Originally published 9/12/2021
The Duke University authors of a case study reported the amazing results of using bipolar androgen therapy (BAT) for a patient with advanced PCa who was practically at death’s door and felt hopeless.
When diagnosed in his 40s, he had brachytherapy and beam radiation but his PCa recurred. For the next 20 years “he progressed through nearly all standard therapies including androgen deprivation, combined androgen blockade, traditional chemotherapy, targeted therapies and experimental agents.”[i] Finally, for 13 months he was on BAT (supported by an immunotherapy drug called Keytruda) which dramatically controlled his disease.
The team hypothesized that such success may have been attributable to a specific germline mutation that “sensitized the cancer cells to the DNA damage caused by BAT.”
Though understandably excited, they caution, “Single case report outcomes should not be used as evidence of efficacy for treatment regimes. Our case supports further investigation into BAT plus immunotherapy for patients with DNA-repair deficient [castration resistant PCa].” In short, optimism over BAT is justified.
There’s a new kid on the block when it comes to androgen-deprivation therapy (ADT) for metastatic prostate cancer (mPCa). ADT has been the conventional standard of care once the cancer has begun to spread to distant parts of body such as bones or other organs. ADT uses drugs rather than surgical castration to deprive a man’s body of testosterone; other medications can be used to block cells from natural uptake of testosterone. Thus, it’s called chemical castration.
Why androgen deprivation?
Why is this rather drastic cutoff treatment used? Well, since PCa seems to be fueled by testosterone, when the hormone supply goes away, and cancer cells are stopped in their tracks. However, it’s not a cure. Eventually, the cancer cells seem to figure out what’s going on, and outsmart the therapy. At that point, ADT no longer works. When the cancer resumes progression despite the drugs, it’s called castration-resistant prostate cancer, or CRPCa.
Bipolar androgen therapy
In a rather curious irony, new research shows that very high concentrations of male hormones can also slow PCa progression. Dr. Michael Schweizer and team at the University of Washington found that in some mPCa patients, high doses of testosterone can cause cancer cell death. In lab experiments, exposing the cells to high androgen levels caused “the accumulation of DNA damage and the inability to fix that damage” which then “activated self-destruction signals within the cancer cells.”[ii] However, it’s not yet clear which patients respond better to intense androgen exposure or no androgen exposure.
This has led to a new treatment that is under investigation in clinical trials. It is called bipolar androgen therapy (BAT). As the name suggests, it periodically switches from no testosterone to high testosterone, then back again, covering both bases. The theory is designed to “prevent the adaptation of prostate cancer cells to a low-androgen environment.”[iii] In a sense, it keeps the cancer cells guessing so they don’t outsmart the clinical strategy.
Don’t keep the doctors guessing
However, the last thing we want is to also keep the doctors guessing. How can they know if this new treatment is working or not, and for which patients? The medical researchers who are testing BAT need to find out as soon as possible if mPCa is progressing so they can shift gears to another therapy. A multidisciplinary group out of Johns Hopkins and Brazil’s Hospital Moinhos de Vento explored the utility of an imaging isotope used as a radiotracer in PET/CT scans to identify early progression. This kind of imaging highlights cancer cells even in very small concentrations because it targets a cellular molecule called PSMA (prostate specific membrane antigen) that is highly expressed by PCa. Specifically, they put 18F-DCFPyL PET/CT to the test to detect clinical response in six mPCa patients on BAT:
Three of 6 (50%) patients had progression on 18F-DCFPyL PET/CT. … Radiographic progression on CT or bone scanning was observed within 3 mo of progression on 18F-DCFPyL PET/CT. For the 3 patients who did not have progression on 18F-DCFPyL PET/CT, radiographic progression was not observed for at least 6 mo.[iv]
Although the study was small, it’s very promising, since conventional imaging (no radiotracer) missed progression in the three men who were revealed to have progression by 18F-DCFPyL PET/CT. A news story summed up the significance of this discovery, “The finding may fill a need for a new imaging strategy to determine whether patients will respond to bipolar androgen therapy, according to the authors, who pioneered the strategy.”[v]
We agree, and we look forward to larger studies that can confirm this early ray of hope for men with mPCa.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
References
[i] Berger BT, Labriola MK, Antonarakis ES, Armstrong AJ. Response to bipolar androgen therapy and PD-1 inhibition in a patient with metastatic castration-resistant prostate cancer and a germline CHEK2 mutation. BMJ Case Rep. 2023 Jan 18;16(1):e251320.
[ii] CDMRP (Congressionally Directed Medical Research Programs). “High dose testosterone causes DNA damage and suppresses prostate cancer growth.” Posted July 28, 2020. https://cdmrp.army.mil/pcrp/research_highlights/20schweizer_highlight.aspx
[iii] Leone G, Buttigliero C, Pisano C, De Stefano RF et al. Bipolar androgen therapy in prostate cancer: Current evidences and future perspectives. Crit Rev Oncol Hematol. 2020 Aug;152:102994.
[iv] Markowski MC, Velho PI, Eisenberger MA, Pomper MG et al. Detection of Early Progression with 18 F-DCFPyL PET/CT in Men with Metastatic Castration-Resistant Prostate Cancer Receiving Bipolar Androgen Therapy. J Nucl Med. 2021 Sep 1;62(9):1270-1273.
[v] Morton, Will. “PET tracer assesses response to new prostate cancer treatment.” AuntMinnie.com, Sep. 8, 2021. https://www.auntminnie.com/index.aspx?sec=sup&sub=mol&pag=dis&ItemID=133434
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
