Clinical Review

GYNECOLOGIC ONCOLOGY

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Four recent studies add to what we understand about screening and prophylaxis for ovarian and breast Ca


 

References

ObGyns perform most of the screening for cancers of the ovary and breast. The first cancer is especially lethal, though rare, and the second is especially feared among women. This update reviews screening guidelines and recent studies that may affect how we detect and prevent ovarian and breast cancers.

Among the findings:

  • In the only multicenter, prospective, randomized, controlled study to date to look at the use of CA-125 and transvaginal ultrasound screening in a low-risk population of postmenopausal women in the United States, researchers found no evidence to suggest a need to revise the present (1996) ovarian cancer screening guidelines of the US Preventive Services Task Force.
  • Using a Markov decision-analysis model, investigators explored the health effects of prophylactic bilateral salpingo-oophorectomy in women at average risk of ovarian cancer undergoing hysterectomy. They found that removing the ovaries may decrease overall survival.
  • Investigators found the opposite to be true in women with BRCA1 or BRCA2 mutations. Prophylactic bilateral salpingo-oophorectomy greatly reduced the overall mortality rate, as well as the risk of ovarian and breast cancer.
  • In a prospective cohort study of BRCA mutation carriers with no history of breast cancer who underwent prophylactic oophorectomy, researchers found the short-term use of hormone replacement therapy to be safe, with no loss of protection against breast cancer.

No need to revise screening guidelines for ovarian cancer

Buys S, Partridge E, Greene M, et al; for the PLCO Project Team. Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial. Am J Obstet Gynecol. 2005;193:1630–1639.

The need to identify a marker for the early detection of ovarian cancer is especially urgent, given that approximately 75% of women with the cancer present with late-stage disease. Because the disease is rare, finding a cost-effective screening test with good sensitivity and very high specificity (to decrease too many false-positive results) will be challenging.

So far, no prospective, randomized studies of any ovarian cancer screening modality have demonstrated a decrease in mortality—the gold standard of efficacy for any screening test. Therefore, the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer trial is a critical study—it is the only multicenter, prospective, randomized, controlled study in the United States to tackle the question of whether CA-125 and transvaginal ultrasonographic (US) screening will be effective in a low-risk population of postmenopausal women aged 55 to 74.

In this large study, 1 arm underwent ovarian cancer screening with both modalities and the other arm underwent no such screening.

This study reports on baseline, or ‘prevalent,’ cancers

This preliminary report does not comment on the efficacy of ovarian cancer screening; data on the effect of repeated annual screens on detection rates and mortality will become available over the next several years.

Rather, the purpose of this preliminary report was to detail the baseline ovarian cancer screening tests of the 39,115 women randomized to the intervention arm from November 15, 1993, to December 13, 2001. These results describe “prevalent” cancers—that is, cancers that are present on the first screen. The more important information about efficacy of screening will come over the next several years, as “incident” cancers develop.

Roughly 6% of women had at least 1 abnormal finding at baseline

Among 28,506 women with results for both baseline tests, 1,706 had at least 1 abnormal finding:

  • 1,338 had an abnormal transvaginal US scan
  • 402 had an abnormal level on the CA-125 test
  • 34 had abnormalities in both tests
  • 29 malignant neoplasms were identified in this population, 20 of them invasive.

When combined, CA-125 and transvaginal ultrasonography had good positive predictive value

In general, a positive predictive value (PPV) of more than 10% (ie, 10 surgeries to detect 1 cancer) is considered reasonable justification for a screening test. In the PLCO trial, the PPV was 4% for CA-125 alone (16 neoplasms in 402 positive screens), 1.6% for transvaginal ultrasonography alone (22 neoplasms in 1,338 positive screens), and 26.5% if both tests were abnormal (9 neoplasms in 34 positive screens).

When tumors of low malignant potential were excluded, the PPV was 3.7% for an abnormal CA-125, 1.0% for an abnormal transvaginal sonogram, and 23.5% if both tests were abnormal. A PPV of 23.5% for both tests is fairly good (ie, approximately 4 surgeries to detect 1 cancer). However, if only women in whom both screening tests were abnormal went to surgery, 12 of 20 invasive cancers would be missed.

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