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Response to bipolar androgen therapy and PD-1 inhibition in a patient with metastatic castration-resistant prostate cancer and a germline CHEK2 mutation
  1. Benjamin T Berger1,
  2. Matthew K Labriola1,2,
  3. Emmanuel S Antonarakis3 and
  4. Andrew J Armstrong1,2
  1. 1Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
  2. 2Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, North Carolina, USA
  3. 3Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota Academic Health Center, Minneapolis, Minnesota, USA
  1. Correspondence to Dr Benjamin T Berger; benjamin.t.berger{at}; Dr Andrew J Armstrong; andrew.armstrong{at}


We present the case of a patient with germline CHEK2-mutated metastatic castration-resistant prostate cancer (mCRPC) who responded to bipolar androgen therapy (BAT) combined with pembrolizumab after progressing through multiple lines of therapy. The patient was diagnosed in his 40s following an elevated screening prostate-specific antigen and biopsy. Over the course of 20 years, he progressed through nearly all standard therapies including androgen deprivation, combined androgen blockade, traditional chemotherapy, targeted therapies and experimental agents. He was ultimately treated with BAT, whereby the patient’s cycle was between low (castrate) and high (supraphysiological) testosterone levels. This counterintuitive approach resulted in a marked response to BAT plus pembrolizumab consolidation lasting 13 months. His underlying germline mutation in CHEK2, an important mediator of DNA repair, may have sensitised the cancer cells to the DNA damage caused by BAT. Single case report outcomes should not be used as evidence of efficacy for treatment regimes. Our case supports further investigation into BAT plus immunotherapy for patients with DNA repair-deficient mCRPC.

  • Oncology
  • Prostate Cancer
  • Prostate
  • Cancer intervention

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  • Contributors BB drafted the manuscript and designed the figures. MKL and EA supervised the drafting of the manuscript and made critical revisions. AA cared for the patient, conceived the report, directed literature review and made critical revisions to the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.