The development of drug-resistant, neuroendocrine forms of mCRPC


A sophisticated presentation at the annual meeting of the American Society of Clinical Oncology today (on behalf of the West Coast Prostate Cancer “Dream Team”) gave us insights into the the development of neuroendocrine forms of drug-resistant prostate cancer.

Based on samples of tissue from metastatic sites in patients with metastatic, castration-resistant prostate cancer (mCRPC) Small et al. provided preliminary results of a complex study of the pathology and genetics of development of four categories of drug-resistant, mCRPC:

  • The well-known and classic “small cell” subtype of prostate cancer — seen in 12 percent of cases
  • The well-known adenocarcinoma of the prostate — see in 33 percent of cases
  • A completely new “intermediate” histologic category (distinct from small cell carcinoma of the prostate or adenocarcinoma) —  seen in 27 percent of cases
  • A remaining 28 percent of cases of mixed or unclassifiable histologies.

The authors concluded that

  • A new and distinct histologic subtype of neuroendocrine prostate cancer, intermediate between adenocarcinoma and small cell carcinoma, was observable in roughly a quarter of these mCRPC patients.
  • The development of neiroendocrine forms of prostate cancer in mCRPC patients resistant to treatment with abiraterone and/or enzalutamide is far more common than previously appreciated and appears to result in poor survival.

They were also able to derive a 50-gene expression signature that provides us with some initial insight into the biology and potential treatment of neuroendocrine prostate cancer, but we have a way to go in understanding how best to apply such a gene signature.

One Response

  1. Percentage of small cell cases

    I did a double take on the percentage of small cell cases — “seen in 12 percent of cases.” Then I realized the abstract was talking about the percentage in men who were both metastatic and “castration resistant.” As small cell appears in fewer than 1% of all cases at diagnosis, it accounts for an amazingly outsized proportion of cases that are metastatic and CRPC!

    I was diagnosed with a challenging, life-threatening case in December 1999, given a prognosis of just 5 years by respected physicians at two leading centers. Obviously, I have outlived that prognosis and in fact may now be cured. However, at just about the same time a man in one of the divisions I worked with was diagnosed, and he died within 3 to 6 months. I suspect he may have had small cell prostate cancer.

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