Effect of disease prevalence on population-based screening
| Specificity of the screening test (%) | Positive predictive value (%) | |||
|---|---|---|---|---|
| 50% prevalence | 10% prevalence | 1% prevalence | Ovarian cancer (1 case in every 2,500 women) | |
| 90 | 91 | 53 | 9 | 0.4 |
| 95 | 95 | 69 | 17 | 0.8 |
| 99 | 99 | 92 | 50 | 4 |
| 99.9 | 99.9 | 99 | 91 | 29 |
Details of the trial by Gilbert and colleagues
In a recent pilot study, Gilbert and colleagues prospectively analyzed the utility of disseminating information about the symptoms of ovarian cancer to the general public. Following dissemination of information, women who were 50 years or older and who had experienced at least one ovarian cancer symptom longer than 2 weeks underwent CA-125 testing and TVUS. If both tests were normal, CA 125 was repeated; if it was normal again, the patient was discharged from the study.
Patients who had abnormal findings on either test repeated both screening tests, with additional testing performed as necessary. Outcomes of these women were compared with those of women who had been referred to the gynecologic oncology clinic.
Among 1,455 eligible patients, 11 cases of invasive ovarian cancer were diagnosed, four of which (36%) represented early-stage disease. Median CA-125 levels were lower in the study group. In addition, more women in the study group had early-stage disease that was completely resectable, compared with the clinic group, although this difference did not reach statistical significance.
Most cases of ovarian cancer in this study originated in the fallopian tube or peritoneum—not the ovary. In addition to the cases of ovarian cancer, 11 cases of uterine cancer were diagnosed. No patients underwent unwarranted major surgery, and none who were discharged from the study had a diagnosis of gynecologic cancer by 7 months of follow-up.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
TVUS and CA 125 increase the number of cases of ovarian cancer that are diagnosed but do not provide a survival benefit. Identification of cases in the PLCO trial was, therefore, likely the result of lead-time bias—cases of ovarian cancer were detected sooner but not at an early stage.
Routine screening with TVUS and CA 125 are not recommended at this time for women at average risk for ovarian cancer. These and similar screening methods lead to a significant false-positive rate, with surgeries performed for benign indications and a high risk of surgical complications. Further studies to improve the sensitivity and specificity of these tests in women at average risk for ovarian cancer are ongoing.7
Women who have an elevated risk of ovarian cancer, such as women who carry the BRCA mutation or who have a family history of ovarian cancer, may benefit from routine screening because of increased disease prevalence in this population, although studies are needed to determine the best utilization of screening tests.
Women who have symptoms of ovarian cancer should undergo thorough evaluation that may lead to earlier diagnosis and improved outcomes.
Burger RA, Brady MF, Bookman MA, et al; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473–2483.
Perren TJ, Swart AM, Pfisterer J, et al; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484–2496.
Epithelial ovarian cancer frequently expresses vascular endothelial growth factor (VEGF). Lower levels of VEGF are associated with decreased formation of new blood vessels and increased survival.
Bevacizumab is a monoclonal antibody that binds to VEGF and inhibits its biological activity. It has proved to be effective in the treatment of colorectal, lung, and brain cancers.
These two recent trials evaluated the benefit of adding bevacizumab to first-line chemotherapy for ovarian cancer. In the Gynecologic Oncology Group (GOG) trial (Protocol#218), investigators evaluated women with Stage III/IV ovarian cancer. The ICON7 trial also included women who had high-risk early-stage disease.
Both trials randomly assigned women to first-line chemotherapy with carboplatin and paclitaxel plus either bevacizumab or placebo. After completion of initial treatment, maintenance therapy continued for an additional 12 to 16 cycles.
In a third arm of GOG 218, bevacizumab was administered only during the six cycles of initial chemotherapy without any maintenance treatment.
Both trials were powered to detect an improvement in progression-free survival, not overall survival.
Findings of the trials
In GOG 218, approximately 600 women were allocated to each of its three arms. In ICON7, approximately 750 women were allocated to each of its two arms.
Both trials demonstrated a benefit when bevacizumab was added to initial treatment, followed by maintenance therapy. The hazard ratio for recurrent disease was 0.72 (95% CI, 0.63–0.82) and 0.81 (95% CI, 0.70–0.94) in the two trials, respectively, with increased progression-free survival of 1.7 to 3.8 months.