Abstract
Background
Bipolar androgen therapy (BAT) is an emerging treatment strategy for men with metastatic
castration resistant prostate cancer (mCRPC) whereby serum testosterone is cycled
from supraphysiologic to near-castrate levels each month. BAT has been shown to induce
clinical responses in a significant proportion of patients, some of which are extreme.
We explored the clinical and molecular characteristics of patients with mCRPC who
achieved deep responses to BAT.
Methods
We conducted a retrospective analysis of patients with mCRPC treated with BAT at Johns
Hopkins. We identified 22 of 114 (19%) patients with mCRPC who achieved ≥70% PSA reductions
upon treatment with BAT. All patients were treated using 400 mg testosterone cypionate
intramuscularly every 28 days, together with continuous LHRH agonist therapy. Clinical-grade
DNA sequencing was obtained using commercially available assays.
Results
Somatic next-generation sequencing was obtained for 15 of 22 (68%) patients. Of these
15 extreme PSA responders with sequencing data available, All 15 of 15 (100%) harbored
a pathogenic mutation in TP53 and/or a homologous recombination DNA repair (HRD) gene. Among the subset of patients
with measureable disease (N = 15), 10 patients (67%) achieved an objective response
including one patient with a complete response. The median radiographic progression-free
survival of these deep PSA responders was 11.3 months (95% CI, 7.9-25.0 months).
Conclusions
We observed an enrichment of TP53 and HRD mutations in mCRPC patients with extreme PSA responses to BAT, with durability
lasting about a year. These data support the hypothesis that BAT may most benefit
patients with DNA repair-deficient mCRPC. Further studies of BAT in biomarker-selected
mCRPC populations (ie, TP53/HRD-mutated) are warranted.
Keywords
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Article Info
Publication History
Published online: August 15, 2021
Accepted:
August 10,
2021
Received in revised form:
May 14,
2021
Received:
March 22,
2021
Footnotes
Prior Presentation of Work: 2021 Genitourinary Cancers Symposium (GU ASCO).
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
