Ovarian Cancer

What is an Ovarian Cancer

Ovarian cancer is an abnormal growth of cells that forms a mass (malignant tumor) on one or both ovaries.

The ovaries are the parts of the female reproductive system that produce eggs. Women have two ovaries. They are located on either side of the uterus.

7 Interesting Facts of Ovarian Cancer

1. Epithelial ovarian cancer is a common gynecologic malignancy with a variety of histologic subtypes, of which the most common form is high-grade serous carcinoma 
2. Symptoms of ovarian cancer may include bloating or abdominal distention, early satiety or loss of appetite, and pelvic or abdominal pain 
3. Occurs most commonly in postmenopausal women but can affect younger women, particularly those with BRCA1/2 mutations or Lynch syndrome 
4. Diagnosis may be suspected based on presenting symptoms or discovery of an adnexal mass on pelvic examination or imaging
5. Transvaginal and transabdominal ultrasonography are first line imaging modalities and sonographic appearance can indicate whether adnexal mass is most likely to be benign or malignant; definitive diagnosis is established by histopathologic examination of surgically resected ovary in most cases 
6. Recommended treatment varies according to disease stage; standard approach for most patients consists of total abdominal hysterectomy with bilateral salpingo-oophorectomy and comprehensive surgical staging, followed by postoperative chemotherapy
7. Women who are carriers of BRCA1 and BRCA2 gene mutations are at high risk of developing ovarian cancer and should be offered risk-reducing salpingo-oophorectomy after completion of childbearing 

What are the causes?

The cause of ovarian cancer is not known.

What increases the risk of Ovarian Cancer?

You are more likely to develop this condition if you:

• Are 50 or older.
• Have a personal or family history of endometrial, colon, breast, or ovarian cancer.
• Have the genes associated with breast and ovarian cancer (BRCA1 and BRCA2).
• Have used fertility medicines.
• Started menstruating before age 12.
• Started menopause when you were older than 50.
• Became pregnant for the first time at age 35 or older.
• Have never been pregnant.
• Have had hormone replacement therapy.
• Are overweight.
• Have certain inherited genetic conditions that raise the risk of cancer, such as Lynch syndrome.
• Have a history of polycystic ovarian syndrome.
• Have tissues from the uterus growing outside of the uterus (endometriosis).

What are the symptoms of Ovarian Cancer?

In the early stages, ovarian cancer often does not cause symptoms. As the cancer grows, symptoms may include:

• Unexplained weight loss.
• Pain, swelling, and bloating in the abdomen.
• Pain and pressure in your back and pelvis.
• Abnormal bleeding from the vagina.
• Loss of appetite.
• Passing urine often.
• Pain during sex.
• Fatigue.

How is Ovarian Cancer diagnosed?

This condition may be diagnosed based on:

• Your medical history and a physical exam.
• A pelvic and abdominal exam to check your ovaries, uterus, vulva, cervix, vagina, bladder, rectum, and fallopian tubes.
• Tests, such as:
  • An imaging test that uses sound waves to take pictures of your uterus, bladder, ovaries, and fallopian tubes (transvaginal ultrasound). For this test, a sound wave probe is inserted into your vagina.
  • CT scan, PET scan, or MRI.
  • X-rays of the colon and rectum.
  • Blood tests.
  • Taking a small piece of tissue to examine it under a microscope (biopsy).
  • Removing built-up fluid from the abdomen (ascites) to be examined under a microscope (paracentesis).

Your cancer will be assessed (staged) based on how severe it is and how much it has spread.

How is this treated?

This condition may be treated with one or more of the following:

• Surgery to remove one ovary and its fallopian tube (oophorectomy). This may be done to treat cancer in its early stages.
• Surgery to remove the uterus, cervix, fallopian tubes, and ovaries (hysterectomy with bilateral salpingo-oophorectomy). Lymph tissue (lymph nodes) near the tumor and some tissue and fluid from the abdomen may also be removed and analyzed for cancer cells. This is done to treat advanced cancer.
• Chemotherapy. This uses medicines to kill the cancer cells. Chemotherapy may be used before or after surgery.
• Intraperitoneal chemotherapy (IP chemotherapy). Chemotherapy is given directly into the abdomen (peritoneum) through a special tube.
• Targeted therapy. This uses drugs to attack specific areas within cancer cells to kill the cells or stop them from growing.

Follow these instructions at home:

Lifestyle

• Do not use any products that contain nicotine or tobacco, such as cigarettes and e-cigarettes. If you need help quitting, ask your health care provider.
• Do moderate exercise regularly, as told by your health care provider.
• Try to eat regular, healthy meals. Some of your treatments might affect your appetite. If you are having problems eating or with your appetite, ask to meet with a food and nutrition specialist (dietitian).
• Consider joining a support group with others who have cancer. A support group may help you with resources and information to help you cope with your cancer.

General instructions

• Take over-the-counter and prescription medicines only as told by your health care provider.
• Do not drive or use heavy machinery while taking prescription pain medicine.
• If you are taking prescription pain medicine, take actions to prevent or treat constipation. Your health care provider may recommend that you:
  • Drink enough fluid to keep your urine pale yellow.
  • Eat foods that are high in fiber, such as fresh fruits and vegetables, whole grains, and beans.
  • Limit foods that are high in fat and processed sugars, such as fried or sweet foods.
  • Take an over-the-counter or prescription medicine for constipation.
• You may need to have regular blood tests and imaging tests to monitor your response to treatment.
• Keep all follow-up visits as told by your health care provider. This is important.

Additional Info on Ovarian Cancer

Pitfalls

• Fine-needle aspiration biopsy of an ovarian mass is contraindicated if malignancy is suspected 
• Ovarian cancer is histologically and clinically similar to fallopian tube carcinoma and differentiation may be difficult 
• There is no high-quality evidence to support physical examination (bimanual palpation of ovaries) or imaging as screening strategies for ovarian cancer in asymptomatic average-risk women 

Epithelial ovarian cancer is a common gynecologic malignancy and a leading cause of cancer mortality among women; epithelial cell tumors represent most cases, whereas malignant ovarian germ cell or stromal cell tumors are rare 

Serous epithelial ovarian cancer (the most common subtype) is histologically and clinically similar to primary fallopian tube carcinoma and peritoneal carcinoma, and these are often considered a single clinical entity (eg, National Comprehensive Cancer Network issues 1 guideline for all 3 types) (Related: Fallopian tube malignancy)

Classification

• Histologic subtype 
  • Main subtypes
    • High-grade serous carcinoma (70%) 
    • Endometrioid carcinoma (10%) 
  • Less common forms
    • Clear cell carcinoma (10%) 
    • Low-grade serous carcinoma (5%) 
    • Mucinous carcinoma (3%) 
    • Transitional cell carcinoma (Brenner tumor)
    • Carcinosarcoma (malignant mixed müllerian tumor)
    • Seromucinous carcinoma
    • Undifferentiated carcinoma
    • Endometrioid stromal sarcoma
• Molecular subtype (differing mode of carcinogenesis) 
  • Type I
    • Tend to be diagnosed at earlier stage and have better prognosis
    • Consists of:
      • Endometriosis-related subtypes (ie, endometrioid, clear cell, seromucinous)
      • Low-grade serous
      • Mucinous and transitional cell (Brenner tumor)
  • Type 2
    • Typically advanced stage at diagnosis and have poor prognosis
    • Primarily high-grade serous carcinomas
• TNM staging system 
  • Tumor
    • Tx: cannot assess primary tumor
    • T0: no evidence of primary tumor
    • T1: tumor limited to 1 or both ovaries
      • T1a: tumor limited to 1 ovary; capsule intact; no tumor on ovarian surface; no malignant cells in ascites/peritoneal washings
      • T1b: tumor limited to both ovaries; capsule intact; no tumor on ovarian surface; no malignant cells in ascites/peritoneal washings
      • T1c: tumor limited to 1 or both fallopian tubes with any of the following; capsule ruptured, tumor on ovarian surface, or with malignant cells in ascites/peritoneal washings
    • T2: tumor involves 1 or both ovaries with pelvic extension
      • T2a: extension or implants on uterus and/or fallopian tubes; no malignant cells in ascites/peritoneal washings
      • T2b: extension to other pelvic structures; no malignant cells in ascites/peritoneal washings
      • T2c: extension to uterus, tubes, or other pelvic structures; malignant cells in ascites/peritoneal washings
    • T3: tumor involves 1 or both ovaries with peritoneal metastasis outside of pelvis
      • T3a: microscopic peritoneal metastasis outside pelvis (no macroscopic tumor)
      • T3b: macroscopic peritoneal metastasis outside pelvis (2 cm or less in greatest dimension)
      • T3c: macroscopic peritoneal metastasis outside pelvis (more than 2 cm in greatest dimension) and/or regional lymph node metastasis
  • Node
    • NX: regional lymph nodes cannot be assessed
    • N0: no metastasis to regional lymph nodes
    • N1: metastasis to regional lymph nodes
  • Metastasis
    • M0: no distant metastasis
    • M1: distant metastasis (exclusive of peritoneal metastasis)
  • Staging grouping 
    • Stage I: T1 N0 M0
    • Stage IA: T1a N0 M0
    • Stage IB: T1b N0 M0
    • Stage IC: T1c N0 M0
    • Stage II: T2 N0 M0
    • Stage IIA: T2a N0 M0
    • Stage IIB: T2b N0 M0
    • Stage IIC: T2c N0 M0
    • Stage III: T3 N0 M0
    • Stage IIIA: T3a N0 M0
    • Stage IIIB: T3b N0 M0
    • Stage IIIC: T3c N0 M0 or any T, N1 M0
    • Stage IV: any T, any N, M1
• FIGO staging system (International Federation of Gynecology and Obstetrics) 
  • Stage I: tumor is limited to ovaries
    • Stage IA: an encapsulated tumor is located in only 1 ovary (capsule intact); no tumor on ovarian surface and no malignant cells in ascites/peritoneal washings
    • Stage IB: an encapsulated tumor is located in both ovaries; no tumor on ovarian surface and no malignant cells in ascites/peritoneal washings
    • Stage IC: tumor is in 1 or both ovaries with any of the following; surgical spill (IC1), ruptured capsule before surgery or tumor spread to the ovarian or fallopian tube surface (IC2), or malignant cells in ascites/peritoneal washings (IC3)
  • Stage II: tumor involves 1 or both ovaries with pelvic extension or peritoneal cancer
    • Stage IIA: extension of tumor to uterus and/or fallopian tubes
    • Stage IIB: extension of tumor to other pelvic intraperitoneal tissues
  • Stage III: tumor involves 1 or both ovaries with spread into peritoneum outside pelvis and/or metastasis to retroperitoneal lymph nodes
    • Stage IIIA: positive retroperitoneal lymph nodes only (IIIA1), metastasis up to 10 mm in greatest dimension (IIIAi), metastasis greater than 10 mm in greatest dimension (IIIAii), or microscopic extrapelvic peritoneal involvement with or without positive retroperitoneal lymph nodes (IIIA2)
    • Stage IIIB: macroscopic extrapelvic peritoneal metastasis up to 2 cm in greatest dimension, with or without positive retroperitoneal lymph nodes
    • Stage IIIC: macroscopic extrapelvic peritoneal metastasis greater than 2 cm in greatest dimension, with or without positive retroperitoneal lymph nodes (includes extension to capsule of liver or spleen)
  • Stage IV: distant metastasis (exclusive of peritoneal metastasis)
    • Stage IVA: pleural effusion with positive cytology results
    • Stage IVB: parenchymal metastasis and extra-abdominal metastasis

Clinical Presentation

History

• Ovarian cancer can be asymptomatic until an advanced stage; symptoms, when present, are nonspecific
• Symptoms may include: 
  • Bloating or abdominal distention
  • Early satiety or loss of appetite
  • Urinary urgency or frequency
  • Pelvic or abdominal pain
• Less common symptoms include: 
  • Postmenopausal vaginal bleeding
  • Rectal bleeding
  • Weight loss
• Advanced cases may present acutely with symptoms due to pleural effusion or bowel obstruction

Physical examination

• Abdominal or pelvic bimanual examination commonly identifies an adnexal mass; this may be an incidental finding
• Ascites may be detected in a small proportion of patients
• Rarely, inguinal lymph nodes may be palpable

Causes

• Causation and risk factors may vary by distinct histologic subtype of ovarian cancer; hormonal, reproductive, and genetic factors are probably implicated 
• It is now believed that there are 2 separate pathways by which ovarian carcinogenesis occurs and that many ovarian cancers originate from precursor lesions in the fallopian tube (serous tubal intraepithelial carcinoma) or endometrial tissue; hormonal and reproductive risk factors may have more impact on the development of some tumors than others 

Risk factors and/or associations

Age

• Occurs mostly in postmenopausal women, with peak incidence between ages 55 and 64 years, although it can occur in younger women, particularly those with hereditary cancer syndromes 

Genetics

• Hereditary breast and ovarian cancer syndrome (OMIM #604370, #612555, and others) 
  • Cancer predisposition condition caused by mutations in the BRCA1 and BRCA2 genes (DNA repair–associated); various subtypes exist 
  • Increased risks for various cancers: early-onset breast, multiple breast primaries, male breast, epithelial ovarian, fallopian tube, and primary peritoneal
  • Likelihood of identifying a BRCA1 or BRCA2 mutation in a woman with ovarian cancer at any age is around 13% to 18%
• Lynch syndrome and related mismatch repair cancer syndrome (OMIM #120435 and #276300)
  • Condition of constitutional mismatch repair deficiency caused by biallelic mutations in MSH2, MLH1, PMS2, or MSH6
  • Increased risk of ovarian cancer in addition to colorectal and other cancers such as small intestine, hepatobiliary tract, urinary tract, brain, and skin 
• Other inherited germline mutations associated with ovarian cancer include PALB2, BARD1, BRIP1, RAD51C,and RAD51D 

Ethnicity/race

• Incidence is higher in white women compared with black, Asian, or Hispanic women 

Other risk factors/associations 

• The following factors appear to be associated with an increased risk of ovarian cancer: 
  • Family history of ovarian cancer in first-degree relative
  • Polycystic ovarian syndrome
  • Endometriosis
  • Obesity
  • Hormone replacement therapy
  • Unsuccessful infertility treatment (ovarian hyperstimulation)
  • Intrauterine contraceptive use 
  • Cigarette smoking 
• The following factors may be protective: 
  • Multiparity
  • Oral contraceptive use
  • Past breastfeeding
  • Tubal ligation and hysterectomy

Diagnostic Procedures

Primary diagnostic tools

• Diagnosis may be suspected based on presenting symptoms or discovery of an adnexal mass on pelvic examination or imaging
  • Transvaginal and transabdominal ultrasonography are first line imaging modalities 
  • MRI may be performed if ultrasonographic results are suboptimal or if further imaging is required to determine whether surgical evaluation is indicated 
• Preoperative work-up may include: 
  • CT or MRI of abdomen and pelvis; FDG-PET/CT from skull base to mid-thigh is an alternative 
  • Baseline CBC, hepatic function panel, and biochemistry panel
  • Serum levels of CA125 (MUC16; cancer antigen 125) 
    • HE4 (WFDC2; human epididymal protein 4) has been proposed as an additional biomarker; however, this is not recommended routinely in clinical practice 
  • Screening for other tumor markers (eg, carcinoembryonic antigen, inhibin, lactate dehydrogenase, alpha fetoprotein, CA 19-9) if clinically indicated to assess for uncommon histologic subtypes (germ cell or sex cord stromal tumors)
  • β-hCG level to exclude pregnancy in women of childbearing age
  • Chest radiograph or chest CT, if metastatic spread is suspected
  • Nutritional evaluation
• Diagnosis is confirmed by histopathologic examination of surgical specimen
  • Surgical removal of the complete ovary or ovaries, rather than tissue biopsy, is recommended to determine whether ovarian cancer is present
  • Aspiration biopsy of an ovarian mass is contraindicated if malignancy is suspected owing to risk of peritoneal contamination 

Laboratory

• Serum CA125 level (MUC16; cancer antigen 125)
  • Sensitive marker of ovarian cancer but has poor specificity
    • Over 80% of ovarian malignancies express elevated levels of CA125 
    • Elevated levels are more often detected in advanced or recurrent disease
  • The following are considered positive results:
    • Level above 50 units/mL in premenopausal women 
    • Level above 40 units/mL in premenopausal women using oral contraceptives 
    • Level above 30 units/mL in postmenopausal women 
  • Can also be used to assess prognosis and monitor response to treatment
• Serum HE4 level (WFDC2; human epididymal protein 4)
  • Tumor marker secreted and overexpressed by serous and endometrioid epithelial ovarian cancer
  • Serum HE4 level has a very high negative predictive value (about 99%), indicating that almost all patients with negative test results will have benign ovarian pathology 
  • Combination of serum HE4 and CA125 levels has higher sensitivity and specificity than either test used alone 
  • Not routinely used in clinical practice 

Imaging

• Ultrasonography
  • Transvaginal ultrasonography with color Doppler is the preferred modality; some centers perform additional transabdominal scan 
  • Sonographic appearance can indicate whether adnexal mass is most likely to be benign or malignant but cannot definitively determine diagnosis
  • Major ultrasonographic characteristics suggesting malignancy include: 
    • Irregularly shaped solid tumor
    • Tumor with multiple (more than 4) papillary structures
    • Irregularly shaped solid, multiloculated tumor more than 10 cm in largest dimension
    • Tumor that demonstrates very strong flow on color Doppler
    • Ascites
• MRI of abdomen/pelvis
  • Usually indicated to assess for local metastasis after initial ultrasonographic evaluation; may help if diagnosis is unclear based on ultrasonographic findings alone 
    • More specific for diagnosis of malignancy than ultrasonography; may reduce false-positive findings 
    • Superior to CT at detecting local metastasis to bladder, vagina, rectum, and pelvis
  • Findings suggestive of malignancy include presence of vascular vegetations in cystic masses and ascites 
• CT of abdomen/pelvis
  • Usually not useful for diagnosis but may be used to detect local metastases and assess tumor resectability after initial ultrasonography 
  • CT can be helpful for assessing disease in lymph nodes and upper abdomen

Procedures

Laparoscopy or laparotomy

General explanation

• Surgical resection of involved ovary is recommended for a histopathologic diagnosis; intraoperative confirmation by frozen section may assist in surgical management 
  • Bilateral fallopian tubes, ovaries, and uterus are also frequently resected
  • In advanced disease, a tissue specimen may be obtained via core biopsy before neoadjuvant chemotherapy and surgery
• Exploratory laparoscopy may have a role in evaluating patients with advanced ovarian cancer to assess resectability and help determine whether neoadjuvant chemotherapy is indicated before debulking surgery 

Indication

• Suspected ovarian malignancy

Interpretation of results

• Histopathologic analysis of surgical specimen confirms diagnosis, and assigns the histologic subtype and grade 

Differential Diagnosis

Most common

• Benign ovarian cyst
• Primary fallopian tube carcinoma
• Benign fallopian tube cyst 

Pelvic inflammatory disease

Infection of fallopian tube commonly caused by Neisseria gonorrhoeae or Chlamydia trachomatis and resulting in a spectrum of clinical disease Salpingitis (acute edema in fallopian tubes with ascending infection and inflammation)

Pyosalpinx (acute infection with superimposed obstruction of fallopian tube and tube distention with pus)

Tubo-ovarian abscess (acute inflammatory mass surrounding fallopian tube and ovary)

Hydrosalpinx (fallopian tube chronically dilated by adhesions from past pelvic inflammatory disease)

Like ovarian cancer, may present with abdominal/pelvic pain and adnexal mass on bimanual examination

However, acute pelvic inflammatory disease is typically also accompanied by fever and chills, abnormal uterine bleeding, and abnormal vaginal discharge

May occur in postpartum setting or as a result of sexually transmitted infection

Differentiated by history, physical examination, inflammatory markers, diagnostic imaging findings, and microbiologic testing

Ectopic pregnancy

Occurs when fertilized ovum implants outside uterine cavity

Like ovarian cancer, may present with pelvic or abdominal pain and adnexal mass on bimanual examination

Unlike ovarian cancer, may present with vaginal bleeding, syncope, or shock

Patient may have history of previous ectopic pregnancy, pelvic inflammatory disease, tubal sterilization, or tubal surgeries; may currently use an intrauterine device

Differentiated by history, physical examination, β-hCG measurement, and transvaginal ultrasonography

Treatment Goals

• Eradicate tumor
• Prolong disease-free survival

Admission criteria

• Admit patients to hospital for surgery

Recommendations for specialist referral 

• Refer to gynecologic oncologist for clinically suspicious lesions and for comprehensive staging and surgical treatment
• Refer to gynecologic or medical oncologist for management of systemic chemotherapy
• Refer to reproductive endocrinologist for consultation regarding fertility-preservation procedures
• Refer to genetic counselor for breast, ovarian, and colorectal cancer risk evaluation 

Treatment Options

General overview

• Recommended treatment varies according to disease stage
• Standard approach for most patients consists of total abdominal hysterectomy with bilateral salpingo-oophorectomy and comprehensive surgical staging, followed by postoperative chemotherapy
  • Stage IA
    • Patients who wish to retain fertility may undergo unilateral salpingo-oophorectomy along with comprehensive surgical staging 
  • Stage IB
    • Patients who wish to retain fertility may undergo bilateral salpingo-oophorectomy along with comprehensive surgical staging (both ovaries are removed but uterus is spared for possible future pregnancy via in vitro fertilization) 
  • Stages IA through IV
    • Patients with early stage disease who do not wish to retain fertility, and patients with more advanced disease, should undergo total abdominal hysterectomy with bilateral salpingo-oophorectomy
    • Comprehensive surgical staging and debulking surgery are also done: 
      • Aspiration of ascites or peritoneal washing, omentectomy, lymphadenectomy of suspicious lymph nodes, and bilateral pelvic and para-aortic lymph node dissection in case of those with extrapelvic tumor nodules smaller than 2 cm
    • Other debulking procedures for disease involving pelvis and upper abdomen may include radical pelvic dissection, bowel resection, appendectomy, splenectomy, stripping of peritoneal surfaces, partial hepatectomy, partial gastrectomy, and partial cystectomy 
    • Patients with residual disease after surgical debulking/cytoreduction for invasive or peritoneal disease may be candidates for intraperitoneal chemotherapy 
    • Adjuvant IV chemotherapy is indicated after cytoreductive surgery for most patients with the exception of those with stage IA and IB disease 
      • Regimens are selected based on grade and histopathologic findings
  • Patients with poor surgical risk or low likelihood of optimal cytoreduction (eg, diffuse or deep involvement of stomach, bowel, mesentery) 
    • Consider neoadjuvant chemotherapy after histologic confirmation (via core biopsy) 
    • Consider interval debulking surgery with total abdominal hysterectomy with bilateral salpingo-oophorectomy in patients with stable disease or in those with response to chemotherapy
    • There is little difference in outcomes between primary debulking surgery and neoadjuvant chemotherapy followed by interim debulking surgery; however, neoadjuvant chemotherapy may reduce the risk of perioperative complications and need for bowel resection 
• Any additional therapy after the primary therapy (surgery followed by chemotherapy) depends on whether there is remission, residual disease, or recurrent disease
  • For complete clinical remission: observation with monitoring or postremission systemic therapy
  • For progression, persistent disease, or stable disease: clinical trial, recurrence therapy, or supportive care
  • For recurrent disease: tumor molecular testing is recommended before start of any additional therapy 

Rationale 

• Surgery is indicated to completely resect the primary tumor and debulk any extraovarian disease
• Adjuvant chemotherapy is strongly recommended because the risk of metastasis and recurrence is high, even after optimum tumor debulking through surgery
• Maintenance (postremission) chemotherapy is considered optional because of mixed clinical trial data

Outcomes

• Patients with stage IA or IB disease (grade 1 or 2 tumors) have more than 90% survival with surgical treatment alone 
  • Postoperative chemotherapy may prolong survival in patients with these early-stage tumors; however, the magnitude of benefit has not been established in patients with lower risk or optimally staged disease 
  • Current guidelines recommend observation after comprehensive surgical staging for these patients 
• Most other patients are treated with postoperative chemotherapy, which significantly improves recurrence-free survival and overall survival 
• Addition of bevacizumab to conventional postoperative cytotoxic therapy has been shown to further improve progression-free survival, but effect on overall survival is unclear 
• Combining IV and intraperitoneal chemotherapy may achieve greater improvements in recurrence-free survival and overall survival, but risks of serious toxicity are greater than with IV chemotherapy alone 
  • Intraperitoneal chemotherapy is not recommended as a first line treatment 
• Postremission maintenance therapies, given to patients who have had complete clinical remission after first line therapy, show mixed results 

Drug therapy

• Primary systemic chemotherapy regimens 
  • Paclitaxel-carboplatin
  • Carboplatin-liposomal doxorubicin
  • Docetaxel-carboplatin
  • Carboplatin-paclitaxel-bevacizumab
  • Carboplatin (for elderly patients)
• Persistent or recurrent disease 
  • Preferred agents for platinum-sensitive disease
    • Carboplatin-gemcitabine
    • Carboplatin-gemcitabine-bevacizumab
    • Carboplatin–liposomal doxorubicin with or without bevacizumab
    • Carboplatin-paclitaxel
    • Carboplatin-paclitaxel-bevacizumab
    • Cisplatin-gemcitabine
    • Paclitaxel-carboplatin (for elderly patients)
  • Preferred agents for platinum-resistant disease include:
    • Cyclophosphamide-bevacizumab
    • Docetaxel
    • Etoposide-gemcitabine
    • Liposomal doxorubicin with or without bevacizumab
    • Paclitaxel with or without bevacizumab
    • Topotecan with or without bevacizumab
  • Targeted therapies
    • Bevacizumab
    • Olararib (for patients with BRCA-mutated advanced ovarian cancer who have been treated with 3 or more lines of chemotherapy)
    • Niraparib (for patients with high-risk disease who have been treated with 3 or more lines of chemotherapy)
    • Rucaparib (for patients with BRCA-mutated advanced ovarian cancer who have been treated with 2 or more lines of chemotherapy)
    • Larotrectinib (for NRKT gene-fusion positive tumors)
    • Entrectinib (for NRKT gene-fusion positive tumors)
    • Pembrolizumab (for tumors with MSI/ MMR mutations)
    • Pazopanib
  • Hormone therapy
    • Fulvestrant (for low-grade serous carcinoma)
    • Aromatase inhibitors
    • Leuprolide acetate
    • Megestrol acetate
    • Tamoxifen
• Optional maintenance (postremission) chemotherapy regimens (following complete clinical remission in patients with stage II-IV disease) 
  • Paclitaxel
  • Pazopanib
  • Bevacizumab (to be used only if used previously as part of primary therapy if BRCA wildtype or unknown)

Nondrug and supportive care

Tailor supportive care measures to meet each patient’s needs based on age, performance status, disease status, and specific chemotherapeutic agents used; treatment may include: 

• Antiemetic support
• IV fluids
• Nutritional support (enteral or parenteral)
• Bowel regimen to prevent constipation
• Pain management
• Prophylaxis against opportunistic infections
• Management of toxicity/adverse effects associated with specific agents
• Management of menopausal symptoms (Related: Perimenopause and menopause)

Palliative measures may include: 

• Paracentesis
• Ureteral stent
• Gastrostomy tube
• Thoracentesis or pleurodesis

Procedures

Total abdominal hysterectomy with bilateral salpingo-oophorectomy 

General explanation

• Surgical removal of uterus, cervix, both fallopian tubes, and both ovaries, via an abdominal incision
• Comprehensive surgical staging and debulking is done concurrently, including at a minimum: 
  • Evaluation of entire abdominopelvic cavity to determine extent of disease
  • Systematic pelvic and para-aortic lymphadenectomy
  • Infracolic omentectomy
  • Washings of peritoneal cavity
  • Biopsies of any suspicious areas, including abdominal and pelvic peritoneum

Indication

• Suspected ovarian cancer

Contraindications

• Untreated coagulopathy
• Pregnancy

Complications

• Premature menopause
• Ureteral injury
• Urinary incontinence

Special populations

• Elderly patients (older than 70 years)
  • Elderly patients may not tolerate combination chemotherapy regimens, as recommended by the National Comprehensive Cancer Network
  • Alternative regimens may be appropriate for elderly patients with stage I through stage IV epithelial ovarian cancer, including: 
    • Carboplatin every 3 weeks
    • Paclitaxel plus carboplatin every 3 weeks
    • Paclitaxel plus carboplatin weekly for 18 weeks
• Recurrent disease
  • Inform patients of the availability of clinical trials and discuss risks and benefits of various treatments

Monitoring

• Follow up with clinical assessment every 2 to 4 months for 2 years, then every 3 to 6 months for 3 years, then annually thereafter 
  • Retake history and perform physical examination (including breast, pelvic, and rectal examination) at each visit to assess for clinical signs of recurrence
  • Measure serum levels of CA125 or other tumor markers if levels were elevated preoperatively
  • Obtain laboratory test results and imaging (eg, chest radiograph, CT or MRI of chest/abdomen/pelvis; FDG-PET/CT) as clinically indicated 

Complications

• Local invasion
  • Metastasis to peritoneal cavity is common among patients with advanced disease
  • May result in intestinal or ureteric obstruction or ascites
• Distant metastasis
• Premature menopause secondary to oophorectomy (Related: Perimenopause and menopause)
• Complications associated with chemotherapy, including:
  • Myelosuppression
  • Peripheral neuropathy
  • Hepatic or renal dysfunction
  • Metabolic derangements
  • Infusion reactions
  • Opportunistic infections
• Disease recurrence
  • Commonly recurs in extrapelvic locations, usually in association with intraperitoneal recurrence
  • Associated with poor prognosis

Prognosis

• Prognosis is influenced by disease stage, depth of neoplastic invasion, extent of residual disease after surgery, and possibly tumor grade 
  • 5-year survival rates 
    • 92.4% for localized ovarian cancer (approximately 15% of cases)
    • 75.2% for cancer that has spread to regional lymph nodes only
    • 29.2% for cancer with distant metastasis (this represents most cases)
  • The following factors are associated with a favorable prognosis: 
    • Younger age
    • Good performance status
    • Early stage disease
    • Well-differentiated tumor
    • Cell type other than mucinous or clear cell
    • Lower volume of disease before surgical debulking
    • Smaller residual tumor following primary cytoreductive surgery
    • Absence of ascites
    • BRCA1 or BRCA2 mutation carrier

Screening

At-risk populations

• Women who are carriers of BRCA1 and BRCA2 gene mutations are at high risk of developing cancer of ovaries and fallopian tubes and other malignancies 

Screening tests

• Some experts recommend monitoring high-risk women with serum cancer antigen 125 level and transvaginal ultrasonography starting at age 30 to 35 years; however, this screening strategy is of uncertain benefit 
• Routine screening is not recommended for asymptomatic average-risk women 
  • Recommendation applies to all methods: bimanual palpation of ovaries, imaging, and biomarker levels
  • Available evidence suggests that screening for ovarian cancer in asymptomatic women not known to be at high risk for ovarian cancer does not reduce ovarian cancer mortality

Prevention

• Patients with BRCA1 and BRCA2 gene mutations should be offered risk-reducing salpingo-oophorectomy after completion of childbearing (typically between ages 35 and 40 years for BRCA1 mutations and 40 to 45 years for BRCA2 mutations) 
  • Risk-reducing salpingo-oophorectomy between ages 45 and 50 years should also be considered in patients with BRIP1, RAD51C, and RAD51D mutations
• Prophylactic (opportunistic) salpingectomy can be offered to women at risk for ovarian cancer, who have completed childbearing, during benign gynecologic and obstetric surgery

Seek Additional Information

• American Cancer Society: www.cancer.org  
• National Cancer Institute: www.cancer.gov  

Contact a health care provider if you:

• Are not able to follow a prescribed treatment plan or take a medicine.
• Have any symptoms or changes that concern you.
• Have changes in your bowel or bladder habits.

Get help right away if you have:

• A fever or chills.
• Serious side effects or an allergic reaction to a treatment or medicine.
• Back pain that is new.
• Increased pain, swelling, or bloating in your abdomen.

Summary

• Ovarian cancer is an abnormal growth of cells that forms a mass (malignant tumor) on one or both ovaries.
• Symptoms of ovarian cancer may include pain in the abdomen, back, or pelvis. You may also have a loss of appetite and swelling or bloating in the abdomen.
• You are more likely to develop ovarian cancer if you are older than 50, but it can affect younger women, particularly those with the BRCA1 or BRCA2 genes. These genes are associated with breast and ovarian cancer.
• Treatment may include a combination of surgery and medicines that kill cancer cells (chemotherapy).
• You may need to have regular blood tests and imaging tests to monitor your response to treatment.

Sources

National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. Version 1.2020. NCCN website. Updated March 11, 2020. Accessed July 11, 2020. https://www.nccn.org/ Reference