RU2731002C1 - Method of treating prostate cancer - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely oncourology, radiotherapy, and can be used for treating prostate cancer. It is followed by androgen deprivation with zoladex, control of prostate-specific antigen PSA and blood testosterone for correction of treatment, and radiation therapy. Androgen deprivation is performed until blood PSA level is less than 1 ng/ml. Blood testosterone is then determined. If its value is less than 20 ng/dl, Zoladex is administered for following 6 months and the split radiotherapy to 66–70 Gy. If blood testosterone level is detected within 20 ng/dl to 50 ng/dl, administration of Zoladex and daily administration of 100 mg of Casodex for next 9 months and radiotherapy with a split course to total boost dose 70–74 Gy are prescribed. If blood testosterone level is more than 50 ng/dl, androgen deprivation with Zoladex and daily administration of 150 mg Casodex within next 9 months. Every 3 months blood testosterone level is examined and only after testosterone level drops to less than 50 ng/dl, radiation therapy is prescribed by continuous course to total boost dose 76 Gy.EFFECT: method provides higher clinical effectiveness ensured by individualisation of the androgen deprivation and radiation therapy, including with respect to the total radiation dose, which enables reducing the probability of severe radiation complications from the bladder, rectum and, as a result, higher comfort of such patients and optimization of financial costs for their treatment, increased recurrence-free life.1 cl, 7 ex

Description

The invention relates to medicine, to oncourology, radiotherapy, and can be used in the treatment of patients with a malignant tumor of the prostate gland, in which the PSA level of the blood is equal to or exceeds 10 ng / ml, which indicates a high risk of tumor progression.

A known method for choosing tactics for the treatment of locally advanced prostate cancer N0 (RF Patent No. 2680015, IPC A61N 5/10, publ. 2019). Determine the quantitative morphological signs, indicating the differentiation of tumor cells on the Glisson scale. The PSA values are determined, on the basis of which the necessary course of radiation therapy is selected. Radiation therapy is carried out up to SOD 40 Gy at the first stage of the split course, and the irradiation for the entire course is 68-74 Gy.

The disadvantage of this method is a significant decrease in the effectiveness of treatment, which leads to a decrease in life expectancy, since the appointment of radiation therapy is carried out only on the basis of the initial PSA level of the blood and data on the degree of tumor differentiation, and this does not allow determining the most adequate treatment regimen. Refusal to use androgen deprivation in combination with radiation therapy also inevitably negatively affects the survival of patients with prostate cancer.

A known method for choosing tactics for the treatment of locally advanced prostate cancer (RF Patent No. 2524309, IPC A61N 5/10, publ. 2014), including determining the PSA level of the blood. Radiation therapy is performed and zoladex is administered at a dose of 3.6 mg with an interval of 28 days before, during and after the irradiation. If the blood PSA level is below 1 ng / ml, three months after the start of treatment with zoladex, it is continued to be administered for the next 6 months. In this case, radiation therapy is carried out in a split course in the mode of classical fractionation of the radiation dose up to SOD 64 Gy. If a PSA level below 1 ng / ml is detected only six months after the start of the administration of zoladex, it continues to be administered for the next 9 months. In this case, radiation therapy is carried out in a split course in the mode of classical fractionation of the radiation dose up to SOD 70 Gy. If the PSA level is detected after six months above 1 ng / ml, zoladex is administered and casodex is administered daily at a dose of 50 mg for the next 12 months. In this case, radiation therapy is carried out in a split course in the mode of hypofractionation of the radiation dose up to SOD 70 Gy.

The disadvantage of this method is the appointment of radiation therapy and the determination of the duration of androgen deprivation only on the basis of a decrease in blood PSA in response to an induction course of androgen deprivation above or below 1 ng / ml, which does not take into account the individualization of the total dose of radiation and allows only partially create conditions for increasing radiosensitivity tumor cells to radiation therapy.

The closest is a method of treating prostate cancer, including androgenic deprivation with zoladex, control of the level of prostate-specific antigen PSA and blood testosterone for adjusting the treatment, radiation therapy (Zaderin V.P. et al. Intermittent hormone therapy for locally advanced prostate cancer. Bulletin of the Samara Center of the Russian Academy of Sciences. 2009. T. 11.No.5 (2) pp. 460-463). The method includes androgen deprivation with zoladex and casodex, control of the level of prostate-specific antigen (PSA) and blood testosterone for adjusting the treatment, and radiation therapy.

The disadvantages of this method are the insufficient effectiveness of treatment due to the fact that only the maximum androgen deprivation is prescribed without taking into account the initial PSA level and the intensity of its decrease; for an acceptable level of decrease in blood PSA, its rather high value, equal to 4 ng / ml, is taken; the degree of testosterone decrease below the castration level in response to androgen deprivation is not taken into account, which does not allow adjusting the radiation therapy regimen.

The objective of the present invention is to eliminate these disadvantages, increase the effectiveness of treatment by individualizing the appointment of androgen deprivation and radiation therapy, including with respect to the total dose of radiation, which will reduce the likelihood of severe radiation complications from the bladder, rectum and, as a consequence, increasing the comfort of life of such patients and optimizing the financial costs of their treatment, increasing the relapse-free life expectancy.

To solve this problem in a method for treating prostate cancer, including androgenic deprivation with zoladex, control of the level of prostate-specific antigen PSA and blood testosterone to adjust the treatment, conducting radiation therapy, it is proposed to carry out androgenic deprivation until the PSA level of blood is less than 1 ng / ml. After that, the level of testosterone in the blood is determined, and if its value is less than 20 ng / dl, the administration of zoladex is prescribed for the next 6 months and a split course of radiation therapy to SOD 66-70 Gy. If the level of testosterone in the blood is detected in the range from 20 ng / dl to 50 ng / dl, administration of zoladex and a daily intake of 100 mg of casodex for the next 9 months and radiation therapy with a split course up to SOD 70-74 Gy. If the blood testosterone level is more than 50 ng / dl, androgen deprivation with zoladex is continued and daily intake of 150 mg casodex for the next 9 months, the blood testosterone level is examined every 3 months and radiation therapy is prescribed for a continuous course up to SOD 76 Gy only after the level testosterone levels will drop to less than 50 ng / dL.

The proposed method makes it possible to individualize the treatment of prostate cancer by determining the duration and nature of further androgenic deprivation prescribed by the total focal dose of radiation therapy, based not only on the initial blood PSA level, but also taking into account the degree of its decrease and decrease in testosterone level within the castration level in response to carry out androgen deprivation. The claimed approach provides for the appointment of maximum androgenic deprivation for a long time only in the case of insufficient sensitivity in response to monotherapy with zoladex. This approach makes it possible to optimize the financial costs of medical institutions for carrying out therapeutic measures in patients with one of the most common tumor localizations - prostate cancer. Also, the claimed method will reduce the risk and severity of complications that often accompany androgen deprivation, which requires interruption of such treatment and requires additional drug provision. Prescribing the maximum tolerant doses of radiation therapy only in exceptional cases sharply reduces the likelihood of severe radiation complications from the bladder and rectum, which also increases the comfort of life for such patients. The radiation areas are determined individually by the radiotherapist. The main advantage of the proposed approach in its application is the guarantee of a high relapse-free life expectancy of patients with prostate cancer, who were initially diagnosed with a sufficiently high risk of tumor progression.

The method is carried out as follows.

If there is a suspicion of the presence of a neoplastic process in the prostate gland, a PSA blood test is performed, and if the PSA level of the blood is higher than 4 ng / ml, a puncture biopsy of the prostate is prescribed. After the morphological examination of the biopsy specimen establishes the presence of prostate cancer, the degree of differentiation of which according to Glisson corresponds to 7 or more points, a decision is made on the appointment of radiation therapy.

After that, the level of increase in blood PSA is analyzed, and if it is equal to or greater than 10 ng / ml, it is recommended to carry out treatment according to the proposed method. Androgen deprivation is preliminarily prescribed according to known schemes, which includes, for example, monotherapy with zoladex, the administration of which is carried out subcutaneously in the area of the fat fold of the abdomen in a regimen of 3.6 mg once every 28 days. After a decrease in blood PSA to a level of <1 ng / ml is noted, the blood testosterone level is additionally examined, and if the blood testosterone level is ≤20 ng / dl, the administration of zoladex is continued for the next 6 months and radiation therapy is prescribed with a split course until the total focal dose is 66-70 Gy.

If there is a decrease in blood testosterone to a level ranging from more than or equal to 20 ng / dl to less than or equal to 50 ng / dl, split-course radiation therapy is prescribed to a total focal dose of 70-74 Gy and androgenic deprivation is continued, including zoladex and 100 mg of casodex inside daily, for the next 9 months.

If the testosterone level in the blood is more than 50 ng / dl, androgen deprivation is continued, including zoladex and the intake of 150 mg of casodex by mouth daily for the next 9 months.

Every 3 months, blood testosterone levels are examined and radiation therapy is prescribed up to a total focal dose of 76 Gy only when the testosterone level is ≤50 ng / dL.

If the blood testosterone level remains high after 9 months (above 50 ng / dl), then the proposed method cannot be used, and the patient is offered other types of treatment.

Example 1.

Patient Sh is 69 years old. In the study of blood PSA, the level of the latter was 32 ng / ml. The patient underwent a biopsy of the prostate gland, diagnosed with adenocarcinoma of the prostate gland 8 points according to Glisson. Further examination revealed that there was prostate cancer T2HoMo.

3 months after the onset of androgen deprivation with zoladex, it was found that the PSA level decreased to 0.4 ng / ml.

A study of blood testosterone levels showed that it is 19 ng / dL. The patient was prescribed treatment according to the proposed method: the introduction of zoladex for 6 months and radiation therapy was carried out in a split course with the inclusion of seminal vesicles and regional lymph nodes in the volume of irradiation of the prostate gland up to SOD 66Gy.

Control examination 3 years after the completion of treatment established the absence of locoregional and distant progression.

Example 2.

Patient I., 72 years old. In the study of blood PSA, the level of the latter was 26 ng / ml. The patient underwent a biopsy of the prostate gland - diagnosed with adenocarcinoma of the prostate gland 7 points according to Glisson. Further examination revealed that there was prostate cancer T2HoMo.

After 2 months of administration of zoladex in the regimen of 3.6 mg s / c once every 28 days, it was found that the PSA level decreased to 0.8 ng / ml.

The blood testosterone level was measured, which was 15 ng / dl.

The patient was prescribed the administration of zoladex for 6 months and received a split-course radiation therapy with the inclusion of seminal vesicles up to 70 Gy in the volume of irradiation of the prostate gland.

Control examination 4 years after the completion of treatment established the absence of locoregional and distant progression.

Example 3.

Patient J. 65 years old. The patient consulted a urologist for m / f with complaints of difficulty urinating. When examining the PSA level of blood, it was found to increase to 28 ng / ml. The patient underwent a prostate biopsy. After morphological examination of the biopsy, adenocarcinoma of the prostate gland 7 (4 + 3) points according to Glisson was diagnosed.

The patient was treated with zoladex in the regimen of 3.6 mg i / c 1 time in 28 days for 4 months, after which a decrease in the PSA level of the blood to 0.07 ng / ml was recorded.

A study of blood testosterone levels recorded a value of 20 ng / dL.

The patient was prescribed split-course radiation therapy up to 70 Gy and continued androgenic deprivation for 9 months, but using not only zoladex in the 3.6 ng / ml regimen once every 28 days, but also taking casodex daily at a dose of 100 mg.

A control examination 3.5 years after the completion of treatment established the absence of locoregional and distant progression.

Example 4.

Patient K., 71 years old. The examination revealed that the PSA level of the blood is 51 ng / ml. After morphological examination, adenocarcinoma of the prostate gland 7 (4 + 3) points according to Glisson was diagnosed.

The patient was prescribed zoladex in the regimen of 3.6 mg sc once every 28 days for 5 months, which led to a decrease in the PSA level to 0.7 ng / ml,

The blood testosterone level is 50 ng / dl.

The patient was prescribed radiation therapy up to 74 Gy and continued androgenic deprivation for 9 months, but using not only zoladex in the 3.6 ng / ml regimen once every 28 days, but also taking casodex daily at a dose of 100 mg.

A control examination 3.5 years after the completion of treatment established the absence of locoregional and distant progression.

Example 5.

Patient I. 69 years old. Examination diagnosed with prostate cancer T3H0M0. The PSA level of the blood in this patient was 84 ng / ml. The study of the morphological material of the prostate gland established the degree of tumor differentiation 7 (4 + 3) points according to Glisson.

The patient was prescribed an induction course of androgen deprivation, including only zoladex, in a regimen of 3.6 mg once every 28 days. 2 months after the onset of androgenic deprivation, a control study found that the PSA level decreased to 0.5 ng / ml.

However, a study of blood testosterone showed that you keep its level at high levels - 59 ng / dl.

The patient was prescribed androgen deprivation, including zoladex and daily intake of 150 mg of casodex for the next 9 months. After 3 months, a decrease in blood testosterone levels to 41 ng / dL was noted. A continuous course of radiation therapy was prescribed up to a total dose of 76 Gy.

Control examination 2 years after the completion of treatment established the absence of locoregional and distant progression.

Example 6.

Patient I. 76 years old. After examination, the patient was diagnosed with prostate cancer T3H0M0. The PSA level of the blood in this patient was 42 ng / ml. The study of the morphological material of the prostate gland established the degree of tumor differentiation 7 (4 + 3) points according to Glisson.

The patient was prescribed an induction course of androgen deprivation, including only zoladex, in a regimen of 3.6 mg once every 28 days. After 3.5 months after the start of androgen deprivation, a control study found that the PSA level decreased to 0.45 ng / ml.

However, a study of blood testosterone showed that you keep its level at a high level - 62 ng / dl.

The patient was prescribed androgen deprivation, including zoladex and daily intake of 150 mg of casodex for the next 9 months.

Blood testosterone testing was performed every 3 months. After 6 months, a decrease in the level of testosterone in the blood to 47 ng / dL was noted, which served as the basis for the appointment of radiation therapy with a continuous course up to SOD 76 Gy.

Follow-up examination 3.8 years after completion of treatment established the absence of locoregional and distant progression.

Example 7.

Patient B. 65 years old. When examining the PSA level of blood in a patient with prostate cancer, T3H0M0 was 94 ng / ml. The patient was prescribed an induction course of androgen deprivation, including only zoladex, in a regimen of 3.6 mg once every 28 days. 4 months after the onset of androgenic deprivation, a control study found that the PSA level decreased to 0.65 ng / ml.

However, a study of blood testosterone showed that you keep its level at high numbers - 68 ng / dl.

The patient is prescribed androgen deprivation, which includes zoladex and a daily intake of 150 mg of casodex. Only 9 months after the above treatment, the testosterone level decreased to 39 ng / dL. The patient was prescribed radiation therapy with a continuous course to a total focal dose of 76 Gy. A control examination 2.5 years after the completion of treatment established the absence of locoregional and distant progression.

The proposed method was used in 23 patients with prostate cancer. It was noted that the treatment was well tolerated and the quality of life improved, the 3-year survival rate increased to 100%, and the financial costs were optimized for androgen deprivation.

In 2 patients, the testosterone level did not decrease after 9 months, so they were offered a surgical tactic of treatment

The proposed method makes it possible to personalize treatment for prostate cancer in the process of androgen deprivation, which will also increase relapse-free survival and optimize drug provision for this group of patients.

Claims (1)

A method of treating prostate cancer, including androgenic deprivation with zoladex, monitoring the level of prostate-specific antigen PSA and blood testosterone to adjust the treatment, conducting radiation therapy, characterized in that androgen deprivation is performed until the PSA level in the blood is less than 1 ng / ml, after which the level is determined blood testosterone, and if its value is less than 20 ng / dl, the administration of zoladex is prescribed for the next 6 months and a split course of radiation therapy up to SOD 66-70 Gy; if the level of testosterone in the blood is detected in the range from 20 ng / dl to 50 ng / dl, the administration of zoladex and a daily intake of 100 mg of casodex for the next 9 months and radiation therapy with a split course up to SOD 70-74 Gy; if the blood testosterone level is more than 50 ng / dl, continue androgen deprivation with zoladex and daily intake of 150 mg casodex for the next 9 months, the blood testosterone level is examined every 3 months and only after the testosterone level has dropped to less than 50 ng / dl , prescribe radiation therapy with a continuous course up to SOD 76 Gy.