Advances & Insights: Cancer
What the news means for you
John R. van Nagell Jr., MD
Ovarian cancer screening can indeed save lives
The PLCO trial referenced here was started after UK published its first data on ovarian cancer in 1991 in the Journal of Cancer. In fact, the National Cancer Institute (NCI) designed this trial using a lot of data we developed. However, theirs was a multi-institutional trial that involved training a large number of technical staff to do what we had been doing here for years, so their learning curves were high. Additionally, they had a control group of people who were not screened, and their screening was different from ours.
“Seventy percent of patients with abnormal results [screened at UK] were detected with early stage (I or II) ovarian cancer and almost 90 percent of these patients were alive five years after treatment.”
UK screening different from that of PLCO Trial
In the UK study, we screened first with ultrasound, and then if results were abnormal, followed up with a second ultrasound in six weeks. If that was abnormal, a CA-125 test was performed, then we looked at the images of the tumor and tried to assess whether it was benign or malignant. In the UK Ovarian Cancer Screening trial, 70 percent of patients with abnormal results were detected with early stage (I or II) ovarian cancer and almost 90 percent of these patients were alive five years after treatment.
The PLCO trial evaluated patients using a CA-125 test up front as well as ultrasound. If the CA-125 was elevated, they immediately reported that as an abnormality to the patients and their physicians. However, they not tell them what to do. It was the responsibility of the patient's physician to assess the abnormality. So they could elect to perform surgery, whether it turned out to be necessary or not.
“Without screening, two-thirds of patients present with stage III or stage IV ovarian.”
At UK, we used CA-125 testing as a backup only if there was an abnormality in the ultrasound. Another important difference is that we developed an algorithm that outlines the procedure to follow when assessing an abnormality. It takes into account the size of the ovary,the age of the woman, and the presence of a cyst or lesion on the ovary.
A high percentage of patients with advanced ovarian cancer will have elevated CA-125, but in the early stages, the CA-125 is often not elevated. In our trial, only one-fourth of the patients with stage I and II had high levels. Seventy percent of our patients were in the early stages of ovarian cancer. In the PLCO trial, there was a lack of observed stage shifts.
Surgery serves a purpose
In the last five years, one out of five patients we have operated on at UK has had ovarian cancer. What about the other four? There were no severe complications, and it's not realistic to say the surgery was unnecessary. Surgery was necessary to determine whether the mass was benign or malignant.
Without screening, two-thirds of patients present with stage III or stage IV ovarian cancer. At this point, there is only a 30 percent five-year survival rate for ovarian cancer first diagnosed at these stages, and at five years, two-thirds of the women who first enter treatment at these advanced stages will have a recurrence.
According to the UK tumor registry, from 1995 to the present, 741 patients treated for ovarian cancer weren't screened. Of that number, 488 had stage III or IV of the disease. In our screening program, 70 percent of the patients who had ovarian cancer were in stages I or II; 34 percent who were not screened also were in the early stages. Survival rates of the patients in either group were the same because the cancer was detected earlier.
How the screening program works
Participants in the UK Ovarian Cancer Screening Program receive annual screening with ultrasound at no cost. The screening procedure is painless and takes only five or 10 minutes. To be eligible for the program, a woman must be over 50, or if 25 or over, have a documented family history of ovarian cancer.
We hope that in the future annual screening will become routine for all women over 55. Many OB-GYNs have ultrasound equipment in their offices that could be used at the time of the patient's annual pelvic exam. At this time, however, third-party insurers do not cover this exam, and it can be quite expensive. The only other alternative is going through investigational trials such as UK's to get the exam free. Unfortunately, the screening is not perfected to the point now that it can be released to the general public.
Dr. Van Nagell is director of gynecologic oncology at UK Markey Cancer Center and professor of obstetrics & gynecology in the UK College of Medicine.
Ovarian cancer screening tests: Valuable or misleading?
An 18-year, multi-institutional trial conducted by the National Cancer Institute calls into question the value of two screening tests for ovarian cancer. Part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), the study examined the use of blood tests and transvaginal sonogram (TVS) aimed at early detection of the disease. Researchers concluded, however, that the tests not only failed to reduce ovarian cancer deaths but also resulted in false positives, leading to unnecessary surgery.
Ovarian cancer is...particularly lethal because symptoms don't usually appear until the disease is in its advanced stages.
Ovarian cancer is the fifth leading cause of cancer deaths among women in the United States. It is particularly lethal because symptoms don't usually appear until the disease is in its advanced stages. Five-year survival rates at this point are only 30 percent; in contrast, there is a 92-percent survival rate among the women whose cancer is detected in the early stages. Identifying the disease early is crucial; however, there has been no standardized, widespread screening method for ovarian cancer as there is for breast cancer.
How the study was conducted
In the PLCO trial, more than 39,000 postmenopausal women at 10 screening centers across the United States were chosen to receive annual screenings and compared to the same number who received standard care at the same medical centers. In the standard care group, most women underwent bimanual examination with ovarian palpation. The first group was screened with a blood test for CA-125, a protein released by ovarian cancer, and TVS. If results were abnormal, participants and their physicians were notified, and it was up to them to determine what treatment should follow.
In the screening group, 118 women died from ovarian cancer; 100 died in the control group. In addition, 1,080 women in the screening group underwent surgery to remove possible ovarian tumors that turned out to be harmless. Fifteen percent of that group experienced complications such as infections or blood clots. The majority of cancers found in both groups were stage III and stage IV. Treatments were similar and included surgery followed by systemic therapy. The results were published in the June 8, 2011, issue of the Journal of the American Medical Association.
Limitations of the study
Researchers in this trial observed no stage shift – that is, a decrease in the absolute number of late-stage cases in the intervention group compared with the usual-care group. A stage shift is necessary for a mortality benefit to be realized. However, there were more advanced cancers in the intervention group than in the usual-care group. Therefore, researchers concluded that the screening wasn't effective in finding early stage ovarian cancer. Additionally, they made no recommendation for the type of suspected cancer should receive nor the type of surgeon who should perform the removal of the ovaries.
There were no uniform treatment guidelines for women who had a screening abnormality in the PLCO trial. Also, there was no secondary testing prior to surgery. If a patient had an abnormal screening result, her primary care physician was informed and the treatment given was left up to each physician. Therefore, the time of treatment and the type of treatment were variable. In many cases in the intervention group, there was a significant delay of up to nine months from the detection of an abnormality on screening to surgical intervention.
Since 1986, the University of Kentucky's Gynecological Oncology Division has conducted an ongoing study using TVS to screen for ovarian cancer. It is one of the largest ovarian screening programs in the world.
For more information, see:
- Effect of screening on ovarian cancer mortality(UKCTOCS), JAMA, v. 305, no. 22, June 8, 2011, pp. 2295-2303.
- Ovarian cancer screening with annual transvaginal sonography: Findings of 25,000 women screened, Cancer, v. 109, issue 9, May 1, 2007, pp. 1887-1896
- Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, National Cancer Institute
- Ovarian cancer, Health Information, UK HealthCare
UK HealthCare Cancer Services - Markey Cancer Center
For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.