Testosterone suppression in the treatment of recurrent or metastatic prostate cancer — A Canadian consensus statement

Abstract

Testosterone suppression, achieved through orchiectomy or medically induced androgen-deprivation therapy (ADT), is a standard treatment for men with recurrent and metastatic prostate cancer. Current assay methods demonstrate the capacity for testosterone suppression to <0.7 nmol/l, and clinical data support improved outcomes from ADT when lower levels are achieved. Practical clinical guidelines are warranted to facilitate adoption of 0.7 nmol/l as the new standard castrate testosterone level.A pan-Canadian group of experts, representing diverse clinical specialties, identified key clinical issues, searched and reviewed relevant literature, and developed consensus statements on testosterone suppression for the treatment of prostate cancer. The expert panel found that current evidence supports the clinical benefit of achieving low testosterone levels during ADT, and encourage adoption of ≤0.7 nmol/l as a new castrate level threshold. The panel recommends regular monitoring of testosterone (e.g., every 3-6 months) and prostate-specific antigen (PSA) levels as clinically appropriate (e.g., every 3-6 months) during ADT, with reassessment of therapeutic strategy if testosterone is not suppressed or if PSA rises regardless of adequate testosterone suppression. The panel also emphasizes the need for greater awareness and education regarding testosterone assay specifications, and strongly promotes the use of mass spectrometry-based assays to ensure accurate measurement of testosterone at castrate levels.

Discordance between testosterone measurement methods in castrated prostate cancer patients

“…The most important consequence would be to not recognize a patient as being CRPC rather than suboptimally castrated. Based on IA testosterone level determination, prostate-specific antigen (PSA) levels and metastatic status, it is now recommended to either change the ADT drug, or add bicalutamide, enzalutamide or abiraterone acetate (Canadian guidelines) (10, 24). Herein, we propose an updated clinical decision algorithm based on the one by Klotz et al .…”

“…Herein, we propose an updated clinical decision algorithm based on the one by Klotz et al . (10), which introduces serum testosterone level measurement by MS when PCa patients under ADT are measured with testosterone levels >0.7 nM by IA (Fig. 5, orange panel).…”

“…This algorithm involves regular testosterone measurements to guide clinicians in their decision making. Therefore, having accurate testosterone measurements is instrumental in the clinical management of PCa patients under ADT (10).…”

“…Recent studies have suggested that testosterone levels <0.7 nM under ADT are associated rather with a longer time to castration-resistant prostate cancer (CRPC) or death compared to higher testosterone levels (4, 12, 13, 14, 15, 16, 17). Contemporary electrochemiluminescent immunoassay methods have a lower LLOQ (around 0.4 nM), thus lower castration testosterone levels are now targeted (<0.7 nM) (10).…”

Clinical Recommendation for Diagnostics, Treatment and Monitoring of Patients with Prostate Cancer

“…Ako se zabilježe vrijednosti testosterona > 0,7 nmol/L nužno je zamijeniti agonist LH-RH, uvesti antiandrogen ili bolesniku izvesti bilateralnu orhidektomiju. 2,36 Potpuna androgena blokada istodobnim provođenjem kastracijskog liječenja i primjenom antiandrogena ima minimalan učinak na ukupno preživljenje te se ne smatra standardnim liječenjem (IC). 4,37 U bolesnika s primarno metastatskim, kastracijski "naivnim" rakom prostate uz kastracijsku terapiju treba razmotriti dodatno liječenje:…”