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Prostate Cancer: Brachytherapy

Guidelines and review literature: (EAU Guidelines Prostate Cancer) (S3-Leitlinie Prostatakarzinom) (Walsh-Campbell Urology).

Low-dose-rate (LDR) brachytherapy

Low-dose-rate (LDR) brachytherapy, also known as permanent brachytherapy, uses permanently implanted radioactive seeds. Radiation sources for LDR brachytherapy include ¹²⁵I (I-125) and ¹⁰³Pd (Pd-103), and less commonly ¹⁹⁸Au (Au-198). The low photon energy of the radiation sources results in a limited extent of radiation within the tissue (the Greek word brachys means short or near). Careful planning of the implant locations can therefore spare sensitive organs such as the urethra and rectum. The half-life of the radiation effect is 60 days for ¹²⁵I and 17 days for ¹⁰³Pd. In Germany, ¹²⁵I is used predominantly.

Indications:

Brachytherapy is suitable as primary treatment for localized prostate cancer with low-risk or favorable intermediate-risk disease. The EAU guideline defines the following criteria: clinical stage T1–2a, no more than 50 % involved biopsy cores with a Gleason score of 6 (ISUP grade 1), or no more than 33 % involved biopsy cores with Gleason score 3+4 (ISUP grade 2), PSA concentration below 10 ng/ml, prostate volume below 50 ml, and no relevant voiding symptoms (IPSS below 12 and maximum urinary flow rate above 15 ml/s). There is no indication for adjuvant androgen deprivation therapy with LDR brachytherapy in patients with the above risk factors.

Numerous authors question limiting brachytherapy to the above risk factors. In theory, brachytherapy can deliver very high radiation doses to the prostate and its surrounding tissue while precisely sparing vital structures. With adjuvant ADT, generous margins, and a combination with external beam radiotherapy to the pelvic lymph nodes and seminal vesicles, randomized trials have demonstrated an advantage of a brachytherapy boost over external beam radiotherapy alone in intermediate- and high-risk disease (Morris et al., 2017; Rodda et al., 2017). However, compared with external beam radiotherapy alone, late toxicity is markedly increased (18 % vs. 8 % grade ≥ 3).

Contraindications:

Prostate volume above 60 ml, marked voiding symptoms, chronic inflammatory bowel disease, a pronounced resection cavity after TURP, and previous pelvic irradiation of other organs.

Technique:

Imaging and measurement of the prostate in horizontal sections (planimetry) form the basis for planning seed implantation. The horizontal cross-sectional images are transferred to planning software, and the urethra and rectum are marked. For a prescribed radiation dose, the planning software determines the seed distribution and calculates the radiation dose to the urethra and rectum (dosimetry). The prescription dose is 145 Gy for iodine seeds and 125 Gy for palladium seeds. The seeds are implanted transperineally under transrectal ultrasound guidance. The seed positions are entered into the planning software during the procedure. Depending on the delivered radiation dose, the software calculates the positions of the remaining seeds during implantation. This avoids underdosage of prostate regions and toxicity to the rectum and urethra [for technique, see brachytherapy of the prostate]. Within the first six weeks after seed implantation, pelvic CT is performed to document seed position and recalculate the dose. The D90 should exceed 140 Gy, meaning that 90 % of the prostate volume receives a radiation dose of at least 140 Gy.

Results:

In retrospective studies, the oncologic results of LDR brachytherapy for low-risk prostate cancer are comparable with those of external beam radiotherapy and radical prostatectomy; randomized studies with long-term follow-up are lacking (Peinemann et al., 2011). Independent prognostic factors are the radiation dose to the target tissue, PSA level, Gleason score, and number of positive biopsy cores. Adjuvant ADT or additional external beam radiotherapy is not recommended (Potters et al., 2005).

PSA bounce:

A PSA increase after brachytherapy does not necessarily indicate progression of the underlying disease. It may be caused by the radiation effect on prostate tissue and is termed a PSA bounce. This transient PSA elevation usually occurs a few months after seed implantation and may persist until the radiation effect has ended (up to 3 years). PSA bounce occurs in 44 % of men.

Because the median PSA increase during a PSA bounce is below 1 ng/ml, the definition of PSA progression after brachytherapy is the same as after radiation therapy: a PSA increase of more than 2 ng/ml above the post-treatment PSA nadir is considered biochemical recurrence (Roach et al., 2006).

High-Dose-Rate Brachytherapy

High-dose-rate (HDR) brachytherapy (Afterloading) is an effective method of dose escalation. In general, two sessions of afterloading brachytherapy to the prostate are combined with external beam radiotherapy to the prostate (e.g., 50–60 Gy). Highly radioactive nuclides such as ¹⁹²Ir (Ir-192) are used. Because of the biologically potent radiation, calculated EBRT-equivalent doses of 100–130 Gy can be achieved while maintaining a favorable adverse-effect profile.

Indications:

HDR brachytherapy is used primarily for dose escalation in patients with intermediate- or high-risk disease. The role of additional androgen deprivation therapy depends on the risk profile and is often determined in analogy to external beam radiotherapy.

Technique:

With the patient in the lithotomy position, hollow needles are inserted through the perineum into the prostate. Analogous to planning of permanent brachytherapy [see brachytherapy of the prostate], radiation treatment of the prostate is calculated. The highly radioactive source is introduced individually through each hollow needle into the prostate using a remote-controlled afterloading device. Total irradiation time is approximately 10 min.

Results:

In a randomized trial, EBRT plus an HDR boost substantially reduced the risk of recurrence at 12 years compared with EBRT alone (median time to relapse, 137 versus 82 months), but without a proven overall survival benefit. There were no significant differences in severe adverse events (Hoskin et al., 2021).

Prostate cancer radiotherapy

Index

Prostate cancer: experimental therapy

Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

References

EAU Guidelines EAU - EANM - ESTRO - ESUR - SIOG Guidelines on Prostate Cancer, https://uroweb.org/guidelines/prostate-cancer/.

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

Leitlinienprogramm Onkologie (DGU, Deutsche Krebsgesellschaft, Deutsche Krebshilfe): Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms https://www.leitlinienprogramm-onkologie.de/leitlinien/prostatakarzinom/

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

A. W. Partin, C. A. Peters, L. R. Kavoussi, R. R. Dmochowski, and A. J. Wein, Campbell-Walsh-Wein Urology, 12th ed. ISBN-13: 978-1455775675: Elsevier, 2020.

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

Deutsche Version: Therapie des Prostatakarzinoms mit Seeds, Brachytherapie oder HIFU

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