Detecting and Diagnosing Cancer

The early detection and diagnosis of cancer usually increases the chances of successful treatment. In addition, treatments for early cancer are often less complex and less expensive than treatments for more-advanced disease, sparing patients and their families greater hardship. However, too many cancers are still diagnosed at late stages, when effective treatment and long-term survival may not be possible.

Another promise of early detection is the identification of precancerous tissue abnormalities that are destined to become life-threatening cancers, providing an opportunity for even earlier intervention to prevent cancer from developing altogether. Similarly, the ability to accurately identify precancerous tissue abnormalities and early cancers that will not progress to potentially fatal malignancies would also be beneficial, potentially sparing many patients and their families the physical and financial harms of unnecessary treatment.

As has been true for many years, NCI continues to support a broad portfolio of research aimed at improving the early detection and diagnosis of cancer and its precursors. Two major goals of this research are increasing the dissemination of proven methods of detection and diagnosis and developing new and improved methods that are more accurate and of greater value clinically than those available today. Another goal is to produce technologies and tests that are efficient and cost-effective and that can be used in all resource settings. Ultimately, this work should increase the number of cancers for which we have effective screening tests.

Progress in Detecting and Diagnosing Cancer

NCI funding has contributed to many major advances in cancer detection and diagnosis. For example, NCI supported research and consensus development conferences that established the effectiveness of screening mammography in detecting early breast cancer and that provided recommendations for mammography’s use in routine clinical practice. In addition, NCI sponsored the ASCUS-LSIL Triage Study (ALTS), which, in 2003, led to the first Food and Drug Administration (FDA) approval of a human papillomavirus (HPV) test for cervical cancer screening.

Moreover, NCI sponsored large randomized clinical trials that demonstrated the effectiveness of two colorectal cancer screening tests (fecal occult blood test and flexible sigmoidoscopy) and of lung cancer screening with low-dose helical computed tomography in reducing mortality from colorectal cancer and lung cancer, respectively.

Examples of recent NCI-funded accomplishments in cancer detection and diagnosis are described below.

Refining the Liquid Biopsy

The conclusive identification of circulating tumor cells in the blood of patients with cancer more than 60 years ago forecasted the development of the liquid biopsy. In this procedure, cancer cells or their components, such as DNA, can be detected through minimally invasive means in samples of blood or other bodily fluids. Advances in biomedical technology are now bringing the promise of the liquid biopsy for early cancer detection closer to the clinic.

In 2018, a consortium of international and NCI-supported researchers and their colleagues reported the development of CancerSEEK, a blood test that measures the levels of 8 proteins and the presence of mutations in 16 cancer-related genes to detect early-stage cancers. In a retrospective analysis, when this test was applied to blood samples from 1,005 patients with 8 different types of nonmetastatic cancer, the presence of cancer was correctly identified 70% of the time. For five of the eight cancer types for which no screening tests are currently available (ovary, liver, stomach, pancreas, and esophagus), the sensitivity of detecting cancer ranged from 69% (esophageal cancer) to 98% (ovarian cancer).

NCI is supporting research to develop additional liquid biopsy tests for the early detection of cancer. Because all cancer screening tests have both benefits and harms (e.g., false-positive and false-negative test results), it will be critical to determine in prospective studies that the benefits of any test greatly outweigh the potential harms before it is introduced clinically.

Improving Prostate Cancer Diagnosis

The routine collection of prostate tissue through the rectum (prostate biopsy) has led to the increased detection of low-grade cancers, which may not need treatment, and an increase in biopsy-related, potentially life-threatening bacterial infections. Reducing the biopsy rate for men who ultimately prove to have benign conditions or low-grade cancer would therefore be desirable.

In 2018, NCI intramural and NCI-funded extramural researchers reported that a risk prediction model based on multiparametric magnetic resonance imaging (mpMRI) of the prostate, in which specific characteristics of prostate tissue are highlighted to distinguish between healthy and unhealthy tissue, combined with prostate biopsies guided by standard MRI and transrectal ultrasound imaging could reduce the number of unnecessary biopsies by more than a third while still detecting nearly 90% of clinically significant cancers (i.e., those that need treatment).

These researchers and other NCI-funded investigators are studying ways to further refine this approach and to identify biomarkers that can distinguish potentially lethal prostate cancers that need to be treated from low-risk cancers that may not need treatment.

Researchers are studying ways to distinguish potentially lethal prostate cancers that need to be treated from low-risk cancers that may not need treatment.

Enhancing Cancer Detection in Dense Breasts

The ability of mammography to detect breast cancer in women with dense breasts, which have substantially more glandular and connective tissue than fatty tissue, is lower than that for women with predominantly fatty breasts. Therefore, new technology is needed to improve breast cancer detection in women with dense breasts.

In 2004, NCI’s Small Business Innovation Research program began supporting the development of LumaGEM, a molecular breast imaging (MBI) technology that uses small amounts of the radioactive compound 99mTc-sestamibi, which localizes to tumors, to detect breast cancer in women with dense breasts. In 2016, researchers showed that LumaGEM, which has been approved by FDA as an adjunct to mammography, correctly identified 11 invasive tumors that had been missed by standard mammography in a retrospective study involving 1,696 women.

Read about how Kristin from Florida had her breast cancer detected by MBI. NCI continues to support other avenues of research to improve breast cancer detection in all women.

LumaGEM Xray
Credit: Reprinted with permission from AJR Am J Roentgenol ©2018.
Breast cancer detection by molecular breast imaging (MBI). Left: A digital screening mammogram image that was interpreted as negative. Right: MBI showed intense uptake of the radiotracer at the site of a tumor.

Accelerating Cervical Cancer Control

A long-standing issue in reducing the incidence and mortality of cervical cancer is how to make effective cervical screening available in regions or countries that have limited health care resources. Another issue is how to avoid unnecessary follow-up procedures in screened women with precancerous cervical tissue abnormalities that have a low risk of progressing to cancer.

Although human papillomavirus (HPV) testing can sensitively detect precancerous cervical tissue, another “triage” step is needed to identify women with tissue abnormalities that have the highest risk of progressing to cancer. These women, who are infected with the highest-risk HPV types and/or have severely abnormal cervical cells, are usually referred for additional medical tests, including a close examination of the cervix (colposcopy) and, possibly, a biopsy.

To address these issues, a research group led by NCI intramural investigators developed an automated approach that combines HPV testing, HPV typing, and computer-interpreted cervical cell analysis for screening and triage. This approach should eventually be adaptable for widespread use, including in regions and countries that have limited access to expert medical services. The researchers are also investigating the inclusion of specific biomarkers in their triage protocol to further improve its performance.

Opportunities for Greater Progress

Improvements in genomic, proteomic, and imaging technologies are presenting new opportunities for major progress in cancer detection and diagnosis. These advances have the potential to increase our ability to identify and characterize tumor cells and other biomarkers in bodily fluids and are enabling more precise imaging. Research areas poised for greater progress are described below.

Identifying and Validating Biomarkers for Early Cancer Detection and Diagnosis

Recent advances in identifying biomarkers have improved early cancer detection and diagnosis. However, there is a critical need for additional biomarkers to optimize the care of patients with cancer and at-risk individuals. NCI supports several programs to promote research in this area.

There is a critical need for additional biomarkers to optimize the care of patients with cancer and at-risk individuals.

For example, the Consortium for Molecular Characterization of Screen-Detected Lesions, currently led by investigators at eight institutions, supports research on the molecular and cellular features of precancers and early cancers detected through screening tests. The goal of this program is to enable doctors to distinguish precancers or cancers that will not become life-threatening from aggressive cancers that need to be treated.

Another program is the Alliance of Glycobiologists for Detection of Cancer, which supports eight laboratories conducting research on the cancer-related changes in complex carbohydrates (sugars) in cells to identify and validate biomarkers for early cancer detection.

A third program is the Early Detection Research Network, a public–private partnership that provides infrastructure and resources vital to the discovery, development, and validation of cancer-related biomarkers. Accelerating research in this area is a key part of our efforts to reduce the morbidity and mortality of cancer.

Developing Cancer Imaging Technologies

Medical imaging, with traditional x-rays, ultrasound, MRI, computerized tomography (CT), and positron emission tomography (PET), plays a central role in the detection and diagnosis of cancer. Each of these methods, however, has limitations, and ongoing research is investigating ways to improve their utility or develop entirely new technologies for cancer detection.

Ongoing research is investigating ways to develop entirely new technologies for cancer detection.

One newer approach, called digital tomosynthesis, allows 3-dimensional images to be constructed from multiple x-rays taken at different angles. This approach is currently being evaluated in NCI’s Tomosynthesis Mammographic Imaging Screening Trial (TMIST) for the early detection of breast cancer.

Other approaches under investigation for which additional resources will enable greater progress include combining current imaging methods with computerized image analysis (i.e., artificial intelligence/machine learning); the molecular imaging of cancer biomarkers; the use of nanoparticles to detect and image cancer cells; microwave imaging; and photoacoustic imaging, in which laser pulses are used to generate ultrasonic waves in tissues that can be converted into images.

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