Friday, July 18, 2008

Neoplasms: 11

This is the eleventh blog in a series of blogs on neoplasia.

In the past few blogs, I've been trying to explain the disconnect between cancer survival data and cancer death rate data. The cancer survival data seems to indicate that we're making enormous improvements in cancer treatment. The cancer death rate indicates that Americans are dying from cancer at about the same rate as they had been a half-century ago.

Several days ago, I listed over a dozen biases in cancer survival data that contribute to an overly optimistic sense of medical progress.

In this and the next few blogs, I thought I'd review some of these biases. The purpose of this exercise is to explain that the interpretation of survival data is enormously complex and that survival data is probably not the best way to gauge progress in the field of cancer research.

Today, let's look at Second Trial and Stage Treatment Biases.

After a therapeutic trial, clinicians can determine the type of patients who are most likely to benefit from an intervention. For example, a first trial of bone marrow transplantation for patients with metastatic carcinoma may indicate that patients over the age of 55 have very poor response to transplantation. Older individuals with transplants may be more prone to die from the interventional procedure than from their cancer.

On the second trial of the procedure, the clinicians will wisely exclude patients over some determined age (55 in this case). The second trial shows markedly improved survival, compared with the first trial, for those patients receiving bone marrow transplantation. The improvement can be achieved simply through better selection of subjects, and without improving the treatment protocol.

Stage treatment bias is closely related to second-trial bias. If you carefully select a stage of disease that is successfully treated by a particular treatment protocol, you can exaggerate the benefits of your treatment by ignoring disease stages for which your treatment is ineffective.

An example is the use of prostatectomy for prostate cancer, a procedure that is credited with a high cure rate. Prostatectomy is only performed on patients with tumor confined to the prostate. If the prostate cancer has metastasized to lymph nodes in the region of the prostate or to distant organs, prostatectomy is contra-indicated. Why is this? If the cancer has spread beyond the prostate, removing the prostate will not benefit the patient. An apt analogy is closing the barn doors after the horses have fled the farm.

Prostate cancer confined to the prostate is often indolent. By the age 80 to 90 years, 70% to 90% of men have prostate cancer confirmed at autopsy [1,2]. This indicates that prostate cancer is a very common disease that kills only a small proportion of affected individuals. Because prostatectomy is only performed on men whose prostate cancer is believed to be confined to the prostate, the cure rate is high. Restricting treatment to patients who have a stage of disease that is indolent, in most cases, virtually guarantees high survival rates.

1. [Guileyardo JM, Johnson WD, Welsh RA, Akazaki K, Correa P. Prevalence of latent prostate carcinoma in two U.S. populations. J Natl Cancer Inst 65:311-316, 1980.]

2. [Sakr WA, Grignon DJ, Haas GP, Heilbrun LK, Pontes JE, Crissman JD. Age and racial distribution of prostatic intraepithelial neoplasia. Eur Urol 30:138-144, 1996.]

-Copyright (C) 2008 Jules J. Berman

key words: cancer, tumor, tumour, carcinogen, neoplasia, neoplastic development, classification, biomedical informatics, tumor development, precancer, benign tumor, ontology, classification, developmental lineage classification and taxonomy of neoplasms
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