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Prostate Cancer: Results and Side Effects of Brachytherapy

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

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 the urethra, bladder, and rectum can be 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 and partly intermediate-risk prostate cancer. The EAU guideline recommends brachytherapy for the following patients: clinical stage T1–2a, Gleason score 3+3 (ISUP grade 1) with <50% of biopsy cores involved with cancer or Gleason score 3+4 (ISUP grade 2) with <33% of biopsy cores involved with cancer; an initial PSA level of <10 ng/ml; a prostate volume of <50 ml; an IPSS score <12 and maximal flow rate >15 ml/min on urinary flow tests. The German guideline is more restrictive and recommends brachytherapy only for low-risk prostate cancer. There is no indication for adjuvant hormone therapy in LDR brachytherapy with the above-mentioned risk factors.

Some authors use LDR brachytherapy also in unfavorable intermediate-risk and high-risk prostate cancer. Theoretically, brachytherapy offers the possibility to introduce very high radiation doses into the prostate. Treatment results are even better using computer-assisted planning, generous safety distances, adjuvant hormone therapy, appropriate radiation doses, and a combination with external beam radiotherapy. Initial randomized trials have demonstrated an advantage for brachytherapy (compared with percutaneous radiotherapy) in intermediate- and high-risk prostate cancer (Morris et al., 2017) (Rodda et al., 2017b).

Contraindications:

Prostate volume over 60 ml, marked LUTS, chronic inflammatory bowel disease, resection funnel after TURP, previous pelvic irradiation of other organs.

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 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 is not recommended (Potters et al., 2005).

It is pivotal for successful brachytherapy to achieve optimal coverage of the prostate volume with the desired prescription dose. Theoretically, Palladium-103 is more suitable for poorly differentiated prostate cancer, and iodine-125 has advantages in well-differentiated tumors. The side effects are more favorable for palladium, but 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 in 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 for 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 permanent brachytherapy [see section surgical procedures/brachytherapy], the radiation therapy of the prostate is calculated. A remote-controlled afterloading device delivers the radiation source (iridium). For every needle, the position and time of the radiation source are 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% of high-risk prostate cancer; this corresponds to the results of radical prostatectomy. Grade ≥3 genitourinary toxicity is reported to be 5%, and grade ≥3 gastrointestinal toxicity is around 1% (Challapalli et al., 2012).

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/.

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