In the Journals

Serial biomarker levels may better detect epithelial ovarian cancer

Monitoring changes in annual serum cancer antigen 125 levels could detect twice the number of women with invasive epithelial ovarian cancer compared with standard screening strategies, according to study results.

Prior screening trials for ovarian cancer used a fixed threshold of greater than 35 U/mL serum cancer antigen 125 (CA-125) levels to detect potential abnormalities, according to a press release. However, researchers noted that single biomarker thresholds do not account for other possible risk factors that could lead to disease detection and treatment.

“There is currently no national screening program for ovarian cancer, as research to date has been unable to provide enough evidence that any one method would improve early detection of tumors,” Usha Menon, MD, FRCOG, professor of gynecological cancer at the Institute for Women’s Health, University College London, said in a press release.  “These results are therefore very encouraging. They show that use of an early detection strategy based on an individual’s CA-125 profile significantly improved cancer detection compared to what we’ve seen in previous screening trials.”

Menon and colleagues employed a multimodal strategy to screen 46,237 women aged 50 years or older enrolled in the U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Researchers interpreted annual blood tests using a Risk of Ovarian Cancer Algorithm (ROCA), which estimates an individual’s risk for ovarian cancer based on their serial CA-125 profile compared with those of cases and controls.  

Women considered normal risk returned to the annual screening population, whereas intermediate-risk women received additional CA-125 testing and women considered high risk received additional screening and a transvaginal ultrasound. Researchers performed surgical evaluations on women persistently at elevated risk.

The women underwent 296,911 incidence screens between June 2002 and December 2011, which equated to a median number of seven screens per participant (range, 1-10; interquartile range [IQR], 6-8). Median follow-up from most current incidence screen to cancer registration update was 3.1 years (IQR, 2.8-4.1).

Ten percent of annual screens resulted in a recommendation for a repeat screen, and 1.1% of screens prompted clinical evaluation.

Among 640 women who underwent investigative surgery, 133 received invasive epithelial ovarian or tubal cancer diagnoses (stage II, 82%). An additional 22 cases of interval invasive epithelial ovarian or tubal cancer occurred within 1 year of screening.

Median CA-125 serum level was 33.6 U/mL (IQR, 0.21-109.2) in women with screen-detected cancer at the time of the relevant annual screen. Sixty-three women (47.4%) had CA-125 levels greater than 35 U/mL, and the other seventy women (52.6%) had CA-125 levels at or below normal range (≤ 35 U/mL). Only one woman with an interval cancer demonstrated elevated serum levels.

The sensitivity for detection of invasive epithelial ovarian or tubal cancers of the multimodal strategy was 85.8% (95% CI, 79.3-90.9) and the specificity was 99.8% (95% CI, 99.8-99.8).

ROCA alone accounted for 86.5% (n = 134) of diagnoses and had a screening sensitivity of 87.1% (95% CI, 80.8-91.9) and specificity of 87.6%.

Researchers compared these data with sensitivity of using a fixed cut-off rather than serial data. A fixed CA-125 cutoff of greater than 35 U/mL would have resulted in a cancer identification rate of 41.3%, a fixed cutoff of greater than 30 U/mL had an identification rate of 48.4%, and a fixed cutoff of greater than 22 u/mL resulted in an identification rate of 66.5%.

Area under the curve for ROCA was significantly higher than the single biomarker threshold (0.91 vs. 0.86; P = .002).

Data from the trial related to the efficacy of ultrasounds in detection and the effect of screenings on ovarian cancer death are expected later this year, the researchers reported.

“The numbers of unnecessary operations and complications were within acceptable limits and we were able to safely and effectively deliver screening for over a decade across 13 [National Health Service] Trusts,” Menon said. “While this is a significant achievement, we need to wait until later this year when the final analysis of the trial is completed to know whether the cancers detected through screening were caught early enough to save lives.” – by Cameron Kelsall

Disclosure: Menon reports stock ownership in Abcodia. Please see the full study for a list of all other authors’ relevant financial disclosures.

Monitoring changes in annual serum cancer antigen 125 levels could detect twice the number of women with invasive epithelial ovarian cancer compared with standard screening strategies, according to study results.

Prior screening trials for ovarian cancer used a fixed threshold of greater than 35 U/mL serum cancer antigen 125 (CA-125) levels to detect potential abnormalities, according to a press release. However, researchers noted that single biomarker thresholds do not account for other possible risk factors that could lead to disease detection and treatment.

“There is currently no national screening program for ovarian cancer, as research to date has been unable to provide enough evidence that any one method would improve early detection of tumors,” Usha Menon, MD, FRCOG, professor of gynecological cancer at the Institute for Women’s Health, University College London, said in a press release.  “These results are therefore very encouraging. They show that use of an early detection strategy based on an individual’s CA-125 profile significantly improved cancer detection compared to what we’ve seen in previous screening trials.”

Menon and colleagues employed a multimodal strategy to screen 46,237 women aged 50 years or older enrolled in the U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Researchers interpreted annual blood tests using a Risk of Ovarian Cancer Algorithm (ROCA), which estimates an individual’s risk for ovarian cancer based on their serial CA-125 profile compared with those of cases and controls.  

Women considered normal risk returned to the annual screening population, whereas intermediate-risk women received additional CA-125 testing and women considered high risk received additional screening and a transvaginal ultrasound. Researchers performed surgical evaluations on women persistently at elevated risk.

The women underwent 296,911 incidence screens between June 2002 and December 2011, which equated to a median number of seven screens per participant (range, 1-10; interquartile range [IQR], 6-8). Median follow-up from most current incidence screen to cancer registration update was 3.1 years (IQR, 2.8-4.1).

Ten percent of annual screens resulted in a recommendation for a repeat screen, and 1.1% of screens prompted clinical evaluation.

Among 640 women who underwent investigative surgery, 133 received invasive epithelial ovarian or tubal cancer diagnoses (stage II, 82%). An additional 22 cases of interval invasive epithelial ovarian or tubal cancer occurred within 1 year of screening.

Median CA-125 serum level was 33.6 U/mL (IQR, 0.21-109.2) in women with screen-detected cancer at the time of the relevant annual screen. Sixty-three women (47.4%) had CA-125 levels greater than 35 U/mL, and the other seventy women (52.6%) had CA-125 levels at or below normal range (≤ 35 U/mL). Only one woman with an interval cancer demonstrated elevated serum levels.

The sensitivity for detection of invasive epithelial ovarian or tubal cancers of the multimodal strategy was 85.8% (95% CI, 79.3-90.9) and the specificity was 99.8% (95% CI, 99.8-99.8).

ROCA alone accounted for 86.5% (n = 134) of diagnoses and had a screening sensitivity of 87.1% (95% CI, 80.8-91.9) and specificity of 87.6%.

Researchers compared these data with sensitivity of using a fixed cut-off rather than serial data. A fixed CA-125 cutoff of greater than 35 U/mL would have resulted in a cancer identification rate of 41.3%, a fixed cutoff of greater than 30 U/mL had an identification rate of 48.4%, and a fixed cutoff of greater than 22 u/mL resulted in an identification rate of 66.5%.

Area under the curve for ROCA was significantly higher than the single biomarker threshold (0.91 vs. 0.86; P = .002).

Data from the trial related to the efficacy of ultrasounds in detection and the effect of screenings on ovarian cancer death are expected later this year, the researchers reported.

“The numbers of unnecessary operations and complications were within acceptable limits and we were able to safely and effectively deliver screening for over a decade across 13 [National Health Service] Trusts,” Menon said. “While this is a significant achievement, we need to wait until later this year when the final analysis of the trial is completed to know whether the cancers detected through screening were caught early enough to save lives.” – by Cameron Kelsall

Disclosure: Menon reports stock ownership in Abcodia. Please see the full study for a list of all other authors’ relevant financial disclosures.