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Prostate adenocarcinoma definitive brachytherapy HDR

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  • Histologically confirmed intermediate or high risk prostate cancer, non-metastatic (localised)
  • Fit for general or spinal anaesthetic
  • Life expectancy ≥ 10 years
  • Reasonable baseline voiding function e.g. IPSS < 15. Note: If IPSS > 15, formal urodynamic studies should be undertaken

Cautions

  • Patients with poor urinary function (peak urinary flow rate < 15 mL/sec or post void residual > 100 mL) have a higher risk of urinary complications; 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
  • Pacemakers and Implantable Cardioverter Defibrillators (ICDs)
  • Prostate volume in relation to pubic arch interference

Exclusions

  • Previous TURP (patients with minimal volume loss from previous TURP may still be considered if TURP defect is not substantial and satisfactory dosimetry can be achieved)

Links to other regimens

  • Neoadjuvant ADT can be used for volume reduction where the prostate volume is > 50 cc and < 80 cc and there is a significant risk of pubic arch interference.
  • In high risk patients ADT may be continued after radiation therapy treatment for a total of 18 to 36 months.
  • All anti coagulants and aspirin to be stopped 7 days prior to implant.
  • Bowel preparation +/­- dietary modification to be commenced prior to HDR brachytherapy to minimise bowel motions as per departmental protocol.
  • Pelvic floor exercises may be helpful - consider referral to continence nurse or physiotherapist.

There are two techniques for treatment planning after brachytherapy catheter insertion:

Planning technique Description Notes
CT- based planning Volume delineation and treatment planning performed on CT (+/- ultrasound and/or MRI fusion) after patient recovers from anaesthesia.
  • Following catheter insertion and recovery from anaesthesia, patients are transferred to CT scanner (see below).
  • Target volumes, organs at risk and catheter reconstructions are generated on the CT dataset and the patient is returned to the bunker or shielded operating theatre for treatment delivery
Intra-operative ultrasound planningr Volume delineation and treatment planning performed on intra-operatively acquired ultrasound images. The planning and treatment can be completed without moving the patient and during the period of anaesthesia.  

Brachytherapy simulation notes

  • Ultrasound images are acquired < 5mm throughout the prostate volume
  • Once the catheters have been inserted under ultrasound guidance, a CT scan < 5mm slices is performed to verify the catheter placement.
  • The prostate is outlined on each of the TRUS and CT/MRI slices.
  • A PTV margin of up to 5mm may be added to the prostate volume.
  • Base of the seminal vesicles can be boosted if appropriate and technically feasible.
  • Fiducial markers should be implanted into the prostate gland to allow daily localisation for EBRT and to QA the catheter position during HDR brachytherapy treatment.

CT-based simulation for brachytherapy using CT/MRI compatible catheters

Simulation Options Notes
Position
  • Supine
  
Arm/leg/head/neck/shoulder position
  • Arms on chest
  
Immobilisation and supports
  • N/A
 Template is sutured to perineum and brachytherapy catheters locked in position.
Organ pre-requisites
  • Bladder filling
 As per department protocol.
Contrast
  • Contrast
 Diluted contrast can be instilled into bladder and/or balloon to aid in identifying the bladder-prostate interface (via catheter).
Radio-opaque markers
  • Fiducials
 To assess catheter displacement.
Bolus
  • N/A
  
Other imaging
  • Ultrasound
  • MRI
 Intra-operative ultrasound or pre-operative MRI can be used to aid prostate contouring.
CT acquisition
  • 3DCT
 CT acquisition from bottom of SI joints to 1.5cm below the ischial tuberosities.
Medications
  • Analgesia
 Oral, spinal or patient-controlled intravenous analgesia.

CT-based simulation for external beam radiation therapy

Phase Target area Dose prescription Prescription point/ volume Beam type Dose/# Fractions Scheduling
#/day #/fortnight
1 Prostate 18 - 19.5Gy 100% to cover target volume, aiming for a minimum of 95% coverage as per ICRU 58 Iridium 192 radioactive source 6-6.5Gy 3 Minimum of 6 hours apart Fractions 2 to 3 at least 6 hours following previous fraction (can be given at a later time during the patients overall treatment)
OR
1 Prostate 17 - 23.5Gy 100% to cover target volume, aiming for a minimum of 95% coverage as per ICRU 58 Iridium 192 radioactive source 8.5 - 11.75Gy 2 Minimum of 6 hours apart Fraction 2 at least 6 hours following previous fraction (can be given at a later time during the patients overall treatment)
OR
1 Prostate 15 - 19Gy 100% to cover target volume, aiming for a minimum of 95% coverage as per ICRU 58 Iridium 192 radioactive source 15 - 19Gy 1 1 1
External Beam RT
2 Prostate + SV +/- lymph nodes 46 - 50Gy ICRU 50/62/83 Photons
(6-18MV)		 1.8 - 2Gy 23 - 25 1 9 - 10

Prescription notes

  • HDR brachytherapy can be given before, concurrent with or after the external beam radiation therapy.
  • The optimal dose, fractionation and brachytherapy scheduling has yet to be defined. These are reasonable fractionation schedules in current use.
Phase 1 - HDR Brachytherapy
CTV
  • Prostate + proximal seminal vesicles and any extra prostatic or known seminal vesicle invasion
PTV
  • CTV + 0 - 5mm margin
Phase 2 - EBRT

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

Target volume notes

  • The target volumes can be delineated on CT or intra-operative ultrasound images.
Organ Constraints Additional information
Phase 1 - HDR Brachytherapy
Urethra
  • Maximum urethral dose < 120% of the prescribed dose
  • D0.1cc < 120Gy EQD2r
  • D10 < 120Gy EQD2r
  • D30 < 105Gy EQD2r
 NB. EQD2 total dose includes the EBRT component of treatment
Rectum
  • D2cc < 75Gy EQD2r
 NB. EQD2 total dose includes the EBRT component of treatment
Phase 2 - EBRT
Rectum
  • V44Gy < 15%r
  • V41Gy < 20%r
  • V38Gy < 25%r
  • V35Gy < 35%r
  • V29.5Gy < 50%r
 ENZARAD EBRT dose prescription:r
46Gy/ 23#

The following rectal DVHs are largely based on voluming the rectum as follows:
  • The outer wall of the rectum is contoured superiorly from the recto­sigmoid junction (where the rectum turns horizontally into the sigmoid, usually at the caudal border of the sacro­iliac joint) to 1.5cm caudal to the inferior border of the CTV (prostate apex).
  • Superiorly, the anorectal contours should extend at least 5mm beyond the proximal margin of the PTV.
Bladder
  • V47Gy < 15%r
  • V44Gy < 25%r
  • V41Gy < 35%r
  • V38Gy < 50%r
 Dose constraints for the bladder are not well defined. The whole of the external wall of the bladder should be contoured.
Femoral Heads
  • V30Gy < 5%r
 The femoral head is defined from the acetabulum to the inferior edge of the treatment field.

Organs at risk notes

  • Phase 2: Organs are contoured as a solid organ per FROGG Consensus Guideline recommendations.r
Modality Frequency Match point
  • CT
  • Fluoroscopy
  • Each fraction
  • Fiducial markers**

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

Target verification notes

  • **If CT-based planning is used, catheter position should be checked with respect to fiducial markers each fractionr
  • For EBRT target verification, please link to High Risk or Intermediate Risk protocol.
  • Consideration should be given to dose delivered from verification imaging and whether this needs to be accounted for in treatment planning, particularly with respect to critical OARs.

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
Meta-analysis Zaorsky et al, 2015r Yes Yes Dose escalation up to 200Gy BED is associated with improved biochemical disease control.
Phase III trials Hoskin et al, 2012r Yes Yes 37.75Gy/13# EBRT + 17Gy/2# HDR vs 50Gy/20# EBRT alone. By contemporary standards the dose used in the control arm is considered too low. The external beam component of the brachytherapy arm used a biologically equivalent hypofractionated regimen.
Guix et al, 2014r Yes Yes 76Gy 3DCRT (n=223) vs. 46Gy 3DCRT + 2 x 8Gy HDR Brachytherapy (n=222).
Phase II trials Galalae et al, 2004r Yes Yes Pooled analysis of three phase II trials and largest series of HDR boost (611 patients).
Duchesne et al, 2007r Yes Yes Detailed report of toxicity following HDR brachytherapy boost from phase I/II study (N=108). 46Gy/23# EBRT + 16-20Gy/4# HDR.
Observational Studies Khor et al, 2013r Yes Yes Australian matched pair analysis of 688 patients comparing HDR boost to modern EBRT showed improved biochemical control with HDR boost.
Guidelines Date published/revised Supports use Yes/No/NA Is the dose and regimen consistent with the protocol? Comments
GEC-ESTRO 2013r Yes Yes  
ABS 2012r Yes Yes  

Efficacy

Dose Escalation

Multiple randomised trials of external beam radiation alonerrr and a meta-analysis which included brachytherapy boostr have demonstrated improved biochemical relapse free survival when treatment doses were escalated beyond 70Gy. The MDACC RCT comparing dose escalation from 70Gy to 78Gy reported 6 year freedom from failure increasing from 64% to 70%.r Most benefit was demonstrated in men presenting with PSA levels > 10. However, dose escalation via EBRT resulted in markedly increased rectal toxicity.r

Dose escalation via Brachytherapy boost

There are limited RCTs comparing the use of HDR + EBRT and EBRT alone. The study by Hoskin et alr compared HDR brachytherapy + EBRT with EBRT alone reported improved biochemical relapse-free survival in all groups. Mean PSA relapse-free survival in the HDR arm was 5.1 years vs 4.3 years EBRT alone, however, the control arm of the trial was with EBRT doses of 55Gy/20 fractions, is now considered too low.

Other randomised and non-randomised studies have also shown a biochemical control benefit to a brachytherapy boost.

An Australian matched pair analysis of 688 patients compared 344 patients treated with EBRT (46Gy/23 fractions) and HDR boost (19.5Gy/3 fractions) to 344 propensity score matched controls.r 5 and 10 year biochemical control was 70.9% and 32.8% vs 79.8% and 69.2% in the EBRT alone and EBRT + HDR cohorts respectively (HR 0.59, P=0.0011).

A large retrospective study (870 patients) from MSKCC compared patients treated with modern dose-escalated EBRT alone to 86.4Gy (470 patients) to patients treated with combination EBRT and brachytherapy boost (400 patients) and found a significant improvement in biochemical control at 7 years, 81.4% with EBRT alone and 92.0% with EBRT + brachytherapy.r

Fig. 2. Kaplan–Meier survival curves for patients free of biochemical and/or clinical failure and overall survival.

 Solid line: external-beam radiation therapy plus high-dose-brachytherapy boost (EBRT + HDR-BTb). Dashed line: external-beam radiation therapy alone (EBRT). Number of patients at risk is shown against each time interval.
© Hoskin et al. 2012r

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 retention Crook et al, 2001r 1-14% Systematic review.
Severe* late urinary toxicity Hoskin et al, 2012r Prevalence: 8% and 11% at 5 and 7 years, respectively *See table 1 in Hoskin et alr which is adapted from Dische et al.r
Estimated Kaplan-Meier incidence: 26% and 31% at 5 and 7 years, respectively.r
Urethral stricture Sullivan et al, 2009r 8%
(38/474 patients)		 92% of strictures occurred in the bulbomemranous urethra. The overall actuarial rate of grade 2 or more BM stricture was estimated at 10.8% (95% CI 7.0-14.9%).
Severe* late rectal toxicity Hoskin et al, 2012r 0% and 0% prevalence at 5 and 7 years, respectively *See table 1 in Hoskin et alrwhich is adapted from Dische et al.r
Estimated Kaplan-Meier incidence: 7% and 7% for 5 and 7 years, respectively.r
Erectile dysfunction Duchesne et al, 2007r 5 year actuarial incidence and prevalence of Grade 2 or more ED was 77.0% and 45.3%, respectively Among men with no baseline erectile dysfunction and no androgen deprivation.
Urinary Incontinence Morton, 2005r <1% Higher in patients who have had a previous TURP.
Urethro-rectal fistula Deger et al, 2005r 6/442 patients (1.4%) required a colostomy. 5 of these patients also required a urinary diversion. The highest incidence was reported in this Berlin series.
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Version 3

Date Summary of changes
6/07/2015 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.
22/06/2017 Note to OAR table added: EQD2 total dose includes the EBRT component of treatment and transcription of D10/D30 corrected.
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

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https://www.eviq.org.au/p/415

06 Oct 2024