Algorithm-based screening with an assay for the CA-125 cancer antigen plus transvaginal ultrasound detected 19 cancers, 10 of which were stage I or II at diagnosis. In contrast, all but one of the cancers detected in the first year after the screening program ended were stage IIIb to IV, according to Ian J. Jacobs, MD, of the University of New South Wales in Sydney, and colleagues.
Among patients who underwent surgery for cancers detected during screening, all but one had no evidence of residual disease after surgery, they wrote online in Journal of Clinical Oncology.
“Our protocol achieves encouraging performance characteristics, is associated with a low rate of high-volume disease at primary surgery, and had a high zero residual disease rate at low levels of surgical complexity,” the authors concluded. “Risk-reducing salpingectomy-oophorectomy [RRSO] remains the treatment choice for women at high-risk of ovarian/fallopian tube cancer.
“In those not ready or unwilling to undergo surgery, multimodal screening using [CA-125] every 4 months and transvaginal ultrasound … with regular discussions about the effectiveness of RRSO, appears to be a better option than symptom awareness alone. Such screening should not be viewed as an alternative to surgery, but it does seem to offer a better chance of avoiding a diagnosis of advanced, incompletely resectable ovarian/fallopian tube cancer in the interim.”
The impact of screening on the risk of ovarian cancer death remained unclear, they added.
A key take-away from the research is its focus on high-risk patients, said Shannon MacLaughlan, MD, of Stanford University in Stanford, Calif., who was not involved in the study. The results cannot be applied to average-risk women, who have about a 2% lifetime risk of ovarian/fallopian tube cancer. Second, the screening program incorporated regular, ongoing discussion about the risks and benefits of risk-reducing surgery, and some women in the study eventually decided to have surgery.
In the U.S., risk-reducing surgery is recommended for high-risk women after they have completed childbearing, and before age 40 if they are BRCA1 carriers or age 45 if they are BRCA2 carriers.
“Up until now there have been no data demonstrating the utility of screening in this population, though it is common practice in high-risk patients until/unless they are ready to undergo their surgeries,” said MacLaughlan, who is an expert for the Society of Gynecologic Oncology. “This study does help inform us on how to counsel these patients about the utility of screening in high-risk women.”
“That being said, the goal of screening is to save lives, and ideally that means identifying cancers before they happen,” she cautioned. “That was not accomplished in this study, because we simply do not have the ability, with technology currently available, to detect precursor lesions for ovarian cancer. So it is important to acknowledge the limitations of screening and continue to emphasize and recommend risk-reducing strategies for high-risk women, including the use of oral contraceptives and surgical removal of tubes and ovaries when appropriate.”
Jacobs’ group reported findings from phase II of the United Kingdom Familial Ovarian Cancer Screening Study. A pilot study of annual screening with CA-125 in the general population showed improved survival. A subsequent trial of multimodal screening with the risk of ovarian cancer algorithm (ROCA) to interpret CA-125 results demonstrated high sensitivity and specificity, diagnosis of significantly more low-volume disease, and evidence of a survival benefit.
The current report described performance characteristics of ROCA-guided screening in high-risk women.
Investigators at 42 centers enrolled 4,348 women who had ≥10% lifetime risk of ovarian cancer. Patients underwent ROCA screening every 4 months. They had transvaginal ultrasound evaluations annually if ROCA results were normal or within 2 months in the event of an abnormal ROCA result. Patients were encouraged to consider RRSO throughout the trial.
The study population had 13,728 women-years of screening and a median follow-up of 4.8 years. During the screening phase, 19 invasive cancers were diagnosed within 1 year of prior screening, 13 detected at screening and six occult tumors identified at RRSO. Five of 13 screen-detected tumors and five of six occult cancers were stage I-II at diagnosis. The results translated into 94.7% sensitivity for ROCA-based screening to detect invasive ovarian cancers within 1 year.
Seven of the 19 cancers detected during screening were stage IIIb-IV. In the first year after screening ended, 18 additional ovarian/fallopian tube cancers were diagnosed, 17 of which were stage IIIb-IV (P<0.001). Additionally, surgery for the 19 cancers detected during screening resulted in zero residual disease (with lower surgical complexity) in 18 cases as compared with 13 of the 18 cancers detected after screening ended (P=0.09).
Study limitations included the non-randomized design, the unknown mutation status of many of the women, and the small number of incident cancers, which limited power.
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