Bipolar.

Keeping up with the current mood on advanced prostate cancer treatment can leave you wanting a hefty dose of lithium. Should we milk androgen deprivation therapy (ADT) for all its worth or give taxanes a go? Most people can at least agree that once a prostate cancer stops responding to enzalutamide, it’s pretty much at the end of its ADT rope. That is, we could agree until now. Just like in breast cancer, preclinical studies indicate that enzalutamide-resistant cancer cells with constitutively active androgen receptor (AR) splice variants paradoxically die when re-exposed to high-levels of testosterone--giving birth to the concept of “bipolar androgen therapy” (aka BAT). You should at least know what it is, because there’s now a phase 2 trial purporting its safety and effectiveness in 30 enzalutamide-resistant patients. BAT in this study consisted of a daily GnRH agonist (such as Lupron) with 400 mg of testosterone administered every 28 days causing patient to ride a sinus wave of circulating androgen levels. Half of patients achieved a 50% decline in PSA either during BAT or upon a subsequent enzalutamide rechallenge. BAT isn’t a cure, but, as a companion editorial suggests, it’s another step toward understanding the major mood swings of prostate cancer in its love-hate relationship with androgens.