What is hormone-refractory prostate cancer?

Updated: Dec 29, 2020
  • Author: Martha K Terris, MD, FACS; Chief Editor: Edward David Kim, MD, FACS  more...
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In patients with serum testosterone castrate levels, hormone-refractory prostate cancer is defined as 2-3 consecutive rises in prostate-specific antigen (PSA) levels obtained at intervals of greater than 2 weeks and/or documented disease progression based on findings from CT scan and/or bone scan, bone pain, or obstructive voiding symptoms. In a subgroup of patients, the PSA level does not rise at diagnosis or throughout the entire course of the disease.

If given enough time, all patients with metastatic disease become resistant to androgen ablation. The median time to symptomatic progression after a rise in PSA level of more than 4 ng/mL is approximately 6-8 months, with a median time to death of 12-18 months. Once the patient exhibits symptoms, the median survival is less than 1 year. No method predicts whether these patients may benefit from androgen withdrawal versus continued hormone therapy.

Therapeutic options for patients with hormone-refractory prostate cancer are limited, with lack of evidence for long-term survival. The best outcome for these patients is to maintain or to improve their quality of life.

In a large-scale, placebo-controlled trial, denosumab (Xgeva) significantly increased bone metastasis–free survival by a median of 4.2 months compared with the placebo group. Denosumab also notably delayed time to first bone metastasis. Between the groups, overall survival did not differ. Osteonecrosis of the jaw and hypocalcemia were observed in 5% and 2% of patients, respectively. [38] The FDA has approved denosumab for prevention of skeletal-related events (eg, bone fractures and pain) in patients with bone metastases from prostate cancer and other solid tumors.

Short-term palliative response and improved quality of life in these patients is achieved presently by single or multimodal therapies, which may include the following:

  • Second-line hormonal manipulations
  • Addition of antiandrogens
  • Corticosteroids
  • Radiation therapy
  • Chemotherapeutic agents
  • Mitoxantrone
  • Taxanes
  • Bisphosphonates
  • PARP inhibitors
  • Chemohormonal therapy
  • Other investigational approaches

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