Perspective

Task force maintains recommendation against ovarian cancer screening

Maurie Markman
Richard T. Penson

The U.S. Preventive Services Task Force today released a draft recommendation statement and evidence review on ovarian cancer screening that is consistent with its final recommendation in 2012.

The USPSTF’s “D” recommendation advises against screening for ovarian cancer in women who have no signs or symptoms, noting that screening does not decrease the number of deaths from ovarian cancer and may lead to women having unnecessary surgery.

The draft recommendation does not apply to women at high risk for ovarian cancer, such as women with known BRCA1 and BRCA2 mutations.

Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America and a HemOnc Today Editorial Board Member, said he “completely” agrees with the draft recommendation.

“There is no value, and the potential for harm — anxiety, unnecessary invasive diagnostic testing — outweighs the benefit,” Markman told HemOnc Today. “Standard practice has been and continues to be that there is no role for ovarian cancer screening in women without a known genetic/familial risk.”

Ovarian cancer is the eighth most common cancer and fifth most common cause of cancer death among U.S. women. However, false-positive tests can lead to unnecessary surgeries to remove one or both ovaries and the fallopian tubes.

“The current screening tests do not do a good job of identifying whether a woman does or does not have ovarian cancer,” USPSTF chair David Grossman, MD, MPH, senior investigator at Kaiser Permanente Washington Health Research Institute, said in a statement. “The Task Force hopes that in the future, better screening tests for ovarian cancer will be developed.”

The draft recommendation statement and draft evidence review will be posted for public comment through Aug. 14, 2017.

“I agree with the task force, except in the case of a person with a known germline BRCA mutation prior to prophylactic surgery, typically at 40 years old,” Richard T. Penson, MD, MRCP, associate professor of medicine at Harvard Medical School, told HemOnc Today. “As you might suspect, this draft recommendation will not change what is being done in clinical practice.”

In its draft recommendation statement, the USPSTF noted the age-adjusted incidence of ovarian cancer from 2010 to 2014 was 11.4 cases per 100,000 women per year, and that most women with a positive screening test are found to not have ovarian cancer.

The USPSTF also reported that screening with transvaginal ultrasound (TVUS), testing for the serum tumor marker cancer antigen-125 (CA-125), or a combination of both, does not reduce the number of deaths from ovarian cancer.

Penson said he recommends biannual CA-125 and TVUS screenings if there is a family history of cancer at a very young age.

“There are those who claim that an algorithm focusing on the rate of rise of CA-125 in an individual woman over time versus an absolute level to be considered ‘abnormal’ may be more effective as an ovarian cancer screening strategy,” Markman said. “To date, the data supporting this hypothesis remains weak.”

In a separate recommendation statement, the USPSTF advises that women with a family history that indicates they are at risk for BRCA1 or BRCA2 mutations be referred for genetic counseling and, if indicated, genetic testing.

The most significant recent study on ovarian cancer screening is the U.K. Collaborative Trial of Ovarian Cancer Screening, a randomized controlled trial that compares annual multimodal screening vs. TVUS vs. control in 202,638 women aged 50 to 74 years from 13 centers in the United Kingdom. Researchers diagnosed ovarian cancer in 1,282 (0.6%) of the women — 338 (0.7%) in the multimodal screening group, 314 (0.6%) in the TVUS group, and 630 (0.6%) in the no screening group.

“The best interpretation in a prespecified analysis of death from ovarian cancer, which excluded prevalent cases, showed an overall average mortality reduction of 20% (P = .021),” Penson said. “However, there are three main reasons this hasn’t had any impact. First, mortality reduction was not significant in the primary analysis. Secondly, 2,641 women had to be screened annually for 14 years for each life saved. And, thirdly, the morbidity and mortality of laparotomy for a false-positive remains unacceptable.”– by Chuck Gormley

For more information:

Richard T. Penson, MD, MRCP, can be reached at penson.richard@mgh.harvard.edu.

Maurie Markman, MD, can be reached at maurie.markman@ctca-hope.com.

For additional reading:

USPSTF. Draft evidence review for ovarian cancer: screening; Available at: www.uspreventiveservicestaskforce.org/Page/Document/draft-evidence-review166/ovarian-cancer-screening1. Accessed on July 18, 2017.

Maurie Markman
Richard T. Penson

The U.S. Preventive Services Task Force today released a draft recommendation statement and evidence review on ovarian cancer screening that is consistent with its final recommendation in 2012.

The USPSTF’s “D” recommendation advises against screening for ovarian cancer in women who have no signs or symptoms, noting that screening does not decrease the number of deaths from ovarian cancer and may lead to women having unnecessary surgery.

The draft recommendation does not apply to women at high risk for ovarian cancer, such as women with known BRCA1 and BRCA2 mutations.

Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America and a HemOnc Today Editorial Board Member, said he “completely” agrees with the draft recommendation.

“There is no value, and the potential for harm — anxiety, unnecessary invasive diagnostic testing — outweighs the benefit,” Markman told HemOnc Today. “Standard practice has been and continues to be that there is no role for ovarian cancer screening in women without a known genetic/familial risk.”

Ovarian cancer is the eighth most common cancer and fifth most common cause of cancer death among U.S. women. However, false-positive tests can lead to unnecessary surgeries to remove one or both ovaries and the fallopian tubes.

“The current screening tests do not do a good job of identifying whether a woman does or does not have ovarian cancer,” USPSTF chair David Grossman, MD, MPH, senior investigator at Kaiser Permanente Washington Health Research Institute, said in a statement. “The Task Force hopes that in the future, better screening tests for ovarian cancer will be developed.”

The draft recommendation statement and draft evidence review will be posted for public comment through Aug. 14, 2017.

“I agree with the task force, except in the case of a person with a known germline BRCA mutation prior to prophylactic surgery, typically at 40 years old,” Richard T. Penson, MD, MRCP, associate professor of medicine at Harvard Medical School, told HemOnc Today. “As you might suspect, this draft recommendation will not change what is being done in clinical practice.”

In its draft recommendation statement, the USPSTF noted the age-adjusted incidence of ovarian cancer from 2010 to 2014 was 11.4 cases per 100,000 women per year, and that most women with a positive screening test are found to not have ovarian cancer.

The USPSTF also reported that screening with transvaginal ultrasound (TVUS), testing for the serum tumor marker cancer antigen-125 (CA-125), or a combination of both, does not reduce the number of deaths from ovarian cancer.

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Penson said he recommends biannual CA-125 and TVUS screenings if there is a family history of cancer at a very young age.

“There are those who claim that an algorithm focusing on the rate of rise of CA-125 in an individual woman over time versus an absolute level to be considered ‘abnormal’ may be more effective as an ovarian cancer screening strategy,” Markman said. “To date, the data supporting this hypothesis remains weak.”

In a separate recommendation statement, the USPSTF advises that women with a family history that indicates they are at risk for BRCA1 or BRCA2 mutations be referred for genetic counseling and, if indicated, genetic testing.

The most significant recent study on ovarian cancer screening is the U.K. Collaborative Trial of Ovarian Cancer Screening, a randomized controlled trial that compares annual multimodal screening vs. TVUS vs. control in 202,638 women aged 50 to 74 years from 13 centers in the United Kingdom. Researchers diagnosed ovarian cancer in 1,282 (0.6%) of the women — 338 (0.7%) in the multimodal screening group, 314 (0.6%) in the TVUS group, and 630 (0.6%) in the no screening group.

“The best interpretation in a prespecified analysis of death from ovarian cancer, which excluded prevalent cases, showed an overall average mortality reduction of 20% (P = .021),” Penson said. “However, there are three main reasons this hasn’t had any impact. First, mortality reduction was not significant in the primary analysis. Secondly, 2,641 women had to be screened annually for 14 years for each life saved. And, thirdly, the morbidity and mortality of laparotomy for a false-positive remains unacceptable.”– by Chuck Gormley

For more information:

Richard T. Penson, MD, MRCP, can be reached at penson.richard@mgh.harvard.edu.

Maurie Markman, MD, can be reached at maurie.markman@ctca-hope.com.

For additional reading:

USPSTF. Draft evidence review for ovarian cancer: screening; Available at: www.uspreventiveservicestaskforce.org/Page/Document/draft-evidence-review166/ovarian-cancer-screening1. Accessed on July 18, 2017.

    Perspective
    Susan C. Modesitt

    Susan C. Modesitt

    Ovarian cancer is one of the deadliest cancers in the United States, with 22,440 cases and 14,080 deaths expected in 2017. The search for an effective ovarian cancer screening method to improve survival through early detection has long been thwarted.
    The new USPSTF evaluation and recommendations confirm that ovarian cancer screening of normal-risk women does not improve outcomes and, in fact, imparts potentially significant harm due to false-positive screening tests that result in surgery without improving ovarian cancer mortality. The latest USPSTF recommendation reaffirms the consensus of multiple other national organizations — including the FDA, American College of Obstetricians and Gynecologists, and Society of Gynecologic Oncology — that recommend against any screening of normal-risk populations while potentially leaving the door open for screening of women at high risk for ovarian cancer based on inherited genetic predispositions.
    What about ovarian cancer has stymied development of an effective screening paradigm despite overwhelming resources worldwide devoted to the effort? Ovarian cancer misses multiple criteria necessary for diseases that are amenable to successful screening. The first issue is a very low incidence and prevalence of ovarian cancer, which ultimately affects only 1% to 2% of the female population; thus, even a highly sensitive/specific screening test will have relatively poor positive and negative predictive values. Further, it remains unclear if a preclinical, treatable phase of ovarian cancer truly exists or can be detected, and if such detection positively impacts mortality.
    Emerging data have confirmed that ovarian cancer is a much more heterogeneous disease than previously recognized, with multiple likely etiologies. For example, about 65% of high-grade serous “ovarian” cancers likely originate in the fallopian tube. In this scenario, any early detection modalities that rely on radiographic testing — or even serologic testing — may be doomed to failure as dissemination of microscopic cancerous cells occurs prior to the establishment of macroscopic tumor deposits that are radiologically or potentially serologically detectable with current screening regimens. Only time will tell if emerging diagnostics focusing on detection of minute amounts of tumor-related products (eg, cell-free DNA, circulating tumor cells or other changes associated with early carcinogenesis) could ever tip the balance in favor of universal ovarian cancer screening.
    For now, our best strategy to decrease ovarian cancer lethality is to focus continued research efforts on:
    1) Identifying high-risk women who carry an inherited cancer predisposition in order to implement known successful risk-reduction measures that indisputably improve survival, like risk-reducing salpingo-oophorectomy;
    2) Elucidating the myriad pathways leading to ovarian cancer to identify potential novel screening modalities; and
    3) Educating providers about proven effective ovarian cancer risk-reduction measures that are available for all women, like birth control pills for chemoprevention and opportunistic salpingectomies.
    If at all possible, we must focus efforts on ultimately achieving universal ovarian cancer prevention rather than universal ovarian cancer screening.

    References:

    Falconer H, et al. J Natl Cancer Inst. 2015;doi:10.1093/jnci/dju410.

    Jacobs IJ, et al. Lancet. 2016;doi:10.1016/S0140-6736(15)01224-6.

    Modesitt SC. Cancer Screening in Women. In: Alvarez-Secord A and Gehrig P, eds. Gynecologic Oncology, 1st ed. Landes Bioscience; 2009.

    Perets R and Drapkin R. Cancer Res. 2015;doi:10.1158/0008-5472.CAN-15-1382.

    Ring KL, et al. Am J Obstet Gynecol. 2017;doi:10.1016/j.ajog.2017.04.011.

    Siegel RL, et al. CA Cancer J Clin. 2017;doi:10.3322/caac.21387.

    • Susan C. Modesitt, MD, FACS, FACOG
    • High-Risk Breast and Ovarian Cancer Clinic University of Virginia

    Disclosures: Modesitt reports she has no relevant financial disclosures.