Early detection research funded by the NCI's Division of Cancer Prevention has positively steered both public health and clinical outcomes, and set the stage for findings in the next generation of research.
"The National Lung Screening Trial (NLST) was the first randomized study ever to show that a screening test, the low-dose helical CT scan of the chest, could reduce the risk of death in heavy current and former smokers from lung cancer," notes Division Director Barry Kramer, MD (pictured right). Based chiefly on the NLST results involving over 53,000 participants, the US Preventive Services Task Force (USPSTF) recommended that high-risk people be offered a low-dose helical CT scan screening for lung cancer.
Earlier in the division's history, the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) was conducted over 13 years with 155,000 men and women. It continues in follow up through 2015. "The PLCO showed there was not a net benefit, and probably a net harm, to routine screening for prostate cancer," Dr. Kramer said. The USPSTF in 2012 recommended against routine prostate cancer screening in all men based in large measure on the PLCO results.
In the three other study arms, the PLCO trial showed that: chest x-ray does not reduce the risk of death from lung cancer; flexible sigmoidoscopy does substantially reduce the risk of dying of colorectal cancer in the general population; and screening for ovarian cancer with the marker CA125 and transvaginal ultrasound can cause harm and does not reduce cancer deaths.
Data and Specimens
Both of these large trials collected important information about the participants before they were diagnosed with cancer, and this data is already being used in other research. "In the PLCO, we established a biorepository (Cancer Data Access System (CDAS)) of specimens collected from participants, which offers the world's largest characterized cohort of patients who were actively screened for cancer; it's a national resource for all investigators who want to apply for its use in their own studies," said Dr. Kramer.
Accessing Data and Specimens
Researchers who want to use PLCO data and specimens can do so with or without additional NCI funding: CDAS provides data at no cost and the Etiology and Early Marker Studies (EEMS) can provide access to samples for approved projects. To secure funding in addition to approval, researchers can submit applications to the Funding Opportunity Announcement, "Utilizing the PLCO Biospecimens Resource to Bridge Gaps in Cancer Etiology and Early Detection Research," PAR-13-036 (U01)
Studies of biological markers of cancer and cancer risk are also the focus of the Division, mainly through the Early Detection Research Network (EDRN). Over the past few years, the Food and Drug Administrations approved five biomarkers from EDRN. These markers are useful for clinical decision-making in the early stages of prostate and ovarian cancer, and for the detection of liver tumors in people who are at high risk of liver cancer.
Five FDA Approved Diagnostic Tests from EDRN
- %[-2]proPSA – Reduces the number of unnecessary initial biopsies in men with elevated PSA levels.
- PCA3 – Guides repeat biopsy decisions in men at increased risk of prostate cancer.
- OVA1 – Combination biomarker test estimates the risk for ovarian cancer in women with an adnexal mass.
- ROMA (Risk of Ovarian Malignancy) – Test and algorithm estimate the risk of ovarian cancer in women with a pelvic mass.
- DCP and AFP-L3 – Assesses the risk of developing hepatocellular carcinoma.
Because of these enhancements in finding cancer, there has been a growing awareness of the problem of overdiagnosis that is associated with most, if not all, cancer screening. Although tests may be able to find a cancer, cancers grow at different rates. Some cancers may never cause any problems for a person, but treating those cancers may expose an individual to certain harms. EDRN is trying to identify molecular fingerprints that pinpoint slow-growing, screen-detected tumors and distinguish them from the very fast-growing tumors that need to be treated. The Barrett's Esophagus Translational Research Network (BETRNet), another DCP program, is set up to do that specifically for BE.
Additionally, a new DCP Program Announcement is devoted to overdiagnosis, biological studies to look at the mechanisms of progression of early lesions and studies to look at markers of progressive versus non-progressive tumor behavior (Awards for Research on Imaging and Biomarkers for Early Cancer Detection, PAR-13-317 (P01), PAR-13-318 (P50), PAR 13-176 (U01) and PAR 13-177 (R01)).