Radiation Oncology Synopsis

Prostate Brachytherapy

Prostate brachytherapy is used for a single procedure radioactive implant into the prostate using 125I, 103Pd or 131Cs. Each of these isotopes have been used in the treatment of low risk (d'Amico criteria) prostate cancer. The American Brachytherapy Society recommends the following patient characteristics for LDR brachytherapy permanent implant as sole modality treatment:

The advantages of LDR brachytherapy over external beam radiation therapy include:

Relative contraindications to LDR prostate brachytherapy as a sole treatment or as a boost therapy include:

Seminal vesicle involvement as a contraindication to prostate brachytherapy is due the to fact that seminal vesicles are technically difficult to implant with reasonable dose coverage. In addition, seminal vesicle involvement is associated witha a higher risk of regional spread as well as metastatic disease. All these factors will potentially render reduced local control.

Large prostates *> 60 cm3 are more difficult to implant and they have been associated with a higher rate of urinary retention and prolonged obstructive urinary symptoms. Neoadjuvant hormonal therapy has been used to shrink the prostate and decrease the risk of retention. Prostate volumes may be reduced 20% to 40% after 3 months of androgen therapy, but controversy over whether this improves post-implant urinary flow remains. A large retrospective series demonstrated that in patients with IPSS ≥ 15 urinary retention occured in 25$ of those not taking NHT v. 5% in those taking NHT. (Stone 2009 J. Urol.

Since obstructive signs are common after implant. Pre-existing symptoms increase the risk and severity of these side effects.

Androgen deprivation prior to brachytherapy is primarily used to decrease the size of the prostate gland. This has the following potential benefits:

Several retrospective studies have failed to demonstrate androgen suppression improves cancer control outcomes in combination with LDR brachytherapy.

Sources and their characteristics

Isotope T-half Dose (monotherapy) Dose (with EBRT) Energy
125I 60 d 145 Gy 28 keV
103Pd 17 d 125 Gy 100 Gy 21 keV
131Cs 10 d 115 Gy 30 keV

Techniques

Prior to transperineal prostate implant, open laparotomy was used for seeding the prostate. Presently the prostate is loaded using TRUS guided transperineal implantation technique. Some centers also use fluoroscopic imaging to check depth of needle in the prostate to insure base coverage prior to dropping the seeds.

Prior to treatment a pre-implant volume study is obtained this volume study has two purposes: to assess the prostate volume and architecture (median lobe size, if any, pubic arch interference) and to develop a preliminary seed distribution plan for ordering radioactive seeds.

Pubic arch interference is interference by the pubic arch with needle path insertions. Obstruction of the anterior aspect of the prostate by the pubic arch occurs more frequently in patients with large prostate and usually interferes with anterior most needles and lateral most needles. The trans rectal ultrasound study is used to compare the largest prostate diameter with the narrowest portion of the pubic arch. Other than hormonal downsizing, the use of an extended lithotomy position and possibly Trendelenburg may help.

Prescription isodose volumes are able to reach about 3 mm beyond the prostate. To provide extracapsular coverage, seeds may be linked in vicryl sutures which are then placed in the peripheral portions of the prostate. The links will hold the seeds in place, provide there is sufficient tissue anchorage.

Dosimetry

In prostate LDR brachytherapy, there are two common dose descriptors in use. The D90 dose describes the dose that covers 90% of the prescribed dose. The goal of D90 is ≥ 90% of the prescribed dose.

The V100 volume is the volume receiving 100% of the prescribed dose. The goal of the implant in this formulation is V100 > 90%.

D90 describes how hot or cold the implant is with respect to the prescribed dose and V100 describes how well the implant covers the desired target. Retrospective studies have identified D90 (not D100) as a better predictor of long-term biochemical control. D90 may be a better predictor of outcomes because it is less sensitive to small differences in the contouring on prost implant CTs.

Other implant measures include RV100 which is the volume of rectum in cm 3 receiving 100% of the prescribed dose and Ur150 is the volume of the urethra receiving 150% of the prescribed dose.

The goals of the implant are to limit the doses to rectum and urethra: Rectum (RV100) to no more than 0.5 cm3; Urethral (Url150) to no more than 30% of the urethra.

EBRT + Brachytherapy Boost v. EBRT alone

Hoskins enrolled 220 patients with T1-T3 localized disease and pre-treatment PSA < 50 ng/ml. These patients were randomized to EBRT alone (55 Gy at 2.75 Gy/fraction, 20 fractions) or EBRT plus HDR brachytherapy (EBRT 37.75 Gy/13 fractions at 2.75 Gy/fx → HDR 8.5 Gy x 2 fractions over 2 days). Mean PSA RFS was 5.1 years in the combined arm and 4.3 years in the EBRT alone arm. The non-standard fractionation dose schedules make it difficult to interpret this study.

HDR Brachytherapy

HDR brachytherapy uses high dose rate sources, generally 192Ir to treat prostate cancer. Ir-192 has a half life of 73.8 days. HDR dose/fractionation schedules for prostate cancer monotherapy have been described by Martinez et al at Wm.Beaumont Hospital and California Endocurietherapy Center and are treated by those groups according to the following schedule:

Prognosis

Long term BCC varies from 82% to 94% at 8 years. (Kourkourakis 2009 Adv. Urol.) There is no clear data showing that NHT confers a relapse free survival advantage with brachytherapy. Retrospective comparisons do not suggest taht NHT improves RFS. Potters did a match pair analysis published in 2000 and reported that the addition of NHT did not improve brachytherapy outcomes. Specifically, five year PSA relapse free survival was not improved at 87.1% compared with 86.9%. (p=0.935). (JCO 2000)

I-125 and Pd-103 both appear similar in effectiveness. The Seattle Isotope trial randomized low-risk prostate cancer patients to I-125 and Pd-103. The found no difference in 3 year BC-FFF at 89% compared with 91%, p=0.76. They also found no differences in morbidity of treatment. (Wallner, 2003 IJROBP)

Toxicity

The most common side effects of prostate brachytherapy are obstructive uropathies and impotence. Rectal toxicity is relatively rare. Erectile dysfunction can be treated with phophodiesterase inhibitors. 50% of those patients who become impotent after brachytherapy can achieve functional erections with these agents

Urinary symptoms are more intense and occur earlier but resolve more quickly in brachtherapy patients treated with Pd-103. In the Seattle Isotope Trial, at 1 month post implant I-125 had a mean IPSS/AUA score of 14.8 compared with 18.6 for Pd-103 patients. At six months post implant, AUA scores were 12 for I-125 and 9.9 for Pd-103. (herstein 2009 Cancer)

Herstein also reported an overall incidence of 9% late rectal bleeding with no significant difference between Pd-103 and I-125. There was a trend toward more radiation proctitis with I-125 but not statistically significant.

HDR toxicities are similar to LDR toxicities.