Colorectal Cancer: Screening Options and Potential Emerging Role for Pharmacists

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. This year alone, more than 150,000 new cases of CRC will be diagnosed, and more than 53,000 people will die from a disease that is not only treatable when discovered early but also preventable.

Yet, 1 in 3 people are not up-to-date with CRC screening. The COVID-19 pandemic impacted screening by causing canceled or delayed colonoscopies and postponed physician visits, which should have included recommendations for CRC screenings. Additional screening barriers include disparities in care for underserved populations, lack of awareness, fear or concerns about the colonoscopy procedure or required prep for it, lack of recommendations by health care providers, or insurance issues.

Delaying regular screenings or follow-up on abnormal results for these reasons or barriers could mean CRC is not detected until later stages. Unfortunately, nearly 63% of newly diagnosed patients have advanced CRC, which requires more aggressive treatment and reduces the associated 5-year survival rate to as low as 14%. In contrast, if detected early, patients with CRC have a 5-year survival rate of 92%.

The Pharmacist’s Role: Earlier Screening is the Key to Prevention

Access, convenience, and options

Pharmacists hold a trusted position in their communities and patients see their pharmacists more than twice as often as their primary care providers. In addition, patients visit the pharmacy 35 times a year compared to just 4 visits to see medical providers.

The pharmacists’ role in providing direct patient care and impacting health outcomes holds great potential. Today, pharmacists are perceived as a partner in care and can influence adherence to provider-prescribed treatment plans, such as prescription fulfillment and screenings.

One example is the Kentucky Board of Pharmacy’s 2021 approval of the pharmacy protocol that specifies the criteria and procedures for a pharmacist to provide education and information specific to CRC. As part of the protocol, when appropriate, a pharmacist may initiate noninvasive, stool-based CRC screening with a customer by distributing a take-home fecal immunochemical test (FIT) or stool DNA test (e.g., sDNA-FIT)—making it even easier for patients to follow their health care providers’ recommended screening guidelines.

These patients can now take care of their CRC screening at their local pharmacy—the same place they go for a flu shot, COVID-19 vaccination, or regular prescriptions. The protocol was approved following advocacy efforts to remove barriers to screening in Kentucky by the Colon Cancer Prevention Project and Fight Colorectal Cancer (Fight CRC).

CRC is treatable and preventable when caught early. Providing people with additional options to get screened saves more lives, a position that resonates with the American Association of Colleges of Pharmacy’s Oath of the Pharmacist vow. Removing barriers to access and opening paths to prevention and detection align with the pharmacists’ promise to advance health equity and embrace and advocate for changes that improve patient care.

Most CRC develops from precursor polyps, the most common neoplastic finding in colonoscopy. Colonoscopy has a 3.5% false-negative rate for detecting CRC, but its significant advantage is the ability to remove premalignant lesions discovered during the screening or surveillance procedure.

The potential for these polyps to become malignant correlates with the polyp's type, size, and degree of dysplasia. Advanced adenomas (AA) are considered the most concerning and high-risk type of polyp. Secondary prevention of CRC involves screening at-risk populations to detect and remove early-stage cancers and adenomatous polyps.

The American Cancer Society and the United States Preventative Task Force (USPSTF) recommend secondary prevention in average-risk individuals, including beginning screening at age 45. While the USPSTF does not specify the advantages of any screening strategy, colonoscopy remains the gold standard for CRC screening and detecting colorectal lesions. Despite this, compliance with colonoscopy is not optimal due to discomfort and unpleasant preparation procedures.

Limitations include the risk of complications, cost, and access. By contrast, the ideal CRC screening method would be low-cost and noninvasive, with good patient acceptance and high sensitivity and specificity values.

FIT, which detects hemoglobin in the stool, has been used with some success. FIT has a low sensitivity for colon adenomas (66–80% sensitivity for CRC) and poor precursor lesion detection rates (only 10–28% for AA). But even with an excellent specificity (93–95%), the aggregate metrics limit its effectiveness.

It is well known that not all colorectal adenomas will progress to CRC. Increasing the sensitivity for high‐risk adenomas can raise the detection rates for these lesions. Therefore, it is imperative to explore alternative or complementary strategies with the potential to improve CRC screening performance, especially for the detection of cancers at their early stages and AA.

Identifying novel protein biomarker panels with higher sensitivities for high‐risk adenomas and CRC than FIT will improve current screening strategies. These additional biomarkers could aid in enhancing the sensitivity for early detection of CRC. The development of tests performed on stool samples that see indirect signs of CRC, such as occult blood or genetic and epigenetic alterations related to the presence of CRC, has been achieved with good results.

One attractive category of molecules considered for stool-based CRC screening is RNA. RNA-based biomarkers can be measured in small sample volumes with simple economic assays. Combining specific stool‐based RNA biomarkers outperform hemoglobin and DNA in detecting molecularly defined high‐risk adenomas.

Host mRNA has also been investigated in stool as a potential biomarker. In one study, a multitargeted stool RNA (mt-sRNA) assay combined 8 stool-derived eukaryotic RNA (seRNA) biomarkers, patient demographic information (smoking status), and a FIT to detect colorectal neoplasia.¹

In stool samples using a robust predictive model, the test attained a 95% sensitivity for CRC, 62% sensitivity for AA, 25% sensitivity for other non-AA, 80% specificity for hyperplastic polyps, and 85% specificity for no findings on a colonoscopy. This study demonstrated that specific RNA expression alterations in colon tissue prove valuable in early CRC diagnosis and potentially prognosis prediction and targeted therapy. More recently, a multitarget mRNA assay demonstrated a significant strengthening of both sensitivity and specificity for CRC detection.

In summary, the cost-benefit of such new methods for the health care system may encourage changes to current screening recommendations. The high cost of CRC treatment, particularly for more advanced diseases, is considered to improve the cost-effectiveness of CRC screening. Furthermore, higher threshold costs for a biomarker test that could significantly increase the sensitivity of AA detection while maintaining reasonable specificity would likely be cost-effective relative to currently available noninvasive tests.

Reference

1. Barnell EK, Kang Y, Barnell AR, et al. Multitarget stool RNA test for noninvasive detection of colorectal neoplasias in a multicenter, prospective, and retrospective cohort. Clin Transl Gastroenterol. 2021;12(5):e0036.

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