Dr. Gentry with CRS recently sat down to discuss how genetics play a role in evaluating risk for colon cancer and how CRS is using new technology to treat patients.
Watch the video and read the full article, written by Ted Bosworth, below.
Oncotype DX® Colon Cancer Assay for Stage II Colon Cancer Integrates Colorectal Surgeons into Multidisciplinary Care
By Ted Bosworth
A genomic test for evaluating recurrence risk in stage II colon cancer offers members of the Colon and Rectal Specialists, LTD, Richmond, Virginia, a group surgical practice, an opportunity to more effectively participate in multidisciplinary care.
This genomic tool, called the Oncotype DX® Colon Cancer Assay, reveals the underlying biology of an individual’s tumor and allows surgeons to guide patients to make a more informed choice about their postsurgical treatment. It also promises improved quality of care and has the potential to improve long-term outcomes.
The Oncotype DX Colon Cancer Assay employs a 12-gene panel to create a Recurrence Score® result that quantifies a patient’s individual risk of recurrence following surgery. These scores have repeatedly been shown to correlate with recurrence risk, providing critical information about the potential value of adjuvant therapies.(1,2)
Although resection alone is curative in approximately 70% to 80% of patients with stage II colon cancer,(3) this leaves a substantial proportion of patients with an opportunity to benefit from adjuvant therapy while sparing those who would not.
Prior to the integration of the genomic test, “there was really no consistent pattern among our surgeons on whether or not they were referring the patient to an oncologist after surgery”, observed Cary L. Gentry, MD, Colon and Specialists, LTD, Richmond, Virginia.
Although the members of this surgical group were aware of evidence of the variability in risk of recurrence among patients with stage II colon cancers, it was an internal survey analysis of the practice’s patterns that led the group to question whether there were opportunities to improve care.
In the practice analysis, stage II colon cancers over a recent 1-year period were found to be more common than members of the surgical group had anticipated. Of the 140 resections performed for colon cancer, 38% were stage II. The group was particularly concerned about managing risk of T3 cancers, which represented about 83% of the stage II malignancies.
Although patients with T4 classified tumors were routinely referred to oncologists for counseling about the potential benefits of adjuvant therapy, there was no policy for referrals or counseling for patients with T3 classified tumors. T3 cancers have a recurrence rate of approximately 15% within 5 years.(4) It was this population of patients that concerned the members of the surgical group.
“The evidence suggests that some T3 cancers act like T4 cancers,” explained Dr. Gentry. “This is something that is not well differentiated on the basis of traditional pathological features. We decided we needed to look for tools to stratify these patients by risk of recurrence. With the Oncotype DX® scoring, we are now able to perform that stratification and provide a basis on discussing with patients risk of recurrence.”
The concept that behavior differs among cancer of the same type and stage has been the basis of a profound evolution in oncology. Molecular subtyping is being increasingly performed to direct therapy in a broad number of cancers, including colorectal malignancies. Genome sequencing has demonstrated that driver mutations differ among malignancies affecting a single organ, meaning that the fundamental disease processes in two cancers of the same type and stage can differ. In several cancers, progress in identifying molecular features has led to individualized and highly targeted therapies.
For the surgical group in Richmond, the adoption of the Oncotype DX assay represents a shift in approach. Based on growing recognition that the standard of care is shifting to multidisciplinary management, the members of the group determined that they needed to become more involved in the care of patients after surgery, even when complete resections were successful.
The practice survey revealed that not only are stage II colon cancer patients not being referred in any formalized way to an oncologist after surgery, but that there was inconsistency in management of care even among patients who were referred to an oncologist after surgery, according to Dr. Gentry.
In the current Richmond practice, the Oncotype DX assay is now performed on all stage II colon cancer patients undergoing surgery. Based on the biology of tumors, T3 colon cancers with mismatch repair (MMR) proficient malignancies and high scores have recurrence rates that overlap with T4 malignancies.1 In contrast, patients with MMR deficient T3 malignancies have such low recurrence rates that no benefit is predicted from chemotherapy.
“The evidence suggests that biology matters,” Dr. Gentry said, noting members of his 8-surgeon group concluded that it was no longer appropriate to divorce surgery from “the comprehensive, multidisciplinary approach to cancer care taking place in the twenty-first century.” The Oncotype DX® assay has become an integral tool with the group practice for linking surgical care to the subsequent strategies to improve outcome. In particular, the results of the test provide a basis for surgeons to work with patients in managing risk.
Precision medicine starts with personalized risk assessment. “We want to be in a position of educating our patients about risk of recurrence after surgery, and the Oncotype DX assay allows us to start that conversation,” said Dr. Gentry. The surgical team now participates in individualized or enhanced risk management discussions while arming patients with information that can guide subsequent conversations with an oncologist. The goal is to guide patients to the best possible outcome.
The Oncotype DX assay is straightforward. The test results are displayed in two ways. One provides the estimated recurrence risk over 3 years after surgery alone, and the second provides the estimated rate of recurrence over 5 years if adjuvant chemotherapy is provided. This equips patients and physicians with information essential for a benefit-to-risk calculation derived from further therapy.
“As we looked back on our practice data, we determined that the Oncotype DX assay could afford us the opportunity to have an individualized conversation about recurrence risk. Each patient has to reach their own conclusions about whether to seek adjuvant treatment, but objective information can reassure patients about the decision they reach,” explained Dr. Gentry. “Patients are increasingly well informed and active in their treatment decisions. We feel that it is very important for us, as surgeons, to provide substantive data that can help in judging their treatment options.”
1. Gray RG, Quirke P, Handley K, et al. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol. 2011;29:4611-9.
2. Venook AP, Niedzwiecki D, Lopatin M, et al. Biologic determinants of tumor recurrence in stage II colon cancer: validation study of the 12-gene recurrence score in cancer and leukemia group B (CALGB) 9581. J Clin Oncol. 2013;31:1775-81.
3. Fuzun M, Terzi C, Sokmen S, Unek T, Haciyanli M. Potentially curative resection for locoregional recurrence of colorectal cancer. Surg Today. 2004;34:907-12.
4. O’Connel J Maggard M, KO C. Colon Cancer Survival Rates With the New American Joint Committee on Cancer Sixth Edition Staging. J Natl Cancer Inst2004;96: 1420-5.