Sunday, September 20, 2015

The Future of Prostate Cancer Treatment

On July 17, 2015 I was diagnosed with high risk but localized prostate cancer.  In the subsequent two months I have learned just about everything there is to know about the treatment and prognosis of prostate cancer  Prostate cancer is an adenocarcinoma which forms from mucous producing tissue.  It is a common form of cancer, in addition to the prostate, of the lungs, pancreas, colon, and others.  Consequently, though I am specifically studying prostate cancer, the advances in treatment will have importance over a broader range of cancers, among which are some of the most deadly.

We are probably closing in on very high 'cure' rates for many of the more stubborn cancers by utilizing multimodal approaches.  For example  the treatment that I have chosen begins with four to six months of multi-drug neoadjuvant treatment.  The three drugs I will be taking are Lupron, Cassodex and Metformin.  This will be followed by Intensity Modulated Radiation Therapy (IMRT).  This will take between 6 and 8 weeks.  Then we will use the same drugs for adjuvant treatment, except we will add a statin.

Here is the logic.  Lupron and Cassodex, in combination, lower available testosterone to nearly zero.  Prostate cancer needs testosterone to survive and grow.  Lupron stops the 90% to 95% of the testosterone made by the testicles and Cassodex interferes with the availability of the remaining 5% to 10%.  The result is that the prostate cancer cells have no access to testosterone.  

These drugs do not constitute a cure because over about three years, the cancer evolves into one that survives despite the absence of testosterone.  However, the two in the short term shrinks the tumor by as much as 50%.  This allows the largest radiation dose to be focused on a smaller volume.

Lupron, Metformin and, perhaps, a very low carbohydrate diet, weaken the cancer cells more than normal cells.  Consequently, after four to six months treatment radiation therapy is much more successful.  This may partially be due to prostate cancer's relative inability to metabolize ketone bodies.  Both Metformin and a ketogenic diet lower glucose availability which doesn't much affect normal cells but starves cancer cells.  

Lastly, both Lupron and Metformin through metabolic modifications of reactive oxygen species, make the cancer cells more susceptible to radiation damage.

After the radiation therapy the vast majority of cancer cells have died.  However, even a few escapes can eventually grow into a new, more resistant cancer.  So, after the radiation therapy, we want to make the body's environment as hostile to the cancer as possible.  This is done first with a continued testosterone starvation using Lupron and Cassodex.  Between the two 99% of testosterone is either turned off or unavailable to the cancer

However, we also want to continue with the combination of Metformin and a statin.  In one study, Metformin use reduced risk of disease specific mortality (DSM) by 24% for every six months of use.  Another study found that combining Metformin and statins result in a 40% reduction in DSM.

The key to this is that Casodex, Metformin and statins attack the cancer in different ways. While Metformin weakens the cancer cells to radiation in the neoadjuvant phase, it has a different role in the adjuvant phase.  There is a cellular mechanism called apoptosis by which a cell recognizes that it is not well and commits suicide.  Clearly, because cancer cells are not well, in order to survive apoptosis must be turned off.  Metformin appears to turn it back on again.

What this means is that the cells that are not susceptible to Casodex are susceptible to Metformin and may be susceptible to statins.  In addition to these three drugs, I will continue to use a ketogenic diet to control my diabetes.  Consequently, cancer cells that survive the radiation therapy will need to survive testosterone starvation, glucose starvation and an assault of apoptosis.  That is a really hostile environment for the cancer.

There is no literature on this four pronged approach.  I may be the first patient to try it.  Also, most of the research, especially on combined Casodex and Metformin, has been on patients with metastatic prostate cancer, where the objective is not a cure but to slow the march toward mortality.  Such a broad spectrum assault on just a handful of PCa 'escapes' may be unique.

A promising fifth assault is a vaccine Provenge which sensitizes the body's immune system to PCa cells.  It is approved for use when there is pathological evidence of metastasis and is not intended as a cure, but rather to extend life.  It does so, on average by four months and costs $100,000.  It is generally, therefore, not being used.  However, it is not being tested as a normal adjuvant treatment designed not to attack a massive body wide cancer but to eradicate any escaped cancer cells after radiation or radical prostatectomy.  There, because it does not work like the other adjuvant treatments, it may be the straw that breask the cancer's back.

Also, it may be overkill in my situation.  We are not even sure that there has been any escape and BCR is assessed in my case at 70% probability.  There is a 30% chance that none of this is necessary.  However, I'm not willing to bet with the odds not in my favor.

Lastly, on average BCR takes place 27 months after treatment and with just some of the adjuvant treatment, that is delayed to 36 months.  Then, on average, it takes about five years before there is clinical evidence of cancer.  That is if it happens.  About 65% percent of the time BCR is not followed by clinical evidence of cancer.  Once the first signs of cancer are found, on average it is 8 years to death.

What that means is that IF BCR happens for me and IF it leads to clinical evidence of cancer, my average life expectancy from the time of treatment is 36+60+96=192 months or 16 years.  There is a very good chance that during that 16 years new treatments will be developed that can extend that even further.

Metformin and statins are some of the most widely prescribed drugs, are very cheap and have benefits for most older men even if there is no benefit for prostate cancer.  I am fortunate that I have a oncologist who is willing to go with me on my rather novel preadjuvant and adjuvant therapy.  My belief is that if the radiation therapy can lower my PSA into normal ranges, the four barreled adjuvant therapy of Lupron (which is standard), Casodex, Metformin and statin will place me in the 75% of men who never develop clinical relapse.

If you find yourself confronted with a diagnosis of prostate cancer and about 15% of all men will, don't let your doctors lead down a conservative treatment road unless you have very low risk prostate cancer.  You have one shot at this.  If you have a radical prostectomy and your PSA doesn't drop to zero, they will likely recommend salvage radiation therapy, but the benefit, while measurable, is not wonderful.  If you go directly to radiation therapy as I am, don't allow them to skimp on neodjuvant or adjuvant therapy.  As I said, you have one shot at it.  If it doesn't work, your options decrease quickly.

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