Diagnosis and outcome

Medical knowledge, all scientific knowledge, is statistical. Even in the simplest, most straightforward experiment, there is some level of imprecision, some degree of unavoidable ambiguity ( error). All results are expressed some margin of error.

Medical data often has a very wide margin of error. Reasons for this include the heterogeneity of the population studied. Often, what we call a “diagnosis” can be resolved into more than one disease entity. Until we knew better, no distinction was made between estrogen receptor positive estrogen receptor negative breast cancer.Now, these different entities are often treated in different ways. sometimes, a new treatment defines a new subgroup. tratuzamab makes Her2 expression important in breast and stomach cancers, Rituximab makes the CD 20 a critical factor in the treatment of lymphoma.
In my opinion, the true value of a diagnosis is how it defines treatment. The diagnosis and treatment outcome are inseparable. If a diagnosis gives a 30% response rate to treatment, it is a poor diagnosis. A diagnosis of lung cancer, in the absence of molecular definition,  is hardly more than a guess, regardless of the details appended. A diagnosis of CML, with a bcr-abl translocation is a strong statement that leads to a near 100% probability of response.

Response is not the point. People living better and longer is the point. Response is a useful measure that hints that a treatment is on the right track. The documentation and publication of a response is a public service, but, aside from the psychological lift, it does not necessarily benefit the patient.

There are unfounded beliefs in the practice of ooncology Probably the most destructive of these is the idea that efficacy is a function of toxicity. The more toxic the therapy, the more powerful it is, the more cancer it kills. This is an unfounded belief, not evidence based and not scientific.
It is true that some cancers can be cured by very toxic treatment, and at this time, extremely dangerous and toxic treatment is the only known way to reliably treat many leukemias, certain lymphomas, etc. But oral, low side effective  tyrosine kinase inhibitors, like imatinib, are more effective in the treatment of chronic myelogenous leukemia than a life endangering, life altering bone marrow transplant.

A related, unfounded belief is that the microscopic appearance of a tumor, and the pathologist’s impression of its aggressiveness should determine the toxicity of the therapy; The most primitive of cancer, testicular cancer, is among the most reliably curable. And it is the most normal appearing elements of that cancer ( teratoma) that is the most difficult to eliminate. The microscopic “aggressiveness” estimate of the pathologist is an aggregate of the number of cells in mitosis ( the act of division), how bizarre the cells look, how different from normal they are, etc. These parameters do not correlate with outcome. A high mitotic rate could confer increased susceptibility to treatment ( even treatment that is not directed at mitosis). Bizarre appearing cells may be programmed for death under certain conditiona