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Can ultrasound screening improve survival in ovarian cancer?

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Use caution in interpreting results, commentators warn

Use a measure of caution when interpreting the results of the study by van Nagell et al., Sharon E. Robertson, MD, MPH, and Jeffery E. Peipert, MD, PhD, said in an invited commentary. First, they noted the “surprisingly high” rate of ovarian cancer (271 per 100,000) – although it may improve the predictive value of ultrasound screening, when one applies the test sensitivity and specificity the trial reported to the general population, “the positive predictive value falls to an unacceptable 0.7%.”

They also questioned the rationale for comparing the study population to an unscreened cohort of women with ovarian cancer referred to the University of Kentucky. “However, are we really comparing apples to apples?” they asked, noting “important key baseline differences” between the two groups, including that the screened cohort “could have contained an unbalanced proportion of genetically related ovarian cancers.” They also noted the risk profile of the unscreened cohort is unknown.

Addressing the differences in survival rates between screened and unscreened patients, Dr. Robertson and Dr. Peipert noted the study population had a higher rate of type I tumors than that seen in National Cancer Institute data for the general population (27% vs. 11%), along with the absence of genetic analysis. “For these reasons, we cannot confidently agree with the authors’ conclusion that the ultrasound screening reduced ovarian cancer mortality,” they stated.

They commended the Kentucky group for a “landmark study,” but added, “the evidence that screening for ovarian cancer improves survival remains elusive.” They called for more evidence before widespread screening programs are implemented.

Dr. Robertson and Dr. Peipert of Indiana University, Indianapolis, commented on the article by van Nagell et al. in Obstetrics and Gynecology (2018 Nov;132[5]:1089-90. doi: 10.1097/AOG.0000000000002962). Dr. Peipert disclosed relationships with Cooper Surgical/Teva, Merck, and Bayer. Dr. Robertson had no relevant financial relationships.



Annual ultrasound screening of asymptomatic women at risk of epithelial ovarian cancer can lead to lower staging of cancer at detection and improved survival, compared with no screening, according to a prospective clinical trial that followed more than 46,000 women over 2 decades.

“The findings of this study support the concept that a major predictor of ovarian cancer survival is stage at detection,” said John R. van Nagell Jr., MD, of the University of Kentucky–Markey Cancer Center, Lexington, and his coauthors. “The 10-year survival of women whose ovarian cancer was detected at an early stage (I or II) was 35% higher than that of women diagnosed with stage III cancer.” Study results were published in the November issue of Obstetrics & Gynecology.

The study evaluated 46,101 women enrolled in the University of Kentucky Ovarian Cancer Screening Trial over 30.5 years. Trial participants, all of whom had annual ultrasound screening, were age 50 and older, or 25 and older with a family history of ovarian cancer. Overall, 23% and 44% of the women had a family history of either ovarian or breast cancer, respectively. Women in the study had an average of seven scans each. The unscreened comparator group was women with ovarian cancer referred to the UK Markey Cancer Center.

The study detected 71 cases of invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential. None of the women with these tumors had a recurrence. Among the invasive cancers, the majority were either stage I (42%) or II (21%), and none were stage IV. The median age of these patients was 66 years. Of the low-malignancy tumors, 27% were stage I and 73% stage II, with none stage III or IV. A total of 699 women (1.5%) with persistent ovarian tumors had surgery.

Screened women also had improved survival compared to unscreened women: 86% vs. 45% at 5 years, 68% vs. 31% at 10 years (P less than .001).

However, the study also showed a high overall incidence rate for ovarian cancer, including false-positive and false-negative cases, compared with National Cancer Institute reports in the Kentucky state cancer profile: 271 per 100,000 vs. 10.4/100,000.

The study also looked at the economics of annual screening. “Ovarian screening reduced the 10-year mortality by 37% and produced 416 life years gained,” Dr. van Nagell and his coauthors said. Based on an estimated cost of $56 for each transvaginal ultrasound scan, that translates into a cost of $40,731 for each life year gained.

One concern of screening ultrasound is the high false-positive rate. “Although the sensitivity of transvaginal ultrasonography in detecting an ovarian abnormality is high, it has been unreliable in differentiating benign from malignant ovarian tumors,” they said. While they noted the accuracy of assessing malignancy has improved, the risk of complications in women who have surgery for benign tumors is an ongoing concern. “Additional research is necessary to identify high-risk populations who will benefit most from screening.”

Dr. van Nagell and his coauthors reported having no financial relationships. The study was supported by research grants from the Kentucky Department of Health and Human Services and the Telford Foundation.

SOURCE: Van Nagell JR Jr et al. Obstet Gynecol. 2018 Nov;132[5]:1091-100. doi: 10.1097/AOG.0000000000002921.

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