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Prostate Brachytherapy – LDR

Prostate Cancer Epidemiology

There will be 164,690 new cases (19% of all cancers in males) and 29,430 prostate cancer death in the US in 2018(1)

 

Prostate Cancer Treatment Options

Treatment options in general include active surveillance, radical prostatectomy with or without adjuvant and salvage radiation, prostate brachytherapy with or without adjuvant EBRT and or ADT.  Updated guidelines for patient selection, workup, treatment, post implant dosimetry, and follow-up are provided in ABS guidelines for LDR and HDR(2).

 

Prostate Brachytherapy - Indications

Prostate brachytherapy (PB) is a standard treatment option of patients with organ confined prostate cancer. Excellent long-term results have been published for all risk groups(3). Low Dose Rate (LDR) Monotherapy is appropriate for low and low-tier intermediate risk prostate cancer.  For most men with high-tier intermediate risk cancer, brachytherapy boost with Low Dose Rate (LDR) or High Dose Rate (HDR) brachytherapy, in combination with External Beam Radiation Therapy (EBRT) with or without Androgen Deprivation Therapy (ADT) for 9-12 months is appropriate. LDR or HDR brachytherapy boost in combination with EBRT and ADT (12-36 months) is appropriate for high risk disease.  HDR monotherapy is still evolving and early results are encouraging.  Based on 3 RTC showing superior PSA outcomes with EBRT and Brachytherapy boost vs EBRT alone(4)(5),(6)  2017 ASCO/ CCO prostate brachytherapy guideline recommends patients be offered prostate brachytherapy if eligible, establishing prostate brachytherapy as a standard of care in prostate cancer in all risk groups(7).

 

Prostate Brachytherapy – Contraindications(2)

As per ABS guidelines, absolute contraindications for LDR include:

  • Limited life expectancy
  • Unacceptable operative risks
  • Distant metastases
  • Absence of rectum such that TRUS guidance is precluded
  • Large TURP defects, which preclude seed placement and acceptable radiation dosimetry
  • Ataxia telangiectasia

 

Prostate Brachytherapy – Relative Contraindication

  • High IPSS (>15-20)
  • History of prior pelvic radiotherapy
  • TURP
  • Large median lobe
  • Gland size>60 cm3 at time of implantation
  • Inflammatory bowel disease
  • Gross seminal vesicle involvement

 

Use of ADT and Brachytherapy

There are significant uncertainties regarding the role of androgen deprivation therapy (ADT) with brachytherapy. Existing evidence shows no benefit of adding ADT to PB in low-risk and favorable IR patients. Unfavourable IR, favourable HR patients and those with suboptimal dosimetry may have up to 15% improvement in PSA PFS, with uncertain impact on Cause Specific and Overall Survival(8).

 

Expected Outcomes

Long term outcomes will dependent on treatment given and risk group stratification. They may vary between institutions.  In general, long term outcomes in all risk groups are very favourable PSA progression free survival with long 10 year follow up, suggesting ablative effects of brachytherapy.  Low and low- tier intermediate risk patients, have 85-95% long term PSA RFS, Intermediate risk 70-95%, and 85-90% in combination with EBRT (either LDR or HDR boost). Patients with high risk disease have up to 50% chance of PSA control, addition of EBRT increase PSARFS to 60-70% and addition of both, EBRT and ADT, up to 85%(3).  

 

Standard Doses

125I – Monotherapy 140-160Gy
125I – Boost 108-110Gy

103Pd – Monotherapy 110-125Gy
103Pd – 90-100Gy

131Cs – Monotherapy 100-115Gy
131Cs – Boost 70-80Gy

 

Side effects

Moderate irritative ad obstructive urinary symptoms are expected in 50% of the patients. Median time for IPSS to return to baseline is 12 months. Ten years after PB, the majority of patients (>90%) will have very little or no urinary symptoms. Worse toxicity is seen with larger prostate volume, and worse baseline urinary function. Incidence of acute urinary retention is < 5-10%, and is more likely in patients with worse baseline urinary function, significant median lobes, and those with larger prostate size. Incidence of TURP (transurethral resection of the prostate) and urethral strictures requiring dilatation is <1-2% with monotherapy(9). Incontinence develops in 40% and 15% of those who undergo TURP and urethral dilatation for stricture respectively. Mild self-limiting rectal irritation affects 20%-30% of patients in the first 1-2 years after the implant. Rectal bleeding is reported in 2-7% of patients. Grade 4 rectal fistula is rare (0.5%).  5 year Erectile function (EF) after brachytherapy depends on pre-treatment function, comorbidity and age.  EF preservation rate at 5 years for ages <55, 56-59, 60-64, 65-69, and > 70,  is about 80%, 75%, 60%, 40%, and 25%, respectively. 50 % of EF decline is related to aging(10).   EBRT and LDR boost have more long term GU and GI toxicity than PB alone (RTOG 0232 https://www.astro.org) (late grade > 2:  53% vs 37%, late grade >3: 12% vs 7%). Likewise, EBRT and LDR boost have more late long term GU and GI toxicity than EBRT alone with cumulative incidence of grade 3 GU toxicity of 18% vs 5.2% and grade 3 GI toxicity of 8.0%  vs. 3.2%. (11)

 

Training requirements

Formal training in LDR brachytherapy is available in several institutions ion the US Canada and Europe. In Addition, ABS is making hands on workshops available for residents and junior staff on annual bases (link here).

The fundamental aspects of training include proficiency in:

  • Understating indications and contraindications for LDR brachytherapy
  • Patient and side effect management
  • US volume study
  • US prostate anatomy and contouring
  • OR implant procedure
  • CT and MR post implant contouring
  • Dosimetry interpretation
  • Basic concepts of LDR physic and radiobiology
  • Quality Assurance procedure

 

References

(1) Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017 Jan;67(1):7-30.

(2) Davis BJ, Horwitz EM, Lee WR, Crook JM, Stock RG, Merrick GS, et al. American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy. Brachytherapy 2012 Jan-Feb;11(1):6-19.

(3) Grimm PD, Billiet I, Bostwick DG, Dicker A. P., Frank SJ, Immerzeel J, et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int 2012;109(supp 1):22-29.

(4) Morris WJ, Tyldesley S, Rodda S, Halperin R, Pai H, McKenzie M, et al. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer. Int J Radiat Oncol Biol Phys 2016 Nov 24.

(5) Hoskin PJ, Rojas AM, Bownes PJ, Lowe GJ, Ostler PJ, Bryant L. Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer. Radiother Oncol 2012 May;103(2):217-222.

(6) Sathya JR, Davis IR, Julian JA, Guo Q, Daya D, Dayes IS, et al. Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol 2005 Feb 20;23(6):1192-1199.

(7) Chin J, Rumble RB, Kollmeier M, Heath E, Efstathiou J, Dorff T, et al. Brachytherapy for Patients With Prostate Cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update. J Clin Oncol 2017 May 20;35(15):1737-1743.

(8) Keyes M, Merrick G, Frank SJ, Grimm P, Zelefsky MJ. American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy-A systematic literature review. Brachytherapy 2017 Jan 16.

(9) Keyes M, Miller S, Pickles T, Halperin R, Kwan W, Lapointe V, et al. Late urinary side effects 10 years after low-dose-rate prostate brachytherapy: population-based results from a multiphysician practice treating with a standardized protocol and uniform dosimetric goals. Int J Radiat Oncol Biol Phys 2014 Nov 1;90(3):570-578.

(10) Keyes M, Pickles T, Crook J, McKenzie M, Cheung A, Spadinger I, et al. Effect of aging and long-term erectile function after iodine-125 prostate brachytherapy. Brachytherapy 2015 May-Jun;14(3):334-341.

(11) Rodda S, Tyldesley S, Morris WJ, Keyes M, Halperin R, Pai H, et al. ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer. Int J Radiat Oncol Biol Phys 2017 Jan 6.