1. Home
  2. Radiation oncology
  3. Urogenital
  4. Prostate

Prostate adenocarcinoma definitive brachytherapy permanent seeds LDR

On this page
Expand all Collapse all Back to top
  • Histologically proven low to intermediate risk prostate cancer (ISUP 1-3)r
  • Clinical stage T1c-­T2N0 or N0M0
  • Gleason score < 7
  • Fit for general or spinal anaesthetic
  • Life expectancy > 10 years
  • PSA < 20ng/mL

Cautions

  • PSA 10-20 ng/mL is acceptable provided there are no other high risk features as per ABS guidelinesr
  • Patients with poor urinary function (peak urinary flow rate <10 mL/sec or postvoid residual > 100 mL) have a higher risk of post-implant urinary obstruction and require urological assessment prior to considering implant
  • Obstruction resulting from a large median lobe or high bladder neck may be managed (e.g. with a mini TURP or bladder neck incision) three months prior to implant, to allow healing
  • Non-rheumatoid collagen vascular disorders
  • Inflammatory bowel disease and/or history of adhesions/bowel obstruction
  • Previous high dose RT to pelvis
  • Prostate volume in relation to pubic arch interference

Exclusions

  • Large TURP defect which precludes seed placement and acceptable dosimetry

Note

  • Intermediate risk patients may not be suitable for seed brachytherapy monotherapy if they have high volume disease, predominant Gleason pattern 4 and more than only one adverse risk feature
  • Patients with minimal volume loss from previous TURP may still be considered if satisfactory dosimetry can be achieved
  • Pelvic floor exercises may be helpful - consider referral to continence nurse or physiotherapist

Links to other regimens

At the volume study:

  • ADT (3 to 6 months) can be used to reduce prostate volume prior to a planned repeat volume study.

Prior to implant:

  • All anti coagulants and aspirin to be stopped 7 days prior to implant.
  • Selective alpha blockers should be considered prior to the implant (e.g. tamsulosin).r
  • Patient to be educated on the procedure as well as radiation safety issues.
  • Patient to commence appropriate bowel preparation as per department policy.

At time of implant:

  • Antibiotics should be administered intraoperatively and considered postoperatively.

Post implant:

  • Post seed implant dosimetry should be performed for QA purposes.r
  • Department protocol will determine the timing of post implant dosimetry which is generally performed on Day one or Day 30 +/- 7 days.
  • Consider chest x-ray.
  • If a Urologist has been involved in the care of the patient they should be contacted if urinary retention develops.

Note:

In the unfortunate event of a patient's death within 20 months following permanent I-125 seed implant, please refer to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) Safety Guide which outlines radiation safety processes to be followed. Link to ARPANSA recommendations for Radiation Protection in the Event of the Death of a Patient Undergoing Treatment with Brachytherapy Sources In Situ.

There are three techniques for seed implants currently in use:

Simulation technique Description Notes
Preplanning A transrectal ultrasound volume study is performed prior to seed insertion where the seed placement is planned and treatment plan/dose delivery is calculated.
  • Patient in dorsolithotomy position.
  • The urethra is visualised using a urethral catheter or aerated gel.
  • Transrectal ultrasound (TRUS) prostate volume study (anaesthetic may be used) is performed prior to implant using a stepper stabiliser unit.
  • Ultrasound images are taken < 5mm steps from base to the apex of the prostate using the stepper.
  • The prostate capsule and urethra are outlined on each slice and the data is inserted into a planning computer to calculate the exact number and position of seeds required for the implant.
  • The patient then returns for the implant at a later date. It is important to avoid delay between the Volume Study and actual implantation (i.e. >2 months), so as to avoid changes in the prostate contour between planning and treating times.
  • Recommend seed calibration to be performed as per regulatory guidelines.
Real time intraoperative Volume study is performed at time of implant and treatment plan/dose delivery is calculated intraoperatively.r
  • Patient lying in a dorsolithotomy position.
  • Under anaesthetic a TRUS is performed with a stepper stabilising unit attached.
  • The plan is created during the procedure.
  • Seeds are implanted during the imaging study and dose delivered is calculated during the implantation process.
Real time interactive As for real time intraoperative (above) but seed placements are updated in real time, to allow replanning if necessary during implant.
  • Patient lying in a dorsolithotomy position.
  • Under anaesthetic a TRUS is performed with a stepper stabilising unit attached.
  • The plan is created during the procedure.
  • Seeds are implanted during the imaging study and dose delivered is calculated during the implantation process.
Phase Target area Dose prescription Prescription point/ volume Beam type Beam energy Dose/# Fractions Scheduling
1 Prostate 145Gy to cover the PTV V100 to cover target volume, with a minimum of 90% coverage as per TG43 guidelinesr Iodine 125 permanent seeds 0.3 - 0.5mCi per seed implanted (up to 120 seeds per implant) 145Gy 1 - implantation Permanent seeds may be implanted either:
1. Post preplanning volume study
OR
2. During real time intraoperative planning

Prescription notes

  • Planning targets for the prostate:
    • D90 > 145Gy
    • V100 > 90%
    • V150 > 45-65%
    • V200 < 20%r
Phase 1
CTV
  • Whole prostate as defined by the capsule
PTV
  • CTV + margin expansions:
    • 3 - 5 mm anteriorly and laterally,
    • 0 - 2 mm posteriorly and
    • 0 - 5 mm superiorly and inferiorly

Margin ranges have been agreed by the Radiation Oncology reference committee and are reflect safe clinical practice.

Target volume notes

  • The recommendations are consistent with the ESTRO target volume guidelines.r
Organ Constraints Additional information
Urethra
  • Max urethral dose < 217Gy (150% isodose)
  • D10 < 150% of prescription doser
  • D30 < 130% of prescription doser
  • UV5 < 150% (217Gy)r
  • UV30 < 125% (181Gy)r
  
Rectum
  • D2cc < 145Gy (100% isodose)r
  • RV100 ideally < D1cc on day 1r
 To minimise rectal toxicities, rectal volumes > 2.5 cm3 should be minimised.r
Modality Timing
  • Fluoroscopy
  • Intraoperative
  • CT
  • Consider chest x-ray
  • Post implant dosimetry*: Day one or Day 30 +/- 7 days

Target verification recommendations reflect the minimum imaging required for the safe delivery of this protocol

Target verification notes

*Post Implant Dosimetry
  • The following dose parameters should be reported:
    • Prostate
      • D90 (in Gy and percent)
      • V100 and V150 (in percent)
    • Urethra (where possible to measure)
      • UV150 (in volume)
      • UV5, UV30 (percent)
    • Rectum
      • RV100 (in volume)
  • Implant quality should be stratified to identify poor quality implants:
    • Good: D90 > 130.5Gy (90%)
    • Adequate: D90 > 116 – 130.5Gy (80 - ­90 %)
    • Poor: D90 < 116Gy
  • Clinical discussion required if poor quality implant
  • Recommended OAR limits on post implant dosimetry:
    • Rectal V100 < 1.3ccr

The side effects listed below are not a complete list of all possible side effects for this treatment and should only be used as a guide.

Acute: Short term side effects during or within a few weeks post radiation therapy (usually temporary)
Perineal bruising and swelling
Fatigue

Read more about fatigue.
Irritative or obstructive urinary symptoms

Bladder spasms, dysuria, nocturia, frequency, incontinence, urgency, retention.
Proctitis

Including diarrhoea, increased bowel frequency, rectal urgency, pain and bleeding.

Read more about proctitis.
Urinary retention +/- clots

Late: Long term side effects - months to years post radiation therapy (may be permanent)
Sexual dysfunction - male

Including erectile dysfunction, impotence, dry and/or painful ejaculation, haematospermia and reduction in ejaculate. Patients should be offered sexual counselling to manage potential late effects related to sexual function.
Obstructive urinary symptoms and urinary retention
Perineal discomfort
Rectal ulceration
Urethral stricture
Proctitis

Read more about proctitis.
Prostatorectal fistulas

Rare, but increased risk in the setting of subsequent rectal biopsies which are contraindicated.
Urinary incontinence
Second malignancy
Source Study & year published Supports use
Yes/No/NA		 Is the radiation dose and fractionation consistent with the protocol? Comments
Comparative analysis Grimm et al,2012r Yes   Comparative analysis of studies of curative prostate cancer treatment including 52,087 patients in total. 33 studies of seed monotherapy (14,236 patients) reviewed.
Phase III trials Giberti et al, 2009r Yes Yes Radical Retropubic prostatectomy vs brachytherapy seed implants for low risk prostate cancer. 200 patients randomized and 5 year mean follow up.
Case series Zelefsky et al, 2007r Yes Yes - 144Gy 1,831 patients treated with I-125 seeds with a median follow-up of 32 months reported an 8 yr PSA relapse free survival for low and intermediate risk prostate cancer of 82% and 70% respectively (p<0.001).
Kittel et al, 2015r Yes Yes - 144Gy 1,989 patients (1,219 low risk) treated with I-125 seeds with a median follow-up of 81 months.10 year biochemical control was 87% for low risk, and 79% for low-intermediate risk patients.
Stock et al, 1998r Yes Yes - median 140.8Gy 134 patients with T1-2 prostate cancer implanted with I-125 seeds. Improvements in freedom from biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year FFBF rates for patients with D90 values <100Gy, 100-119.9Gy, 120-13.9Gy, 140-159.9Gy, and > 160Gy were 53, 82, 80, 95, and 89%, respectively (p=0.02).
Stone et al, 2007r Yes Yes - 167Gy Long term toxicity.
Keyes et al, 2006r Yes Yes - 144Gy Urinary retention decreased with experience from 17% to 6.3% (first 200 patients vs last 200 patients of total 805).
Guidelines Date published/revised

Supports use Yes/No/NA

 Is the dose and regimen consistent with the protocol? Comments
ABS Davis et al, 2012r Yes Yes  
ASTRO/ACR Rosenthal et al, 2011r Yes Yes  
ESTRO/EAU/EORTC Ash et al, 2000r Yes Yes  
ESTRO/EAU/EORTC (Target volumes) Salembier et al, 2007r Yes Yes  

Efficacy

Outcome Study Nos. of patients (experimental/control) Effect Comment
Failure free survival Zelefsky et al, 2007r 1831 8 year PSA relapse free survival for low, intermediate and high risk patients was 74%, 61% and 39% respectively.  
Kittel et al, 2015r 1989 For low risk patients, 5 and 10 year biochemical relapse free survival (BRFS) was 95% and 87%, respectively. For low-intermediate risk patients, 5 and 10 year BRFS was 90% and 79%, respectively. 61% were low risk, 30% were intermediate risk, and 4% high risk
Overall survival Zelefsky et al, 2007r 1831 8 year overall survival for low, intermediate and high risk patients was 81%, 71% and 63% respectively.  
Kittel et al, 2015r 1989 For low risk patients, 5 and 10 year OS was 95% and 78%, respectively. For low-intermediate risk patients, 5 and 10 year OS was 93% and 74%, respectively.  

Results from the comparative studyr by the Prostate Cancer Results Study Group comparing treatment options with long term follow up in relation to PSA progression free survival, indicated that in the low and intermediate risk patient groups, higher average PSA progression free survival was reported for brachytherapy than for radical prostatectomy or external beam radiation therapy.

© BJUI Grimm 2012r

The single institution study by Kittel et alr of 1,760 patients reported 5 and 10 year biochemical PFS of 95.3 and 81.5%, respectively, in patients with low risk disease.

© Int J Radiat Oncol Biol Kittel 2015r

The single institution study by Grimm et al of 125 patients reported a 10 year biochemical PFS of 87% in patients with low risk disease (PSA < 10, Gleason Sum 2­-6, T1­-2b) and 85% overall. PSA declined over time (80% of patients had a PSA < 2 after 18 months and 80% had PSA < 0.2 after 6 years, with absolute PSA and bPFS curves merged at 10 years.r

Dose response relationships using permanent seed brachytherapy were reported in the study by Stock et al,r patients receiving D90 < 140Gy had a 4 year freedom from biological failure rate of 68% vs 92% for patients with D90 > 140Gy (p=0.02) and PSA relapse free survival of 68% vs 96% respectively. Multivariate analysis based on dose, PSA, Gleason score and staging identified that dose was the most significant predictor of biochemical failure, with the dose response being more pronounced in patients with PSA > 10ng/mL.r

A pooled study of 1,831 patients treated with I-125 seeds with a median follow ­up of 32 months reported an 8 year PSA relapse free survival for low and intermediate risk prostate cancer of 82% and 70% respectively (p<0.001). For patients receiving doses of 90% (D90) to the prostate = 130Gy, the 8 year PSA relapse free survival probability using the ASTRO definition was 93% vs 76% (D90 = 130Gy)(p<0.001).r

Toxicity

A summary of the most clinically significant toxicities associated with this protocol are included in the table below:

Toxicity Study/Year Incidence of event or % Comment
Acute urinary (all) Zelefsky et al, 2007r

23% (grade 1)
38% (grade 2)
6% (grade 3)

Acute urinary retention developed in 8%. Grade 2 GU toxicity was higher in those with baseline IPSS > 12.
Urinary incontinence was reported in less than 1%.
Acute rectal (all)

37% (grade 1)
3% (grade 2)
1% (grade 3)

  
Late urinary (all)

32% (grade 1)
19% (grade 2)
4% (grade 3)

 4% urethral stricture. Chronic urethritis developed in 19%.
Late rectal (all)

17% (grade 1)
7% (grade 2)
1% (grade 3)

 7% developed late rectal bleeding.
Rectal bleeding Stone et al, 2007r

24% (years 1 - 3)
2.8% (at 5 years)

  
Erectile dysfunction Zelefsky et al, 2007r 43% of previously potent patients 50% for patients treated with androgen deprivation therapy, 39% for patient treated with brachytherapy alone.

Toxicity Notes

  • Up to 15% of patients may develop acute urinary retention in the few days post implant which resolves within 2 weeks in the majority of patients.r
  • A multivariate analysis by Keyes et al indicated that poor baseline urinary function, large prostate volume, significant oedema of the prostate after the procedure and implant order are all significant predictors for development of acute urinary retention (AUR).r
  • Grade 2 or higher rectal toxicities increased from 4% to 9% in patients where the rectal volume exceeded 2.5 cm3.r
  • Erectile Dysfunction results – meta-analysis showed seed brachytherapy has a lower impotency rate compared to other conventional treatments when age adjusted potency rates are considered.r
[%id%]
[%title%]
[%abstract%]

Flinders Filters has partnered with eviQ to build reliable, robust search filters to retrieve core high level evidence on topics of significance to eviQ. The project goal is the provision of a sustainable model for evidence retrieval to ensure ongoing currency of content.

These search filters have been developed to retrieve the most up to date evidence from PubMed, in real time, using specifically designed search filters built to meet our needs.

Searches can be used when a protocol is scheduled for review or at any time you choose. Please click on the Specific, Balanced and Sensitive tabs below to access the Pubmed searches.

Specific Balanced Sensitive
restricted to retrieving randomised control trials and systematic reviews.

is the middle ground between sensitive and specific searches.

retrieves all clinically relevant evidence - generally a broader search on a given topic.

Access Flinders Filters, a division of the Flinders Digital Health Research Centre at Flinders University to read more about research solutions to searching problems.

Troubleshooting

Occasionally the searches may not display correctly or take too long to load (and will eventually timeout). This may be caused by Internet Explorer being unable to handle long URL's. You can rectify this by using Firefox, Safari or Google chrome. It is always a good idea to clear the cache regularly to ensure you are getting the most up to date search.

Feedback

If you identify any new articles that you believe should be included in the content, please use the feedback button below to inform us of the name of the article(s). 

Version 3

Date Summary of changes
8/07/2015 Approved and published on eviQ.
30/04/2017

Protocol reviewed at August 2016 RCM.
Approved and published to eviQ.
Review group 2.
31/05/2017 Transferred to new eviQ website.
09/10/2017 Literature search added.
26/04/2021 Title updated as per RCM held 15 October 2020. Review at next urogenital RCM.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

Send feedback for this page

First approved:
Last reviewed:
Review due:

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/416

06 Oct 2024