current data indicate that the androgen receptor continues to play a major role in the control of prostate cancer growth even when serum levels of testosterone are in the castrate range (less than 50 ng/dL).
androgen deprivation treatment focusing on medical/surgical castration is the initial systemic approach for patients with metastatic prostate cancer.
castration resistance does not equal hormone resistance.
all of the above adequately describe the castration-resistant state.
in patients with castration-resistant disease, responses to subsequent androgen-receptor–targeted treatments continue to show a benefit.
Careful clinical monitoring of patients in clinical practice, including regular physical exams and sequential assessments of radiologic parameters and serum prostate-specific antigen (PSA) levels, facilitates early identification of patients who are becoming resistant to secondary hormonal manipulations.
The vast majority of patients treated with endocrine manipulations will develop evidence of disease progression and eventually require chemotherapy.
Determination of castration resistance requires clinical evidence of disease progression to primary and secondary hormonal manipulations.
The definition of castration resistance is based on well-defined clinical and pathologic criteria such as Gleason score and extent of disease.
Docetaxel infusion every 3 weeks (as many as 10 cycles) given in conjunction with daily oral prednisone is the standard schedule that has been shown to prolong survival and improve quality of life compared with mitoxantrone.
Significant clinical benefits are seen in patients regardless of their age, functional status, and presence or absence of pain.
Patients demonstrating rising serum PSAs during the first three cycles of treatment should be taken off treatment because it is not effective.
Patients with metastatic castration-resistant disease who have favorable functional status (fully ambulatory, asymptomatic), no visceral involvement, and normal hemoglobin and serum lactate dehydrogenase (LDH) have survival outcomes frequently in excess of 2 years.
Frequent toxicities associated with docetaxel treatment include fatigue, myelosuppression, modest neuropathy, lacrimation, and nail changes, among others. Routine evaluation before each cycle is indicated.
Cabazitaxel was shown to prolong survival compared with mitoxantrone in patients previously treated with docetaxel.
Patients demonstrating disease progression after docetaxel can still survive longer than 1 year with cabazitaxel treatment.
Data on the TROPIC trial suggest that patients who fail to respond or develop early evidence of disease progression after docetaxel may benefit from cabazitaxel.
The toxicity pattern of cabazitaxel suggests a lower incidence of neuropathy, fatigue, lacrimation, and nail changes but has a higher incidence of neutropenic fever and diarrhea compared with docetaxel.
All of the above are correct.
CYP17 inhibitors target androgen synthesis both of adrenal and intracrine source and yield significant benefit in patients treated with first-line gonadal suppression who subsequently develop evidence of disease progression. This effect has been shown in patients with or without previous treatment with docetaxel.
Enzalutamide is a more recent nonsteroidal antiandrogen that differs from the first-generation compounds (flutamide, bicalutamide, and nilutamide) based on a greater AR affinity, AR nuclear translocation, and DNA binding. Most patients with castration-resistant disease benefit from treatment, which was shown to be significantly superior to placebo in prospective randomized trials.
The side effects with abiraterone acetate include a mineralocorticoid excess state (efficiently prevented by a concomitant administration of prednisone), fatigue, abnormal liver function tests, possible cardiac toxicity, and potential drug interactions.
The benefits from CYP17 inhibitors (abiraterone) and AR antagonists (enzalutamide) are most likely more pronounced in patients who have not received prior docetaxel treatment.
All patients with known bone metastasis should be carefully assessed clinically for the possibility of epidural cord or nerve root compression. Administration of high-dose dexamethasone and early magnetic resonance imaging (MRI) should be used, and more definitive treatment with radiation or neurosurgical decompression should be considered.
Most current systemic treatments are effective for managing extensive bone metastasis even if there is evidence of nerve root or cord compression.
Administration of narcotic analgesics is the appropriate management, and if pain management becomes more challenging, patients should be referred to hospice.
Patients with back pain and stable skeletal radiographs should be treated with narcotic analgesics and corticosteroids. If improvement occurs, no further evaluation is necessary.
If the PSA is not rising and the workup with a bone scan and CT scans reveal stable disease, it can be assumed that cord compression or other complex neurologic involvement is unlikely.
These patients usually benefit from hormonal therapy including all ARtargeted compounds
Serum PSA is low or undetectable and the PSA stains in tumor biopsies are usually negative. These tumors do not express androgen receptors.
A small proportion of patients demonstrate evidence of a rapidly progressing disease predominantly involving visceral sites, with low or no PSA expression. Biopsy is indicated because it will affect treatment decisions.
All statements are correct except a
Patients with this clinical syndrome often demonstrate anaplastic tumors at biopsy, some with small-cell features, and most stain positive for neuroendocrine markers. Platinum-based chemotherapy has been show to offer some benefits for patients with the small-cell variety, whereas those with anaplastic tumors that are not of the small-cell subtype should be treated with taxane-based chemotherapy.
Radium-223 is an alpha-emitting radiopharmaceutical that has recently shown to be associated with a survival advantage compared to symptomatic/palliative care.
Alpha particles are approximately 7000 times heavier than beta particles, and as few as one or two hits can be sufficient to cause cell death, in comparison with hundreds or thousands of hits required from beta particles. In addition, alpha particles have a very short path length (less than 100 μm), which may spare surrounding healthy bone marrow, thereby limiting hematologic toxicities.
It was approved only for patients who have received prior docetaxel treatment.
Radium-223 infusion has shown a very favorable toxicity spectrum with low hematological toxicity rates.
It is indicated for patients with bone metastasis, hemoglobin greater than 10 g/L and lymph-node metastasis smaller than 3 cm.
Sipuleucel-T is a treatment option for patients with minimally or asymptomatic metastatic prostate cancer. Treatment is generally very safe. There is no evidence that sipuleucel-T treatment causes symptomatic relief, any clinically meaningful PSA declines, or delay in disease progression. The drug was approved based on a survival benefit compared to placebo.
Sipuleucel-T should be offered to patients with no evidence of metastasis as long as their disease is castration resistant.
Sipuleucel-T is approved for all patients with castration-resistant disease as long as they are symptomatic.
Sipuleucel-T treatment results in PSA declines and prolongation of progression-free survival, but no survival improvements.
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