Prostate brachytherapy

This section aims to provide background information on low dose-rate (LDR) brachytherapy seed implantation, what it is, how it is done, patient-selection criteria and its clinical benefits.

Radioactive seed implantation (LDR brachytherapy)

Brachytherapy is an increasingly popular alternative to radical surgery and radiotherapy for many patients with early, localised prostate cancer. It involves the transperineal placement of radioactive seeds directly into the prostate under ultrasound guidance, and aims to deliver a high dose of radiation to the prostate (145 Gray (Gy)). The procedure can be carried out as a day case, and many patients experience no immediate morbidity and can continue to work or travel as they please. As detailed below, the benefits far outweigh any disadvantages, and brachytherapy has, therefore, become a very attractive option for those seeking to minimise the inconvenience associated with other radical treatments. The method is outlined in the Figure 1 below.

Advantages of transperineal brachytherapy

• Avoids the physical trauma of a major surgical procedure
• An outpatient procedure requiring minimal hospitalisation
• Allows for precise placement of the seeds offering more tailored treatment for the patient.
• Procedure causes minimal bleeding
• Has relatively few long-term side-effects
• Allows relatively quick recovery and return to normal activity for the patient
• One-off, minimally invasive procedure
• Well tolerated by all patients in poor medical condition
• Maintains sexual potency in many patients
• Has produced good long-term clinical outcomes
• Demonstrated cost-effective treatment option

Disadvantages of transperineal brachytherapy

• Patients can experience transient urinary irritative symptoms
• Close contact with small children and pregnant women should be avoided in the first two-months following treatment

Typical seed-implantation technique

Brachytherapy, using radioactive seeds of iodine-125 or palladium-103, does not require a surgical incision and is performed on an outpatient, or short inpatient, basis, under general or spinal (epidural) anaesthesia. The doctor locates and views the prostate using transrectal ultrasound. The ultrasound images are imported into a computer and the position of the needles and seeds is planned. The doctor then inserts the needles through the skin between the scrotum and rectum and guides them into the prostate using the ultrasound images. The optimisation of placement of these sources is performed using computer-assisted dosimetry software either before or during the procedure. After the procedure the dosimetric parameters are verified using computerised dosimetry. The number of needles varies from patient to patient, but usually between 15 and 25 are used. Through these needles, about 100 (usually between 70 and 150) radioactive seeds are inserted into the prostate. The computer can update the dose distribution within the prostate resulting from the seed implantation. This allows the doctor to modify the position of subsequent seed placement. The needles are then removed. The seeds remain in the prostate permanantly, slowly giving out radiation until they are no longer radioactive. This period is about six months for iodine seeds and two months for palladium seeds. During this time, the patient must observe minimal radiation precautions. Travel and contact with adults are not restricted; however, small children and pregnant women should not be in direct contact with the patient for prolonged periods during these two months. Sexual intercourse can usually be resumed after about one month.

After the implant, the patient goes to the recovery room for a few hours. X-rays and CT scans are usually then undertaken, and the Foley catheter is removed. The patient goes home after recovering from the anaesthesia. Most patients are able to resume their normal activities within a few days.

Follow-up

The patient returns for an examination after 4 — 6 weeks, at 6 months and then on a yearly basis. A digital rectal exam is performed and prostate-specific antigen (PSA) levels are checked.

Variations in brachytherapy technique

Two-stage technique (Seattle approach)

The original technique, a 'two-stage' procedure, requires two hospital visits, the first for a pre-implant planning session, followed 2 — 4 weeks later by the second at which the implant is carried out. This technique, popularly known as the 'Seattle technique', was introduced in the late 1980s by Grimm and Blasko in Seattle. It is the technique most commonly used in the USA and the UK and has excellent disease-free survival data at 12 years, with outcomes that are comparable to surgery.

For further information visit the website of St Luke's Cancer Centre, Guildford. (www.prostatecancercentre.com). St Luke's Cancer Centre recently presented updated data on their 5 year biochemical relapse-free survival experience.

St Luke's 5 Year Data

Modern brachytherapy techniques use advances in ultrasound imaging, computer hardware and software development to provide implants under real-time ultrasound guidance coupled with a dynamic assessment of the implant. It is now possible to carry out brachytherapy as a single-visit/day-case procedure.

Single-visit intra-operative dynamic prostate brachytherapy (the Potters' approach)

Louis Potters, of the New York Prostate Institute, developed his intra-operative dynamic approach while working at Memorial Sloane Kettering Cancer Centre. It makes use of the principle of inverse treatment planning and uses modern hardware and software developments to deliver a dynamic real-time implant with intra-operative dosimetry. It affords a control and flexibility for seed placement not previously available. This allows optimisation of the dosimetry to maximise treatment of the prostate while minimising the dosage to the urethra and the rectum.

The link below gives a more detailed explanation and visualisation of the Potters' approach as used at Guy's and St Thomas' Hospital and the Cromwell Hospital, London.

Potters technique

Brachytherapy vs surgery Guy's and St Thomas' Foundation Trust, London

Other variations

Some treatment can also include the addition of 3 — 5 weeks of external beam radiation and/or hormone treatments in addition to brachytherapy in selected patients. It is also possible to use 2 — 4 high dose-rate (HDR) brachytherapy treatments along with 3 — 5 weeks of external beam radiation.

Details on these techniques and the associated outcomes can be seen in the attached presentations, and within Section 2.4, UK Brachytherapy Centres.

Patient selection

The EAU/ESTRO/EORTC (European Association of Urology/European Society for Therapeutic Radiology and Oncology/European Organisation for Research and Treatment of Cancer) guidelines published in 2000, gave the patient-selection criteria for brachytherapy monotherapy shown in Table 1 for patients with localised disease. It should be noted that the risk groups described in the European guidelines (do well, fair and do poorly) correspond to the low-, intermediate- and high-risk groups described in most US papers.

Table 1 — Indication for prostate brachytherapy monotherapy¹

	Recommended Do well	Optional Fair	Investigational Do poorly
PSA (ng/ml)	<10	10 — 20	>20
Gleason score	5 — 6	7	8 — 10
Stage	T1c — T2a	T2b — T2c	T3
IPSSa	0 — 8	9 — 19	>20
Prostate volume (g)	<40	40 — 60	>60
Qmax ml/sb	>15	15 — 10 <10
Residual volume (ml)			>200

Reproduced with the permission of a leading brachytherapy centre, the Prostate Cancer Centre, Guildford the following three tables indicate the suitability of a patient with different parameters for different treatment options. It should be noted that the best available medical evidence would suggest that there is no discernable difference in the cure rates for patients with similar risk prostate cancer treated either by radical prostatectomy, brachytherapy or conformal beam radiotherapy (the latest machines allowing radiation doses of 72Gy or more to be given). Also indicated is the likelihood of side effects occurring with a particular treatment option. The risk of such side effects developing can be very variable and dependent on the skill and experience of the treating clinicians. Patients should enquire about the complication rates at the actual hospital they are considering being treated at.

Table 2

The suitability of a treatment for a newly diagnosed prostate cancer is indicated by the number of green or red dots present.

Table 3

The suitability of a treatment for a recurrent localised prostate cancer following radiotherapy treatment. Patients will normally have been re-investigated by an MRI and bone scan to ensure that there is no evidence that the cancer has spread outside the gland. The suitability of each second-line or salvage treatment is indicated by the number of green or red dots present.

Table 4

The possibility of a treatment to cause a specific side effect when treating a newly diagnosed prostate cancer is indicated by the number of green or blue dots present.

Clinical results

Results from various studies of the success of brachytherapy are given in the tables below.

Table 5 Low-/intermediate-risk patients treated with brachytherapy monotherapy

Series	Year	No of patients	Failure definition	Follow-up years	PSA progression-free survival (%)
Khaksar et al3	2006	300	ASTRO	5	93
Potters et al4	2005	1449	ASTRO	12	81
Joseph et al5	2004	667	ASTRO	8	75
Battermann et al6	2004	351	ASTROa	13	72
Beyer et al7	2003	551	ASTRO	10	98
Grimm et al8	2001	125	ASTRO modified	10	87

Table 6 PSA progression-free survival for patients with intermediate-/high-risk prostate cancer treated with seed implant/external beam radiotherapy (EBRT) combined treatment

Series	Year	No of patients	PSA failure definition	Follow-up years	PSA progression-free survival intermediate/high (%)
Sylvester et al10	2007	223	ASTRO modified to 2 rises	15	80 / 67
Khashkar11	2006	300	ASTRO	3.75	75 / 80
Critz and Levinson12	2004	1469	PSA <0.2ng/ml	10	80 / 61
Merrick et al13	2004	46	ASTRO	7	84
Stock et al14	2004	132	ASTRO	5	85 / 76

References