What is Brachytherapy?
The term Brachytherapy derives from the Greek prefix braqui, meaning short, since radiation of the prostate is carried out from within the prostate (a short distance), in comparison to external radiotherapy from outside the body. Prostate cancer is as a dose-dependent tumour, meaning that the greater the dose of radiation administered, the greater the control over the tumour. With external radiotherapy, doses of 75-77Gy cannot be exceeded, given that in order for the radiation to reach the prostate from outside the body it has to pass through the bladder and/or the rectum (-the end section of the intestine), and this causes adverse effects in these organs, such as cystitis radical, radical proctitis, bleeding in urine or rectum, impotency (the nerves involved in erection are located between the rectum and prostate), etc. With brachytherapy the radiation is produced from within the prostate and for this reason the dose administered is 140-150 Gy (double that of external radiotherapy). Both the bladder and the rectum receive little radiation in brachytherapy, and adverse effects to these two organs, as well as the nerves involved in erection, are avoided. Treating prostate cancer with brachytherapy is not new – in 1911 Pasteur treated a patient suffering with this form of cancer with a radio needle through a urethral catheter. Since the early 70’s permanent implants of Iodine-125 have been used; however it was not until the incorporation of transrectal ultrasound in the 80’s that the placement of the radioactive sources (seeds) inside the prostate could be monitored. More than 150,000 patients have been treated all over the world with this method. It is considered safe and to have very few side-effects when carried out with what is termed the “real-time dynamic” technique
What is real-time dynamic brachytherapy?
Brachytherapy was initially carried out using the “pre-plan” technique, in which the patient’s treatment was planned some 15-21 days before the definitive implantation of the radioactive seeds. At the moment of implantation, if the patient is not placed in exactly the same position as had been planned, some of the radioactive seeds may be implanted outside of the prostate or close to the urethra, this causing severe urinary problems or acute urine retention. With the technique known as “real-time dynamic” the planning and implantation are both carried out at the same time, and the 60 to 120 seeds used (depending on prostate size), are implanted one by one, the placement of the seeds throughout the process is monitored via transrectal ultrasound imaging. This method ensures that the seeds are not located near to the urethra, outside the prostate or inside the bladder. The “real-time dynamic” technique allows the surgeon to make adjustments during operation itself, ensuring an optimum distribution of radioactive seeds and the dose applied for each patient’s needs.
Although the Real dynamic time technique is recent, many centres using Brachytherapy continue to use the “pre-plan” technique.
Although the real-time dynamic technique is recent and safer, many centres using brachytherapy continue to use the “pre-plan” technique.
What are the advantages of real-time dynamic brachytherapy?
1 – External radiotherapy requires 35 daily sessions (Monday to Friday) while Brachytherapy requires just one.
2 – The radiotherapy dose received by the prostate in Brachytherapy is 145 Gy, while the dose in external radiotherapy cannot exceed 75-77 Gy so as to avoid vesical or rectal problems.
3 – The fall in the dose of radiation is fast, the surrounding tissues thus receive a very low or null dose of radiation.
1- Spinal anaesthesia is employed, while surgery requires a general anaesthetic.
2- The patient can be discharged from hospital, without a catheter, after just a few hours whereas radical prostatectomy requires a stay of between 4 and 8 days, and a vesical catheter for between 12 and 21 days.
3- In surgery there is a 50-70% risk of sexual impotency and urinary incontinence for at least 2-3 months, whilst with brachytherapy the risk of sexual impotency is less than 5% with an absence of urinary incontinence. The impotence resulting from brachytherapy (less than 5% probability) can, in the majority of cases, be treated with oral medication such as Cialis®, Levitra® or Viagra®. This is another of the advantages of brachytherapy.
4- Treated with Brachytherapy, the patient can quickly resume his daily activities – from within a few hours to a few days, according to the activity in question.
What is the procedure for real-time dynamic brachytherapy?
Titanium-coated cylinders 4.5mm long and 0.8mm in diameter (the seeds) are injected into the prostate through the perineum (the area between the anus and testes) using needles, where they will remain permanently.
Inside each of the cylinders there is a silver rod infused with radioactive material (Iodine-125 or Palladium-103), both isotopes emitting gamma radiation. The dose administered is a measure of the cell damage caused when live tissue absorbs this radiation; it is measured in Greys. Both isotopes emit the radioactive dose over a long period of time (6-12 months). The half-life of Iodine-125 is 60 days, and after six months, its activity is 10%; at one year it is 0%. The activity of the Iodine-125 seed varies between 0.3 and 0.55 mCi. In general, in the case of small prostates, seeds with lower activity are used, while for larger prostates seeds of higher activity are employed. Similar results are obtained, whether using Iodine-125 or Palladium-103.
A multi-disciplinary team is involved in the brachytherapy procedure, comprising a urologist (who applies the needles), a radiation oncologist (who implants the seeds), a medical physicist (who determines the locus of needle placement, the number of seeds to implant and the dose of radiotherapy to administer), and an anaesthetist. After undergoing a spinal anaesthesia, the patient is placed in a forced gynaecological position, and a saline and povidone enema is administered to remove any faeces or mucus that might interfere with the ultrasound image of the prostate. Following this, a vesical catheter is placed. Once the ultrasound probe has been inserted into the rectum, prostate volume is determined; incisions are made in the prostate gland from base to apex every 5mm (volumetrics).
The distribution of radioactivity is calculated by computer, 75% of radioactivity being deployed around the periphery of the prostate (using peripheral needles) and the remaining 25% into the interior of the prostate (central needles). The urethra is thus protected from receiving excessive radiation.
The number of peripheral needles necessary for the implant is calculated on prostate length plus 1. For example, if 80 seeds are to be implanted, 75% of which will be implanted through peripheral needles, and the prostate measures 3cm, 75% of 80 = 60, and the number of peripheral needles is determined thus: 60 ÷ (3+1)= 15.
Axial imaging is used to guide the insertion of the needles 1cm apart. The needles at the rear must be at least 7mm from the front of the anterior rectal wall.
Sagittal longitudinal ultrasound is used guide the implantation of the seeds, and this is carried out from the base of the prostate to the apex using a Mick applicator loaded with a metal cartridge of 15 seeds. The central needles and the corresponding seeds are inserted following the same technique as the peripheral needles.
The average dose of radiation applied to the prostate is 145Gy. Total treatment time is two hours. Once the procedure is performed, a measure of radiation is taken at the level of the pubic symphysis, at one metre’s distance, and at the urine-collection bag. The vesical catheter remains in place until the following morning, this being removed before the patient’s discharge.
After the operation, anti-inflammatories and alpha-blockers are given to lessen the swelling caused by the implantation and to favour urination. Treatment with alpha-blockers will continue for 3-12 months depending on possible urinary problems.
With time, and due to the effect of the radiation, the prostate will reduce 40-50% in size.
What type of patient is real-time dynamic brachytherapy recommended for?
Best results from brachytherapy are had when patients are diagnosed with the so-called low-risk tumours. In these cases, the PSA count is less than 10ng/ml, the tumour is equal to or less than T2b and the Gleason score 3+3. Rates of cure with brachytherapy for these patients is superior to those with radical surgery and is without the adverse effects. Several studies consider that cases with a Gleason score of 3+4 can also benefit from brachytherapy.
What type of patient is brachytherapy contraindicated for?
1- Life expectancy of less than 5 years
2- In cases of severe infravesical urinary obstruction with a urine flow of less than 7 ml/s
3- Previous significant TUR of the prostate
4- Prostate volume greater than 90g.
What are the results for real-time dynamic brachytherapy?
More than 150,000 prostate cancer patients have been treated with brachytherapy in the world. In the USA there are centres with more than 20 years’ experience using this technique. Of all prostate cancer patients treated in the USA in the year 2000, approximately 30% were treated with external radiotherapy, 30% with radical prostatectomy, and more than 30% with brachytherapy. In 2005 the percentage of patients receiving brachytherapy had increased to more than 50%, the rest being treated with external radiotherapy or radical surgery.
Where patients have low-risk tumours (PSA <10, Gleason <7 and a clinical stage < T2c), the disease-free survival rate at 10 years is between 85 and 94%. Where the tumour is intermediate-risk (Gleason 7 or PSA 10-20), the disease-free survival rate is 75-85%. Where the patients receive brachytherapy, the PSA falls slowly, reaching the lowest point (nadir) after 2-3 years. During monitoring slight transitory rises in PSA (PSA bounce) is seen in around 35% of cases between the first and third year of treatment, this being of no clinical significance and is probably due to localised necroses or prostatitis.
Results from a combined treatment of external radiotherapy with brachytherapy have not proven to be more effective than those from brachytherapy alone.
The treatment is not considered successful when there are three consecutive increases in PSA values.
What are the side-effects of real-time dynamic brachytherapy?
During the first 2-3 months following the implantation there may be urethral problems, characterised by frequent urination, difficulty urinating, and occasionally urgent urination. The majority of patients showing symptoms can carry on with a practically normal lifestyle, following some hygienic and dietary provisions, and with anti-inflammatory medication and alpha-blockers. The symptoms begin to disperse after 3 months, until they recede completely. Studies show there is no incontinence, even in cases with previous TUR of the prostate, provided real-time brachytherapy is undertaken. All studies in the field agree that out of all prostate cancer treatments, real-time dynamic brachytherapy is the one that least affects sexual function (sexual function is preserved in 75-100% of cases).
The incidence of rectal complications is very low, with figures of less than 2%. Urine retention is seen in less than 3% of cases.
In our experience (since 2003), we have seen no cases of proctitis or urine retention.
What is the follow-up procedure for patients treated with brachytherapy?
Four weeks after treatment a CT scan should be taken to calculate the actual dosimetric coverage (the dose of radiation to the prostate, bladder and rectum). The best results are obtained where the dose measured one month after the implant is greater than 140Gy. Subsequent tests monitor PSA every four months during the first year, and then every six months.
Protection from radiation
The risk of radiation to the patient and those in his environment is a subject that often worries patients. In fact, Iodine-125 is a low-level radioactive element, and the radioactivity is considerably reduced by the tissues surrounding the prostate; therefore, no noteworthy radiation can be registered close to the patient. However, in organs close to the prostate, such as the rectum and bladder, a small quantity of radiation is noted, which in the case of real-time dynamic brachytherapy is much lower than when external radiotherapy is used.
Precautions related to radioprotection
a- Pregnant women
Women who are pregnant or likely to become pregnant should not remain in direct contact with the patient for prolonged periods of time during the first two months following implantation, although there is absolutely no risk of radiation at a distance of 30cm. A pregnant woman can stay in the same room as the patient at all times, respecting the distance of 30cm.
b- Children
As above, direct, prolonged contact between the patient and children is not advisable during the first two months. Although the patient can give hugs and kisses, children should not spend too long sitting on the patient’s lap.
c- Sexual relations
The patient can resume sexual relations using condoms. Sperm may be of a dark colour for some weeks due to the bleeding during the implantation procedure, but this is clears up with consecutive ejaculations. Use of condoms is not necessary after two months.
d- Ejection of Iodine seeds with urine
Spontaneous ejection of a seed while urinating may occur during the first week following implantation, although this is unlikely.
e- In the case of subsequent surgery
If the patient needs surgery in the pelvic zone (bladder, rectum, prostate etc.), for whatever reason, he should advise the surgeon about the implanted radioactive seeds in the prostate.
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