Epithelial carcinoma is the most common type of primary ovarian malignancy. There are several histologic subtypes including serous, endometrioid, clear cell, and mucinous. Of these, serous histology is the most frequently occurring.
There is growing evidence that epithelial ovarian cancer with high-grade serous histology originates from the fallopian tubes and, more specifically, that serous intraepithelial carcinoma of the fallopian tube (STIC) lesions are likely the precursor to high-grade serous ovarian and primary peritoneal cancer. Thus, high-grade serous cancers of the ovary, peritoneum, and fallopian tube are now considered one clinical entity and managed similarly.
Risk Factors
Age over 40 years, White race, nulliparity, infertility, history of endometrial or breast cancer, and family history of ovarian cancer have been consistently found to increase the risk of invasive epithelial cancer. Increased parity, use of oral contraceptive pills (OCPs), history of breastfeeding, tubal ligation or salpingectomy, and hysterectomy are associated with a decreased risk of ovarian cancer.
Patients with a family history of ovarian, breast, endometrial, or colon cancer are at increased risk of developing ovarian carcinoma.
Genetic syndromes such as hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 genotypes) and Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC] syndrome) are associated with increased risk of ovarian cancer. Up to 25% of patients with ovarian cancer have germline pathogenic mutation. Germline genetic testing is recommended for all newly diagnosed epithelial ovarian, tubal, and primary peritoneal cancers.
In patients with hereditary ovarian cancers, the most common mutations (found in approximately 10% of cases) are found in breast cancer type 1 or 2 susceptibility genes (BRCA1 and BRCA2). These are tumor suppressor genes which are inherited in an autosomal dominant fashion. The lifetime ovarian cancer risks of mutated BRCA1 and BRCA2 carriers are 35% to 60% and 10% to 25%, respectively.
Lynch syndrome encompasses individuals with pathogenic mutations in DNA mismatch repair genes (specifically, MLH1, MSH2, MSH6, PMS2) or the epithelial cell adhesion molecule (EPCAM) gene. These are also inherited in an autosomal dominant manner. These individuals have an increased risk of multiple cancer types including ovarian cancer, with a lifetime risk of 1% to 38% depending on the gene that is mutated.
Other genes associated with increased ovarian cancer risk include BRIP1, NBN, PALB2, RAD51C, RAD51D, and STK11.
Environmental factors may play a role in ovarian cancer. There is an increased risk of mucinous carcinoma with smoking. There is no conclusive evidence linking talc exposure with risk of ovarian cancer. There is inconsistent data on obesity and ovarian cancer risk.
Reproductive factors play an important role in ovarian cancer risk. One or more pregnancies/births, breastfeeding, and OCP use can reduce ovarian cancer risk by 30% to 60%, whereas nulliparity is associated with an increased risk. Patients with infertility have an elevated risk of ovarian cancer, independent of nulliparity, and ovarian stimulation for in vitro fertilization may increase the risk of borderline epithelial ovarian tumors. Data has not supported an association between fertility medications and risk of ovarian cancer, though their use has not been clearly separated from the risk that nulliparity and infertility confer.
Tubal ligation/salpingectomy and hysterectomy with ovarian preservation both lower the risk of ovarian cancer, consistent with the hypothesis that ovarian cancer, specifically serous histology, may originate in the fallopian tubes. There is growing evidence for salpingectomy as a primary prevention for ovarian cancer (see “Screening and Prevention”).
Screening and Prevention
Early ovarian cancer is often asymptomatic. No available screening test has sufficient positive predictive value for early-stage ovarian cancer.
Current screening recommendations. There is no evidence that screening tests, including CA-125, ultrasound, or pelvic examination, reduces mortality from ovarian cancer in average-risk patients and potential harms exist due to invasive diagnostic testing from false-positive results. Therefore, routine screening is not recommended. The American College of Obstetricians and Gynecologists (ACOG) advises the obstetrician-gynecologist to remain vigilant for the early signs and symptoms of ovarian cancer (see “Presentation and Diagnosis”). Educating patients on symptoms is also important.
Screening Tests without Proven Benefit
Cancer antigen 125 (CA-125) is an ovarian cancer tumor marker. A level >35 U/mL in postmenopausal patients is usually considered abnormal. However, this biomarker alone is neither sufficiently sensitive nor specific enough to be diagnostic for ovarian cancer.
CA-125 levels may be elevated in several benign conditions (such as pelvic inflammatory disease, endometriosis, fibroids, pregnancy, hemorrhagic ovarian cysts, liver disease) as well as in other malignant conditions (including breast, lung, pancreatic, gastric, and colon cancer).
CA-125 is normal in approximately half of patients with stage I ovarian cancer. The most effective use is following serial CA-125 levels to monitor response to treatment and to detect recurrence in patients with known ovarian cancer.
Other biomarkers that may be elevated in patients with ovarian cancer include human epididymis protein 4 (HE4), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9). Of these, only HE4 is approved for use to monitor for disease progression when an ovarian cancer diagnosis is established. None have shown benefit for routine screening.
Biomarker panels such as OVA1, Over, and Risk of Malignancy Algorithm (ROMA) use a combination of biomarkers to predict likelihood of malignancy when an adnexal mass is present. However, they have not proven effective in screening for ovarian cancer in otherwise asymptomatic patients.
Multimodal screening using CA-125 measurement with transvaginal ultrasonography yields a higher specificity and positive predictive value than either modality alone but does not reduce overall ovarian cancer mortality and therefore its use in routine screening is not supported.
In average-risk women, the UK Collaborative Trial of Ovarian Cancer Screening (UKTOCS) demonstrated no difference in mortality due to ovarian cancer when comparing annual multimodal screening versus annual transvaginal ultrasound screening versus no screening in average-risk women.
In patients with elevated genetic risk of ovarian cancer, two randomized trials suggest that multimodal screening may result in earlier stage at diagnosis of ovarian cancer, but the impact on survival is not known. Because of the potential harms of false-positive results during screening, guidelines are conflicting on whether screening should be offered in this patient population.
Prevention Strategies
OCP prophylaxis is the only documented method of chemoprevention for ovarian cancer, with a risk reduction of approximately 50%. Longer duration of use is associated with further reduction in risk, and the protective effect persists for 10 or more years after discontinuation. The use of OCPs in BRCA mutation carriers also confers a decreased risk of ovarian cancer, though counseling on the risks/benefit profile are personalized given the potential increased risk of hormone-sensitive breast cancer particularly in BRCA2 patients.
Risk-reducing bilateral salpingo-oophorectomy (BSO). Individuals who are at high risk of ovarian cancer (eg, Lynch syndrome, BRCA mutations) and have completed childbearing should consider prophylactic BSO between ages 35 and 45 (depending on their specific genetic risk), or 10 years prior to the age of diagnosis of an affected family member.
Salpingectomy has recently emerged as a strategy for primary prevention of ovarian cancer, with risk reduction of up to 80%. Salpingectomy at the time of tubal ligation, hysterectomy, or other pelvic surgery should be considered for ovarian cancer risk reduction.
Presentation and Diagnosis
Presentation. Although some individuals with early disease experience symptoms, the majority are asymptomatic. Most patients are diagnosed with advanced disease (65% of cases are diagnosed at stage III or higher) when they have acute or subacute symptoms. Other patients have incidental findings concerning for malignancy with a pelvic mass on physical exam or on imaging obtained for another indication.
Acute presentations include symptoms usually related to advanced disease such as ascites, pleural effusion, bowel obstruction, and/or venous thromboembolism.
Subacute presentation includes symptoms such as abdominal bloating, early satiety, weight loss, constipation, anorexia, urinary frequency, dyspareunia, fatigue, and irregular menstrual bleeding.
Diagnosis. Ovarian cancer can only be diagnosed by histologic evaluation. Initial evaluation depends on patient presentation but usually includes imaging studies (transvaginal ultrasound [TVUS] and/or computed tomography [CT] of the chest, abdomen, and pelvis), serum biomarkers (eg, CA-125), and possibly fluid cytology or omental/pleural biopsies in the setting of concern for metastatic disease. Biopsy of an isolated ovarian mass is not recommended due to the risk of rupture and spread of malignant cells within the abdominal cavity.
ACOG recommends referral to a gynecologic oncologist in the following situations:
Elevated serum CA-125 (>35 for postmenopausal patients; >200 for premenopausal patients [though it should be noted that the cutoff of 200 is based on expert opinion and is not evidence based]) or elevated score on other formal risk assessment (eg, Risk of Ovarian Malignancy Algorithm)
Ultrasound findings concerning for cancer (papillary or solid components, irregularity, high color Doppler flow, presence of ascites); elevated risk based on ultrasound scoring system from the International Ovarian Tumor Analysis Group
Physical exam findings concerning for a nodular or fixed pelvic mass, presence of ascites
Evidence of abdominal or distant metastasis
Ultimately surgery is often necessary to confirm the diagnosis. If ovarian cancer is suspected, a surgeon capable of performing an adequate staging procedure should be available, preferably a gynecologic oncologist, to optimize outcomes in cases of malignancy
Ovarian tumors during pregnancy are very rare. The incidence of an adnexal mass during pregnancy ranged from 0.05% to 2.4%. Most adnexal masses discovered during the first trimester resolve by the second trimester. However, approximately 1% to 6% of these masses are malignant.
Epithelial ovarian tumors account for 50% of ovarian malignancies diagnosed in pregnancy (of these 50% are borderline and 50% are invasive), while germ cell tumors (primarily dysgerminoma) account for approximately 30% to 35%.
Masses are usually diagnosed during routine ultrasonography or at the time of cesarean section. Most patients (74%) are diagnosed with stage I disease.
Early-stage disease can be treated with conservative surgery in the second trimester of pregnancy, usually with good maternal and fetal outcomes. Late-stage and high-grade disease should be treated aggressively after appropriate counseling with the patient.
Staging and Prognosis
Ovarian cancer is surgically staged (Table 54-2). The importance of complete surgical staging in treatment planning and prognosis cannot be overemphasized. The standard surgical approach is laparotomy via a vertical midline incision to allow for adequate exposure, though minimally invasive techniques are acceptable in apparent early-stage disease when performed by an experienced surgeon (Table 54-3). With minimally invasive surgery, there are technical concerns for intact removal of the specimen, seeding of malignant cells to port sites, and capacity to thoroughly evaluate the entire abdominal cavity at the time of surgery. For these reasons laparotomy remains the standard approach in the case of advanced disease. Randomized controlled trials are currently ongoing to determine if surgical debulking in the setting of metastatic disease can be safely performed with minimally invasive techniques. In patients with advanced disease, systematic lymphadenectomy is not necessary at the time of debulking surgery and only suspicious lymph nodes should be removed.
| Stage | Tumor Characteristics |
|---|---|
| I | Tumor limited to ovaries (one or both) or fallopian tube(s) |
| IA | Tumor limited to one ovary (capsule intact) or fallopian tube, no surface involvement of ovary or tube; no malignant cells in ascites or peritoneal washings |
| IB | Tumor limited to both ovaries (capsules intact) or both fallopian tubes, no surface involvement of ovaries or tubes; no malignant cells in ascites or peritoneal washings |
| IC | Tumor limited to one or both ovaries or fallopian tubes, with any of the following:
1C1: Surgical spill 1C2: Tumor is found on external surface of ovary or fallopian tube; or capsule has ruptured before surgery IC3: Malignant cells detected in ascites or peritoneal washings |
| II | Tumor involves one or both ovaries or fallopian tubes with extension within the pelvis (uterus, bladder, sigmoid colon, rectum) or primary peritoneal cancera |
| IIA | Extension and/or implants on the uterus and/or fallopian tube(s) and/or ovaries |
| IIB | Extension to and/or implants on other pelvic intraperitoneal tissuesb |
| III | Tumor involves one or both ovaries or fallopian tubes, or primary peritoneal cancer, with peritoneal metastasis outside the pelvis and/or metastasis to the retroperitoneal (pelvic and/or para-aortic) lymph nodes |
| IIIA1 | Positive retroperitoneal (pelvic and/or para-aortic) lymph nodes only (histologically confirmed) IIIA1(i): metastasis up to 10 mm in greatest dimension; IIIA2(i): metastasis more than 10 mm in greatest dimension |
| IIIA2 | Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes |
| IIIB | Macroscopic extrapelvic peritoneal metastasis no more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes |
| IIIC | Macroscopic extrapelvic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes |
| IV | Distant metastasis, including pleural effusion with positive cytology; liver or splenic parenchymal metastasis; metastasis to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside the abdominal cavity) |
| IVA | Pleural effusion with positive cytology |
| IVB | Liver or splenic parenchymal metastases; metastases to extra-abdominal organs (including lymph nodes outside the abdominal cavity); umbilical involvement; transmural involvement of intestine with mucosal involvementc |
aIt is not possible to have stage I primary peritoneal cancer.
bInvolvement of the sigmoid colon is considered stage II; however, transmural bowel infiltration with mucosal involvement is stage IVB.
cExtension of tumor from the omentum to the liver or spleen (surface/capsular involvement) is considered stage IIIC; liver or splenic parenchymal involvement is considered stage IVB.
Adapted from Mutch DG, Prat J. 2014 FIGO staging for ovarian, fallopian tube and peritoneal cancer. Gynecol Oncol. 2014;133(3):401–404. Copyright © 2014 Elsevier. With permission.
| Obtain ascites for cytologic evaluation |
| Washings from the pelvis, gutters, and diaphragm |
| Systematic exploration of all organs and surfaces |
| Hysterectomya |
| Bilateral salpingo-oophorectomya |
| Omentectomy |
| Removal of enlarged pelvic and para-aortic lymph nodes suspicious for disease |
| Multiple biopsy specimens from peritoneal sites |
|
aUterus and contralateral ovary be preserved in select patients, particularly if future fertility is desired.
Ovarian cancer can spread by direct extension, by exfoliation of cells into the peritoneal cavity (transcoelomic spread), via the bloodstream, or via the lymphatic system. The most common pathway of spread is transcoelomic. Cells from the tumor are shed into the peritoneal cavity and circulate following the clockwise path of the peritoneal fluid. All peritoneal surfaces are at risk. Lymphatic spread to the pelvic and para-aortic lymph nodes can occur. Hematogenous spread to the liver or lungs can occur in advanced disease.
Prognostic Factors
The most important prognostic factors are stage, histology of the tumor, amount of residual disease remaining after initial debulking surgery, and age of the patient. Understanding the genetic characteristics of the tumor can also greatly influence prognosis.
The 5-year survival rate of patients with epithelial ovarian cancer correlates directly with tumor stage (Table 54-4).
| Stage at Diagnosis | Stage Distribution (%) | 5-y Relative Survival (%) |
|---|---|---|
| Localized | 18 | 92.4 |
| Regional | 20 | 72.9 |
| Distant | 55 | 31.5 |
| Unknown | 6 | 36.4 |
From NCI/SEER. Accessed December 9, 2023. https://seer.cancer.gov/statfacts/html/ovary.html
The histology of ovarian neoplasms can be described as benign, borderline, or malignant. Borderline tumors (previously known as tumors of low malignant potential) are a unique entity of noninvasive neoplasms without definitive malignant features, but that can have intraperitoneal spread. Approximately 15% of all epithelial ovarian tumors are classified as borderline, and they are often found in younger patients. They are most commonly of serous histology (85%), followed by mucinous. The staging system for borderline tumors is the same as ovarian cancers (Table 54-2). Prognosis is significantly better in borderline tumors compared to malignant tumors with 5-year survival rates of 96% to 99% in stage I to III, and >75% in stage IV.
There are five main histologic subtypes of epithelial ovarian carcinoma: serous, endometrioid, clear cell, and mucinous. Other less common subtypes include carcinosarcoma and undifferentiated/dedifferentiated carcinoma.
Serous is the most common histologic subtype and split into high and low grade, which are considered fundamentally separate diseases.
High-grade serous carcinoma (HGSC) accounts for 70% to 80% of all malignant ovarian tumors. The mean age at diagnosis is 57 years. Most patients present at advanced stages where the 5-year survival rate is 25% to 32%. This histologic subtype now includes transitional cell carcinoma, which was historically considered a separate histology.
Low-grade serous carcinoma (LGSC) is relatively rare, accounting for less than 5% of ovarian carcinoma cases. The mean age at diagnosis is 56 years. This subtype also tends to present at advanced stages and 5-year survival at advanced stage is 40% to 54%. Serous borderline tumor is suspected to be the precursor to LGSC.
Endometrioid is the next most common histology, accounting for 10% of ovarian cancers. The mean age at diagnosis is 56 years. Most are early stage when diagnosed and are chemosensitive, therefore these patients have good prognosis with a 5-year survival rate of 83% to 87% at stage I to II disease. Though survival drops to 45% at advanced-stage disease. This subtype is associated with endometriosis. In addition, about 15% to 20% of patients will have concurrent endometrial cancer.
Clear cell carcinoma accounts for 5% to 10% of all ovarian cancers. The mean age at diagnosis is 57 years. While patients often present at early stages, those patients with advanced stage have overall worse prognosis compared to serous and endometrioid histology given the chemoresistant nature of this histologic subtype. The 5-year survival of advanced-stage clear cell carcinoma is 22%. Clear cell carcinoma is also associated with, and may arise from, endometriosis and carries an increased risk of vascular thrombotic events and paraneoplastic hypercalcemia.
Mucinous carcinoma accounts for 3% to 4% of ovarian cancers. The mean age at diagnosis is 54 years. Nearly all patients present with early-stage disease. Mucinous borderline tumors are often present with this subtype and may represent a precursor to this malignant histology subtype. This subtype is also associated with pseudomyxoma peritonei, a condition where there is gelatinous mucus or ascites in the abdomen. However, the primary tumor in the setting of pseudomyxoma peritonei is usually gastrointestinal origin (most often appendiceal). As such, patients with mucinous ovarian carcinoma should undergo colonoscopy and esophagogastroduodenoscopy to rule out an underlying gastrointestinal primary.
Carcinosarcoma, also known as malignant mixed müllerian tumor, accounts for 2% to 7.5% of ovarian carcinomas. The mean age at diagnosis is 75 years. This subtype tends to present at advanced stages with malignant epithelial (most commonly high-grade serous) and stromal elements. The prognosis is overall poor, with a 5-year survival rate of 16% for patients with advanced disease.
Undifferentiated/dedifferentiated carcinoma is a rare, highly aggressive subtype that presents at advanced stages and has an overall poor prognosis, with case series reporting a median survival of 3 months from diagnosis.
The amount of visible residual disease after debulking surgery—also called cytoreduction (defined as removal of as much tumor as possible during surgical exploration)—strongly impacts overall survival. Cytoreduction is categorized as: no gross residual (no visible residual disease); optimal cytoreduction (visible residual disease less than 1 cm in maximum diameter or thickness); suboptimal cytoreduction (visible residual disease greater than 1 cm in maximum diameter or thickness). The largest diameter of residual disease inversely correlates with survival. Thus, patients that are not candidates for optimal primary cytoreduction should be considered for neoadjuvant chemotherapy.
Patients who are diagnosed at a younger age have a more favorable prognosis. This is likely a result of a combination of factors including lower-grade tumors and better baseline functional status.
The genetic characteristics of ovarian tumors can help identify patients who will benefit from targeted maintenance therapy, such as poly(ADP-ribose) polymerase inhibitors (PARPi).
Management of Epithelial Ovarian Cancer
Treatment of epithelial ovarian cancer depends on the stage, histologic subtype, type of disease (eg, primary or recurrent), previous treatment, and the patient's performance status.
Borderline Tumors
Borderline tumors are initially managed with surgical resection of the presenting tumor. Patients who do not desire future fertility should undergo complete staging, which can help detect occult invasive disease. However, because of the excellent prognosis, in young patients with early-stage disease who desire future fertility, the option of conservative surgery with unilateral salpingo-oophorectomy, or even with unilateral cystectomy, should be discussed. Lymphadenectomy is often omitted from surgical staging as it does affect survival, though suspicious lymph nodes should be removed. Risk of recurrence after conservative surgery is 7% to 30% and occurs an average of 10 years after initial diagnosis. There is a 1% to 2% risk of progression to invasive cancer. When recurrence occurs, full surgical staging is recommended. Chemotherapy is rarely indicated for this disease.
Early Invasive Disease (Stage I or II)
Initial surgical resection is necessary for establishing a histologic diagnosis and appropriate staging. Fertility-preservation is associated with similar outcomes in early-stage disease. If intraoperative findings are consistent with stage I disease and the contralateral ovary is normal in appearance, unilateral salpingo-oophorectomy with thorough surgical staging may be performed. The uterus and normal-appearing contralateral ovary may remain in situ. The patient should be counseled about the potential for a second primary in the preserved ovary, and a total hysterectomy with removal of the remaining tube and ovary should be considered after childbearing is completed.
Chemotherapy. For patients with low-grade stage IA or IB disease, chemotherapy is not required. However, for patients with stage IC or II disease and those with high-risk features such as high-grade, clear cell histology at any stage, or carcinosarcoma at any stage, postoperative platinum-based chemotherapy is recommended. See Chapter 56.
Radiation therapy is used infrequently in the treatment of early-stage ovarian cancer.
Advanced Invasive Disease (Stage III or IV)
Advanced disease requires a combination of surgical debulking and platinum-based chemotherapy.
Primary cytoreductive surgery should be performed at time of diagnosis if optimal cytoreduction is feasible.
For patients with unresectable advanced disease where optimal cytoreduction is unlikely at time of presentation, or who are poor surgical candidates, neoadjuvant (preoperative) chemotherapy should be considered. Randomized trial data has demonstrated that neoadjuvant chemotherapy followed by surgical debulking is not inferior to primary debulking surgery in these patients. However, complete resection of all macroscopic disease remains the main predictor of overall survival. Neoadjuvant chemotherapy is typically platinum and taxane based (eg, carboplatin and paclitaxel).
Adjuvant (postoperative) chemotherapy is recommended for all patients with advanced disease. This typically consists of 3 to 6 cycles of combination platinum-based chemotherapy depending on if neoadjuvant chemotherapy was administered. Concurrent antiangiogenic therapy such as bevacizumab, a monoclonal antibody inhibitor of vascular endothelial growth factor 1, can also be considered in conjunction with platinum-based chemotherapy.
Following primary treatment (cytoreductive surgery and chemotherapy), most patients will achieve clinical remission, but the risk of recurrence is high. Patients with advanced disease who have partial or complete response to primary treatment can therefore be considered for maintenance treatment to lengthen time to recurrence. Options for maintenance therapy depend on presence of germline and somatic genetic mutations and the use of bevacizumab during primary chemotherapy. For example, maintenance bevacizumab should only be given if it was also given during primary chemotherapy. Patients with germline or somatic BRCA mutations, or with homologous recombinant deficient tumors are the most likely to benefit from PARPi maintenance.
Posttreatment Surveillance
Patients who achieve remission following primary treatment should be monitored for recurrence. This includes office visits with physical and pelvic exams every 2 to 4 months for the first 2 years, 3 to 6 months for the next 3 years and annually thereafter.
If initially elevated, CA-125 is a reliable marker of disease recurrence with a sensitivity of 62% to 94% and specificity of 91% to 100%. Levels are often elevated 2 to 5 months prior to clinical detection of recurrence. However, routine CA-125 surveillance has not been shown to impact overall survival.
Radiographic imaging with CT, magnetic resonance imaging (MRI), or positron emission tomography (PET) should be obtained when clinically indicated (new symptoms, new exam findings, rising CA-125). Second-look surgery by laparotomy or laparoscopy was historically performed in clinical trials but does not offer any therapeutic benefit and is not routinely performed.
Secondary cytoreductive surgery can be considered for patients with few sites of recurrence and platinum-sensitive disease (recurrence more than 6 months after platinum-based chemotherapy). Achieving complete secondary cytoreduction is associated with longer overall survival.
Second-line chemotherapy options are primarily grouped based on platinum sensitivity. A patient's disease is considered platinum sensitive if recurrence occurs more than 6 months after completion of platinum-based therapy. Patients with platinum-sensitive disease can be offered retreatment with a platinum-based chemotherapy regimen with response rates ranging from 50% to 60%. For patients with platinum-resistant disease, there are multiple chemotherapy options, but response rates are overall lower compared to platinum-sensitive disease.
There is also a role for targeted therapy in recurrent or persistent disease. The addition of bevacizumab given with second-line chemotherapy has been shown to improve response rates in both platinum-sensitive and platinum-resistant disease. For patients with DNA mismatch repair-deficient or microsatellite-unstable disease or with high tumor mutational burden (10 muts/mega base), treatment with an immune checkpoint inhibitor such as pembrolizumab is Food and Drug Administration (FDA) approved for recurrent disease.
Endocrine therapy such as aromatase inhibitors, leuprolide acetate, megestrol acetate, and tamoxifen can be considered for patients with recurrence with few symptoms, though response rates are low.
Radiation therapy is generally not used except for palliation of distant metastases.
Maintenance therapy after relapse is nuanced and depends on prior treatment exposure and tumor characteristics. For patients with platinum-sensitive recurrence that is BRCA wildtype, bevacizumab can be used for maintenance therapy. For patients with BRCA-mutated platinum-sensitive recurrence, bevacizumab remains an option, but PARPi may also be considered for maintenance if the patient has not previously been exposed to a PARPi during prior treatment.
Complications of Advanced Ovarian Cancer
Many patients with ovarian cancer develop intestinal obstruction, either at initial diagnosis or with recurrent disease. Obstruction may be related to mechanical blockage or carcinomatosis. Correction of intestinal obstruction at initial treatment is usually possible; obstruction associated with recurrent disease, however, is a more complex problem. Some of these obstructions may be treated conservatively with IV hydration, total parenteral nutrition, and gastric decompression. The decision to proceed with palliative surgery must be based on the physical condition of the patient and expected survival. If patients are unable to undergo surgery or are judged to be poor operative candidates, placement of a percutaneous gastric tube may offer some symptomatic relief. A large bowel obstruction is a surgical emergency due to the risk of cecal perforation. Often, a diverting colostomy is required to avoid significant morbidity and mortality; colorectal stents can sometimes be considered to avoid ostomy placement.
Ascites is often present at diagnosis in patients with advanced ovarian cancer as tumor cells produce fluid that fill the peritoneal cavity. This almost always resolves following debulking surgery and adjuvant chemotherapy. Persistent ascites at the completion of primary therapy can be difficult to manage and is a poor prognostic sign. For many years, the only treatment option was serial paracentesis; however, bevacizumab may help to reduce the production of malignant ascites in patients with recurrent disease.
Pleural effusion is also a common presenting symptom at time of diagnosis. Similar to ascites, it is managed by treatment of the cancer and can otherwise be addressed with serial thoracentesis or placement of a chest catheter for drainage.
Survival
Stage. Patients with local (stage I) disease have about 92% 5-year survival rate. In contrast, overall survival for patients with distant disease on presentation (majority of the cases) is 31.5% (Table 54-4).
Age. The 5-year overall survival rate by age is 72.8% for patients younger than 50 years old, 54.7% for patients 50 to 64 years old, and 34% for patients older than 64 years old.
Performance status. The ECOG Performance Status Scale describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability. See Table 54-5. Performance status often influences decisions regarding chemotherapy or clinical trial eligibility.
| ECOG Score | |
| 0 | Fully active, able to carry out predisease activities without restriction |
| 1 | Restricted in physically strenuous activity but ambulatory; able to carry out light work (eg, light housework) |
| 2 | Ambulatory, capable of all selfcare but not able to carry out any work activities; up and about >50% waking hours |
| 3 | Capable of only limited selfcare; confined to bed or chair >50% waking hours |
| 4 | Completely disabled; unable to carry out any selfcare; totally confined to bed or chair |
| 5 | Dead |
Most patients will have short-term side effects from treatment, but it is important to be aware of long-term physical effects of treatment. Some patients will have irreversible peripheral neuropathy from platinum-based chemotherapy. Other common lasting effects are fatigue, anxiety/depression, GI toxicity, sexual dysfunction, and other menopausal symptoms. It is important to distinguish these symptoms as sequelae from treatment versus new symptoms that could represent recurrent disease.