the cancer is when diagnosed (the cancer stage), as well as the presumed type and grade of cancer. The surgeon, who is usually a specialized gynecologic oncology surgeon, may remove one (unilateral oophorectomy) or both ovaries (bilateral oophorectomy), the Fallopian tubes (salpingectomy), the uterus (hysterectomy), and the "omentum (omentectomy). Typically, all of these are removed. For low-grade, unilateral stage-IA cancers, only the involved ovary (which must be unruptured) and Fallopian tube will be removed. This can be done especially in young people who wish to preserve their fertility. However, a risk of microscopic metastases exists and staging must be completed. If any metastases are found, a second surgery to remove the remaining ovary and uterus is needed. "Tranexamic acid can be administered prior to surgery to reduce the need for blood transfusions due to blood loss during the surgery.
If a tumor in a premenopausal woman is determined to be a low malignant potential tumor during surgery, and it is clearly stage I cancer, only the affected ovary is removed. For postmenopausal women with low malignant potential tumors, hysterectomy with bilateral salpingo-oophorectomy is still the preferred option. During staging, the appendix should be examined or removed. This is particularly important with mucinous tumors. In children or adolescents with ovarian cancer, surgeons typically attempt to preserve one ovary to allow for the completion of "puberty, but if the cancer has spread, this is not always possible. Dysgerminomas in particular tend to affect both ovaries: 8–15% of dysgerminomas are present in both ovaries. People with low-grade (well-differentiated) tumors are typically treated only with surgery, which is often curative. In general, germ cell tumors can be treated with unilateral surgery unless the cancer is widespread or fertility is not a factor.
In advanced cancers, where complete removal is not an option, as much tumor as possible is removed in a procedure called "debulking surgery. This surgery is not always successful, and is less likely to be successful in women with extensive metastases in the peritoneum, stage- IV disease, cancer in the "transverse fissure of the liver, "mesentery, or diaphragm, and large areas of ascites. Debulking surgery is usually only done once. More complete debulking is associated with better outcomes: women with no macroscopic evidence of disease after debulking have a median survival of 39 months, as opposed to 17 months with less complete surgery. By removing metastases, many cells that are resistant to chemotherapy are removed, and any clumps of cells that have died are also removed. This allows chemotherapy to better reach the remaining cancer cells, which are more likely to be fast-growing and therefore chemosensitive.
Interval debulking surgery is another protocol used, where neoadjuvant chemotherapy is given, debulking surgery is performed, and chemotherapy is finished after debulking. Though no definitive studies have been completed, it is shown to be approximately equivalent to primary debulking surgery in terms of survival, and shows slightly lower morbidity.
There are several different surgical procedures that can be employed to treat ovarian cancer. For stage I and II cancer, laparascopic (keyhole) surgery can be used, but metastases may not be found. For advanced cancer, laparoscopy is not used, since debulking metastases requires access to the entire peritoneal cavity. Depending on the extent of the cancer, procedures may include a bilateral salpingo-oophorectomy, biopsies throughout the peritoneum and abdominal lymphatic system, "omentectomy, "splenectomy, "bowel resection, diaphragm stripping or resection, "appendectomy, or even a posterior "pelvic exenteration.
To fully stage ovarian cancer, "lymphadenectomy should be included in the surgery, but a significant survival benefit to this practice may not happen. This is particularly important in germ cell tumors because they frequently metastasize to nearby lymph nodes.
If ovarian cancer recurs, secondary surgery is sometimes a treatment option. This depends on how easily the tumor can be removed, how much fluid has accumulated in the abdomen, and overall health. It can be helpful in people who had their first surgery done by a generalist and in epithelial ovarian cancer. Secondary surgery can be effective in dysgerminomas and immature teratomas.
The major side effect of an oophorectomy in younger women is early "menopause, which can cause "osteoporosis. After surgery, hormone replacement therapy can be considered, especially in younger women. This therapy can consist of a combination of estrogen and progesterone, or estrogen alone. Estrogen alone is safe after hysterectomy; when the uterus is still present, unopposed estrogen dramatically raises the risk of "endometrial cancer. Estrogen therapy after surgery does not change survival rates. People having ovarian cancer surgery are typically hospitalized afterwards for 3–4 days and spend around a month recovering at home. Surgery outcomes are best at hospitals that do a large number of ovarian cancer surgeries.
It is unclear if "laparoscopy or "laparotomy is better or worse for FIGO stage I ovarian cancer.["needs update] There is also no apparent difference between total abdominal hysterectomy and supracervical hysterectomy for advanced cancers. Approximately 2.8% of people having a first surgery for advanced ovarian cancer die within two weeks of the surgery (2.8% "perioperative mortality rate). More aggressive surgeries are associated with better outcomes in advanced (stage III or IV) ovarian cancer.
"Chemotherapy has been a general "standard of care for ovarian cancer for decades, although with variable protocols. Chemotherapy is used after surgery to treat any residual disease, if appropriate. In some cases, there may be reason to perform chemotherapy first, followed by surgery. This is called "neoadjuvant chemotherapy", and is common when a tumor cannot be completely removed or optimally debulked via surgery. Though it has not been shown to increase survival, it can reduce the risk of complications after surgery. If a unilateral salpingo-oophorectomy or other surgery is performed, additional chemotherapy, called "adjuvant chemotherapy", can be given. Adjuvant chemotherapy is used in stage 1 cancer typically if the tumor is of a high histologic grade (grade 3) or the highest substage (stage 1c), provided the cancer has been optimally staged during surgery. "Bevacizumab may be used as an adjuvant chemotherapy if the tumor is not completely removed during surgery or if the cancer is stage IV; it can extend progression-free survival but has not been shown to extend overall survival. Chemotherapy is curative in approximately 20% of advanced ovarian cancers; it is more often curative with malignant germ cell tumors than epithelial tumors.
Chemotherapy in ovarian cancer typically consists of "platins, a group of "platinum-based drugs, combined with non-platins. Common therapies can include "paclitaxel, "cisplatin, "topotecan, doxorubicin, "epirubicin, and "gemcitabine. "Carboplatin is typically given in combination with either "paclitaxel or "docetaxel; the typical combination is carboplatin with paclitaxel. Carboplatin is superior to cisplatin in that it is less toxic and has fewer side effects, generally allowing for an improved quality of life in comparison, though both are similarly effective. Three-drug regimens have not been found to be more effective, and platins alone or nonplatins alone are less effective than platins and nonplatins in combination. Chemotherapy can be given "intravenously or "in the peritoneal cavity. Though intraperitoneal chemotherapy is associated with longer progression-free survival and overall survival, it also causes more adverse side effects than intravenous chemotherapy. It is mainly used when the cancer has been optimally debulked. Intraperitoneal chemotherapy can be highly effective because ovarian cancer mainly spreads inside the peritoneal cavity, and higher doses of the drugs can reach the tumors this way.
Chemotherapy can cause "anemia; intravenous iron has been found to be more effective than oral "iron supplements in reducing the need for "blood transfusions. Typical cycles of treatment involve one treatment every 3 weeks, repeated for 6 weeks or more. Fewer than 6 weeks (cycles) of treatment is less effective than 6 weeks or more. Germ-cell malignancies are treated differently than other ovarian cancers — a regimen of "bleomycin, "etoposide, and cisplatin (BEP) is used with 5 days of chemotherapy administered every 3 weeks for 3 to 4 cycles. Chemotherapy for germ cell tumors has not been shown to cause "amenorrhea, infertility, "birth defects, or "miscarriage. "Maintenance chemotherapy has not been shown to be effective.
In people with BRCA mutations, platinum chemotherapy is more effective. Germ-cell tumors and malignant sex-cord/stromal tumors are treated with chemotherapy, though dysgerminomas and sex-cord tumors are not typically very responsive.
Platinum-sensitive or platinum-resistant
If ovarian cancer recurs, it is considered partially platinum-sensitive or platinum-resistant, based on the time since the last recurrence treated with platins: partially platinum-sensitive cancers recurred 6–12 months after last treatment, and platinum-resistant cancers have an interval of less than 6 months. Second-line chemotherapy should be given only after the cancer becomes symptomatic, because no difference in survival is seen between treating asymptomatic (elevated CA-125) and symptomatic recurrences.
For platinum-sensitive tumors, platins are the drugs of choice for second-line chemotherapy, in combination with other cytotoxic agents. Regimens include carboplatin combined with "pegylated liposomal doxorubicin, "gemcitabine, or "paclitaxel. Carboplatin-doublet therapy can be combined with paclitaxel for increased efficacy in some cases. Another potential adjuvant therapy for platinum-sensitive recurrences is "olaparib, which may improve "progression-free survival but has not been shown to improve "overall survival. ("Olaparib, a "PARP inhibitor, was approved by the "US FDA for use in BRCA-associated ovarian cancer that had previously been treated with chemotherapy.) For recurrent germ cell tumors, an additional 4 cycles of BEP chemotherapy is the first-line treatment for those tho have been treated with surgery or platins.
If the tumor is determined to be platinum-resistant, "vincristine, "dactinomycin, and "cyclophosphamide (VAC) or some combination of paclitaxel, gemcitabine, and "oxaliplatin may be used as a second-line therapy.
For platinum-resistant tumors, there are no high-efficacy chemotherapy options. Single-drug regimens (doxorubicin or "topotecan) do not have high response rates, but single-drug regimens of topotecan, pegylated liposomal doxorubicin, or gemcitabine are used in some cases. Topotecan cannot be used in people with an intestinal blockage. Paclitaxel used alone is another possible regimen, or it may be combined with liposomal doxorubicin, gemcitabine, cisplatin, topotecan, "etoposide, or "cyclophosphamide. ( See also Palliative care below.)
Dysgerminomas are most effectively treated with radiation, though this can cause infertility and is being phased out in favor of chemotherapy. Radiation therapy does not improve survival in people with well-differentiated tumors.
In stage 1c and 2 cancers, radiation therapy is used after surgery if there is the possibility of residual disease in the pelvis but the abdomen is cancer-free. Radiotherapy can also be used in palliative care of advanced cancers. A typical course of radiotherapy for ovarian cancer is 5 days a week for 3–4 weeks. Common side effects of radiotherapy include diarrhea, constipation, and frequent urination.
Despite the fact that 60% of ovarian tumors have "estrogen receptors, ovarian cancer is only rarely responsive to hormonal treatments. Estrogen alone does not have an effect on the cancer, and "tamoxifen and "letrozole are rarely effective.
Immunotherapy is a topic of current research in ovarian cancer. In some cases, the antibody drug "bevacizumab, though still a topic of active research, is used to treat advanced cancer along with chemotherapy. It has been approved for this use in the European Union.
Specific follow-up depends on, for example, the type and stage of ovarian cancer, the treatment, and the presence of any symptoms. Usually, a check-up appointment is made about every 2 to 3 months initially, followed by twice per year for up to 5 years. For epithelial ovarian cancers, the most common test upon follow-up is CA-125 level. However, treatment based only on elevated CA-125 levels and not any symptoms can increase side effects without any prolongation of life, so the implication of the outcome of a CA-125 test should be discussed before taking it. The recommendation as of 2014 is recurrent cancer may be present if the CA-125 level is twice normal. Treating a recurrence detected by CA-125 does not improve survival.
For women with germ-cell tumors, follow-up tests generally include "alpha-fetoprotein (AFP) and/or "human chorionic gonadotropin. For women with "stromal cancers, tests for hormones like estrogen, testosterone, and "inhibin are sometimes helpful. Inhibin can also be useful for monitoring the progress of sex-cord tumors, along with "mullerian inhibiting substance. AFP can also be used to monitor Sertoli-Leydig tumors. In dysgerminomas, "lactate dehydrogenase and its two "isozymes (LDH-1 and LDH-2) are used to test for recurrence.
Women with ovarian cancer should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or "tumor markers begin rising. Imaging without these indications is discouraged because it is unlikely to detect a recurrence, improve survival, and because it has its own costs and side effects. However, CT imaging can be used if desired, though this is not common. If a tumor is easily imaged, imaging may be used to monitor the progress of treatment.
"Palliative care focuses on relieving symptoms and increasing or maintaining quality of life. It has been recommended as part of the treatment plan for any person with advanced ovarian cancer or patients with significant symptoms. In platinum-refractory and platinum-resistant cases, palliative non-platin chemotherapy is the main treatment.
Palliative care can entail treatment of symptoms and complications of the cancer, including pain, nausea, constipation, ascites, "bowel obstruction, "edema, "pleural effusion, and "mucositis. Especially if the cancer advances and becomes incurable, treatment of symptoms becomes one of the main goals of therapy. Palliative care can also entail helping with decision-making such as if or when "hospice care is appropriate, and the preferred place for the patient at end of life care.
Bowel obstruction can be treated with "palliative surgery ("colostomy, "ileostomy, or internal bypass) or medicine, but surgery has been shown to increase survival time. Palliative surgery may result in "short bowel syndrome, "enterocutaneous fistula, or re-obstruction; or may not be possible due to the extent of obstruction. Other treatments of complications can include "total parenteral nutrition, a low-residue diet, palliative "gastrostomy, and adequate pain control. Bowel obstruction can also be treated with "octreotide when palliative surgery is not an option. Cancer can also block the "ureters, which can be relieved by a "nephrostomy or a "ureteric stent. Ascites can be relieved by repeated "paracentesis or placement of a "drain to increase comfort. Pleural effusions can be treated in a similar manner, with repeated "thoracentesis, "pleurodesis, or placement of a drain.
Radiation therapy can be used as part of the palliative care of advanced ovarian cancer, since it can help to shrink tumors that are causing symptoms. Palliative radiotherapy typically lasts for only a few treatments, a much shorter course of therapy than non-palliative radiotherapy. It is also used for palliation of chemotherapy-resistant germ cell tumors.
Ovarian cancer usually has a relatively poor "prognosis. It is disproportionately deadly because it lacks any clear early detection or screening test, meaning most cases are not diagnosed until they have reached advanced stages. However, in some cases, ovarian cancer recurrences are chronically treatable.
Ovarian cancer metastasizes early in its development, often before it has been diagnosed. High-grade tumors metastasize more readily than low-grade tumors. Typically, tumor cells begin to metastasize by growing in the peritoneal cavity. More than 60% of women presenting with ovarian cancer have stage-III or stage-IV cancer, when it has already spread beyond the ovaries. Ovarian cancers shed cells into the naturally occurring fluid within the abdominal cavity. These cells can then implant on other abdominal (peritoneal) structures, including the uterus, "urinary bladder, "bowel, "lining of the bowel wall, and "omentum, forming new tumor growths before cancer is even suspected.
The five-year survival rate for all stages of ovarian cancer is 46%; the one-year survival rate is 72% and the ten-year survival rate is 35%. For cases where a diagnosis is made early in the disease, when the cancer is still confined to the primary site, the five-year survival rate is 92.7%. About 70% of women with advanced disease respond to initial treatment, most of whom attain complete remission, but half of these women experience a recurrence 1–4 years after treatment. "Brain metastasis is more common in stage III/IV cancer but can still occur in cancers staged at I/II. People with brain metastases survive a median of 8.2 months, though surgery, chemotherapy, and "whole brain radiation therapy can improve survival.
Ovarian cancer survival varies significantly with subtype. Dysgerminomas have a very favorable prognosis. In early stages, they have a five-year survival rate of 96.9%. Around two-thirds of dysgerminomas are diagnosed at stage I. Stage-III dysgerminomas have a five-year survival of 61%; when treated with BEP chemotherapy after incomplete surgical removal, dysgerminomas have a 95% two-year survival rate. Sex-cord-stromal malignancies also have a favorable prognosis; because they are slow-growing, even those with metastatic disease can survive a decade or more. Low malignant potential tumors usually only have a bad prognosis when there are invasive tumor implants found in the peritoneal cavity.
Complications of ovarian cancer can include spread of the cancer to other organs, progressive function loss of various organs, ascites, and intestinal obstructions, which can be fatal. Intestinal obstructions in multiple sites are the most common proximate cause of death. Intestinal obstruction in ovarian cancer can either be a true obstruction, where tumor blocks the "intestinal lumen, or a pseudo-obstruction, when tumor prevents normal "peristalsis. Continuous accumulation of ascites can be treated by placing a drain that can be self-drained.
There are a number of prognostic factors in ovarian cancer. Positive prognostic factors - those indicating better chances of survival - include no residual disease after surgery (stage III/IV), complete macroscopic resection (stage IV), BRCA2 mutations, young age (under 45 years), nonserous type, low histologic grade, early stage, co-occurrence with endometrial cancer, and low CA-125 levels. There is conflicting evidence for BRCA1 as a prognostic factor. Conversely, negative prognostic factors - those that indicate a worse chance of survival - include rupture of the ovarian capsule during surgery, older age (over 45 years), mucinous type, stage IV, high histologic grade, clear cell type, upper abdominal involvement, high CA-125 levels, the presence of tumor cells in the blood, and elevated "cyclooxygenase-2.
Expression of various mRNAs can also be prognostic for ovarian cancer. High levels of "Drosha and "Dicer are associated with improved survival, whereas high levels of let-7b, "HIF1A, "EphA1, and "poly(ADP-ribose) polymerase are associated with worse survival. Cancers that are positive for "WT1 carry a worse prognosis; estrogen-receptor positive cancers have a better prognosis.
Overall five-year survival rates for all types of ovarian cancer are presented below by stage and histologic grade:
The survival rates given below are for the different types of ovarian cancer, according to "American Cancer Society. They come from the "National Cancer Institute, SEER, and are based on patients diagnosed from 2004 to 2010.
|Invasive epithelial ovarian cancer|
|Ovarian stromal tumors|
|Germ cell tumors of the ovary|
|Fallopian tube carcinoma|
|Low malignant potential tumors|
Ovarian cancer frequently recurs after treatment. Overall, in a 5-year period, 20% of stage I and II cancers recur. Most recurrences are in the abdomen. If a recurrence occurs in advanced disease, it typically occurs within 18 months of initial treatment (18 months "progression-free survival). Recurrences can be treated, but the disease-free interval tends to shorten and chemoresistance increases with each recurrence. When a dysgerminoma recurs, it is most likely to recur within a year of diagnosis, and other malignant germ cell tumors recur within 2 years 90% of the time. Germ cell tumors other than dysgerminomas have a poor prognosis when they relapse, with a 10% long-term survival rate. Low malignant potential tumors rarely relapse, even when fertility-sparing surgery is the treatment of choice. 15% of LMP tumors relapse after unilateral surgery in the previously unaffected ovary, and they are typically easily treated with surgery. More advanced tumors may take up to 20 years to relapse, if they relapse at all, and are only treated with surgery unless the tumor has changed its histological characteristics or grown very quickly. In these cases, and when there is significant ascites, chemotherapy may also be used. Relapse is usually indicated by rising CA-125 levels and then progresses to symptomatic relapse within 2–6 months. Recurrent sex cord-stromal tumors are typically unresponsive to treatment but not aggressive.
Globally, as of 2010, about 160,000 people died from ovarian cancer, up from 113,000 in 1990. As of 2014, more than 220,000 diagnoses of epithelial ovarian cancer were made yearly. In 2010, in the United States, an estimated 21,880 new cases were diagnosed and 13,850 women died of ovarian cancer. Around 1800 of the new diagnoses were sex-cord or stromal tumors. In the United Kingdom as of 2014, approximately 7,000–7,100 yearly diagnoses were made and 4,200 deaths occurred. It is the 5th most common cancer in UK women. Ovarian cancer is most commonly diagnosed after menopause, between the ages of 60 and 64. 90% of ovarian cancer occurs in women over the age of 45 and 80% in women over 50. Germ cell tumors and sex cord-stromal tumors are far less common than epithelial tumors in US women, with incidence of 0.4 per 100,000 women and 0.2 per 100,000 women, respectively. When diagnosed in young people, they make up 1% of overall ovarian cancer.
The overall lifetime risk is around 1.6% (one woman in 48–70). The risk in the UK is similar, at 1.7% (one woman in 60). "Ashkenazi Jewish women carry mutated BRCA alleles at a rate five times that of the rest of the population, putting them at higher risk for ovarian cancer. Black women are at double the risk for sex cord-stromal tumors compared to non-Black women.
In the US, ovarian cancer affects 1.3–1.4% and is the cause of death of about 1% of women. This made it the fifth-leading cause of cancer-related deaths with an estimated 15,000 deaths in 2008. Ovarian cancer represents approximately 4% of cancers diagnosed in women. It occurs more commonly in developed countries. Ovarian cancer is the fifth-most common cancer in women in the UK (around 7,100 women were diagnosed with the disease in 2011), and it is the fifth-most common cause of cancer death in women (around 4,300 women died in 2012). In the United States, it is also the fifth-most common cancer in women but the fourth-most common cause of cancer death. It is the most deadly gynecologic cancer. In 2014, the incidence rate for women in developed countries was about 9.4 per 100,000, compared to 5.0 per 100,000 in developing countries. In the US, the incidence rate in women over 50 is approximately 33 per 100,000. In the UK, the incidence rate over the whole population is 21.6 per 100,000. In Europe, "Lithuania, "Latvia, "Ireland, "Slovakia, and the "Czech Republic have the highest incidences of ovarian cancer, whereas "Portugal and "Cyprus have the lowest incidences. The overall incidence in Europe is approximately 5–15 per 100,000 women.
The rate of ovarian cancer between 1993 and 2008 decreased in women of the 40–49 age cohort and in the 50–64 age cohort, possibly due to this group's widespread adoption of oral contraceptives. This decrease made it the ninth-most common cancer in women.
Malignant germ cell tumors are the type of ovarian cancer most likely to occur during "pregnancy. They are typically diagnosed when an adnexal mass is found on examination (in 1–2% of all pregnancies), a tumor is seen on ultrasound, or the parent's level of alpha-fetoprotein is elevated. Dermoid cysts and dysgerminomas are the most common germ cell tumors during pregnancy. Germ cell tumors diagnosed during pregnancy are unlikely to have metastasized and can be treated by surgery and, in some cases, chemotherapy, which carries the risk of birth defects. Yolk sac tumors and immature teratomas grow particularly quickly and are usually treated with chemotherapy even during pregnancy; however, dysgerminomas that have been optimally debulked may be treated after childbirth.
Ovarian tumors have been reported in "equine "mares. Reported tumor types include teratoma, "cystadenocarcinoma, and particularly "granulosa cell tumor.
Researchers are assessing different ways to screen for ovarian cancer. Screening tests that could potentially be used alone or in combination for routine screening include the CA-125 marker and transvaginal ultrasound. Doctors can measure the levels of the CA-125 protein in a woman’s blood; high levels could be a sign of ovarian cancer, but this is not always the case, and not all women with ovarian cancer have high CA-125 levels. Transvaginal ultrasound involves using an ultrasound probe to scan the ovaries from inside the vagina, giving a clearer image than scanning the abdomen. The UK Collaborative Trial of Ovarian Cancer Screening is testing a screening technique that combines CA-125 blood tests with transvaginal ultrasound. Several large studies are going on, but none has identified an effective technique. In 2009, however, early results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) showed that a technique combining annual CA-125 tests with ultrasound imaging did help to detect the disease at an early stage. However, it's not yet clear if this approach could actually help to save lives—the full results of the trial will be published in 2015. One major problem with screening is no clear progression of the disease from stage I (noninvasive) to stage III (invasive) is seen, and it may not be possible to find cancers before they reach stage III. Another problem is that screening methods tend to find too many suspicious lesions, most of which are not cancer, but malignancy can only be assessed with surgery. The ROCA method combined with transvaginal ultrasonography is being researched in high-risk women to determine if it is a viable screening method. It is also being investigated in normal-risk women as it has shown promise in the wider population. Studies are also in progress to determine if screening helps detect cancer earlier in people with BRCA mutations.
Research into various prognostic factors for ovarian cancer is also going on. Recent research shows that "thrombocytosis predicts lower survival and higher stage cancer. Ongoing research is also investigating the benefits of surgery for recurrent ovarian cancer.
While an active area of research, no "immunotherapy has been shown to be effective as of 2013. However, trials of the antibody and "VEGF inhibitor "bevacizumab, which can slow the "growth of new blood vessels in the cancer, have shown promising results, especially in combination with "pazopanib, which also slows the process of blood vessel growth. Bevacizumab has been particularly effective in preliminary studies on stage-III and -IV cancer and has been cited as having at least a 15% response rate. It is being investigated particularly in mucinous ovarian cancers. Bevacizumab can also be combined with platinum chemotherapy, a combination that has had positive preliminary results in PFS, but equivocal results regarding overall survival. One disadvantage to these treatments is the side effect profile, which includes "high blood pressure and "proteinuria. The drug can also exacerbate bowel disease, leading to "fistulae or "bowel perforation. "Vintafolide, which consists of an "antifolate conjugated with "vinblastine, is also in clinical trials; it may prove beneficial because "folate receptors are overexpressed in many ovarian cancers. Another potential immunotherapy is "trastuzumab (Herceptin), which is active against tumors positive for Her2/neu mutations. Other angiogenesis inhibitors are also being investigated as potential ovarian cancer treatments. "Combretastatin and "pazopanib are being researched in combination for recurrent ovarian cancer. Trebananib and "tasquinimod are other angiogenesis inhibitors being investigated. The "monoclonal antibody "farletuzumab is being researched as an adjuvant to traditional chemotherapy. Another type of immunotherapy involves "vaccines, including "TroVax.
An alternative to BEP chemotherapy, a regimen of 3 cycles of "carboplatin and "etoposide, is a current topic of research for germ cell malignancies.
"Intraperitoneal chemotherapy has also been under investigation during the 2000s and 2010s for its potential to deliver higher doses of cytotoxic agent to tumors. Preliminary trials with cisplatin and paclitaxel have shown it is not well tolerated, but does improve survival, and more tolerable regimens are being researched. Cisplatin and paclitaxel are both being researched as intraperitoneal chemotherapy agents. A specific chemotherapy regimen for rare clear-cell cancers is also under investigation: "irinotecan combined with cisplatin.
"PARP inhibitors have also shown promise in early trials, particularly in people with BRCA gene mutations, since the BRCA protein interacts with the PARP pathway. It is also being studied in recurrent ovarian cancer in general, where preliminary studies have shown longer PFS. Specifically, "olaparib has shown greater survival compared to doxorubicin, though this treatment is still being investigated. It is not clear yet which "biomarkers are predictive of responsiveness to PARP inhibitors. "Rucaparib is another PARP inhibitor being researched in BRCA-positive and BRCA-negative recurrent advanced ovarian cancer. "Niraparib is a PARP inhibitor being tested in BRCA-positive recurrent ovarian cancer.
"mTOR inhibitors were a highly investigated potential treatment in the 2000s and 2010s, but the side effects of these drugs (particularly "hyperglycemia and "hyperlipidemia) were not well tolerated and the survival benefit not confirmed. PI3 kinase inhibitors have been of interest, but they tend to be highly toxic and cause "diarrhea. Another investigated drug is "selumetinib, a "MAPK inhibitor. It improved survival, but did not correlate with any mutations found in tumors.
"Tyrosine kinase inhibitors are another investigational drug class that may have applications in ovarian cancer. Angiogenesis inhibitors in the "receptor tyrosine kinase inhibitor group, including "pazopanib, "cediranib, and "nintedanib, have also been shown to increase progression free survival (PFS), but their benefit for overall survival has not been investigated as of 2015. Preliminary research showed that cediranib combined with platins in recurrent ovarian cancer increased the time to second recurrence by 3–4 months and increased survival by 3 months. MK-1775 is a tyrosine kinase inhibitor that is being used in combination with paclitaxel and carboplatin in platinum-sensitive cancers with p53 mutations. "Nintedanib is being researched as a potential therapy in combination with cyclophosphamide for people with recurrences.
Hormone therapies are a topic of current research in ovarian cancer, particularly, the value of certain medications used to treat breast cancer. These include "tamoxifen, "letrozole, and "anastrozole. Preliminary studies have showed a benefit for tamoxifen in a small number of people with advanced ovarian cancer. Letrozole may help to slow or stop growth of "estrogen receptor positive ovarian cancer. Anastrozole is being investigated in postmenopausal people with estrogen receptor-positive cancer.
Research into mitigating side effects of ovarian cancer treatment is also ongoing. Radiation fibrosis, the formation of scar tissue in an area treated with radiation, may be relieved with "hyperbaric oxygen therapy, but research has not been completed in this area. Treatment of ovarian cancer may also cause people to experience psychiatric difficulties, including "depression. Research is ongoing to determine how counseling and psychotherapy can help people who have ovarian cancer during treatment.
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