Permanent Brachytherapy (BT) is a form of radiotherapy where small seeds containing radioactive sources (Palladium 103/Pd-103 or Iodine 125/I-125) are implanted into the prostate under ultrasound guidance. This is a minimally-invasive treatment completed in one 90-minute surgical procedure.

Each seed continuously releases a small quantity of radiating energy to a limited portion of prostatic tissue. The "short" range of action of each seed and the very high accuracy of the implant mean no damage prostate-adjacent structures such as rectum, bladder and urethra, differing from external beam radiotherapy. Moreover, the high number of sources implanted in the prostate (on an average 80-100 for Pd-103 and 70-90 for I-125) mean tumors can be treated with an extremely high dose of radiation (13,500 rads or 135 Gy for Pd-103 and 14,500 rads or 145 Gy for I-125).

Since the seeds are radioactive sources, each isotope decays in a specific time. Palladium (half-time -T1/2 17 days) releases 90% of its initial energy within 2 months and loses all of its energy in 6 months, whilst for iodine (half-time 60 days), these times increase to 6 months and 1 year respectively. The seeds will then be inactive in the prostate and undetectable throughout the patients' life.

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In the Seventies, prostate implants of radioactive sources were made by abdominal surgical incision. The seeds where therefore inserted freehand into the prostate however the complete lack of precision of this technique led to very unsatisfactory results. As a matter of fact, inside the prostate gland, thee were some cold areas without seeds which did not receive a radiation dosesufficient to destroy cancer. The results were disappointing and caused a loss of interest in this method.

Towards the end of the Eighties, new knowledge and sophisticated technologies allowed some researchers in North America to standardize an innovative and precise implant technique which required no any surgical incisions:

-the introduction of ultrasound-guided prostate biopsies and the diffusion of specific prostate antigen (PSA) as a reliable screening test for prostate cancer led to diagnose prostate cancer at earlier stages which in turn allowed for better therapy than in the previously;

-new knowledge became available about the features of radioactive substances such as Pd-103 and I-125 for treatment purposes;

-the introduction of transrectal ultrasound, CT and MRI meant that the gland morphology could be studied with greater accuracy;

-the introduction of dedicated software meant the radioactive sources' distribution inside the gland can be studied (treatment plan);

-the introduction of software for ultrasound devices meant the needles and the seeds can be placed with great precision in the prostate according to the treatment plan.

The modern implant technique involves the radioactive sources being released inside the prostate by means of thin needles placed under ultrasound guidance through the skin of perineum (the region between the anus and the scrotum). The result is an evenly spaced distribution of seeds and therefore the release necessary radiation dose to destroy tumor cells throughout the gland.

The oncologic results published about patients treated with this innovative implant technique for localized prostate carcinoma have resulted in wide interest in the scientific community. As a matter of fact, the cure rates (expressed as patients who are alive without biochemical disease progression i.e. without PSA subsequent increase ) for the first series of patients treated about 12 years ago, are comparable with those of surgery (radical prostatectomy) and higher than for conventional radiotherapy with external beam (retrospective comparisons).

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INDICATIONS FOR BRACHYTHERAPY

Gynecologic position: the thighs bent at 90° on the abdomen and opened symmetrically

Uroflowmetry

Brachytherapy (BT) can and should be proposed as an alternative to radical prostatectomy for patients suffering from clinically-localized prostate adenocarcinoma. Each patient has his own clinical physical and psychological characteristics which will lead his doctor to suggest the most suitable treatment (brachytherapy, surgery or other treatments for prostate cancer).

BT is proposed as a monotherapy in localized prostate cancer with low risk of extracapsular extension. In patients with intermediate or high risk of extracapsular disease, it is proposed in conjunction with external beam radiotherapy (EBRT).

Besides oncologicparameters, it is vital to select patients accurately so as to reduce the risk of side-effects and possible complications.

BT can be proposed to patients with a gland weight between 20 and 60 cc, maximum urine flow > 12 ml/s, post-voiding residue < 50 cc and IPSS < 19.

The implant of radioactive sources can be performed under total loco-regional or local anesthesia and is completed in less than 90 minutes. It is a minimally-invasive treatment which does not require any surgical incision. It does not cause bleeding and does not expose to the possible thromboembolic complications reported for pelvic surgery.
(BT advantages-disadvantages)

Prior to hospitalization for the implant, patients undergo standard tests in out patients (blood count, chest X-ray, ECG) and are evaluated by the anaesthetist to assess the most suitable kind of anesthesia.

Pre-operative checks can also include an andrological examination to evaluate the erectile function of the patients (history, objective examination, dynamic penile echocolordoppler, night penile rigidometry, filling-in of a IIEF (International Index of Erectile Function) questionnaire.

In the days prior the implant, the patients should follow a diet low in fibers and avoid fizzy drinks.

Any anticoagulant or antiaggregant treatment (Aspirin) must be discontinued or replaced about one week before implant as per the Specialist's instructions.

The night before and the morning of the implant enemas will be administered. Good bowel preparation means the removal of faecal residues from the rectum resulting in better quality ultrasound transrectal images.

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The implant is performed either in day surgery or during a two day stay in hospital.

The procedure is performed in theatre using total, spinal or even local anesthesia and generally takes under 90 minutes.

The patient lies on the operating table adopting gynecological position. An ultrasound probe is inserted into the rectum to show the prostate gland. The vesical catheter serves as a marker for urethra and bladder.

By means of special, very thin needles, an average of 80-100 radioactive seeds are inserted into the prostate, each seed is 5 mm long and 0.8 mm thick. All the procedure is performed in a sterile medium. The needles are inserted through the perineum under ultrasound guidance accurately into the parenchyma gland using a special template applied to the ultrasound probe. The whole procedure is performed under constant ultrasound and radiological checks as per the treatment plan drawn up by the Radiation Oncologist and the Physicist.

The accuracy of the implant is one of the key factors for successful treatment . At the end of the procedure, an ultrasound and radiological examination confirms that there are no "cold" prostate areas which have not been treated properly. Should there be any tadditional seeds can be implanted.

An urethrocystoscopy is performed at the end of the procedure to remove any seeds displaced in the bladder and/or urethra. A temporary vesical catheter is placed and removed few hours later.

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AFTER IMPLANT:
Course, Behavior Rules
and Early Side-Effects

Check on the implant quality by pelvic CT: even distribution of the seeds in the prostate

Check on the implant quality: 3D reconstruction of seed distribution in the prostate

At the end of the procedure, the patient is transferred to his room. An ice-package is placed under the scrotum to reduce the edema (swelling) caused by the needles going through the perineum. Antibiotics are administered to prevent possible infections together with antiphlogistics, pain-killers and low-dosed steroids to reduce prostate edema. In most of cases, the vesical catheter is removed a few hours after the implant. Patients treated under spinal or local anesthesia will be allowed to eat the same evening.

In some centers patients are discharged the day of the implant.

When the patient is discharged, he will be given antibiotics, antiphlogistics and/or pain-killers and alpha-blockers (to improve micturition) to take home. The length of time will vary according to the patient. It is suggested that the patient avoids intense physical activity for the first 2 days of recovery at home. After this he will be soon able to resume normal daily activities.

General side-effects from the radiation are infrequent and even less after a BT as the radiation effect is confined to a limited body area. Tiredness can occur but stronger symptoms such as nausea, vomiting, chronic diarrhea are absent.

In the days after implant it is possible:

These symptoms can be important and peak about 3 weeks after the implant with Pd-103 and 4/5 weeks after the implant with I-125 but tend to regress gradually and spontaneously as the seeds lose their energy. These symptoms can last with varied intensity for 3-12 months after the implant but can be relieved with specific therapies (which will be suggested to each patient) and by following some simple behavior rules (avoid alcoholic beverages, caffeine, spicy and hot foods, limit the use of bicycle, exercise bike and motorbike).

About 10% of the patients suffer from acute urinary retention which entails temporary placement of a vesical catheter or suprapubic tube.

After implant, seeds can on rare occasions be ejected with urine, therefore in the first few days a filter should be used (a simple colander). The patients must contact the Specialist to dispose the radioactive sources which have been ejected.

Patients can resume normal sexual activity quite soon after brachytherapy but must respect some radioprotective measures to protect their partner (limit partner exposure, at a meter distance, to less than 20 hours per week in the first months after implant).
During the first few incidences of sexual intercourse, the seminal fluid can appear dark. This temporary aspect must not be considered alarming because it is due to the release of small quantities of clotted blood in the sperm. Only exceptionally, during the first sexual intercourse, seeds can be found in sperm. For this reason, it is advisable to use a condom in the first months after implant. Two months after Pd-103 and 4 months after implant with I-125 sources, the seeds which could be ejected are no longer significantly radioactive to radioprotective purposes. About 1/3 of the patients also report burning or discomfort during ejaculation.

If erectile dysfunction should appear, a temporary rehabilitation treatment with Sildenafil (Viagra) or Prostaglandins can be prescribed.

.It is important to underline that, apart for the exceptional cases described above, neither the urine nor the sperm of the patients are radioactive.

About 3 weeks after the implant of Pd-103 sources and 4 weeks after implant of I-125 sources, the quality of implant will be evaluated by pelvic CT and/or MRI. The diagnostic images allow for the reconstruction of the implant and to check of the dosimetric coverage (post-planning). If the implant quality does not turn out to be satisfactory, the treatment will be completed by placing additional seeds in the uncovered areas or with an external beam radiation cycle.

As with every medical procedure, there is a remote probability that long-term or even permanent complications occur. These possibilities must be discussed before treatment with the Specialist.

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SAFETY: PRECAUTIONS AND BEHAVIOR NORMS

Patients undergoing permanent brachytherapy present a relevant radiation sources only at distances under 1 meter.

A patient who has undergone BT should, for a period of 2/4 months after implant of Pd-103 or I-125 respectively, respect some radioprotective rules to limit exposure to his relatives and the community. This is namely the period when the activity of the sources implanted into the prostate gradually decreases till it reaches irrelevant radioprotective levels. After this the patients can resume all their normal activities without any precaution. The seeds will stay in the prostate all through their lives undetected.

The following are some radioprotective rules for patients undergoing BT suggested by the Medical Physics Department of San Raffaele Scientific Institute in Milan

Urine, feces and sperm do not contain seeds and therefore are not radioactive.

After the implant, the seeds can on rare occasion be ejected with urine. Therefore in the first days, it is advisable to use a filter (a simple colander). The patient must contact the Specialist to dispose the radioactive source which has been ejected. The seeds are implanted permanently in the prostate, but there is a remote chance that, during the first sexual intercourse a single seed can be found in sperm. For this reason it is advisable to use a condom in the first months after the implant.

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CONTROLS:
FOLLOW-UP SCHEME

About 3/5 weeks after the implant, the patient will undergo pelvic CT and/or MRI to evaluate the quality of the implant and ensure that all the prostate has received a proper dosimetric coverage (radiation dose). The modern implant technique allows for a quality control in real time during the procedure and therefore an inadequate dosimetric coverage is very unlikely. Should an insufficient implant quality result, the treatment will be completed by adding other seeds in the uncovered areas or an external beam radiation cycle.

Furthermore an uroflowmetry is performed which evaluates the post-voiding residue, urinary culture, PSA and an andrological visit (including filling in an IEF International Index of Erectile Function questionnaire). Particular care is given to the quality of the patients' life which is evaluated by means of an IPSS International Prostate Symptom Score questionnaire and of a questionnaire about quality of life which is specific for patients with prostate carcinoma, FACT-P.

The patients are then monitored with PSA test every 3-4 months for the first year after the implant and then every 6 months.

In the first 2 years following the implant, ups and downs in PSA levels can be recorded which do not have any pathological meaning.

The following results can be interpreted as possible indicators of treatment failure:

PSA above 0.3 ng/ml 24 months after implant
3 consecutive increases in PSA values
The Specialist can suggest a bone scan and prostatic biopsies under ultrasound guidance as well as an abdomen CT. If these tests show a relapse of the disease at prostate level, there are several treatment options: surgery to remove the prostate (radical prostatectomy), hormone therapy (androgenic blockade) or still experimental treatments such as cryosurgery or thermotherapy.

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