JNF, I think that all changed when the results of the Phase 2 AVIAS trial were released in February. It provides the first randomized clinical trial evidence there is no benefit to taking dutasteride during intermittent ADT. I expect that many MOs are changing their protocols based on it - if they are going to stick with their old ways even in light of better data, why bother doing the studies?
In the AVIAS trial, the men were on CAB (a GnRH agonist and bicalutamide) and were hormone responsive, defined as PSA below 1 ng/ml. They randomly got dutasteride or placebo, and continued on it during the off-cycle. Both groups reached the same PSA nadir while on ADT, whether they took dutasteride or not. What happened then may surprise you: "Patients treated with dutasteride had a more rapid recovery of PSA and testosterone
in the off-treatment interval compared to placebo (p < 0.0001)."
I think we have to take seriously Klotz's ending cautionary note:
The PSA kinetics might be accelerated by the presence of 5ARI-resistant prostate cancer cells. It is also possible that 5ARIs exert a deleterious effect on prostate cancer in this situation, promoting more rapid recovery of PSA than expected.
5ARis may exert a selective pressure favoring DHT-independent cancer cells in the advanced/recurrent cancer setting. It is not the first time that a medicine that may be beneficial in one setting may be harmful in another. There is evidence, for example, that testosterone helps keep healthy prostate cells healthy in the pre-cancerous setting, while blocking testosterone kills prostate cancer cells in the advanced cancer setting. 5ARis are the best, indeed the only, prevention for PC. It may
even shrink some low grade cancers that are already there - a potential benefit for those on active surveillance. But once the cancer has progressed to high grade, I think one should be cautious about
taking it in light of AVIAS.