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I have at least three thoughts on the issue of curing advanced prostate cancer. First, the number of new treatments that are life prolonging has been incredibly gratifying. See my posts on abiraterone, enzalutamide, apalutamide, Sipuleucel-T, and Radium 223, to say nothing of cabazitaxel and docetaxel. That said, my second comment (and yes, I DO say this in the clinic to try and keep some perspective on a deadly, but often slow disease) is that “if you die of a heart attack or a stroke, we call that a CURE!” Many patients have very slow moving prostate cancer that just grows old with them, and some of the drugs listed above can slow it down still further, even though the side effects (particularly of ADT itself) are definitely unpleasant. The third thought is an old saw: “For every complex problem, there is a simple answer, and it is often wrong.” I looked it up, and it is attributed to H.L. Mencken, who actually said, “Explanations exist; they have existed for all time; there is always a well-known solution to every human problem — neat, plausible, and wrong.” I found he also said, “We are here and it is now: further than that, all human knowledge is moonshine”. Pretty cynical, but we digress…
Thus, the article that made me think about how complex a problem prostate cancer actually presents us was this one. The authors are very much the Who’s Who of prostate cancer research, and what they did was sequence the exomes from 1,013 prostate cancers. They were looking for so called, “driver mutations”, that is, mutations in a gene(s) that are the underlying cause, or at least the accelerators of prostate cancer. Their abstract conclusion states, “We find that the incidence of significantly mutated genes (SMGs) follows a long-tail distribution, with many genes mutated in less than 3% of cases. We identify a total of 97 SMGs, including 70 not previously implicated in prostate cancer…”
This means that although we might see some drugs developed for the most common mutated driver genes, there lurks a host of others for which developing a drug for the very small number of patients (even if that is possible – not all mutated genes are “druggable”) with a given driver may not be economically attractive. And then there is the issue that if one of the common driver pathways (for example the androgen receptor) is effectively knocked out, as has been done with the second generation inhibitors, it is likely there are other mutated drivers in the wings.
On the other hand, the study of metastatic prostate cancer has uncovered a wealth of new genomic classifiers that may be of real utility in further separating the “bad” cancers from the more indolent variety. As they state, “this analysis, which includes more advanced cases, has identified new and biologically and clinically relevant events and creates an opportunity to prospectively assess a metastasis-associated genomic marker for clinical stratification in localized prostate cancer.” All well and good, but don’t forget the issue of tissue heterogeneity. If you biopsy one metastatic site, or even one site within the primary tumor, you might get a different answer from a site only a few millimeters away or from a different metastasis, as I previously pointed out in another very sophisticated article by some of the same authors.
Nevertheless, be of good cheer. To have so many outstanding biologists and physician scientists uncovering the underlying mechanisms of prostate cancer is a good thing. The more we learn, the more opportunities we have to slow the disease down, even if there may never be a “cure” other than a heart attack. Immortality may be elusive, but your friends and family are not…carpe diem!
5 responses to “Are we any closer to cure? (yes and no)”
You haven’t mentioned immunotherapy in any of your blogs.
I have been getting excellent results from Odivo immunotherapy infusions.
My PSA went from over 200 to less than 2 in just a few weeks
There are a few unpleasant side effects like dry
mouth and rashes.
Great to hear from you and I’m delighted that Opdivo (nivolumab) is working. I covered it and some other immunotherapies here: https://prost8blog.com/?s=nivolumab. (or just search for immunotherapy on my blogsite). So far as I know, it has not been approved for treating prostate cancer, so medicare/insurance may not pay and it is expensive. There is another case report of good response here: https://doi.org/10.1016/j.clgc.2017.05.005. However, in general, I would say you are somewhat the (good for you!!) exception based on this study which is ongoing: http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.5035. Keep up the response and enjoy the Masters!
i am currently awaiting my 5th injection of radium 233. mild side effects but feeling good. cheers john
Good morning, Dr. Glode. Your recent post appeared on Tim’s e-mail this AM. I am really not a computer person but have kept his site for a year as the kids have advised me to do so. Otherwise, I am still 20th century with landline only and TV antennae! Anyway, I wanted to take this opportunity to thank you and Dr. Hardenburgh again for all you did for Tim. You two were the strength in the latter years of his battle. My faith, sweet family, and wonderful friends near and far sustain me. It has been a bit overwhelming these past 6+ months trying to take care of so much paperwork in spite of the fact that we were well organized. I am seeing the light at the end of the tunnel at last, but am now the yardman, car washer, fix it person, financier, errand runner, etc.! I will probably spin off some of his duties to hired help as my back aches, hands are numb from raking oak leaves and hairs, and my 15 yr. old Prius needs a good washing! Otherwise, I am managing but definitely have down days occasionally. I have joined a 6 week grief group at our Catholic Church which I know will be helpful. I do feel I am being proactive but still really miss my honey and always will. I am hoping to escape the TX summer heat and head to CO for some relief. If you and Dr. H. are at Shaw when I am there, I will stop by for a quick “hello”. All the best to you two and your dear families. Again, thanks – Barb 🙂
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Thanks for the updates. We always like to hear from our extended families and the patients we love and miss.