A Patient’s Story: “When Too Much of a Bad Thing Can Be Good!”

My name is Bryce Olson. I’ve been battling aggressive stage IV metastatic prostate cancer in my bones for eight-and-a-half years. I’ve been on thirteen completely different lines of drug therapy, including standard of care drugs, off-label drugs, and clinical trial drugs. But this lucky number thirteen deserves some attention, because you won’t see it promoted from the pharmaceutical industry. As a patient, I felt morally obligated to get the word out and felt that ZERO Cancer was the perfect place to explain it. In honor of Prostate Cancer Awareness Month, I wanted to share what I did in hopes that others may also benefit.

A number of years ago, I started SequenceMe so cancer patients could learn more about the importance of cancer genomic profiling and how it can open more treatment doors beyond the standard of care. Genomic sequencing of my prostate cancer has been incredibly informative to me and my medical teams. The insights from these diagnostic tests have given me tremendous hope, empowered me to make treatment decisions together with my oncologists, and have extended my life significantly. If you want to learn more about how this could be useful for metastatic prostate cancer patients, please watch this short video.

I don’t want to imply that my journey has been easy; I’ve had some very scary times. In June of this year, I dropped out of a novel clinical trial that simply wasn’t working. Then, I didn’t get the response I hoped for from seven rounds of Cabazitaxel + Carboplatin. My back was against the wall; my PSA rose to over 300. I had tumors all over the place in my bones, was losing weight and was getting weaker. If I didn’t catch a break soon, I wondered if I would see past 2022.

I had heard of BAT (Bipolar Androgen Therapy). I knew that Johns Hopkins had been running multiple clinical trials on BAT. I was fascinated with the idea. What man going through advanced prostate cancer therapy wouldn’t want to get a surge of testosterone again? But, I was also very leery of this. I didn’t know a single advanced prostate cancer patient personally who had done it; after all, introducing testosterone back into my system could be like pouring gasoline on a fire. It would be a controversial, paradoxical move. Could too much of a bad thing actually be good? I dug into the Patient’s Guide to BAT that had been written by Johns Hopkins doctors. Here’s what I found out:

BAT is designed to repeatedly shock the prostate cancer cells by alternating between polar extremes of high and low testosterone levels. Bipolar androgen therapy (BAT) is a new treatment concept for men whose prostate cancer has become resistant to standard hormone-blocking therapy.

As you all probably know, male hormones, including testosterone, are called androgens. Treatment to shut down male hormones is known as androgen deprivation therapy, or ADT. Antiandrogens are “second-generation” drugs that block the action of androgens in the prostate cancer cell, and these include Xtandi, Erleada, and Nubeqa. Zytiga is included in this group, although it works differently.

Androgens (testosterone) drive prostate cancer growth. The way they do that is by binding to a protein within the cells called the androgen receptor (also known as AR). Primary ADT like Lupron or Eligard work by stopping the production of testosterone, so the AR doesn’t have as much testosterone to bind to. Antiandrogens block any remaining androgens from binding by gumming up the receptor. Initially, primary ADT and second-generation antiandrogen therapies work great. But over time, prostate cancer cells respond to the low testosterone conditions by markedly increasing the level of the AR to catch any testosterone that remains after therapy. This is basically a genomic alteration called “AR Copy Number Gain” that allows the cancer cells to evolve by adding tons of androgen receptors (AR), and that enables it to grow again despite the low level of testosterone in the body.

So, dear reader, are you potentially like me? Are you also an advanced cancer patient whose cancer cells have evolved over the years? Have you essentially bred a population of cancer cells that is able to function in an androgen deprived environment from years of ADT?

In the answer to these questions is yes, consider what might happen if you actually flooded the cancer cells with androgens (testosterone). Your prostate cancer sure wouldn’t need all of those extra androgen receptors that it acquired, because it would see a ton of androgens floating around and could easily catch them with many fewer receptors.  Would the cancer potentially get confused by the flooding? Yes, it could!

What I learned from reading the BAT Patient Guide was that patients like me who were CRPC and had high levels of AR had a better chance of responding to this treatment. A patient can determine if they have high levels of AR (ie. “AR Copy Number Gain”) by doing cancer genomic profiling from Tempus or Foundation Medicine. Turns out, I had this DNA alteration. I also had a P53 mutation and that mutation, along with mutations in the genes BRCA2 or other DNA repair enzymes, may be more likely to have a significant response to BAT. Then, I asked my oncologist, Dr. Rana McKay at UCSD, for support in getting the therapy. She reached out to the team at Johns Hopkins to get the protocol, which is basically an injection of 400mg of Depo Testosterone that I get every 6 weeks (the original JH study was every 4 weeks) while I stay on Lupron the whole time. I’m also adding Pembrolizumab (Keytruda) every 6 weeks as well, since there is some evidence that testosterone turns on immune functions in prostate cancer cells, and we felt this could be an interesting combination.

Now, for the results.

I had an exceptional response. My PSA dropped from 307 to 5 after the first cycle. It continued to drop from 5 to 1.5 after the second cycle. At the beginning of each cycle, my testosterone levels are high due to the injection; this confuses my cancer that is mostly castrate resistant (CRPC), and those cancer cells die. Then, over a 6-week period, my testosterone levels go back to castrate levels, and the castrate resistant cancer cells that are still alive start to grow again…until I freak them out with another surge in testosterone – hence the “bipolar” nature of this. I’m heading into my fourth cycle on September 12. When we look at imaging results (PSMA PET Scan), it’s remarkable – there’s significantly less disease. In addition, I feel amazing. All the nausea, appetite suppression, and fatigue I was suffering from the previous toxic therapies is gone. I have much more energy, more muscle mass, and improved sexual function.

There are three reasons why I wanted to get this story out:

1. BAT is super inexpensive and accessible. Depo Testosterone costs between fifty and two hundred dollars for each cycle. Compare that to any other prostate cancer therapy, and it’s a huge bargain. It’s easy to get. However, there is no incentive for drug companies to promote this, because it’s not a new drug and there are no profits to be made. You won’t see any ads or promotion for this therapy. That means if you want to try this, you as the patient are going to need to get educated and make a case to your doctor for it.
2. BAT is very tolerable and improved my quality of life. I did have a temporary testosterone stimulated release of inflammatory factors that made bone pain significantly worse for about four days on my first cycle. This happened most likely because I already had some bone pain from cancer. In all honesty, I may have been excluded from the Johns Hopkins studies because of this. But we did it anyway, and I was able to alleviate the pain with a five-day course of steroids. Also, there is some risk of stroke or heart attack for people with underlying congestive heart failure or cardiovascular challenges. But for me, as stated above, it was all upside. I got my energy back, increased muscle mass, got my appetite back, got improved sexual function, and just feel amazing compared to how I felt before (after the initial bone pain flare on the first cycle of the drug.)
3. BAT can restore sensitivity to hormone‐blocking therapy. I’m super excited about this. As you can read about in the Patient Guide, one of the Johns Hopkins trials had patients with CRPC who progressed on Xtandi get treated with BAT. Once BAT stopped working, the patients were re-treated with the Xtandi. Remarkably, for the patients who received Xtandi then BAT and the Xtandi again, 70 percent had a PSA response to the re-challenge with Xtandi. In another study, for patients who received Xtandi directly after Zytiga, the PSA response was 25 percent and time to PSA progression was about four months. For those patients who received BAT directly after Zytiga and then received Xtandi after BAT, the PSA response was almost 80 percent with a time to PSA progression of about eleven months. The overall survival for patients who received BAT then Xtandi was about thirty-seven months compared to about twenty-nine months for those receiving Xtandi alone. This is like resetting the clock. I’m hoping that I, too, will get a response to second generation anti-androgens again if I fail BAT and move onto Xtandi or Nubeqa.

In summary, is this going to work for every advanced CRPC prostate cancer patient? No. You can read the Patient Guide and look at the efficacy and percentages. But, if you are an advanced metastatic prostate cancer patient who is running out of options and whose cancer has evolved in a similar way as mine, you might get a nice benefit. Have a conversation with your doctor about this potentially transformational therapy idea. 

Best of luck!