Standard and Non-standard Diagnostic Approaches
Many people do not appreciate what a critical issue getting the diagnosis right is in cancer. Some leading cancer authorities recognize that the reading of pathology reports is often the weak link in cancer treatment. The error rate in some hospitals is remarkably high. If you get the diagnosis wrong, you get the treatment wrong. So the value of getting a second reading—preferably from outside your medical center—can be significant. Some cancer centers do this routinely—especially if they are not certain of the reading. But it is certainly worth considering.
Diagnostic Tests: General Information
In order to get the right cancer treatment for you, getting the diagnosis right is the most important first step.
In order to get the right cancer treatment for you, getting the diagnosis right is the most important first step. Conventional oncology care includes standard tests that will be performed to find out about the cancer itself:
- The type of cancer (breast, colon, and so on).
- The stage of the cancer (anywhere from precancerous to metastasized to other parts of the body); for more information on staging, see the National Cancer Institute: Cancer Staging.
- The grade of the tumor (how aggressive the cancer is, how likely it is to grow and spread); for more information on grading see the National Cancer Institute: Tumor Grade.
Then, depending on the kind of cancer you have, additional tests may include these:
- Molecular and genomic testing to further characterize your cancer. For example, for breast cancer, your cancer will be assessed for estrogen and/or progesterone hormone receptors, as well as genetic mutations in the BRCA 1 and BRCA 2 genes.
- Lab tests on blood and other samples to assess other evidence of cancer activity. Tumor markers such as PSA in prostate cancer are an example. A baseline level of tumor markers is important to compare levels before and after treatment and in follow-up after treatment is complete.
- Testing to see if cancer has impaired organ and other bodily function
Non-standard Diagnostic Tests
All the tests listed above are fairly standard with a conventional cancer care diagnosis and workup. Integrative oncology clinicians will often assess other measures of health as well as recommend additional testing, such as chemosensitivity testing, in making an integrative treatment plan. For instance, during a cancer work-up, integrative oncologist Dr. Keith Block will look at these factors:
- The pathology of your cancer from conventional diagnostic tests results.
- What you eat and how you care for yourself (your biography).
- Biochemical disruptions that can promote cancer (your biology) such as insulin resistance and inflammation; he may run lab and other tests to measure some of these disruptions. The biography and biology of the person tell him about the environment (also known as the “soil” or “terrain”) hosting the cancer.
- Perhaps advice to bank live tumor tissue to be examined for chemosensitivity testing or perhaps for an autologous cancer vaccine.
- Perhaps targeted molecular testing not only to see if some targeted therapy may be useful, but also to see if there may be some specific nutraceuticals or nutritional supplements to prescribe.
Getting the Diagnosis Right
Many of your surgeon’s or oncologist’s treatment recommendations will be based on what the pathologist finds, so an accurate pathology report is vital. Unfortunately, some people diagnosed with cancer may discover later that the pathology report was wrong—they don’t have cancer. Or perhaps they may have a different cancer than what was diagnosed. One indicator that a diagnosis was wrong is that virtually all treatments that usually work fail to work.
Oncology has been undergoing a “molecular and genomic revolution” since the 1990s. Molecular profiling, the basis of personalized or precision medicine, looks for genes and proteins in cancer cells or in cells related to cancer growth, such as blood vessel cells. Some of these genes and protein molecules may actually block other genes that tell the cell to stop dividing or to undergo programmed cell death. Many of these gene/protein markers exist.
Success of Targeted Therapies
A 2018 review of genome-driven cancer therapies that target aberrations on tumor cells estimated that the percentage of US patients with cancer who might benefit from genome-targeted therapy in 2006 was 0.70 percent, and in 2018 it had increased to 4.90 percent. Thus to date these drugs have helped a very small minority of patients with advanced cancer.6
Targeted Therapies and Your Cancer
A targeted agent does not yet exist for every genomic abnormality, nor does having a targeted agent always mean your tumor will respond to the drug. Regardless, the field is burgeoning so that either now, or not far into the future, one or more targeted agents may be worth considering for your cancer.
Many integrative oncologists see value in obtaining test results that may identify nutraceuticals and nutritional supplements targeting errant pathways driving the tumor.
Testing for risk of recurrence is becoming routine for certain cancers, such as early stage breast and prostate cancers. Test results provide additional information on how aggressive a cancer is and how likely it is to recur. For instance, the OncotypeDXTM or the MammaPrint tests evaluate a sample of breast cancer cells for certain genes that are characteristic of cancer. Analysis gives the cells a recurrence score indicating the likelihood for the breast cancer to recur within the first 10 years after diagnosis. National treatment guidelines for a low recurrence score of an ER-positive breast cancer would recommend using only endocrine therapy instead of more aggressive treatment. Testing may be able to spare someone from going through chemotherapy needlessly. A similar test for prostate cancer, called the Oncotype DX®, predicts if a prostate cancer is likely to grow and spread.
Other Names for Chemosensitivity Testing
If chemotherapy and/or targeted therapies are indicated to treat your cancer, the next step is to determine which drug or drugs are best. Right now, oncologists primarily rely on studies of drugs tried in large groups of people with cancer that predict how the “average” patient will respond. Doctors will typically recommend a protocol of drugs based on clinical trial results that determine fixed doses, routes and schedules of administration. To some degree, oncologists will also consider a person’s general physical condition to adjust dosages or drug choice appropriately. But even with all these considerations, doctors still cannot be certain that a particular drug will kill a particular person’s cancer cells.
Improvements in Chemosensitivity Testing
Originally, chemosensitivity testing looked at drugs’ effects on cancer cell proliferation (growth), not the effects on apoptosis (programmed cell death). These earlier tests were not useful, and because of that, chemosensitivity testing lost favor with oncologists. Even with the superior effectiveness of the newer apoptotic assays, many oncologists are not likely to use this testing or bring it up as an option. Therefore, if you want this testing, you are likely going to have to take the initiative with your oncologist and request tests that seem indicated.
The Importance of Live Cells
Tissue samples on slides or in paraffin blocks will not work in chemosensitivity testing. The cells must be alive, and so arrangements for chemosensitivity testing need to be made ahead of the time that the tissue is removed.
BCCT advisor Brian Bouch, MD, explains chemosensitivity testing for cancer patients.
Proponents of chemosensitivity testing say this is a useful tool to help figure out which drugs a specific tumor is or isn’t sensitive to. This technique evaluates cancer cells in the lab to determine which drugs and even which natural substances elicit the best response.11 One method of chemosensitivity testing involves overnight shipping of cancer tissue obtained at biopsy or during surgery to a specialized lab. With this technique, cancer cells are separated into clusters, with each cluster then exposed to a different chemotherapy or targeted therapy. Those drugs that cause cell death apoptosis) in the cancer cells are identified as the ones the cancer is sensitive to. The lab prepares a report recommending drugs that are highly, moderately or not likely to kill cancer cells. Robert Nagourney, MD, founder and medical director of Nagourney Cancer Institute, which performs chemosensitivity testing, explains that the testing will often suggest less toxic drugs or combinations than standard protocols. Other methods of chemosensitivity testing are done on circulating tumor cells; however these methods have not be validated and their specificity and sensitivity (measures of accuracy and reliability) have not yet been determined.
Chemosensitivity Testing Considerations
Breast cancer medical advocate and BCCT advisor Gwen Stritter, MD, offers several considerations if you are thinking about chemosensitivity testing.
Take-Homes about Chemosensitivity Testing
- Though promising, chemosensitivity testing is considered experimental, and ASCO advises oncologists not to use this testing for determining treatment except in clinical trials.
- Some experts predict that functional profiling, including chemosensitivity testing, will become useful in the clinical setting within the next few years.
- Most oncologists will not use these test results in planning first-line treatment.
- Some physicians may use chemosensitivity testing results in planning your treatment, usually in situations where the tumor is progressing despite standard treatment, for second and third-line treatment or when the cancer has recurred.
- Some patients have had chemosensitivity testing done, only to find out afterwards that their doctors will not use the results.
- Some patients, many with progressive or recurrent cancer, have pursued having chemosensitivity testing and worked with doctors who used test results to plan treatment.
- This testing is not covered by Medicare. Private insurance may cover some of the costs. Some labs can link you to financial assistance programs to help cover costs.
In sum, though we may someday soon see this type of testing routinely used in clinical practice, there is not yet enough good clinical trial evidence for most oncologists to be comfortable using it. A few integrative oncologists do use test results, but mostly with cancers that have not responded to first-line treatments or that have recurred.
Finding Chemosensitivity Testing
Chemosensitivity testing is performed in a specialized lab, not in your hospital lab. Many European labs provide this test, which is much more common in Europe compared to the US, and in German Cancer Clinics in particular. A number of labs in North America also perform this testing. Several BCCT advisors are impressed with Dr. Robert Nagourney’s Rational Therapeutics chemosensitivity testing lab in Long Beach, California. Dr. Renneker is also impressed with Weisenthal Lab in Orange County, California. Note that the Weisenthal Lab not only does chemosensitivity testing, but can also test sensitivity for some immunologicals and natural medicines.
A liquid biopsy is a test done on a sample of blood or other fluid to look for cancer cells from a tumor that are circulating in the blood or for pieces of DNA from tumor cells that are in the blood. A liquid biopsy may be used for several reasons:17
- To find or diagnose cancer at an early stage
- To identify useful therapies
- To assess treatment effectiveness
- To check for recurrence or molecular changes happening in a tumor
Many other additional tests, both novel and standard, can provide information about your cancer cells or your terrain, which hosts the cancer cells. For instance, The Moss Report for Prostate Cancer describes two novel tests, The 4K Test and the Prosta Scint®, as well as a number of genetic tests for this cancer. Moss also provides a list of the various genetic tests, the companies that provide them, when the tests are performed, what’s analyzed, what it tells you and the benefits. See Moss Reports (purchase required).
Commercial Genomic/Molecular Testing Companies
BCCT advisor Mark Renneker, MD, explains that many hospitals say they can do genomic profiling, but in reality results are not as thorough as those from larger, better established commercials companies. We provide a listing of companies that Dr. Renneker has assessed favorably, and which are generally highly regarded by oncologists and which insurance usually pays (but check with your insurance):22
Written by Laura Pole, RN, MSN, OCNS, and Nancy Hepp, MS; most recent update on February 16, 2021. BCCT is grateful for review and revisions regarding chemosensitivity testing from our advisor Lise Alschuler, ND, FABNO.