Aggressive Forms of Prostate Cancer

Dr. Snuffy Myers talks about Prostatepedia’s August issue on aggressive forms of prostate cancer.

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In August, we’re talking about what used to be thought of as a rare form of metastatic prostate cancer but now appears to be quite common. In this month’s guest commentary, Dr. Neeraj Agarwal summarizes the problem of neuroendocrine cancer and frames the conversations that follow. You will notice a broad consensus among our experts that metastatic prostate cancer is a heterogeneous disease. Unfortunately, the large randomized Phase III trials that established our current treatment guidelines behave as if all metastatic prostate cancers are alike. As this is clearly not the case, treatment guidelines need to be interpreted with prostate cancer’s heterogeneity in mind. This is especially true if your PSA is low for the amount of cancer that you have; if you have lytic bone metastases; or if your cancer is predominately in your liver, lung, or other organs rather than in your bone. If your cancer fits this picture, the conversations that follow may help you better understand your treatment options.

These atypical prostate cancer presentations are poorly served by standard treatments and yet we haven’t really defined yet what the proper treatment might be.

Drs. Ana Aparicio, Himisha Beltran, and Daniel George have thought creatively about how we might better treat men with these atypical prostate cancer presentations.

It is already clear that patients with this aggressive presentation vary in their response to existing drugs as well as to agents currently in development. A key step will be to find molecular markers that predict which treatments are likely to be most effective for each patient. This type of research, while still early in the process, is progressing rapidly.

We now have laboratory models for neuroendocrine and anaplastic prostate cancers. It is possible to rapidly test agents in these models; that process has identified promising agents.

I think estradiol is one of these promising agents. One of my patients illustrates this nicely. A young man had at initial diagnosis a Gleason 10 prostate cancer with a 14-day doubling time. His cancer became PSA negative while he was on Lupron (leuprolide) and Casodex (bicalutamide). He developed a large lytic metastasis in his pelvis. I asked a radiation oncologist to radiate his pelvic lytic lesion and then started him on estradiol. He entered a complete remission that lasted eight years. After eight years, he developed an oligometastatic recurrence that I again asked a radiation oncologist to treat with radiation. He entered a remission. He finally developed metastatic cancer of the pancreas and is now receiving chemotherapy.

Over the years, I have seen estradiol result in multi-year cancer control in other patients with a similar presentation. I never understood how hormonal therapy like estradiol could work in a group of patients notorious for being unresponsive to hormonal treatment. But we now know that estradiol can act through the estrogen receptor beta to block the action of a protein called snail (SNAI) that is important in neuroendocrine transformation and metastatic spread.

My point is that a diagnosis of aggressive prostate cancer doesn’t mean you’ve only got a few months left. Years-long disease control can happen. It is in your best interest to seek out an expert in this form of prostate cancer—even if you have to travel great distances to see him or her.


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