Brachytherapy (radiation therapy) of prostate cancer

Brachytherapy (interstatic radiotherapy) is a high-tech method that emerged at the junction of radiotherapy and minimally invasive urology. The technique of brachytherapy was described in 1983, it allowed the development of preoperative three-dimensional planning of source placement and postoperative dosimetry. Brachytherapy is based on the introduction of microcapsules containing the isotope ¹²⁵ 1 into the prostate tissue .

Microcapsules - a closed source of low-activity radiation, having specified radiation characteristics. Modern closed systems for interstitial radiation therapy for prostate cancer titanium microcapsules measuring 4.5x0.8 mm with a wall thickness of 0.05 mm. Inside the capsule is the isotope ¹²⁵ 1, absorbed on a silver or graphite matrix, and their ends are hermetically sealed with a laser beam. Microcapsules are used in the form of so-called free grains or. Which is more promising, they are fixed on a polymer absorbable filament.

[1], [2]

Brachytherapy (radiation therapy) of prostate cancer: indications

• Histologically confirmed adenocarcinoma of the prostate.
• Clinical stage T1-2s. Absence of clinical signs of tumor spread and low risk of damage to seminal vesicles or regional lymph nodes according to MPT, KT.
• Life expectancy after implantation is more than 10 years (patients under 75 years old).

[3], [4], [5]

Brachytherapy (radiation therapy) of prostate cancer: contraindications

• Bone metastases according to osteoscintigraphy data from ⁹⁹ Tc.
• The prostate volume is more than 60 cm ³ (according to TRUS).
• More than a third of the volume of the prostate is closed by a lumbar arch.
• The concentration of PSA is more than 30 ng / ml.
• IVO (Qmax <12 ml / s with a voiding volume of 100 ml) and the presence of residual urine, and also if there are or may be indications for surgical treatment.
• Acute prostatitis and other infectious and inflammatory diseases of the urogenital system.
• Hemorrhagic diathesis.

[6], [7], [8]

Examination of patients

• Interrogation of a patient for making an anamnesis:
  • anamnesis of the disease, diagnostic measures
  • previous treatment of adenoma and / or prostate cancer;
  • therapeutic history and status;
  • drug intolerance;
• Finger rectal examination;
• Laboratory methods of research
  • clinical blood test:
  • PSA;
  • blood chemistry;
  • coagulogram:
  • general urine analysis:
  • bacteriological analysis of urine with the definition of the degree of bacteriuria and antibioticogram.
• ECG
• Radiography of the chest.
• MRI of the pelvic organs.
• Osteoscintigraphy.
• Ultrasound of the kidneys, prostate, abdominal organs and retroperitoneal space.

An important point, which largely determines the results of brachytherapy, is the proper selection of patients. The technology of selection is based on the evaluation of clinical and laboratory indicators, digital rectal examination, on the precise determination of prostate volume. Performing transrectalysis multifocal prostate biopsy method that allows you to correctly establish the diagnosis, determine the degree of differentiation of the tumor, its prevalence in the organ. It is extremely necessary to perform MRI of the pelvic organs to determine the stage of the malignant process, and also, which is extremely important in performing the operation, - to identify the relationship between the prostate and the lumbar arch. The study is most informative when using a rectal coil. Brachytherapy Planning

The dose for treatment of most solid neoplasms exceeds the sensitivity threshold for the surrounding tissues. In the case of treatment of prostate cancer by the method of remote radiation therapy, the dose of radiation, which ensures the death of the tumor, considerably exceeds the level of tolerance of healthy tissues. Escalation of doses up to 75 Gy and above allows achieving local control in most cases. Studies by Zelefsky et al. (1998) showed a direct correlation between the clinical results and the dosed dose. Radical radiation therapy usually means a dose of at least 70-75 Gy, and increasing it to 80 Gy and above inevitably leads to the development of complications. The location of the prostate in the center of the small pelvis and close proximity to important organs (bladder, rectum, urethra), causes certain difficulties in the course of remote therapy. The use of the interstitial technique solves the problem of further escalating the dose. The main goal of brachytherapy is the exact delivery of a high dose of radiation energy to the target organ. In this case, the main condition is to provide the maximum dose in the target organ, leaving intact surrounding healthy sensitive tissues intact. In brachytherapy of the prostate, a technique is used that provides doses to the target organ more than 100 Gy.

For example, 145 Gy, delivered with ¹²⁵ I, is equivalent to a dose of 100 Gy, obtained by fractionating at 2 Gy on a facility with ⁶⁰ Co. Currently, the American Association of Medical Physicists (AARM TG-43) recommended ¹²⁵ G for monotherapy ¹²⁵ I for 96% of the prostate volume, and for booster irradiation up to 100 Gy after remote radiation therapy at a dose of 40-45 Gy. Usually in this situation it is recommended to conduct remote radiation therapy at a dose of 45 Gy for 25 fractions (1.8 Gy / fraction) followed by brachytherapy ¹²⁵ I at a dose of 110 Gy. A number of authors insist on the advisability of a combination of remote radiation therapy and brachytherapy for patients with an average and high risk of extracapsular proliferation. This group of patients is characterized by the presence of a stage> T2b, PSA> 10 ng / ml and morphological stage according to Gleason> 6.

[9], [10], [11], [12], [13]

Neoadjuvant hormonal therapy

With a prostate volume of more than 60 cm ^{3, the} branches of the pubic bone cover part of the organ and make it impossible to implant radioactive capsules in the anterolateral part of the gland. This situation can be detected during preoperative planning, which barks the ability to determine the relative location of the pubic koai and prostate. The volume of the gland less than 45 cm ³ serves to some extent as a guarantee against such problems. The use of analogues of gonadotropin releasing hormone in the form of monotherapy or in combination with antiandrogens is justified in patients with large volume of the gland and allows to hope for a noticeable decrease in the volume of the prostate, which, in turn, makes it possible to perform implantation of radioactive capsules. The neoadjuvant use of antiandrogens also makes it possible to hope for an improvement in the long-term outcome of treatment by decreasing the volume of the tumor node. This is important, since the same dose is more effective with a smaller volume of growth. At the same time, this allows us to reduce the number of implants and reduce the cost of the intervention.

Brachytherapy technique

The technique of brachytherapy consists of two stages. To perform the most accurate and effective distribution of radiation dose in the prostate by means of a computer-based planning system, it is necessary to obtain accurate information on the form and volume of the gland. This is achieved with the help of the TRUS, during which a series of transverse ultrasound sections of the prostate with a co-ordinate grid superimposed on them. TRUSS is performed in the patient's position for lithotomy. During the study, a series of images of the transverse sections of the prostate are obtained with a pitch of 5 mm. An established urethral catheter allows you to clearly locate the urethra and avoid the entry of grains into its lumen. The volume of the prostate is studied by a urologist, a medical physicist and a nurse in the X-ray operating room, in conditions as close as possible to those for implantation. The resulting images serve as the basis for creating a 3D model in the planning system installed on the computer. This is necessary to determine the location of radiation sources. Preliminary calculation of doses is necessary to determine the approximate number of implants.

Implantation is performed under epidural anesthesia. After performing anesthesia, the patient is placed in the position on the back, as well as when performing a study of prostate volume. Methol assumes the implantation of radioactive capsules (needles, grains) under the control of TRUS. The needles are placed in such a way that 75% of the implants are located in the peripheral zone, and 25% in the central region. First set the central needles, then calculate how many more needles and how they need to be set so that the whole volume of the prostate is irradiated. Implantation begins with the grains located in the anterior parts of the prostate and continue in the direction of the rectum. At the end of the operation, radiographs of the pelvic organs are performed for postoperative control of the location of the grains.

When discharging patients are given the following instructions: a short course of alpha1-adrenoblockers and antibiotics is necessary; it is desirable to abstain from sexual activity for 2 weeks: it is mandatory to hold CT in 4-5 weeks to evaluate the results of brachytherapy and further treatment planning. Postoperative dosimetry allows you to compare the real location of the sources with the preoperative plan. For the recognition of implants, the use of CT is most acceptable. The images are exported to the planning system and the volumes of the prostate are calculated, which have received 90, 100 and 150% of the dose (D90, D100, D150) - these are the indicators of the quality of the performed implantation. Data allows you to analyze the presence of systematic errors and provide an opportunity to correct them in the future.

[14], [15], [16]

Brachytherapy (radiation therapy) of prostate cancer: the results of treatment

After brachytherapy, PSA concentrations fluctuate for several years. The criteria used to assess the effectiveness of operative and radiotherapy differ from each other. The European database for 2005 included 1,175 patients who underwent brachytherapy in several centers. The results vary: the absence of biochemical recurrence in 5-year follow-up was recorded in 70-100% of patients with prostate cancer with a baseline PSA concentration of less than 10 ng / ml, 45-89% with a PSA level of more than 10 ng / ml. The results of treatment of patients with a morphological stage according to Gleason 7 and more are characterized by a worse prognosis, the period before the occurrence of biochemical relapse is about 4 years. The results of a 10-15-year follow-up of patients with prostate cancer who have undergone brachytherapy have been published. Specific survival was 98% after 10 years. According to Ragde et al., The relapse-free survival after interstitial therapy of 229 patients with prostate cancer (T1a-3a, average PSA concentration 10.9 ng / ml, G2-10) during the follow-up period from 18 to 144 months. Was 70%. 66% in the monotherapy group, and 79% in the case of brachytherapy in combination with radiotherapy, with a specific survival rate of 98%. Criteria for getting rid of prostate cancer were: PSA <0.5 ng / ml; metastasis (based on the results of radiation research methods) and biopsy data. The method of brachytherapy for effectiveness is comparable to a radical operation.

Results of brachytherapy application

Author of the study	Number of patients	Biochemical relapse	Observation terms, years
Grimm	125	14.9%	10
Beyer Brachman	695	29%	5
Radge	147	34%	10
Grado	490	21%	5
Stock, Stone	258	25% (PSA <20 |	4
Zeletsky	248	29%	5
Crrtz	689	12%	5
Blasko	534	15/	10

[17], [18], [19]

Brachytherapy (radiation therapy) of prostate cancer: complications

The most frequent complications of brachytherapy are radiation reactions (radiation prostatitis, urethritis, proctitis). Prostatitis and urethritis are clinically manifested in the form of dysuria of varying severity and duration within one year after brachytherapy on average in 80% of cases. Urinary incontinence is observed for the most part in patients who have undergone TURP with a frequency of up to 4.7%. Of the complications observed urethral stricture in 0-8% observation, acute retention of urination to 22%, bleeding - up to 2%. Proctitis after brachytherapy is mild and occurs in 2-10% of patients, and erectile dysfunction is observed in 16-48% of patients.

[20], [21]