Prostate cancer is the most prevalent malignancy in men in Europe and the United States. And in China, its incidence is also increasing year by year. It is estimated that in 2015, there were 60,300 new cases of prostate cancer and about 26,600 deaths in China.
Most patients with prostate cancer in China already have metastases at the time of initial diagnosis. The current first-line treatment option for patients with advanced metastatic prostate cancer remains endocrine therapy, but after an average of 18 to 24 months of endocrine therapy, almost all patients will progress to castration-resistant prostate cancer, CRPC. Once a patient enters the CRPC stage, the prognosis is generally poor.
For this reason, the Chinese Anti-Cancer Society has organized a consensus for urologic oncologists to help develop the best treatment plan for patients with CRPC. The main contents are summarized below:
Definition of CRPC
CRPC refers to prostate cancer that progresses despite continuous androgen deprivation therapy.
The diagnosis of CRPC requires both of the following 2 conditions:
- Serum testosterone at depleted levels (<1.7 nmol/L);
- Biochemical progression: rise in prostate-specific antigen (PSA) measured on 3 consecutive occasions 1 week or more apart, with two consecutive increases of 50% or more from the nadir and PSA>2 μg/L; or imaging progression: 2 or more new lesions on bone scan or soft tissue lesions that meet solid tumor response evaluation criteria lesion enlargement.
Treatment for CRPC
| New endocrine therapeutics |
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| Cytotoxic drugs |
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| Immunotherapy drugs |
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| Drugs related to bone metastasis treatment |
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Treatment strategies for CRPC
CRPC without metastasis (stage M0)
- Patients with a rapid PSA doubling time (<8 months) are prone to distant metastases and therefore imaging should be performed every 3 to 6 months. For patients with slower PSA multiplication times (>12 months), imaging should be performed every 6 to 12 months.
- Adjustment of endocrine therapy based on regular evaluation is recommended. First-generation anti-androgens (flutamide, bicalutamide), estramustine, steroid hormone therapy, or anti-androgen withdrawal therapy may be used depending on the patient’s condition.
- For some patients, local therapies such as subtractive prostatectomy or prostate specific radiotherapy may be considered if they are well informed.
Metastatic CRPC without pain or mild pain symptoms (stage M1)
- Patients with debulking alone: addition or switch to first-generation anti-androgens or corticosteroids resulted in a transient decrease in PSA in 30% of patients (level of evidence 3).
- Patients already on combination androgen blockade therapy: Withhold anti-androgen drugs and observe for response to withdrawal of anti-androgen therapy.
- Abiraterone 1 000 mg (1 d/d) in combination with prednisone 5 mg (2 d/d)
- Enzalutamide 160 mg (1 time/d)
- Docetaxel 75 mg/m (1 time every 3 weeks) combined with prednisone 5 mg (2 times/d)
Metastatic CRPC with significant pain symptoms (stage M1)
- Docetaxel 75 mg/m (once every 3 weeks) in combination with prednisone 5 mg (2 doses/d)
- Abiraterone 1 000 mg (1 time/d) combined with prednisone 5 mg (2 times/d) or enzalutamide 160 mg (1 time/d).
Metastatic CRPC progressing after chemotherapy (stage M1)
- Cabazitaxel 25 mg/m (once every 3 weeks) combined with prednisone 5 mg (2 doses/d).
- Abiraterone 1 000 mg (1 d/d) combined with prednisone 5 mg (2 d/d).
- Enzalutamide 160 mg (1 d/d).
- Other treatment options (unknown survival benefit): if chemotherapy was assessed as effective before interruption of docetaxel chemotherapy, chemotherapy may be tried again. Mitoxantrone combined with prednisone may relieve symptoms of pain caused by prostate cancer.
CRPC in specific pathological types
Patients who do not respond to first-line androgen deprivation therapy and who progress clinically or on imaging but do not have an elevated PSA should consider prostate cancer with neuroendocrine differentiation or small cell carcinoma of the prostate and may be considered for a definitive diagnosis with a focal puncture biopsy. Combination chemotherapy regimens, such as cisplatin combined with etoposide or carboplatin combined with etoposide, can be used for these patients.
M1-CRPC in poor physical status
The fitness status score developed by the Eastern Cooperative Oncology Group (ECOG) is often used to classify patients with oncology. Oncology patients with a fitness status score ≤1 typically tolerate these treatments, whereas patients with a fitness status score ≥2 are less likely to benefit from these treatments. Therefore, the following treatment regimen is recommended for patients with M1-CRPC who have poor fitness status:
- Not receiving docetaxel chemotherapy.
- Abiraterone 1 000 mg (1 time/d) in combination with prednisone 5 mg (2 times/d) or enzalutamide 160 mg (1 time/d).
- Poor physical status due to tumor: Patients who are previously fit but have severe pain, weakness, and weight loss due to rapid tumor progression in the skeleton or parenchymal organs may try docetaxel or mitoxantrone chemotherapy, however, treatment doses and toxic adverse effects must be considered.
- Patients with M1-CRPC with poor fitness status due to bone pain: 223Ra may prolong survival in patients with CRPC with low fitness status score and bone metastases alone with bone pain. If the poor fitness score is due to bone pain, treatment with 223Ra may benefit such patients.
- Previous docetaxel chemotherapy:
Can be treated with best supportive care, abiraterone, enzalutamide, or radionuclides.
Bone related treatment
- Treatment to prolong survival: For patients with CRPC with bone metastases only, 223Ra therapy is recommended once every 4 weeks for 6 courses.
- Supportive therapy: 223Ra every 4 weeks for 6 courses.
- Supportive therapy: denosumab 120 mg or zoledronic acid 4 mg every 4 weeks to prevent bone-related events.
- Palliative radiotherapy.
- Palliative radiotherapy.
- Most prostate cancer bone metastases are sensitive to radiotherapy. External radiation radiotherapy targeting specific lesions can result in partial or complete pain relief in the vast majority of patients.
- For patients with CRPC with multiple bone metastases, treatment with systemic 89Sr radionuclide therapy may be effective for symptomatic relief but carries the risk of severe bone marrow suppression and transfusion dependency.
- Spinal cord compression is suspected and requires immediate diagnosis and treatment. Treatment options are surgical tumor reduction + radiotherapy, internal fixation + radiotherapy, or radiotherapy + steroid therapy.
Optional treatment
- Estramustine and estrogen
- Clinical trials: Due to the poor long-term prognosis of patients with CRPC, patients are recommended to actively participate in clinical trials of new drugs.