Clearer Diagnostics, Improved Chances: The Big-Picture Impacts of Improved Cancer Diagnostic Testing

Detecting cancer early, when it is easier to treat, can improve patient outcomes and save lives. However, current diagnostic testing technologies have pitfalls that impair their ability to detect early-stage cancer. These shortcomings include limitations in sensitivity and specificity, accessibility and invasiveness. The oncology field would greatly benefit from advances emphasizing simple, efficient diagnostic testing that can potentially improve patient access and outcomes.

The role of diagnostics in cancer detection and treatment

As the first step in a patient’s cancer journey, the timing of diagnosis can majorly impact the outcome. Early-stage cancer diagnosis is associated with higher survival rates, better care experiences, lower treatment morbidity and improved quality of life. However, some estimates indicate as many as 50% of patients don’t receive a confirmed diagnosis until their cancer is more advanced and has spread from the original site.

Despite its advantages, achieving a timely diagnosis is an ever-moving target. Implementing screening protocols is an essential contributor to early cancer detection. While screening efforts have been successful with certain types of cancer, an analysis of screening efforts across cancers reveals inherent deficiencies. Ineffective cancer screening protocols can result in diagnosing cancers that are unlikely to spread or be symptomatic in a patient's lifespan (overdiagnosis), delayed diagnosis, false positives or ineffectiveness within specific populations, especially the uninsured. For example, mammograms, the primary screening tool for breast cancer, have limited accuracy in detecting malignancies. Roughly half of women undergoing annual mammograms receive a false-positive result at some point. There is a clear need for improvement in early cancer detection, with the hope that more patients can benefit.

Improving cancer diagnostics: shifting to simplicity and accuracy

Ultimately, overcoming the pitfalls in cancer screening programs to reduce the likelihood of late-stage cancer diagnoses will require time and collaboration across medical, behavioral and social disciplines. However, an opportunity for near-term improvement is the technology used in diagnostic testing.

Imaging techniques, such as mammography or MRI, are sensitive but are not inherently cancer-specific. Imaging may be useful for analyzing morphological changes to tissue but cannot necessarily determine whether these changes are due to cancer. Current molecular-based methods for cancer screening and diagnosis include hereditary marker tests to determine risk, liquid biopsy tests that detect changes in DNA or RNA in blood, and tumor-specific protein biomarker analysis. These methods vary in their level of invasiveness, effectiveness for early-stage cancers, cost and need for specialized equipment or training. Methods that assess circulating tumor DNA (ctDNA) in the bloodstream, for example, are limited because ctDNA is typically present at very low concentrations and may not be shed from all early-stage cancers.

When aiming to improve early cancer detection, it’s worth evaluating current trends in diagnostic research and innovation. Many newer and emerging technologies focus on assessing mutations to genetic material, which can increase patient risk for specific cancers. The insight these technologies provide requires nuanced interpretation because genetic material merely represents instructions for assembling proteins. Though altered proteins created from mutated genetic instructions are responsible for cancer, genetic mutations do not always result in the production of altered proteins. Ultimately, these in-depth methods are valuable, but their nuance and the advanced technology they require make them a cost- and expertise-prohibitive early detection tool.

What if early detection innovation instead focused on methods that are simple, efficient and accurate? For example, cancer-associated alterations in protein structure, glycosylation and protein-protein interactions, as opposed to genetic mutations, are the actual drivers and manifestations of cancer. Methods that assess proteins and, more specifically, the changes to proteins in cancer cases can expand the diagnostic landscape, providing physicians with more manageable, less invasive and easier-to-interpret results. 

Prostate cancer as the case study for improved screening and diagnostics

Prostate cancer, the second most common cancer among American men, is an excellent example of the need for improved, accessible screening and diagnostics. The current standard for prostate cancer screening is a prostate-specific antigen (PSA) test, which looks for elevated levels of the protein biomarker PSA in the blood, as an indicator of prostate disease. If PSA levels are elevated, follow-up testing, such as a biopsy, is performed to establish a cancer diagnosis.

As a cancer screening tool, the PSA test has limitations, particularly its lack of specificity for prostate cancer. Individuals with elevated PSA could have other conditions, like an enlarged prostate, or be on medications that influence PSA. For example, PSA test results are affected by medications used to treat benign prostatic hyperplasia, a common condition in the population of men screened for prostate cancer. Thus, elevated PSA results can come with additional, unnecessary testing. Only 30–45% of men with elevated serum PSA levels (above 4 ng/mL) have prostate cancer diagnosed upon biopsy, and up to 75% of all biopsies are negative for high-grade disease. Biopsy is not only unpleasant and stressful for patients; it also carries the risk of infection and life-threatening sepsis.

The PSA test is also associated with overdiagnosis, specifically detecting cancers unlikely to spread or become symptomatic in the patient's lifespan. In these cases, treatment often causes more harm than benefit. Overdiagnosis is predicted to occur in 20 to 50% of men diagnosed with prostate cancer through standard screening. While screening provides clear benefits, like the decrease in prostate cancer death rates over the last 30 years, there is a need for more advanced tools that provide better risk-to-benefit ratios for patients.

Although genetic tools can be applied to prostate cancer diagnostics, tools that focus on changes to PSA structure are proving to be a promising development. Because they detect changes in structure rather than concentration, these methods aren’t impacted by the same factors that can impact a PSA test. Evidence suggests that tests focusing on changes to the structure of a protein biomarker such as PSA can improve the ability of physicians to identify patients at greatest risk for prostate cancer with equal sensitivity to standards of care while reducing unnecessary biopsies and overdiagnosis.

While early cancer diagnosis provides clear patient benefits, current cancer diagnostic tools often fall short. Prostate cancer isn’t the only case study for more accurate and accessible cancer detection methods. Screening isn’t recommended in the United States for pancreatic, ovarian or testicular cancer due to the lack of specific and sensitive diagnostic methods that provide more benefit than harm. Innovations in the cancer diagnostic space, particularly those focusing on simple but effective diagnostic methodologies, could make cancer screening and early detection more straightforward, improving access and outcomes for patients.

About the author

Dr. Arnon Chait is the chief executive officer of Cleveland Diagnostics. An entrepreneur, scientist and educator, Dr. Chait’s extensive multidisciplinary background spans physics, engineering and bioscience. As CEO, he applies his extensive experience commercializing innovative science to drive forward Cleveland Diagnostics’ vision of bringing early cancer detection into everyday practice with advanced testing that is both simple and affordable.