Monitoring Treatment Response in Colorectal Cancer

Despite multidisciplinary and multimodality approaches to the management of colorectal cancer (CRC), there is an increasing need to define how clinicians monitor response to novel therapies in this patient population. Monitoring how disease responds to therapy requires standardization to optimize patient outcomes. However, how to best to achieve this has been debated among clinicians treating these patients. Furthermore, there may not be just 1 best approach.

To examine the current approaches and challenges to monitoring response of CRC, researchers conducted a literature review of studies using PubMed and OVID library. The investigators focused specifically on patients with stage 2 and stage 3 rectal cancer who undergo neoadjuvant chemoradiation therapy (nCRT) and patients with metastatic CRC. They also discussed current strategies for therapy and reviewed the data regarding modalities for monitoring response [J Cancer. 2014;5(1):31-43].

In an interview with First Report Managed Care, Scott R. Steele, MD, department of surgery, Madigan Army Medical Center, Tacoma, Washington, coauthor of the study, said what is significant about the study’s findings is that, “Overall, we are doing an excellent job incorporating these studies to determine how a patient is doing, predicting response or recurrent disease, and there are tests on the horizon that may improve this ability even further.”

Colon Cancer Therapy

Current treatment for colon cancer therapy remains primarily surgical. For stage 1 through stage 3 colon cancer, resection to R0 status along with a proper lymphadenectomy, is the mainstay of therapy. Patients with stage 3 and select stage 2 disease may also benefit from adjuvant chemotherapy, although neoadjuvant therapy has little role for localized, resectable colon cancer. The researchers noted that exceptions to this treatment strategy occur in patients presenting with locally advanced near-obstructing colon cancer in which a full evaluation has not been performed, or in patients with known metastases that are potentially resectable.

Although data are limited on this cohort, researchers highlighted a retrospective study of 33 patients with potentially resectable, nonmetastatic, locally advanced adherent colon cancer who had received nCRT following multivisceral resection. After 3 years, these patients had an overall survival of 85.9% and disease-free survival of 73.3%. Considering the results, Dr. Steele and colleagues said that it may be feasible and beneficial to treat locally advanced adherent colon cancer with neoadjuvant instead of traditional initial primary resection. The findings also underscore the need to identify patients with an appropriate response to allow for clear margins.

Metastatic Colon Cancer Therapy

Treatment of this cancer primarily consists of systemic chemotherapy with FOLFOX/FOLFIRI (5 FU, leucovorin, oxaliplatin versus 5FU, leucovorin, and irinotecan), and in select cases, resection of the primary and/or metastatic lesion. Historically, metastatic cancer has been treated only with chemotherapy and biologics, with resection and diversion reserved for patients who became obstructed, perforated, or bled.

Currently, there appears to be good data showing improved survival and quality of life with resection of the primary tumor before symptoms, even in patients with metastatic disease, according to the researchers. Treatment of metastatic colon and rectal cancer also depends on whether the metastases are widespread, involve multiple organs, and are potentially resectable.

Rectal Cancer Therapy

Treatment of rectal cancer has evolved. With advances in stapler technology and operative technique, a better understanding of the margin necessary to ensure a better balance between oncologic outcome and functional outcomes, sphincter-sparing surgery has been increasingly used for the treatment of distal cancers of the rectum.

Studies have validated the use of neoadjuvant chemoradiation in the treatment of American Joint Cancer Committee stage 2 and stage 3 rectal cancer, as well as the use of chemotherapy for palliation and cure in lymph node-positive and metastatic colon cancer. After reviewing the studies, the researchers recognized that nCRT provides not only an improved local control and sphincter-sparing ability, but also similar quality of life and overall survival, making it the preferred treatment option for locally advanced rectal cancer lesions.

Modalities for Monitoring Tumor Response

Pathologic examination of the post treatment surgical specimen is the gold standard for monitoring response to therapy. Researchers also reviewed the data regarding modalities for monitoring response, including imaging and serum testing.

Digital rectal examination (DRE) is routinely used to gauge the size of the lesion, presence of ulceration, location of the lesion relative to the anal verge, functional status of the sphincter complex, and percentage of the lumen occluded. The test is not without limitations. The researchers highlighted a study that showed DRE underestimated the extent of rectal cancer response after nCRT in 78% of patients, therefore limiting its utility in this role. However, DRE is a risk-free simple test that can be performed repeatedly to assess tumor response.

Carcinoembryonic antigen (CEA) serum test is currently the most widely used tumor marker for colon cancer. The researchers determined that CEA is beneficial when used in conjunction with imaging modalities for determining recurrence. This test can also be used in specific circumstances as a marker of prognosis and tumor response for patients with rectal cancer who initially have high values that decrease after nCRT. Furthermore, CEA has benefitted patients undergoing systemic therapy for metastatic colon cancer.

The issue of imaging in the staging and recurrence of CRCs has improved over the last 20 years. Computed tomography, positron emission tomography, and magnetic resonance imaging are used to monitor tumor responses throughout the body and employed in different circumstances. Overall, each has been validated in the monitoring of patients with CRC and residual tumors, according to the researchers.

Endoscopy is useful as an adjunct in detecting intralumenal recurrence; however, the researchers noted that it is not beneficial in assessing tumor response outside of the limited information gained by direct examination of intralumenal lesions.

Dr. Steele acknowledged challenges in monitoring treatment responses for CRC patients. “First, it is important that we educate both patients and physicians regarding the need for expectations [in terms of] treatment response and how that may effect changes in treatment,” he said. “Second, due to the limitations in the tests themselves, we may not always know if the changes demonstrated represent residual disease (meriting further work-up or therapy), or benign changes from the tissue and avoid over-treating or subjecting [the patient] to unnecessary testing.”

Study Conclusions

The monitoring of colorectal metastases has undergone few changes in the past decade. However, with improvements in systemic therapy, liver-directed therapy, and with clinicians’ understanding of how to treat the primary tumor, overall survival may continue to increase. On the other hand, changes in how clinicians treat rectal cancer have led to a new age of therapy guidance by imaging and pathology.

“Despite tremendous improvements in overall care of the colorectal cancer patient, we still have a long way to go,” said Dr. Steele.