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  • Review Article
  • Published:

The evolution of brachytherapy for prostate cancer

Nature Reviews Urology volume 14, pages 415–439 (2017)Cite this article

Subjects

Key Points

  • Brachytherapy and brachytherapy boost with low-dose-rate brachytherapy (LDR-BT) or high-dose-rate (HDR)-BT can be used as first-line therapies in the management of prostate cancer patients of all National Comprehensive Cancer Network (NCCN)-defined risk groups

  • LDR-BT, consisting of a single implant, typically uses 125I or 103Pd; by contrast, HDR-BT consists of 1–3 implants and uses 192Ir

  • Benefits of HDR-BT over LDR-BT include the ability to use the same source for other cancers, lower operator dependence, and fewer acute irritative symptoms

  • Benefits of LDR-BT include more favourable scheduling logistics, lower initial capital equipment costs, non-requirement of a shielded room, completion in a single implant, and more robust data from clinical trials

  • Outcomes of HDR-BT and LDR-BT are similar to those of other treatment options, including external beam radiotherapy (EBRT) and surgery, and brachytherapy can also be used in combination with EBRT in intermediate-risk and high-risk disease

  • Severe toxicities of HDR-BT and LDR-BT are rare, although the rate of urethral stricture is increased when brachytherapy boost is performed; incontinence is not associated with any radiotherapy modality

Abstract

Brachytherapy (BT), using low-dose-rate (LDR) permanent seed implantation or high-dose-rate (HDR) temporary source implantation, is an acceptable treatment option for select patients with prostate cancer of any risk group. The benefits of HDR-BT over LDR-BT include the ability to use the same source for other cancers, lower operator dependence, and — typically — fewer acute irritative symptoms. By contrast, the benefits of LDR-BT include more favourable scheduling logistics, lower initial capital equipment costs, no need for a shielded room, completion in a single implant, and more robust data from clinical trials. Prospective reports comparing HDR-BT and LDR-BT to each other or to other treatment options (such as external beam radiotherapy (EBRT) or surgery) suggest similar outcomes. The 5-year freedom from biochemical failure rates for patients with low-risk, intermediate-risk, and high-risk disease are >85%, 69–97%, and 63–80%, respectively. Brachytherapy with EBRT (versus brachytherapy alone) is an appropriate approach in select patients with intermediate-risk and high-risk disease. The 10-year rates of overall survival, distant metastasis, and cancer-specific mortality are >85%, <10%, and <5%, respectively. Grade 3–4 toxicities associated with HDR-BT and LDR-BT are rare, at <4% in most series, and quality of life is improved in patients who receive brachytherapy compared with those who undergo surgery.

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Figure 1: Comparison of LDR-BT, HDR-BT, and EBRT.
Figure 2: The evolution of brachytherapy for prostate cancer.
Figure 3: Target volume definitions.
Figure 4: Dosimetric comparison of LDR-BT versus HDR-BT.
Figure 5: BED versus α/β curves for fractionated radiotherapy for prostate cancer.
Figure 6: Characteristic PSA curves after treatment.

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Authors and Affiliations

  1. Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, 19111–2497, Pennsylvania, USA

    Nicholas G. Zaorsky & Eric M. Horwitz

  2. Department of Radiation Oncology, Mayo Clinic, 200 First St SW, Charlton Bldg/Desk R - SL, Rochester, 5590, Minnesota, USA

    Brian J. Davis

  3. Department of Radiation Oncology, Brigham and Women's Hospital, 75 Francis St BWH. Radiation Oncology, Boston, 02115, Massachusetts, USA

    Paul L. Nguyen

  4. Department of Radiation Oncology, University of Virginia, 1240 Lee St, Charlottesville, 22908, Virginia, USA

    Timothy N. Showalter

  5. Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, HA6 2RN, Middlesex, UK

    Peter J. Hoskin

  6. Department of Radiation Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, 135–8550, Tokyo, Japan

    Yasuo Yoshioka

  7. Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, M4N 3M5, Ontario, Canada

    Gerard C. Morton

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  1. Nicholas G. Zaorsky
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  2. Brian J. Davis
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  3. Paul L. Nguyen
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  4. Timothy N. Showalter
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  6. Yasuo Yoshioka
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  8. Eric M. Horwitz
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Contributions

All authors researched data for the article, N. G. Z., B. J. D., P. L. N, T. N. S, P. H., Y. Y., and G. C. M made a substantial contribution to discussion of content. N. G. Z. and E. M. H. wrote the manuscript. All authors reviewed and edited the manuscript before submission.

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Correspondence to Nicholas G. Zaorsky.

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DATABASES

Protein Data Bank

FURTHER INFORMATION

The Cancer Genome Atlas

PowerPoint slides

Glossary

Remote afterloading system

(RALS). Integral to HDR-BT, a RALS automatically deploys and retracts a single small radioactive source along the implant needle at specific positions delivering ≥12 Gy/h. The RALS enables a physician to control the position where the HDR source stops for a predetermined time period (the dwell position and dwell time).

Hypofractionated radiation therapy

A type of EBRT that is delivered as a single 2.1–3.5 Gy fraction lasting 15 min per day, 5 days per week, for about 4 weeks.

Stereotactic body radiation therapy

(SBRT). A type of EBRT delivered as a single fraction ∼ 6.0–9.0 Gy lasting up to 45 min per day, for a total of about five treatments over about 2 weeks.

Gross tumour volume

(GTV). The demonstrable extent and location of the malignant growth; it consists of the primary tumour, which for prostate cancer has historically been defined as the entire gland as well as any visualized extension into surrounding normal tissues, the regional lymph nodes, or distant metastases based on clinical data.

Clinical target volume

(CTV). This volume encompasses the GTV as well as areas at risk for subclinical cancer involvement. The CTV can include a margin around the prostate GTV and adjacent regions at risk of having subclinical disease.

Planning target volume

(PTV). This volume encompasses the CTV plus an additional margin to account for patient movement, setup error, and organ movement

Dwell positions

The positions where a 192Ir source is located during HDR-BT. A combination of dwell positions in different needles enables the delivery of a predetermined dose to the CTV.

Dwell times

The times that the 192Ir source spends in a predetermined dwell position during HDR-BT. A longer dwell time in a position translates to a greater dose deposited in the volume around the position.

Equivalent dose in 2 Gy fractions

(EQD2). The “2 Gy-per-fraction equivalent dose.” EQD2 = n*d*((d + α/β)/(2 + α/β)). The EQD2 uses a mathematical conversion of fractions and dose per fraction, similar to the BED. In this formula, n is the number of radiation fractions and d is the dose size per fraction.

D90

In prostate cancer brachytherapy, this is the minimum dose in the hottest 90% of a volume, in Gy. The prostate D90% should be >100%. This constraint ensures the prostate volume receives adequate dose.

V100

In prostate cancer brachytherapy, this is the percentage of a structure receiving 100% of the dose. For example, the V100 for the prostate should be >90%, meaning that 100% of the prostate CTV should receive more than 90% of the prescribed dose.

V150

In prostate cancer brachytherapy, this is the percentage of a structure receiving 150% of the dose. The V150 for the prostate CTV should be <50–60%, meaning that <50–60% of the CTV should receive >150% of the prescribed dose.

UV150

In prostate cancer brachytherapy, this is the volume of the urethra receiving 150% of the prescribe dose. UV150 of the urethra should be 0%, meaning that 0% of the volume should receive 150% of the prescribed dose.

UV5

In prostate cancer brachytherapy, this is the average dose to 5% of the urethral volume receiving the highest dose. The UV5 should receive <150% of the dose.

UV30

In prostate cancer brachytherapy, this is the average dose to 30% of the urethral volume receiving the highest dose. The UV30 should be <125% of the dose.

D10

The average dose to 10% of a volume, in Gy. The urethra D10 should be <150% of the prescribed dose. This constraint limits the dose to the urethra.

D30

The average dose to 30% of a volume, in Gy. The urethra D30 should be <130% of the prescribed dose. This constraint limits the dose to the urethra.

RV100

In prostate cancer brachytherapy, this is the volume of the rectum receiving 100% of the dose, and should be <1 cc.

D2cc

The average dose to 2 cc of a volume.

D0.1cc or Dmax

The average dose to the hottest point of a volume. The term “D0.1cc” is sometimes used because this approximates the maximum dose to the smallest volume that can be calculated on a computer.

Hotspot

A colloquialism used to describe volume outside the PTV which receives a dose >100% of the specified PTV dose.

α/β ratio

The α/β ratio describes the shape of the cell survival curve and the gradient of the two components of cell kill, α and β. The α/β ratio is used to describe the dose response of radiation on different tissues. Prostate cancer cells have a relatively low α/β ratio of 1.5, implying that those cells are more sensitive to doses delivered in larger fraction size. In the radiobiological linear quadratic equation, it is the dose at which cell killing due to the linear and quadratic components are equal.

Biologically equivalent dose

(BED). A more conceptually useful measure of biological damage to cells than physical dose. It takes into account the α/β ratio, number of radiation fractions, and fraction size. BED = (nd[1 + d/(α/β)]). In this formula, n is the number of radiation fractions and d is the dose size per fraction.

Intensity-modulated radiation therapy

(IMRT). An advanced form of high-precision radiation that conforms the treatment volume to the shape of the tumour. The dose distribution created by IMRT is characterized by a concavity or invagination of the edge of the higher doses away from the rectum, rather than a straight edge through the rectum as seen with 3D conformal radiation therapy.

Multi-leaf collimator

(MLC). A device made up of individual leaves of a high atomic numbered material that can move independently in and out of the path of an X-ray beam to contour its shape to a tumour.

Phoenix definition

Used for measuring biochemical failure after radiotherapy for prostate cancer, defined as the PSA nadir value plus 2 ng/ml.

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Zaorsky, N., Davis, B., Nguyen, P. et al. The evolution of brachytherapy for prostate cancer. Nat Rev Urol 14, 415–439 (2017). https://doi.org/10.1038/nrurol.2017.76

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