One of the greatest challenges facing clinicians in treating cancer is early diagnosis when there is sufficient time to utilize multiple treatment algorithms. Current diagnostic tools, which include various blood marker-based immuonoassays, imaging techniques, and biopsy analysis, provide valuable information but have inherent limitations in sensitivity and specificity, involve invasive scoping, and remain expensive. In addition, these tools remain effective only when the tumor frequency is greater than 1–10%; hence these tests do not provide early detection.
Although currently available tools have played an important role in increasing survival of cancer patients overall, the need for new, advanced diagnostic tests to provide meaningful prognostic information, screen for cancer, detect recurrence early, and monitor progression and therapeutic response in real time still remains significant.
Cancer cells are characterized by genetic mutations that make them reproduce constantly. Completion of the Human Genome Project has lead to a growing understanding of the molecular etiology of cancer development and growth and the mutations that cause them. This has lead to an explosion of companies offering molecular-based tumor diagnostic assays that can quantitatively and qualitatively measure disease predisposition, predict response to therapy, monitor disease progression, and predict recurrence. Growing numbers of specific and costly treatment options with relatively low response rates have created a need for diagnostic tools that aid in correct therapeutic selection and monitoring of treatment response.
The vast majority of traditional cancer drugs do not differentiate among patients who are high responders, poor responders, and nonresponders. Nonresponders are at risk for adverse drug events because of the way they metabolize drugs.
Cancer Care Paradigm
The advent of molecular diagnostics has completely changed the paradigm of cancer patient care. In the future, an oncology patient’s care would be composed of the following tests:
1. Predisposition assay
2. Diagnostic/screening assay
3. Disease-recurrence assay
4. Companion diagnostic to stratify responsiveness to therapy
This new patient-care paradigm will substantially improve patient outcomes and pave the way for personalized, targeted medicine by reducing misdiagnosis and adverse reactions and eliminating unnecessary expensive downstream tests, thereby reducing overall healthcare expenditures.
For example, for women with a medical and family history of breast/ovarian cancer, a positive result on a BRCA1 or 2 test for breast/ovarian cancer means a patient has up to an 85% chance of developing breast cancer, and up to a 55% chance of developing ovarian cancer during the course of her life. These tests can potentially save $100,000 in the cost of caring for her after a diagnosis. Tamoxifen given prophylactically to asymptomatic women who have markers for the disease tends to be effective in half of all patients.
Similarly, testing for breast cancer recurrence provides patients and doctors with an opportunity to predict, with a high degree of accuracy, the likelihood of breast cancer recurrence and survival and the potential benefit (or lack thereof) of chemotherapy treatment.
However, it is critical to keep in mind that determining the appropriate markers requires exhaustive validation studies with large data sets for analysis. In addition, cancer is a heterogenic disease; biomarkers identified today may change/evolve into new sets of indicative biomarkers. Also, one must be aware that there may be legal complexities associated to outcomes of these tests. Thus, determining the appropriate population and performing rigorous validation studies with well-defined end points is essential to establish value to patient care.
Furthermore, physician education, FDA approval, and obtaining coverage and appropriate reimbursement remain barriers to widespread adoption. For instance, tumor marker CA 125 is sometimes used to screen women who have an increased risk for ovarian cancer. Scientists are still studying whether measurement of CA 125, along with other tests and exams, is useful to find ovarian cancer before symptoms develop. According to the NCI, CA 125 measurement is not sensitive or specific enough to be used to screen all women for ovarian cancer. The CA 125 test is mostly used to monitor response to treatment and check for recurrence in women with ovarian cancer.
The next five years will likely see robust growth in the area of cancer-based pharmacogenetic tests, as a growing number of tests are being developed for detecting polymorphisms known to be associated with drug toxicity or efficacy. HER-2/neu testing for stratifying responders to Herceptin was the first FDA-approved pharmacogenetic test, and may well be just the tip of the iceberg.
For instance, testing for BCR/ABL genetic defects not only predicts response to Gleevec but also directs quicker intervention in case of chronic myeloid leukemia relapse. Additionally, there has been widespread concern about the safety of Iressa for the general population, given that only about 10% to 20% of the population seems to respond favorably. Testing for SNPs in the epidermal growth factor receptor (EGFR) can aid in predicting the response of non–small-cell lung cancer to Iressa or other EGFR drugs such as Erbitux.
Still another targeted drug is Irinotecan, a commonly prescribed treatment for advanced colon and rectal cancer that can cause dangerous or lethal reactions in up to 30% of recipients. Pharmacogenetic test UGT1A1, a test for the metabolism of Irinotecan, identifies patients who may be at increased risk of adverse reaction to the drug.
Notwithstanding all these challenges, TSG believes that molecular diagnostic tests are revolutionizing cancer care by providing clinically relevant information early and reducing morbidity and healthcare costs. We believe these tests are poised to become increasingly critical components of cancer disease management.