Brachytherapy (radiation therapy) for prostate cancer

Brachytherapy (interstitial radiotherapy) is a high-tech method that emerged at the junction of radiotherapy and minimally invasive urology. The brachytherapy technique 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 are a closed source of low-activity radiation with specified radiation characteristics. Modern closed systems for interstitial radiation therapy of prostate cancer are titanium microcapsules measuring 4.5 x 0.8 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, more promisingly, they are fixed on a polymer absorbable thread.

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Brachytherapy (radiation therapy) for prostate cancer: indications

• Histologically confirmed adenocarcinoma of the prostate.
• Clinical stage T1-2c. absence of clinical signs of tumor spread and low risk of damage to the seminal vesicles or regional lymph nodes according to MRI, CT.
• Life expectancy after implantation is more than 10 years (patients up to 75 years of age).

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Brachytherapy (radiation therapy) for prostate cancer: contraindications

• Bone metastases according to ⁹⁹ Tc bone scintigraphy.
• Prostate volume is more than 60 cm3 ⁽ according to TRUS data).
• More than a third of the prostate volume is covered by the pubic arch.
• PSA concentration is more than 30 ng/ml.
• IVO (Qmax<12 ml/s with a urination volume of 100 ml) and the presence of residual urine, as well as if there are or may be indications for surgical treatment.
• Acute prostatitis and other infectious and inflammatory diseases of the genitourinary system.
• Hemorrhagic diathesis.

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Examination of patients

• Interviewing the patient to obtain anamnesis:
  • medical history, diagnostic measures
  • previous treatment of prostate adenoma and/or cancer;
  • therapeutic history and status;
  • drug intolerance;
• Digital rectal examination;
• Laboratory research methods
  • clinical blood test:
  • PSA;
  • biochemical blood test;
  • coagulogram:
  • General urine analysis:
  • bacteriological analysis of urine to determine the degree of bacteriuria and an antibiogram.
• ECG
• Chest X-ray.
• MRI of the pelvic organs.
• Osteoscintigraphy.
• Ultrasound of the kidneys, prostate, abdominal organs and retroperitoneal space.

An important point that largely determines the results of brachytherapy is the correct selection of patients. The selection technology is based on the assessment of clinical and laboratory parameters, digital rectal examination, and accurate determination of the prostate volume. Performing transrectal and multifocal prostate biopsy is a method that allows you to correctly establish a diagnosis, determine the degree of tumor differentiation, and 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 when performing surgery, to identify the relative position of the prostate and the pubic arch. The study is most informative when using a rectal coil. Brachytherapy planning

The dose for treating most solid tumors exceeds the sensitivity threshold for surrounding tissues. In the case of treating prostate cancer with external beam radiation therapy, the radiation dose that ensures tumor death significantly exceeds the tolerance level of healthy tissues. Dose escalation to 75 Gy and higher allows achieving local control in most cases. Studies by Zelefsky et al. (1998) showed a direct dependence of clinical results on the delivered dose. Radical radiation therapy usually implies a dose of at least 70-75 Gy, and its increase to 80 Gy and higher 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 conducting a course of external beam therapy. The use of the interstitial technique solves the problem of further dose escalation. The main goal of brachytherapy is the precise delivery of a high dose of radiation energy to the target organ. The main condition is to provide the maximum dose in the target organ, leaving the surrounding sensitive healthy tissues untouched. Prostate brachytherapy uses a technique that provides doses of more than 100 Gy to the target organ.

For example, 145 Gy delivered with ¹²⁵ I is equivalent to a dose of 100 Gy delivered in 2-Gy fractions using a ⁶⁰ Co unit. The current American Association of Physicists in Medicine (AAPM TG-43) recommendation for ¹²⁵ I monotherapy is 144 Gy to 96% of prostate volume, and for booster irradiation up to 100 Gy after external beam radiation therapy at a dose of 40-45 Gy. In this situation, it is usually recommended to perform external beam radiation therapy at a dose of 45 Gy in 25 fractions (1.8 Gy/fraction) followed by ¹²⁵ I brachytherapy at a dose of 110 Gy. A number of authors insist on the advisability of a combination of external beam radiation therapy and brachytherapy for patients with an average and high risk of extracapsular spread. This group of patients is characterized by the presence of stage >T2b, PSA> 10 ng/ml and morphological stage according to Gleason >6.

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Neoadjuvant hormonal therapy

If the prostate volume is more than 60 cm3, ^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. Such a situation can be identified during preoperative planning, which makes it possible to determine the relative position of the pubic bone and the prostate. A gland volume of less than 45 cm3 ^serves to some extent as a guarantee against such problems. The use of gonadotropin-releasing hormone analogues as monotherapy or in combination with antiandrogens is justified in patients with a large gland volume and allows us to hope for a noticeable decrease in the prostate volume, which, in turn, makes it possible to implant radioactive capsules. Neoadjuvant use of antiandrogens also allows us to hope for improved long-term treatment results due to a decrease in the tumor node volume. This is important, since the same dose is more effective with a smaller tumor volume. At the same time, this allows us to slightly reduce the number of implants and reduce the cost of the intervention.

Brachytherapy Technique

The brachytherapy technique consists of two stages. To perform the most accurate and effective distribution of the radiation dose in the prostate using a computer planning system, it is necessary to obtain accurate information about the shape and volume of the gland. This is achieved using TRUS, during which a series of transverse ultrasound sections of the prostate are obtained with a coordinate grid superimposed on them. TRUS is performed with the patient in the lithotomy position. During the examination, a series of images of transverse sections of the prostate are obtained with a step of 5 mm. The installed urethral catheter allows for precise localization of the urethra and avoids the ingress of grains into its lumen. The study of the prostate volume is performed by a urologist, a medical physicist and a nurse in the X-ray urological operating room, under conditions as close as possible to those during implantation. The obtained images serve as a basis for creating a three-dimensional model in the planning system installed on the computer. This is necessary to determine the location of the radiation sources. A preliminary calculation of the doses is necessary to determine the approximate number of implants.

Implantation is performed under epidural anesthesia. After anesthesia, the patient is placed in a supine position, just as when performing a prostate volume examination. The method involves implantation of radioactive capsules (needles, grains) under TRUS control. The needles are placed so that 75% of the implants are located in the peripheral zone, and 25% in the central zone. First, the central needles are installed, then it is calculated how many more needles and how they need to be installed so that the entire prostate volume is irradiated. Implantation begins with the grains located in the anterior sections of the prostate and continues in the direction of the rectum. At the end of the operation, X-rays of the pelvic organs are performed for postoperative control of the location of the grains.

At discharge, patients are given the following instructions: a short course of alpha1-adrenoblockers and antibiotics is required; it is advisable to abstain from sexual activity for 2 weeks; CT scanning is mandatory after 4-5 weeks to assess the results of brachytherapy and further treatment planning. Postoperative dosimetry allows comparing the actual location of the sources with the preoperative plan. CT is most suitable for identifying implants. Images are exported to the planning system and the prostate volumes that received 90, 100 and 150% of the dose (D90, D100, D150) are calculated - these are indicators of the quality of the implantation performed. The data allows analyzing the presence of systematic errors and provides an opportunity to correct them in the future.

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Brachytherapy (radiation therapy) for prostate cancer: treatment results

Fluctuations in PSA concentrations are observed for several years after brachytherapy. The criteria used to evaluate the effectiveness of surgical and radiation treatments differ. The European database for 2005 included 1175 patients who underwent brachytherapy in several centers. The results obtained vary: the absence of biochemical recurrence during 5-year follow-up was recorded in 70-100% of patients with prostate cancer with an initial PSA concentration of less than 10 ng/ml, in 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 higher are characterized by a worse prognosis, the period until the occurrence of biochemical recurrence is about 4 years. The results of 10-15-year follow-up of prostate cancer patients who underwent brachytherapy have been published. Specific survival was 98% after 10 years. According to Ragde et al., relapse-free survival after interstitial therapy in 229 patients with prostate cancer (T1a-3a, mean PSA concentration 10.9 ng/ml, G2-10) over an observation period of 18 to 144 months was 70%. Moreover, in the monotherapy group - 66%, and in the case of brachytherapy in combination with EBRT - 79%, while the specific survival was 98%. The criteria for getting rid of prostate cancer were: PSA <0.5 ng/ml; metastases (according to the results of radiation research methods) and biopsy data. The brachytherapy method is comparable in effectiveness to radical surgery.

Results of brachytherapy

Author of the study	Number of patients	Biochemical relapse	Observation period, 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

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Brachytherapy (radiation therapy) for prostate cancer: complications

The most common complications of brachytherapy are radiation reactions (radiation prostatitis, urethritis, proctitis). Prostatitis and urethritis are clinically manifested as dysuria of varying severity and duration within one year after brachytherapy in an average of 80% of cases. Urinary incontinence is observed mostly in patients who have undergone TUR of the prostate with a frequency of up to 4.7%. Other complications include urethral strictures in 0-8% of cases, acute urinary retention in up to 22%, and bleeding in 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.

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