Introduction
Ovarian cancer is a group of diseases that originates in the ovaries or in the related areas of the fallopian tubes and the peritoneum. It is the second most common gynecological cancer in the United States and causes more deaths than any other cancer of the female reproductive system.1,2 According to the latest United States cancer statistic data visualizations, it most commonly affects White, non-Hispanic women at 9.8 cases per 100,000 women and women between the age of 75-79 years at 38.1 cases per 100,000 women.2 The American Cancer Society estimates about 19,710 women will receive a new diagnosis of ovarian cancer and approximately 13,270 women will die from the disease in 2023.3
Etiology
The exact cause of ovarian cancer is largely unknown, but new research indicates that it begins in the cells at the tail ends of the fallopian tubes and not in the ovary itself as previously believed. Some researchers believe that a relationship between ovulation and the risk of developing ovarian cancer exists. This theory was developed because pregnancy and taking oral contraceptive medication lowers the risk of ovarian cancer and reduces the number of times the ovary releases an egg.4 Indeed, a 30% to 60% decreased risk for ovarian cancer is associated with 1 or more pregnancies and/or births, oral contraceptive use, and/or breastfeeding.5 Another theory involves cancer-causing substances entering the body through the vagina and passing through the uterus and fallopian tubes to reach the ovaries. Finally, it is possible that male hormones (androgens) can cause ovarian cancer.4
Recent studies have allowed researchers to understand how certain mutations, inherited or acquired, may lead to ovarian cancer. Inherited mutations linked to an increased risk of ovarian cancer include mutations in the BRCA1 and BRCA2 genes,4 which account for about 15% of patients with ovarian cancer.5 Genes related to other family cancer syndromes, including PTEN (PTEN tumor hamartoma syndrome), STK11 (Peutz-Jeghers syndrome), and MUTYH (MUTYH-associated polyposis) and genes that may cause hereditary nonpolyposis colon cancer (MLH1, MLH3, MSH2, MSH6, TGFBR2, PMS1, and PMS2) have also been linked to an increased risk of ovarian cancer.4 Acquired genetic changes may occur from radiation or carcinogens, but no single environmental or carcinogen has been linked to ovarian cancer. Tests to identify acquired mutations such as those in the TP53 tumor suppressor gene or HER2 oncogene may help predict the disease prognosis.4
Screening and Diagnosis
Ovarian cancer is difficult to diagnose at an early stage due to the location of the ovaries and the biology of such an epithelial cancer. Symptoms of ovarian cancer include bloating, pelvic or abdominal pain, difficulty eating or feeling full quickly, and urinary symptoms such as urgency or frequency. Routine screening is not recommended in the general population. Several large prospective trials5 have evaluated screening for ovarian cancer with serum CA-125 and ultrasound and determined that screening may increase the likelihood of diagnosis at an early stage. However, screening did not improve overall ovarian cancer-related mortality and may result in false positives. For those with high-risk factors, risk-reducing salpingo-oophorectomy is recommended over screening. Other biomarkers have been explored in addition to CA-125, but data is limited, and many do not increase early enough to be useful in detecting early-stage cancer. Thus, no screening tests are available for ovarian cancer.5
Patients presenting with clinical signs/symptoms of ovarian cancer may undergo a combination of biopsies and imaging tests for diagnosis. First, a physical examination along with determining the patient’s history should be performed. If ovarian cancer is suspected, the primary workup for patients with clinical signs or symptoms should include an abdominal/pelvic ultrasound and/or abdominal/pelvis computed tomography (CT)/magnetic resonance imaging scans.5 A complete blood count and a blood chemistry that includes liver function and calcium should also be performed. CA-125 should be measured, but is only elevated in about 80% of ovarian cancers overall and 50% in early-stage cancer.6 A chest CT may be performed if there is concern for metastatic or disseminated disease. Workup should also include nutritional status and gastrointestinal evaluation if clinically indicated.5 If any test is abnormal or suspicious for ovarian cancer, the patient should be referred to a gynecologic oncologist.5,6
Treatment and Management
The primary treatment for ovarian cancer is surgical staging and debulking surgery followed by systemic chemotherapy, in some cases. Surgery alone, followed by observation, may be sufficient for patients with early-stage disease. Certain histologic subtypes may be treated with adjuvant therapy with hormonal agents. In patients with advanced-stage ovarian cancer who are not good candidates for upfront primary debulking surgery, neoadjuvant chemotherapy (NACT) with interval debulking surgery should be considered. Using Poly (ADP-ribose) polymerase (PARP) inhibitors for ovarian cancer treatment is increasingly being supported by emerging data.5
Most patients with ovarian cancer should receive adjuvant chemotherapy after primary surgery. Observation is only considered in select patients with stage I disease, depending on the cancer histologic type and substage.5 Women with a favorable surgical profile may receive neoadjuvant chemotherapy or undergo cytoreduction surgery. Results from the ACTION 2003, Bolis 1995, ICON1 2003, and trope 2000 trials showed that patients with early-stage ovarian cancer who underwent adjuvant chemotherapy had better overall survival and progression-free survival compared with those who did not receive it.7 Options for postoperative treatment in patients with advanced ovarian cancer include platinum-based intravenous (IV) chemotherapy, platinum-based IV/intraperitoneal (IP) chemotherapy, and platinum-based IP chemotherapy plus bevacizumab. Numerous clinical trials have compared IV chemotherapy regimens for postoperative treatment, but do not show significant differences in efficacy between the regimens. Thus, several options are available for IV chemotherapy. However, paclitaxel 175/carboplatin is the most commonly used regimen and is considered the standard postoperative chemotherapy for ovarian cancer.5
Although several maintenance therapies have been studied in ovarian cancer, little evidence exists showing benefit with platinum-based agents or anti-angiogenic inhibitors. In contrast, PARP inhibitors have become first-line therapies for maintenance and for recurrent disease. Indeed, the phase III PAOLA-1 trial showed a progression-free survival benefit of 4.5 months in the group that received olaparib and bevacizumab maintenance vs placebo and bevacizumab. As a result, this combination was awarded FDA approval as a first-line maintenance after treatment for patients with ovarian cancer after initial platinum-based chemotherapy with partial or complete response.7
Patients with suspected or confirmed ovarian cancer should be referred to a gynecologic oncologist who should be involved in assessing whether a patient is a good candidate for neoadjuvant therapy and consideration of laparoscopic evaluation to determine whether debulking surgery is feasible. Symptom management and best supportive care is recommended for all patients and if appropriate, patients should be referred for palliative care.5
Conclusion
Ovarian cancer remains one of the deadliest cancers in women with a difficult diagnosis in the early stages. Future research should focus on diagnosing the cancer at an earlier and more curable stage and development of effective treatment strategies for advanced disease.
References
1. Basic information about ovarian cancer. Centers for Disease Control and Prevention. Published August 31, 2022. Accessed March 30, 2023. https://www.cdc.gov/cancer/ovarian/basic_info/index.htm
2. United States Cancer Statistics: Data Visualizations. Centers for Disease Control and Prevention. Published November 2022. Accessed April 3, 2022. https://www.cdc.gov/cancer/ovarian/statistics/index.htm
3. Key statistics for ovarian cancer. American Cancer Society. Updated January 12, 2023. Accessed March 30, 2023. https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html
4. What causes ovarian cancer? American Cancer Society. Updated April 11, 2018. Accessed March 30, 2023. https://www.cancer.org/cancer/ovarian-cancer/causes-risks-prevention/what-causes.html
5. NCCN clinical practice guidelines in oncology: ovarian cancer, including fallopian tube cancer and primary peritoneal cancer (Version 1.2023.) National Comprehensive Cancer Network. Accessed April 3, 2023. https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf
6. Doubeni CA, Doubeni ARB, Myers AE. Diagnosis and management of ovarian cancer. Am Fam Physician. 2016;93(11):937-944. https://www.aafp.org/pubs/afp/issues/2016/0601/p937.html
7. Arora T, Mullangi S, Lekkala MR. Ovarian cancer. StatPearls Publishing; 2023. Accessed April 3, 2023. https://www.ncbi.nlm.nih.gov/books/NBK567760/