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Hormone-refractory prostate cancer - Treatment
Last reviewed: 06.07.2025
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Hormone-refractory prostate cancer is a heterogeneous disease that includes several subgroups of patients with different average life expectancies.
Approximate life expectancy of patients with hormone-refractory prostate cancer depending on the clinical picture
Clinical picture |
Estimated life expectancy of the patient |
Asymptomatic PSA elevation |
|
No metastases Minimum metastases A large number of metastases |
24-27 months 16-18 months 9-12 months |
| Symptomatic increase in PSA | |
Minimum metastases A large number of metastases |
14-16 months 9-12 months |
A large number of terms have been used to define prostate cancer that progresses after initially effective treatment. However, it is necessary to distinguish androgen-independent but hormone-sensitive prostate cancer from truly hormone-refractory prostate cancer. In the former case, secondary hormonal manipulations (withdrawal of antiandrogens, estrogens, glucocorticoids) usually have a different effect.
Criteria for hormone-refractory prostate cancer
- Castration level of testosterone in serum.
- Two or more results with a PSA level 50% above the nadir in three consecutive tests with an interval of 2 weeks.
- Discontinuation of antiandrogens for at least 4 weeks (necessary to confirm the diagnosis of hormone-refractory prostate cancer).
- Increased PSA despite secondary hormonal manipulation (necessary to confirm the diagnosis of hormone-refractory prostate cancer).
- Progression of metastases in bones or soft tissues.
Evaluation of the effectiveness of treatment of patients with hormone-refractory prostate cancer
Although there is no complete understanding of how treatment affects PSA levels, this marker is one of the main predictors of patient survival. PSA levels should be assessed in conjunction with clinical data.
Thus, a long-term (up to 8 weeks) decrease in the amount of PSA by more than 50% during treatment, as a rule, predetermines a significantly longer life expectancy for patients.
In patients with symptomatic metastatic bone lesions, a decrease in pain intensity or its complete disappearance can serve as parameters for assessing the effectiveness of treatment.
[ 7 ], [ 8 ], [ 9 ], [ 10 ], [ 11 ]
Androgen blockade in patients with hormone-refractory prostate cancer
Progression of prostate cancer against the background of castration means the transition of the disease to an androgen-refractory form. However, before establishing this diagnosis, it is necessary to make sure that the level of testosterone in the blood corresponds to the castration level (less than 50 ng / dl).
Despite the transition of prostate cancer to a hormone-refractory form, androgen blockade must be maintained. The data that maintaining androgen blockade allows prolonging the life of patients is contradictory, but most scientists agree on its necessity.
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Second line hormonal treatment
For patients with prostate cancer progression against the background of androgen blockade, the following therapeutic options are possible: discontinuation of antiandrogens, addition of antiandrogens to therapy, treatment with estrogens, adrenolytics and other new drugs currently being studied.
Regardless of the initial choice of hormonal treatment (medicinal/surgical castration or ionotherapy with antiandrogens), it is necessary to create maximum androgen blockade by adding antiandrogens or LHRH analogues to the treatment regimen, respectively.
In the future, if the antiandrogen flutamil is used to treat a patient, it can be replaced with bicalutamide at a dose of 150 mg, the effect of which is seen in 25-40% of patients.
A mandatory condition for initiating the second line of hormonal treatment is determining the amount of testosterone in the blood and maintaining it at the castration level.
In case of further progression of the disease, one of the therapeutic options is the discontinuation of antiandrogen drugs. In this case, antiandrogen withdrawal syndrome (a decrease in the PSA level by more than 50%) occurs in about a third of patients with hormone-refractory prostate cancer within 4-6 weeks after stopping the drug. The duration of the effect, as a rule, does not exceed 4 months.
Considering that about 10% of circulating androgens are synthesized by the adrenal glands, their removal from the blood (bilateral adrenalectomy, drug ablation) can stop the progression of hormone-refractory prostate cancer since some tumor cells, as a rule, retain hormonal sensitivity. To achieve this goal, ketoconazole and glucocorticoids are used; the response to treatment with these drugs occurs on average in 25% of patients (duration about 4 months).
As a second-line treatment, it is also possible to use high doses of estrogens, the effect of which is presumably realized through a direct cytotoxic effect on tumor cells. The clinical effect, achieved on average in 40% of patients, is often accompanied by complications from the cardiovascular system (deep vein thrombosis of the lower extremities, myocardial infarction).
Non-hormonal treatment (cytotoxic drugs)
Currently, several chemotherapy regimens are used for prostate cancer in patients with hormone-refractory disease. Slightly more effective (based on the analysis of patient survival) are treatment regimens using docetaxel compared to mitoxantrone and combinations of the latter with prednisolone. The severity of side effects does not generally differ when using different regimens. The average survival time of patients treated with docetaxel is 15.6-18.9 months. The time of administration of chemotherapeutic drugs is usually determined individually; the potential benefit from the use of chemotherapeutic agents and possible side effects should be discussed with each patient.
One of the most effective therapeutic regimens at present is the use of docetaxel at a dose of 75 mg/m2 every 3 weeks. When using docetaxel, side effects usually occur: myelosuppression, edema, fatigue, neurotoxicity, liver dysfunction.
Before treatment, a double confirmation of the progressive increase in the PSA level against the background of the hormone therapy is required. For a correct interpretation of the effectiveness of cytotoxic treatment, the PSA level before its start should be more than 5 ng/ml.
Combinations of docetaxel with calcitriol are currently being studied, as well as alternative chemotherapy regimens using pegylated doxorubicin, estramustine, cisplatin, carboplatin and other agents with encouraging results.