In May 2021, CNN chief international anchor Christiane Amanpour was diagnosed with ovarian cancer. She revealed that diagnosis to her viewers on June 15, 2021 after a 4-week hiatus: “I’ve had successful major surgery to remove it, and I’m now undergoing several months of chemotherapy for the very best possible long-term prognosis, and I’m confident.”
She went on to say: “I’m telling you this in the interest of transparency, but in truth really mostly as a shout-out to early diagnosis.” She said she wanted to “urge women to educate themselves on this disease; to get all the regular screenings and scans that you can; to always listen to your bodies; and of course, to ensure that your legitimate medical concerns are not dismissed or diminished.”
In an interview with “Good Morning America” last month, Amanpour gave an update as she was about to undergo her 18th and final round of chemotherapy. She described the treatment as “grueling, fatiguing, [and] tiring,” both emotionally and physically.
However, Amanpour says that she has a “very good prognosis” because her cancer was detected early. Once again, she stressed that women need to know more about the disease and to act as their own health advocate. “I would not be swayed when I felt a pain that was unusual and I pursued it until the very end of getting my first ultrasound, which is the benchmark for then having a baseline to know whether you’ve caught it early in time and therefore ‘cure’ it, or not,” she said. “[Ovarian cancer] is very difficult to detect and that’s what I want women to understand.”
In January 2021, we did an article about Kardashian make-up artist Hrush Achemyan’s ovarian cancer. As that article covers most of the basics about this disease, today I would like to concentrate on the issues highlighted by Amanpour herself — early diagnosis and screening.
The earlier ovarian cancer is caught, the better chance a person has of surviving 5 years after being diagnosed. For ovarian cancer, 16.3% of cases are diagnosed at the local stage. The 5-year relative survival for localized ovarian cancer is 92.6%. But that drops to 30.3% for women with distant disease — and 57% of cases are diagnosed with distant disease.
Signs and Symptoms
According to NCI, ovarian, fallopian tube, or peritoneal cancer may not cause early signs or symptoms. When signs or symptoms do appear, the cancer is often advanced. Signs and symptoms include the following:
- Pain, swelling, or a feeling of pressure in the abdomen or pelvis
- Urinary urgency or frequency
- Difficulty eating or feeling full
- A lump in the pelvic area
- Gastrointestinal problems such as gas, bloating, or constipation
These symptoms often go unrecognized, leading to delays in diagnosis. Efforts have been made to enhance physician and patient awareness of the occurrence of these nonspecific symptoms.
A few studies have looked at symptoms women may have in the months prior to their diagnosis of ovarian cancer. For example, Barbara Goff and colleagues found that when the symptoms of bloating, abdominal or pelvic pain, difficulty eating, and urinary symptoms occur 12 times or more a month, that ovarian cancer must be included in the differential diagnosis and ruled out as a cause.
Lloyd Smith and co-authors found that one-third to one-half of patients developing ovarian cancer report symptoms 3 or more months prior to diagnosis. Abdominal bloating and pain are most common, although other gastrointestinal and urinary symptoms as well as fatigue/malaise may be part of the symptom complex.
A study by Rossing et al. conducted in-person interviews of over 800 women who had the diagnosis of ovarian cancer and 1,300 population-based control subjects. A symptom index was considered positive when pelvic or abdominal pain or bloating or feeling full was reported at least daily for at least 1 week, with an onset of less than 12 months before diagnosis or a reference date (for control subjects).
The team found that those diagnosed with ovarian cancer usually had a positive symptom index within 5 months of diagnosis. In addition, symptoms (except for nausea) were less likely to have occurred with early-stage than late-stage ovarian cancer. The researchers also estimated that using symptoms to trigger medical evaluation for ovarian cancer would lead to the diagnosis of cancer in one out of 100 women in the general population with those symptoms.
All agree that a screening test that can be done on the general population and that would be able to reliably detect ovarian cancer at an early stage would be a game-changer. Unfortunately, no such screen test currently exists.
Screening tests that have been studied include the following:
- Pelvic exam
- Transvaginal ultrasound (TVU)
- Serum cancer antigen 125 (CA-125)
There is a lack of evidence that current screening procedures show a mortality benefit. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial looked at the use of CA-125 (positive =35 U/ml) annually for 6 years along with transvaginal ultrasound for 4 years. The ovarian cancer mortality rate was 4.4 deaths per 10,000 person-years in the intervention arm and 3.8 deaths per 10,000 person-years in the usual-care arms, respectively.
The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) looked at screening with TVU with/without multimodal screening with CA-125 levels. Patients were also assessed using the Risk of Ovarian Cancer Algorithm two-staged ovarian screening strategy that incorporates change of CA-125 over time and age to estimate the risk of ovarian cancer. Women with high-risk scores are then referred for transvaginal ultrasound.
That trial also found no mortality benefit of screening. (Multimodal screening was associated with a non-significantly lower mortality than with no screening — 15% lower mortality). Ultrasound-only screening also resulted in non-significantly lower mortality (11%).
The studies also looked at possible harms that might result from the screening regimens. Based on solid evidence, screening for ovarian cancer does result in false-positive test results. Screened women had higher rates of oophorectomy and other minor complications such as fainting and bruising.
According to NCI, 9.6% of screened women had false-positive results, resulting in 6.2% undergoing surgery. The surgical complication rate was 1.2% for all screened women. Oophorectomy rates were 85.7 per 10,000 person-years among screened women and 64.2 per 10,000 person-years among usual-care women. Minor complications with screening were 58.3 cases per 10,000 women screened with CA-125 and 3.3 cases per 10,000 women screened with transvaginal sonogram.
Possibilities for the Future?
Several candidate screening tests are currently being studied. Serum tumor markers other than CA-125 are under investigation. Human epididymis protein 4 (HE4) is produced by most, but not all, epithelial ovarian cancer cells. Li et al. report that HE4 may be superior to CA-125 as an ovarian cancer marker because it has the ability to distinguish benign diseases from malignancies, especially in premenopausal women. The combined use of HE4 with CA-125 may also show promise.
Other markers under investigation include serum lysophosphatidic acid; apoptosis-signaling receptor molecule sFas; liver glycoprotein haptoglobin-α; glycoprotein bikunin; and OVX1, an epitope of high molecular weight mucin-like glycoproteins, which can be detected by radioimmunoassay.
Another area of active investigation involves microRNAs (miRNAs), small single-stranded non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. According to Wu et al., expression of miRNAs is aberrant in various types of cancer, and they are readily and stably detected in circulating body fluids such as serum and plasma.
The researchers found that the serum expression of three miRNAs (miR-200b-3p, miR-200c-3p, and miR-429) was significantly higher in ovarian cancer patients than in healthy controls. In addition, the expression of miR-200a-5p, miR-200b-3p, miR-200c-3p, and miR-429 was higher in ovarian cancer patients compared with those with benign lesions. Further large-scale prospective studies are needed to confirm the clinical relevance of these miRNAs.
Clinical trials focusing on screening for ovarian cancer can be found at ClinicalTrials.gov.
Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children’s Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.