TUSTIN, Calif. (
) --Here are some updates, observations and answers to common questions about
( RPC) as the clock ticks down to the release of data from a clinical validation study of the company's cancer monitoring test Onko-Sure:
Is Onko-Sure more accurate than the carcinoembryonic antigen (CEA) test in monitoring colon cancer?
That's what Radient believes, especially in patients with early-stage colon cancer, which is why the company (and its retail investor fan base) is placing so much emphasis on data from this ongoing validation study. Results are expected before the end of the quarter, which is Thursday.
Both Onko-Sure and CEA are already cleared by the Food and Drug Administration as blood-based tests to monitor the progression of colon cancer. In order to show superiority of Onko-Sure over CEA, Radient purchased from the Mayo Clinic 976 blood samples taken from colon cancer patients in various stages of the disease.
The Mayo Clinic tested these samples using the CEA test, while Radient is testing the same samples using Onko-Sure. The results from the two tests will then be compared against each other. Radient is especially hopeful that Onko-Sure will prove to be more accurate than the CEA test in patients with early-stage colon cancer.
Wait! You just said the Mayo Clinic tested these samples using the CEA test, which means Mayo really is partnered with Radient on this Onko-Sure test! You're a liar!
Wow, take off the tin-foil hat.
tested with CEA. That's it. Radient is conducting the actual validation study on its own. Recall Mayo's public statement regarding the Onko-Sure study:
"Mayo is not engaged in clinical studies with Radient and does not have a partnership agreement with Radient."
Think of this controvery another way: If Mayo were working with Radient on this Onko-Sure study (as Radient has claimed), then why isn't Mayo testing the colon cancer blood samples with CEA and Onko-Sure? Wouldn't it make more sense for Mayo, one of the most prestigious and independent research hospitals in the country, to conduct all the testing? It would certainly lend additional credibility to the results, whatever they might be.
But Mayo isn't doing all the testing. Instead, Radient ran the Onko-Sure tests on its own, which is not exactly the most unbiased way of conducting a clinical trial, even if a third-party statistical group is expected to tabulate the results.
Radient already says that Onko-Sure is superior to CEA, so this new study will definitively prove what we already know.
Not so fast. Radient published some data last year suggesting Onko-Sure works better than CEA in patients who have low levels of CEA.
Radient points to historical studies showing that as many as 50% of colon cancer patients have low CEA values. However, the study from where this conclusion was drawn also shows that, overall, CEA is a more accurate monitoring test for colon cancer than Onko-Sure.
This study is titled "Advantage of the AMDL-Elisa DR-70 (FDP) Assay Over Carcinoembryonic Antigen (CEA) for Monitoring Colorectal Cancer Patients" authored by Andrea Small-Howard, an employee of Radient.
DR-70 is the old name for what is now Onko-Sure. The Onko-Sure study was published in the
Like the ongoing clinical validation study, this older study conducted by Small-Howard also compared Onko-Sure against CEA using blood samples taken from colon cancer patients. Overall, CEA performed better than Onko-Sure:
CEA's specificity was 73% compared to Onko-Sure's specificity of 67%. Specificity measures the proportion of negatives that are correctly identified. Flip the percentage around and you get the rate of false negatives. In this study, in 27% of the samples, CEA said a patient's colon cancer was not growing when in fact the cancer was growing. For Onko-Sure, the false negative rate was higher -- 33%.
When it comes to telling doctors if colon cancer is progressing, the sensitivity of CEA and Onko-Sure was equivalent in the Small-Howard study -- 65%. This means that in 65% of the blood samples tested, both CEA and Onko-Sure correctly said that the colon cancer was getting worse. Conversely, both tests misdiagnosed patients (told them cancer was progressing when it really wasn't) 35% of the time.
For obvious reasons, any cancer-monitoring test with a high false-negative rate and/or low sensitivity is problematic. Doctors don't want to send patients home thinking their cancer is getting better when it's really not, nor do they want to alarm patients by telling them their cancer is still present when in fact it's disappearing or stabilized.
Neither CEA nor Onko-Sure are particularly reliable blood-based tests for cancer monitoring, which is why doctors don't rely on them alone. Radiographic imaging (CT scans, PET scans, etc) and other tests are also used to monitor cancer patients.
If CEA outperformed Onko-Sure, how can Radient claim otherwise?
In the study, Small-Howard also grouped the colon cancer blood samples according to their CEA levels. When CEA levels in the samples were low (30 or below), Onko-Sure did a better job of picking up tumor progression than CEA. Both tests performed equally well when determining when cancer was not progressing, regardless of CEA levels, according to the study.
Low levels of CEA are generally associated with less advanced or earlier stage colon cancer, which is why Radient promotes Onko-Sure as a test that can better monitor patients with early stage colon cancer.
The study doesn't do a good job of explaining the numbers or analysis that went into making the claim of Onko-Sure's superiority in patients with low CEA levels. Small-Howard also doesn't explain why Onko-Sure appears to perform better in early stage colon cancer patients but worse in patients with advanced disease.
The study paper also appears to conduct analyses based on a selective numbers of blood samples. For instance, the graphs used to illustrate Onko-Sure's outperformance in low-CEA samples appears to be missing a considerable number of patient samples. Moreover, the study only enrolled five patients with early stage (Dukes Stage A) colon cancer out of 112 patients overall.
Howard-Small collected 445 samples from 112 colon cancer patients but the sensitivity and specificity results comparing Onko-Sure againts CEA were analyzed off a base of 334 samples, according to the study.
My takeaway from this Howard-Small study is not that Onko-Sure is better than CEA, but that CEA is a remarkably accurate test given that it outperformed Onko-Sure overall even with a significant number of blood samples containing low levels of CEA. Onko-Sure should have performed better, so why didn't it?
Will the latest ongoing Onko-Sure clinical validation study produce more definitive results?
Good question. The answer depends on how well the study is being conducted and analyzed. Radient has been rather opaque about the process, with the exception of the details mentioned above. One thing is for certain: Doctors don't change clinical practice based on results promoted in company press releases.
If Radient is serious about developing Onko-Sure, the company will have to present these new data at a medical conference or have the results published in a peer-reviewed medical journal. Radient may even have to submit new data to FDA, if the company wants to make new medical claims about Onko-Sure's superiority over CEA or its ability to screen for cancer.
Even then, Radient has to sell Onko-Sure, something the company has been unable to accomplish to date. Onko-Sure sales through the first nine months of 2010 were down significantly from the same time period in 2009. Radient has yet to release full 2010 results but the company is teetering on insolvency and
Does Onko-Sure detect cancer? And if so, doesn't Radient stand to make huge profits if doctors use Onko-Sure as a replacement for colonoscopy?
No, Onko-Sure doesn't detect cancer in patients that are not previously diagnosed with the disease. Confusion over the difference between cancer screening and cancer monitoring runs rampant amongst Radient's retail investor base.
Onko-Sure is a cancer-monitoring test, which means doctors use it to monitor patients already diagnosed with colon cancer. After surgery or some other form of colon cancer treatment like radiation or chemotherapy, doctors will use Onko-Sure (or CEA, more commonly) to determine whether a patient's cancer remains in remission or starts to grow again.
Cancer monitoring is entirely different than cancer screening. In the latter, tests like colonoscopy or fecal occult blood tests are used to find cancer in patients that are not yet diagnosed with the disease. Radient has never conducted a clinical study to assess Onko-Sure as a cancer screening, or cancer-finding, test.
The American Cancer Society maintains guidelines for tests used to detect cancer, preferably when the cancer is at its earliest and most treatable stage.
I do like Exact Sciences. That's true. The rest is just the latest unhinged conspiracy theory making the rounds of the Radient message boards.
Exact Sciences is developing a non-invasive DNA test to detect colon cancer at its earliest and most treatable stage. This still-experimental test, known as Cologuard, is a true cancer screen -- not a cancer-monitoring test like Onko-Sure -- because it's designed to detect pre-cancerous polyps in a patient's colon. Once detected, doctors can follow up with a colonoscopy and if necessary, remove the pre-cancerous polyps before they turn into cancer.
If Radient investors are truly interested in an exciting and promising colon-cancer screening test, they should be checking out Exact Sciences.
And unlike Radient, Exact Sciences and the Mayo Clinic are truly working in a partnership to develop Cologuard. Some of the technology for the screening test was discovered and developed by Mayo researchers and later licensed to Exact Sciences. You can read a story I wrote last year about promising results from a
--Written by Adam Feuerstein in Boston.
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