**3. Brachytherapy in prostate cancer**

In the age of the developed imaging technology (CT, MRI, PET, US), and advanced biochemical markers (tumor-specific and nonspecific), a large number of tumors, including prostate cancer, are being diagnosed in the early stages. In early stages of prostate cancer (T1-T2 N0 M0, PSA <10ng/ml, Gleason Score <6, prostate volume <50ml, maximum urinary flow>15ml/s), in addition to the conventional, laser and robotic prostatectomy, hyperthermia, hormone therapy and brachytherapy is often applied.

In brachytherapy sealed sources of radiation are placed either in direct contact or in proximity of the tumor, so the interstitial brachytherapy for localized prostate cancer often represents the method of choice, and its efficiency is not far behind the effectiveness of surgery, with less morbidity. Brachytherapy allows local application of extremely high doses (up to 160Gy, even more). The effectiveness of prostate cancer brachytherapy is directly correlated with the total dose and precision of administration, which represents its advantage over transcutaneous radiotherapy.

Prostate cancer is usually multicentric, so the brachytherapy target is the entire prostate, and the total dose has to cover the area of about 2-5 mm beyond the prostate capsule. From the point of radiotherapy, particularly brachytherapy, the initial prostate cancer (prostate itself, with or without vesicles involved) represents the ideal target, with adequate spare of the urethra, rectum, bladder and perineal area. Moreover, brachytherapy can be applied within a combined radiotherapy (brachytherapy + transcutaneous radiotherapy) by the additional dose (*boost*), as well as in the case of local recurrence or rest after prostatectomy or transcutaneous radiotherapy.

Brachytherapy for prostate cancer is not a new therapy method, though in the history of medicine it experienced its ups and downs, mainly due to the previous imperfections of visualization techniques and applications, as well as, imperfection in radiation and dosimetric characteristics of the radiation sources, while today it is a routine method of treatment. With the introduction of transrectal ultrasound (TRUS), CT and development of new sources of radiation (103Pd, and 192Ir), techniques of radioisotope implantation (loading and afterloading) and computer systems for brachytherapy planning in routine clinical practice, interstitial brachytherapy for prostate cancer began to experience another upswing, but with markedly better results and lower morbidity.

Today, two modalities for interstitial brachytherapy are applied:


since it is associated with higher malignant potential. Cancer related death for high Gleason

In the age of the developed imaging technology (CT, MRI, PET, US), and advanced biochemical markers (tumor-specific and nonspecific), a large number of tumors, including prostate cancer, are being diagnosed in the early stages. In early stages of prostate cancer (T1-T2 N0 M0, PSA <10ng/ml, Gleason Score <6, prostate volume <50ml, maximum urinary flow>15ml/s), in addition to the conventional, laser and robotic prostatectomy,

In brachytherapy sealed sources of radiation are placed either in direct contact or in proximity of the tumor, so the interstitial brachytherapy for localized prostate cancer often represents the method of choice, and its efficiency is not far behind the effectiveness of surgery, with less morbidity. Brachytherapy allows local application of extremely high doses (up to 160Gy, even more). The effectiveness of prostate cancer brachytherapy is directly correlated with the total dose and precision of administration, which represents its

Prostate cancer is usually multicentric, so the brachytherapy target is the entire prostate, and the total dose has to cover the area of about 2-5 mm beyond the prostate capsule. From the point of radiotherapy, particularly brachytherapy, the initial prostate cancer (prostate itself, with or without vesicles involved) represents the ideal target, with adequate spare of the urethra, rectum, bladder and perineal area. Moreover, brachytherapy can be applied within a combined radiotherapy (brachytherapy + transcutaneous radiotherapy) by the additional dose (*boost*), as well as in the case of local recurrence or rest after prostatectomy or

Brachytherapy for prostate cancer is not a new therapy method, though in the history of medicine it experienced its ups and downs, mainly due to the previous imperfections of visualization techniques and applications, as well as, imperfection in radiation and dosimetric characteristics of the radiation sources, while today it is a routine method of treatment. With the introduction of transrectal ultrasound (TRUS), CT and development of new sources of radiation (103Pd, and 192Ir), techniques of radioisotope implantation (loading and afterloading) and computer systems for brachytherapy planning in routine clinical practice, interstitial brachytherapy for prostate cancer began to experience another upswing,

1. **low dose rate (LDR)**, about 2Gy/day, with low activity 125I sources (from 0.03 to 1.5GBq per seed, max. photon energy of 35.5 keV, the half-life about 60 days in the form of cylinders /height 4.5 mm, 0.8 mm diameter, encapsuled in titanium sleeve/) or 103Pd (Blasko et al., 2000) (dose rate to about 5Gy/day; activity around 0.07GBq per source, the maximum photon energy of 21 keV, the half-life 17 days in the form of cylinder/ height 4.5 mm, 0.8 mm diameter /or spheres/ diameter of about 1 mm /) – a

2. **(high) dose rate (HDR)** about 0.2 to 3Gy / min with radioactive 192Ir source in the form of cylinder /dimensions around 0.6 x3,5 mm / (initial activity of about 370GBq; time

score tumors (8-10) is about 60-80% in 15 years. (Hadzi-Djokic, 2005)

hyperthermia, hormone therapy and brachytherapy is often applied.

**3. Brachytherapy in prostate cancer** 

advantage over transcutaneous radiotherapy.

but with markedly better results and lower morbidity.

Today, two modalities for interstitial brachytherapy are applied:

transcutaneous radiotherapy.

permanent implant;

half-life of 74.2 days, mean photon energy of about 380keV,) - a temporary implantation.

#### **3.1 Low dose rate brachytherapy**

Strictly speaking, from the point of view of radiobiology, the only differences (not great) in the indications for applying permanent (LDR) or temporary implantation (HDR) are mostly related to tumor grade. For example, with low-grade and low-risk tumors (eg Stage<T2a, PSA<10, Gleason Score 2-4) and slow-growing tumors, we expect greater efficiency in the application of permanent implants, while with tumors of high grade and higher risk, higher efficiency is expected from temporary implantation. Although there are relative differences in the indications for application of LDR or HDR brachytherapy, it seems that the predominant technique is the one with permanent implants (LDR). Selection of isotopes (125I or 103Pd) is in the favor of the cheaper iodine, so if otherwise not indicated it's considered that radioisotope 125I is being used in LDR brachytherapy for treating prostate cancer. Permanent implants are rarely used in cases of rest or local recurrence after prostatectomy or transcutaneous radiotherapy. In this case a HDR brachytherapy with 192Ir of initial activity over 370 GBq, by using afterloading device, is applied.

Prostate brachytherapy requires a multidisciplinary approach, which assumes collaboration between urologists, radiation oncologists (brachytherapists), anesthesiologists and brachytherapy physicists. Regardless of which brachytherapy modality is implemented in prostate brachytherapy, and with the aim to providing a top quality treatment, all steps are strictly determined:


(a) (b) (c)

(d) (e)

When using permanent implantation (monotherapy) radiation sources (seeds) remain in the prostate of the patient. It is therefore recommended to the patient a minimal two-week sexual abstinence and avoidance of contact with pregnant women and small children for a minimum of 2 months. A typical therapeutic dose of radiation, when 125I is implanted, is in the range 140-160Gy, and when 103Pd is implanted to about 125Gy. In a case of a "boost" dose, for 125I a somewhat lower dose of 80-120 is applied or to about 90-100Gy for 103Pd.

Prostate cancer with its characteristics and different biological behavior represents a problem in the analysis of brachytherapy final outcomes in terms of overall survival or local control. We are aware that many patients with untreated prostate cancer can survive tens of years, ie. do not die from prostate cancer. Therefore to evaluate the effectiveness of treatment of patients with prostate cancer, as for overall survival and local control, the PSA

Greem and associates (Greem et al., 1997 )provide representation of the results of treatment of patients with permanent implants (monotherapy), showing a five-year survival of NED (no evidence of disease) of 94%, 84% and 54% for low risk, medium risk and higher risk

(a) TRUS guided needles application

(Blasko et al., 2000, Beyer, 2001)

level was adopted.

**3.1.1 Results of low dose rate brachytherapy** 

(d) Isodose transversal view (e) 3D treatment volume

(b) Administrated needles /guides of 192Ir source (c) Radiographic verification of the needles' positions

(With the thanks of the General Hospital Medical System, Belgrade) Fig. 7. Steps in HDR prostate cancer brachytherapy - real patient


Fig. 6. Schematic representation of TRUS-guided brachytherapy with radioactive seeds.

182 Prostate Cancer – Diagnostic and Therapeutic Advances

10. Verification and correction (cistoscopic, fluoroscopic, x-ray (Figure 7. c) - optional CT

11. Computer reconstruction (seeds / LDR / - needles / HDR /, prostate capsule, the position of the urethra and rectum), optimization, plan analysis (the determination of DVH - Dose Volume Histogram, ie. minimum volume of prostate receiving 90%, 100%, 150% and 200% of the total dose, and the dose and volumes that receive critical

12. Irradiation; for HDR brachytherapy: deapplication of needles or observation of the

15. Check-up (of dysuric problems and estimate the degree of proctitis) and discussion

16. Regular checks (during treatment /HDR/ and in 2, 3, 6, 12 and 18 months, then annually - the level of PSA, rectal examination, assessing the level of dysuric problems

Fig. 6. Schematic representation of TRUS-guided brachytherapy with radioactive seeds.

and/or MRI; in case of LDR brachytherapy adding of seeds, if necessary)

radiosensitive structures), (Figure 7. d, e);

14. Patient care (analgesic and antibiotics therapy, toilet)

13. Transport of patient to the patient room

and evaluation of potency)

with the patient, the patient's discharge

patient (LDR)


When using permanent implantation (monotherapy) radiation sources (seeds) remain in the prostate of the patient. It is therefore recommended to the patient a minimal two-week sexual abstinence and avoidance of contact with pregnant women and small children for a minimum of 2 months. A typical therapeutic dose of radiation, when 125I is implanted, is in the range 140-160Gy, and when 103Pd is implanted to about 125Gy. In a case of a "boost" dose, for 125I a somewhat lower dose of 80-120 is applied or to about 90-100Gy for 103Pd. (Blasko et al., 2000, Beyer, 2001)
