1. Is Brachytherapy 125I still needed in Prostate cancer treatment?
Ferry Safriadi
Department of Urology Hasan Sadikin General Hospital
Medical School of Padjadjaran University
Lokakarya BATAN-Radioterapi RSHS, 19 Oktober 2010

2. Introduction Brachys is the Greek word for short.
The term brachytherapy is used for forms of radiotherapy in which the radioactive source is placed close to the target, either on the body surface, within a body cavity (as radium implants for uterine cancer), or interstitially as in brachytherapy for prostate cancer.
Bratt O, BJU 2006

3. Permanent interstitial prostate brachytherapy as a treatment has been performed since the 1960s.
Initially, patients were taken to the operating room for an open lymphadenectomy at which time they underwent placement of iodine 125 seeds.
A transperineal approach was developed as a definitive treatment for localized prostate cancer in The Memorial Sloan-Kettering Cancer Center in the late 1980s.
Thompson et al, J Urol 2007

4. Indication: Prostate cancer with categories:
-Low risk: PSA 10 ng/mL and a Gleason score of 6 or less and clinical stage T1c or T2a
-Intermediate risk: PSA 10 to 20 ng/mL or a Gleason
score of 7 or clinical stage T2b but not qualifying for high risk
Thompson et al, J Urol 2007

5. EAU guidelines : Major: Life expectancy of >10–15 years.
Tumour stage T1c or T2a with no known metastases.
Gleason score ≤ 6 with no significant amount of Gleason grade 4 or 5.
PSA level of < 10 ng/mL.
Prostate volume of < 40–50 mL with no middle lobe.
Heidenreich A et al, Eur Urol 2009

6. Minor:
IPSS of ≤ 8.
Qmax rate > 10–15 mL/s and a PVR urine < 50 mL.
No previous surgery for BPH, at least no visible resection defect.
Recurrent bacterial prostatitis or a history of neisserial infection.

7. Biomolecular changes:
A significant increase in the apoptotic index was detected in post-brachytherapy.
A significant elevation in bcl-2 expression and ratio bcl-2/bax in prostatic tissue in patients with treatment failure.
Szostak MJ et al, J Urol 2001

8. 60% PSA mRNA expression in the peripheral blood was increasing.
iatrogenic shedding of prostate cells.
correlation with biochemical failure after interstitial
brachytherapy.
PSA bounce or spike is a phenomenon that has been described after prostate brachytherapy and is reported to be observed in 17–46% of patients have a transient increase in PSA level of 6–24 months’ duration.
Siddiqua A et al,Urol 2002
Bratt O, BJU 2006

9. The PSA bounce has previously been defined as an increase of 0
The PSA bounce has previously been defined as an increase of 0.1 ng/mL, followed by a subsequent decrease to less than that level; as an increase of 0.2 ng/mL, followed by a decline.
The temporal relationship to fibrosis after implantation suggests that it might be related to relative ischaemia of the gland, leading to increased leakage of PSA by residual benign tissue. it is not related to an increased risk of recurrence.
Caloglu M et al, Urology 2009

10. Technique: A TRUS-based volume prostate volume
determine the number of needles
isotope strength
The radioactive needles are implanted via a transperineal approach under guidance of transrectal ultrasound or magnetic resonance imaging.
Common regimens employ 120 Gy (palladium) or 140 Gy (125I) with postoperative dosimetry performed for each patient.
Bratt O. BJU 2006

13. An indwelling urethral catheter is removed the following day.
A few days of corticosteroids and some weeks of NSAIDs can be used to reduce oedema and thereby the risk of transient urinary retention after implantation.
The urinary side-effects after implantation are reduced by treatment with an α-blocker for some months.

14. Efficacy
J Urol 1999

15. Urology 2003

16. Urology 2009
Patients with a PPBs greater than the median had more than two times the rate of BF compared with those with a PPBs less than the median.

17. J Urol 2005

18. Biochemical freedom from PSA failure (ASTRO) D90 < 140 Gy, or 140 Gy or greater. 10-year FFF was 80% vs 94%
The most important factor to recognize as contributing to these excellent outcomes is that patients should receive at least 140 Gy to 90% of the gland.
Patients who receive less irradiation are more likely to experience failure.

19. J Urol 2007

20. Patients undergoing prostate brachytherapy must receive an adequate radiation dose to eradicate local disease.
HT may benefit local control in patients with intermediate to high risk disease.
Extraprostatic biopsies should be performed in patients with local failure who are considering salvage therapy to rule out SV involvement.

21. Age is not associated with worse brachytherapy outcomes.
J Urol 2009
Age is not associated with worse brachytherapy outcomes.

22. Eur Urol 2003

24. The 6-months costs of brachytherapy and of external beam radiation were $14,000, whilst the costs for radical prostatectomy was $17,000
Norderhaug I et al, Eur Urol 2003
Kohan AD et al, J Urol 2000

25. Complications: Urinary toxicity:
LUTS, urethral stricture, urinary retention (2-22%)
Rectal toxicity:
- Proctitis, recto-urethral fistula.
Erectile dysfunction:
> ½ of the patients have preserved erectile function after 1–3 years, but rates as high as 86% after 3 years.

26. Vargas C et al, J Urol 2005

27. Stone NN et al, Eur Urol 2002

28. The preimplant US-based prostate volume and the baseline IPSS are strong independent factors to predict catheterization after brachytherapy.
Mabjeesh NJ et al, Urology 2007

29. Brachytherapy related urethral stricture disease correlates highly with radiation dose to the BM urethra.
Merrick GS et al, J Urol 2006

30. Comparison of time to return to baseline level of erectile function
J Urol 2002
Comparison of time to return to baseline level of erectile function

31. Merrick GS el al, Urology 2003

32. Health Related Quality of Life
Better urinary continence in those who underwent radiation based therapies, and better bowel function and less urinary irritation in those who underwent surgery.
Sexual function was impaired across all monotherapies but higher scores were seen in men who selected brachytherapy.
Frank SJ et al, J Urol 2007

33. J Urol 2003

34. Conclusions:
The biochemical relapse-free survival was 80–90% for the low-risk group, which compares well with radical prostatectomy and EBRT.
Side effect and HRQOL of brachytherapy is comparable with RRP and EBRT.
 Brachytherapy is still having placed for prostate cancer treatment.

35. THANK YOU