"CSA guided chemotherapy should be compared to empiric treatment by a prospective randomized trial."
How many times have we heard that before? The same people who maintain that assay-directed therapy should not be used until proven in prospective randomized clinical trials, are the same people whose entire careers are utterly dependent upon mega-trials 100% funded by pharmaceutical companies (that, plus fees from speeches they give for these companies), are the same people who control the clinical trials system, the grant review study sections, and the journal editorial boards. That, and trying to invent brand new criteria for validating a laboratory test. Tens of thousands of scientists pushing a goal of finding the tiniest improvement in treatment and fostering redundant problems and rewarding academic achievement and publication above all else.
Even in this age of molecular gene testing and targeted treatments, a first of its kind head-to-head clinical trial comparing gene expression patterns with personalized cancer cytometric testing (also known as functional tumor cell profiling or chemosensitivity testing), personalized cancer cytometrics was found to be substantially more accurate than molecular gene testing (Arienti et al. Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy. Journal of Translational Medicine 2011, 9:94).
http://cancerfocus.org/forum/showthread.php?t=3490
But lets go back to the real standard of validation when it comes to diagnostic tests in cancer medicine: The "Holy Grail" is clinical correlations. The standards used to judge the utility of "all" laboratory and radiographic tests have always been (1) acceptable "accuracy" of clinical correlations and (2) clinical utility, in the judgement of the physician ordering the test.
The preponderance of available evidence (correlation between test results and clinical outcomes) certainly indicates that chemoresponse assays are usefully accurate in taking a long list of drugs with average probabilities of providing clinical benefit and sorting them into drugs with above-average and below-average probabilities of benefit.
This kind of testing may have utility at the time of initial therapy, in instances of severe drug hypersensitivity, failed therapy, recurrent disease and metastatic disease, by providing assistance in selecting optimal chemotherapy regimens.
And let's go to this brand new criteria invented to validate these laboratory tests. It was hoped that something like the Arienti, et al study (above) would be proposed at one of the semi-annual GOG meetings. Perhaps a good three-armed clinical trial: physicians' choice (empiric treatment) vs molecular profiling vs functional profiling?
This issue has been an ongoing saga for some 20 years now. The question that should be addressed is across the board assessment of the relative accuracy of different endpoints. They should answer all the questions at once, not one followed by another. A "battle-of-the-bands" so to speak.
Well, it was proposed, and it was approved, and is in the process of funding. Notwithstanding any help from NIH (and with sequestration upon us), searches for private funding are being pursued.
In the meantime, until the controlled, randomized trialist approach has delivered curative results with a high success rate, the choice of physicians and patients to integrate promising insights and methods like these chemoresponse assays, remains an essential component of this kind of treatment technology. Patients can't wait!