Hormone Refractory Prostate Cancer - Treatment

Hormone refractory prostate cancer is a heterogeneous disease that includes several subgroups of patients with different average longevity.

Approximate life expectancy of patients with hormone-refractory prostate cancer, depending on the clinical picture

Clinical picture	Approximate life expectancy of the patient
Asymptomatic increase in PSA
No metastases The minimum of metastases A large number of metastases	24-27 months 16-18 months 9-12 months
Symptomatic increase in PSA
The minimum of metastases A large number of metastases	14-16 months 9-12 months

A large number of terms were used to determine prostate cancer, progressing after initially effective treatment. However, it is necessary to distinguish between androgen-independent, but hormone-sensitive prostate cancer from true hormone-refractory prostate cancer. In the first case, secondary hormonal manipulation (the abolition of anti-androgens, estrogens, glucocorticoids), as a rule, have a different effect.

[1], [2], [3],

Criteria for hormone-refractory prostate cancer

• Castration level of testosterone in the blood serum.
• Two results or more with a PSA level is 50% higher than a nadir with three consecutive analyzes with a 2-week interval.
• Abolition of anti-androgens for at least 4 weeks (necessary to confirm the diagnosis of hormone-refractory prostate cancer).
• PSA growth, despite secondary hormonal manipulation (necessary to confirm the diagnosis of hormone-refractory prostate cancer).
• Progression of metastases in bones or soft tissues.

[4], [5], [6]

Evaluation of the effectiveness of treatment of patients with hormone-refractory prostate cancer

Despite the lack of a full understanding of how the treatment affects the level of PSA, this marker serves as one of the main predictors of the life expectancy of patients. The level of PSA should be assessed in conjunction with clinical data.

So, a long (up to 8 weeks) decrease in the amount of PSA is more than 50% on the background of treatment. As a rule, predetermines a much longer life expectancy of patients.

In patients with symptomatic metastatic bone disease, a decrease in the intensity of pain or a complete disappearance of the bones can serve as parameters for evaluating the effectiveness of the 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 into the androgen refractory form. Nevertheless, before establishing this diagnosis, you need to make sure that the testosterone level in the blood corresponds to castration (less than 50 ng / dl).

Despite the transition of prostate cancer into a hormone-refractory form, androgen blockade must be maintained. Data for that. That the maintenance of androgenic blockade allows to prolong a life of patients, are inconsistent, however the majority of scientists agree in opinion about its necessity.

[12], [13], [14], [15], [16], [17]

The second line of hormonal treatment

For patients with progression of prostate cancer against the background of androgen blockade, the following therapeutic options are possible: the removal of antiandrogens, the addition of antiandrogens to therapy, the treatment with estrogens, adrenolytic drugs and other new drugs currently being studied.

Regardless of the initial choice of hormonal treatment (drug / surgical castration or ionotherapy with antiandrogens), it is necessary to create maximum androgenic blockade by adding anti-androgen or LHRH analogues to the treatment regimen, respectively.

In the future, if antiandrogen flutamyl is used to treat a patient, it can be replaced with bicalutamide in a dose of 150 mg, the effect is manifested in 25-40% of patients.

A mandatory condition for the initiation of the second line of hormonal treatment is the determination of the amount of testosterone in the blood and maintaining it at the castration level.

In the case of further progression of the disease, one of the therapeutic options is the elimination of antiandrogenic drugs. In this case, the withdrawal syndrome of antiandrogens (PSA reduction of more than 50%) occurs in about a third of patients with hormone-refractory prostate cancer within 4-6 weeks after discontinuation of the drug. The duration of the effect, as a rule, does not exceed 4 months.

Given that about 10% of the circulating androgens are synthesized by the adrenal glands, removing them from the blood (bilateral adrenalectomy, drug ablation) can stop the progression of hormone refractory prostate cancer because some tumor cells tend to retain hormonal sensitivity. To achieve this, use ketoconazole and glucocorticoids, response to treatment These drugs occur on average in 25% of patients with (duration about 4 months).

As the treatment of the second line, it is also possible to use estrogen in high doses, the effect of which, presumably, is realized by direct cytotoxic effect on tumor cells. The clinical effect, achievable on average in 40% of patients, often accompanies complications from the cardiovascular system (deep vein thrombosis of the lower extremities, myocardial infarction).

Non-hormonal treatment (cytotoxic drugs)

Currently, several chemotherapy schemes for prostate cancer are used in patients with hormone-refractory disease. The treatment regimens using docetaxel in comparison with mitoxantrone and combinations of the latter with prednisolone are somewhat more effective (based on an analysis of patients' lifespan). The severity of side effects in general is not different when using different schemes. The life expectancy of patients on the background of treatment with docetaxel is on the average 15.6-18.9 months. The timing of the appointment of chemotherapeutic drugs is usually determined individually, the potential benefit from the use of chemotherapeutic agents and possible side effects must be discussed with each patient.

One of the most effective therapeutic regimens is currently the use of docetaxel at a dose of 75 mg / m - every 3 weeks. When using docetaxel, as a rule, there are side effects: myelosuppression, swelling, fatigue, neurotoxicity, impaired liver function.

Before treatment, it is necessary to confirm the progressive increase of PSA level twice on the background of hormonal therapy. For a correct interpretation of the effectiveness of cytotoxic treatment, the PSA level before its beginning should be more than 5 ng / ml.

Currently, studies of combinations of docetaxel with calcitriol, as well as alternative regimens of chemotherapy using pegylated doxorubicin, estramustine, cisplatin, carboplatin and other agents with encouraging results are being carried out.