I have referred to the following article a few times in response to some posts about the use and timing of ADT when used in addition (adjuvant) to improve outcomes from salvage radiation therapy for BCR for failure after primary prostate treatment (surgical or radiation or other). Also for recurrences in pelvic lymph nodes and oligometastatic PC. These are attempts with “curative intent”, but many times fail.
The addition of short term ADT (sometimes 6 months but often 18-24 months) to the radiation treatments has become de facto standard of care (SOC). And often, per varying protocols from various large clinical trials, the ADT may be started a few months before starting the RT, or simultaneously. Also, some trial protocols have used bicalutamide and similar to block testosterone effects from the androgen “flare” when an ADT drug such as leuprolide or goserelin are first started. Note that the LHRH antagonists degarelix and relugolix do not have the androgen flare.
The article referenced is worth careful consideration by anyone here contemplating salvage radiation therapy to prostate, pelvic node fields and or oligometastatic SBRT. When the clinical trials are analyzed in terms of the timing of beginning ADT, simultaneously with starting RT or not, and whether bicalutamide or glutamine was used to block the testosterone flare, or not. Then it becomes clear that the weight of evidence from these multiple trials pointing to this:
It is actually the unblocked androgen flare given at the same time as starting the radiation that is actually helping to kill the most cancer cells and improving the outcomes. Not the suppression of androgens at that time. And this also appears to be the case for adding adjuvant ADT to docetaxel chemotherapy. Consider discussing the following article with your RO or MO.
ncbi.nlm.nih.gov/pmc/articl...
Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer
Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer
Simple Summary
Prostate cancer tumor growth is stimulated by androgens. Surgical castration or medical castration using long-acting luteinizing hormone-releasing hormone (LHRH) agonists or antagonists is the backbone of the treatments of metastatic disease. Treatment of locally advanced prostate cancer was accomplished with radiation therapy alone until multiple studies showed that combining radiation therapy with LHRH agonists results in significant survival benefit. While the goal of the use of LHRH agonists was to suppress testosterone levels during radiation, we show, through review of previous studies, that survival benefit was achieved only when LHRH was initiated during the course of radiation, and thus androgen flare during the first 1–3 weeks after the initiation of LHRH is most likely the reason for higher survival. Androgens drive tumor cells into mitosis, and mitotic death is the dominant mechanism of tumor cell kill by radiation.
Abstract
Treatment of metastatic prostate cancer was historically performed via bilateral orchiectomy to achieve castration. An alternative to surgical castration is the administration of subcutaneous recombinant luteinizing hormone-releasing hormone (LHRH). LHRH causes the pituitary gland to produce luteinizing hormone (LH), which results in synthesis and secretion of testosterone from the testicles. When LHRH levels are continuously high, the pituitary gland stops producing LH, which results in reduced testosterone production by the testicles. Long-acting formulations of LHRH were developed, and its use replaced surgical orchiectomy in the vast majority of patients. Combining LHRH and radiation therapy was shown to increase survival of prostate cancer patients with locally advanced disease. Here, we present a hypothesis, and preliminary evidence based on previous randomized controlled trials, that androgen surge during radiation, rather than its suppression, could be responsible for the enhanced prostate cancer cell kill during radiation. Starting LHRH agonist on the first day of radiation therapy, as in the EORTC 22863 study, should be the standard of care when treating locally advanced prostate cancer. We are developing formulations of short-acting LHRH agonists that induce androgen flare, without subsequent androgen deprivation, which could open the door for an era in which locally advanced prostate cancer could be cured while patients maintain .
The entire article is worthwhile and breaks down all the major clinical trials supporting this conclusion, with full references. Paul
