In my clinic, American Diseases of the Prostate, as in any clinic that sees a large number of prostate cancer patients, I've encountered prostate cancers that deviate from the well-established behavior of the common adenocarcinoma. One of those unusual forms of prostate cancer is neuroendocrine carcinoma.

Neuroendocrine cells are found in the normal prostate gland, where they have been shown to produce a range of hormones including serotonin, bombesin, and calcitonin. However, we do not know the role these neuroendocrine cells play in normal prostate biology. In the standard adenocarcinoma of the prostate gland, neuroendocrine cells are nearly always found scattered throughout the cancer mass. In this setting, these neuroendocrine cells do not make PSA, are not growing and do not have the androgen receptor. In the test tube, even though the neuroendocrine cells do not grow, the hormones produced by these cells are capable of fueling the growth of the adenocarcinoma cells. One report claimed that in the prostate cancer specimens obtained at surgery, the prostate cancer cells near the neuroendocrine cells were growing more rapidly than those distant from these cells. This suggests that the neuroendocrine cells might fuel prostate cancer progression. In fact, the larger the proportion of the cancer mass composed of neuroendocrine cells at diagnosis, the more likely the patient would do poorly over time.

While serum chromogranin A has generally been found to be the best marker to detect the development of neuroendocrine cells in prostate cancer, there is some evidence that it is more than just a marker. For example, if you add chromogranin A to prostate cancer in tissue culture, it triggers the formation of proteins that improve the cancer cell's resistance to treatment.

In prostate cancer research, there are certain classic studies that define issues with great clarity. In 1991, Kadmon, et al. showed that an elevated chromogranin A level made evolution of hormone resistance more likely. Furthermore, once hormonal therapy started, chromogranin A levels initially increased in many patients, but would later decline back to normal. When chromogranin A levels stayed elevated or when it started to increase late in hormonal therapy, hormone resistance was very likely to follow. This observation has been repeatedly confirmed.

Up to this point, we have been discussing the impact of neuroendocrine cells that are not themselves capable of growth and where the impact appears to be thought an effect on the prostatic adenocarcinoma cells. In small cell carcinoma of the prostate gland we have neuroendocrine cells that are able to rapidly grow and spread. Again, these cells make very little or no PSA and make little or no androgen receptor. While they can make chromogranin A and other neuroendocrine markers, in many cases they make no detectable markers.

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