Prostate Cancer Lab #21: Bipolar Androgen Therapy (Bryce Olson and Bob Gatenby)

“It’s been all upside. I’m living my best life right now on this treatment. What guy wouldn’t want testosterone?” – Bryce Olson

“There’s no reason to be optimistic about this result. As we design the future therapy, doing the same thing over and over again is simply going to give that population time to proliferate.” – Bob Gatenby

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Advanced prostate cancer patient Bryce Olson shared the story of his exceptional response to Bipolar Androgen Therapy (BAT), where high doses of testosterone are alternated with androgen deprivation therapy. Then Bob Gatenby, MD, commented on Bryce’s experience and strategy from his perspective as a leader in adaptive therapy — using evolutionary and game theory to inform cancer treatment strategy. 

Bryce’s Exceptional Response to BAT

Bryce Olson has been heavily treated for his prostate cancer since his diagnosis eight-and-a-half years ago. He has had 12 lines of therapy, including the standard therapy of androgen deprivation since 2014. Somewhat out of desperation, a few months ago Bryce took a flier with BAT, flooding his androgen-deprived cancer cells with testosterone, which normally fuels cancer growth. Six weeks after his first cycle of testosterone, his PSA dropped from 307 to 5, then after the next cycle from 5 to 1.79. It’s been all upside. He’s living his best life – what guy wouldn’t want testosterone? In addition, taking testosterone can restore sensitivity to hormone-blocking therapy again, creating the opportunity to cycle from providing testosterone to androgen deprivation therapy, an adaptive strategy.
It’s criminal not to scale this.

What Does It Take to Choose BAT?

First, most patients and oncologists are not aware of or considering BAT as an option. Pharma won’t push this treatment that only costs $200.

Second, the patient has to be brave enough – taking testosterone can be like throwing gasoline on the fire, feeding cancer growth.

Third, the patient must find a doctor that’s willing to support it.

The Good News

Bryce got the information and insights that predicted that this therapy would work. It has selected cancer cells sensitive to testosterone and done a great job of killing them. It’s a wonderful example of precision medicine. He looked at the evolutionary status of the tumor in a way that revealed an Achilles heel, and he attacked it.

The Bad News

Bryce’s many treatments have made a mess of his tumor population, so no one knows what’s in it, and that’s always a problem. What’s almost certain is that there are cells that are resistant to what has been done. If there are still tumors, there is a small resistant population. Flooding with testosterone is punishing the adaptive strategy to low testosterone. At some point, it’s going to go away. There’s going to be a new strategy that’s evolving. Even cycling between supplying testosterone and depriving androgen will be selecting for androgen-independent cancer growth. There’s no reason to be optimistic in the longer term. Prostate cancer is hard to eradicate.

Strategy: What Should Bryce Do Next?

Humans think linearly, but cancer is a nonlinear system. It might seem that cycling on the hormone path will work, but it’s very hard to predict. Bryce has put the tumor on the mat with BAT. He has a small cancer population, and small populations are vulnerable to extinction. But usually in evolution, the final nail in the coffin (extinction event) is not the same thing that drove the population down originally.

**Should Bryce add a different therapy now when he has a small cancer population?