Dr. med. Dirk Manski



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Prostate Cancer: Brachytherapy


Guidelines and review literature: (EAU Guidelines, Mottet et al, 2015) (S3-Leitlinie Prostatakarzinom der DGU) (Walsh-Campbell Urology 11th Edition).

Low-Dose Rate Brachytherapy for Prostate Cancer

Low-dose rate (LDR) brachytherapy is a type of internal radiation therapy that delivers a high dose of radiation at a low-dose rate from implants placed permanently in the prostate. Typical implants for LDR brachytherapy are 125I (iodine-125) and 103Pd (Palladium-103), not very common is 198Au (gold-198). The low photon energy of the radiation sources limits the radiation to the tissue next to the implant (the greek word brachys stands for "short-distance"). By careful planning of the implant locations, sensitive organs like urethra, bladder and rectum can are spared. The half-life of the radiation effect is 60 days for iodine-125 and 17 days for palladium-103 (Deger et al, 2001).

Indications for Brachytherapy

LDR Brachytherapy is a therapeutic option for low-risk prostate cancer (Gleason score below 7 and PSA < 10 ng/ml). Brachytherapy is not ideal in patients suffering from LUTS due to prostatic obstruction, with a prostate volume over 60 ml, after TURP or with inflammatory bowel disease.  

The limitation of LDR brachytherapy to low-risk prostate cancer is doubted by some authors. Theoretically, brachytherapy offers the possibility to introduce very high radiation doses into the prostate. By using computer-assisted planning, generous safety distances, appropriate radiation doses and combination with external beam radiotherapy, future studies could support the use of brachytherapy in high-risk prostate cancer.

Surgical Technique of Brachytherapy:

Imaging and measuring the prostate in horizontal layers (planimetry) forms the basis for seed implantation planning. The horizontal cross section images are transferred into a planning software. The urethra and the rectum are marked. The software calculates the seed distribution for a desired radiation dose and calculates the radiation dose to the clinical target volume, the urethra and the rectum (dosimetry). The seeds are implanted via a transperineal hollow needle under transrectal ultrasound imaging control. Ideally, the calculation of the radiation dose is updated after each positioning of seeds during the treatment (see section surgical procedures/brachytherapy of the prostate).

Results of LDR Brachytherapy for Prostate Cancer:

The oncological results after LDR brachytherapy are comparable to external beam radiation therapy and radical prostatectomy, however, randomized studies with long-term follow-up do not exist (Peinemann et al, 2011). Independent prognostic factors include the radiation dose of the target tissue, PSA level, Gleason score and the number of positive biopsies. Adjuvant hormonal therapy or additional external irradiation are not recommended (Potters et al, 2005).

It is pivotal for a successful brachytherapy to achieve an optimal coverage of the prostate with the planned radiation dose. Theoretically, Palladium-103 more suitable for poorly differentiated prostate cancer, iodine-125 has advantages in well-differentiated tumors. The side effects are more favorable for palladium, but in clinical studies there are only marginal differences (Peschel et al, 2004).

PSA Bounce and PSA Progression After Brachytherapy:

Up to 44% of men experience a slight increase of PSA after brachytherapy. This is not necessarily a progression of the underlying disease, but is triggered by the radiation effect on the prostate tissue and is called PSA bounce. This transitory PSA increase usually occurs a few months after the seed implantation and can persist until the end of the radiation effects (up to 3 years).

Since the median rise of a PSA bounce is below 1 ng/ml, the definition for PSA progression after brachytherapy is the same as for radiation therapy: a PSA rise above 2 ng/ml over PSA nadir after treatment is regarded as biochemical recurrence (Roach et al, 2006).

 

High Dose Rate Brachytherapy of Prostate Cancer (Afterloading)

High dose rate brachytherapy uses highly radioactive nuclides such as 192Ir (iridium-192) and is very effective for dose escalation in the prostate. In addition to external beam radiotherapy of the prostate (e.g. 50–60 Gy), two sessions of afterloading brachytherapy are added. Due to the biologically potent radiation effect, calculated doses of 100–130 Gy can be achieved with an acceptable side effect spectrum.

Indications for High Dose Rate Brachytherapy of Prostate Cancer

HDR brachytherapy is recommended in patients with high-risk prostate cancer. The need of additional hormonal therapy remains unclear. Since it is standard for external beam radiation therapy in the high-risk group, it is often applied as a case-by-case decision.

Surgical Technique of High Dose Rate Brachytherapy (Afterloading):

Thin hollow needles are inserted in the prostate transperineally using ultrasound guidance. Similar to the planning of the permanent brachytherapy [see section surgical procedures/brachytherapy], the radiation therapy of the prostate is calculated. The radiation source (iridium) is delivered by a remote-controlled afterloading device. For every needle the position and time of the radiation source is calculated and planned by a complex software algorithm. It takes about 10 minutes to deliver the radiation dose.

Results of HDR Brachytherapy for Prostate Cancer:

Studies report durable 10-year freedom from biochemical failure in around 60% for high-risk groups, this corresponds to the results of current series of radical prostatectomy. Grade ≥3 genitourinary toxicity is reported to be 4.5% [range 0–14.4%], and grade ≥3 gastrointestinal toxicity 1% (Challapalli et al, 2012).







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References

Blana u.a. 2004 BLANA, A. ; WALTER, B. ; ROGENHOFER, et a.:
High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience.
In: Urology
63 (2004), Nr. 2, S. 297–300.

Deger u.a. 2001 DEGER, S. ; BOHMER, D. ; ROIGAS, et a.:
[Brachytherapy of local prostatic carcinoma].
In: Urologe A
40 (2001), Nr. 3, S. 181–4

Ganzer, R.; Fritsche, H.-M.; Brandtner, A.; Bründl, J.; Koch, D.; Wieland, W. F. & Blana, A.
Fourteen-year oncological and functional outcomes of high-intensity focused ultrasound in localized prostate cancer.
2013, 112, 322-329.

Morris u.a. 2005 MORRIS, D. E. ; EMAMI, B. ; MAUCH, P. M. ; KONSKI, A. A. ; TAO, M. L. ; NG, A. K. ; KLEIN, E. A. ; MOHIDEEN, N. ; HURWITZ, M. D. ; FRAAS, B. A. ; ROACH, 3rd ; GORE, E. M. ; TEPPER, J. E.:
Evidence-based review of three-dimensional conformal radiotherapy for localized prostate cancer: an ASTRO outcomes initiative.
In: Int J Radiat Oncol Biol Phys
62 (2005), Nr. 1, S. 3–19

Peinemann, F.; Grouven, U.; Bartel, C.; Sauerland, S.; Borchers, H.; Pinkawa, M.; Heidenreich, A. & Lange, S.
Permanent interstitial low-dose-rate brachytherapy for patients with localised prostate cancer: a systematic review of randomised and nonrandomised controlled clinical trials.
Eur Urol, 2011, 60, 881-893.

Pickles u.a. 2005 PICKLES, T. ; GOLDENBERG, L. ; STEINHOFF, G.:
Technology review: high-intensity focused ultrasound for prostate cancer.
In: Can J Urol
12 (2005), Nr. 2, S. 2593–7

Potters u.a. 2005 POTTERS, L. ; MORGENSTERN, C. ; CALUGARU, et a.:
12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer.
In: J Urol
173 (2005), Nr. 5, S. 1562–6
N. Mottet (Chair), J. Bellmunt, E. Briers (Patient Representative), R.C.N. van den Bergh (Guidelines Associate), M. Bolla, N.J. van Casteren (Guidelines Associate), P. Cornford, S. Culine, S. Joniau, T. Lam, M.D. Mason, V. Matveev, H. van der Poel, T.H. van der Kwast, O. Rouvière, T. Wiegel
Guidelines on Prostate Cancer of the European Association of Urology (EAU), https://uroweb.org/guideline/prostate-cancer/.


Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF):
Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 3.1, 2014 AWMF Registernummer: 034/022OL, http://www.awmf.org/leitlinien/detail/ll/043-022OL.html (Zugriff am: 07.02.2016)


Wein, A. J.; Kavoussi, L. R.; Partin, A. P. & Peters, C. A.
Campbell-Walsh Urology
. Elsevier, 2015. ISBN 978-1455775675.


Touma u.a. 2005 TOUMA, N. J. ; IZAWA, J. I. ; CHIN, J. L.:
Current status of local salvage therapies following radiation failure for prostate cancer.
In: J Urol
173 (2005), Nr. 2, S. 373–9

Wirth u.a. 2002 WIRTH, M. P. ; HERRMANN, T. ; ALKEN, et a.:
[Recommendations for permanent, interstitial brachytherapy alone in localized prostate carcinoma].
In: Urologe A
41 (2002), Nr. 4, S. 369–73


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