Brachytherapy for Prostate Cancer

Updated by Anand Shah and György Kovács

BACKGROUND

What are the 2 most common types of prostate brachytherapy (brachy)?

Most common types of prostate brachy:

1. LDR using permanently implanted iodine-125 (I-125) or palladium-103 (Pd-103) radioisotopes.

2. HDR using temporarily implanted iridium-192 (Ir-192).

Which prostate cancer pts are good candidates for LDR brachy monotherapy?

According to the American Brachytherapy Society (ABS) guidelines, low-risk pts with the following characteristics are good candidates for LDR brachy monotherapy:

1. cT1–T2a

2. Gleason score ≤6

3. PSA <10

Select intermediate-risk patients may be candidates, absent other risk factors.

(Davis BJ et al, Brachytherapy 2012)

Why is the presence of seminal vesicle involvement a contraindication to prostate brachy monotherapy?

Seminal vesicle involvement is a contraindication to brachy monotherapy b/c seminal vesicles are technically challenging to implant with acceptable dose coverage and involvement is associated with higher risk of regional spread as well as mets, rendering LC potentially less effective.

List the relative contraindications to prostate LDR brachy.

Relative contraindications to prostate LDR brachy:

1. Severe pre-existing urinary outlet obstruction Sx (International Prostate Symptom Score [IPSS] >20)

2. Previous pelvic RT

3. Transurethral resection defects

4. Large median lobes

5. Prostate gland >60 cc

6. Inflammatory bowel disease

(Davis BJ et al, Brachytherapy 2012)

Why is a prostate size >60 cc a contraindication to prostate brachy?

Large prostate volumes >60 cc are considered a relative contraindication to brachy b/c they have been associated with a higher rate of postimplant urinary retention and prolonged obstructive urinary Sx. Implantation is also more technically difficult. (Davis BJ et al., Brachytherapy 2012)

Is neoadj hormonal therapy (NHT) effective at shrinking prostate size and decreasing the risk of retention?

Prostate volume may be reduced by 25%–40% after 3 mos of androgen deprivation therapy (ADT). Additionally, after 6 mos, there is no further volume reduction. It is controversial whether this decreases the risk of urinary retention. A large retrospective series demonstrated that in pts with IPSS scores ≥15, urinary retention occurred in 25% of those not taking NHT vs. 5% in those taking NHT (p = 0.039). (Stone RG et al., J Urol 2010)

Why is the presence of pre-existing urinary Sx a contraindication to brachy?

Obstructive and irritative urinary Sx are common after brachy, and pre-existing Sx increase the risks and severity of these side effects.

What are the advantages of prostate brachy over EBRT?

Advantages of prostate brachy over EBRT:

1. Decreased integral dose to the pt, particularly to the rectum and bladder, which allows for dose escalation

2. Simplified targeting of RT (i.e., no issues with setup variation, prostate motion, etc.)

3. Shorter Tx course

What is the purpose of ADT prior to brachy?

The purpose of ADT prior to brachy is to downsize large glands prior to implant, thereby potentially:

1. Decreasing urinary Sx postimplant

2. Decreasing operative time and # of seeds required

3. Decreasing rectal dose due to smaller gland size

4. Decreasing chance of pubic arch interference

Note: Several large retrospective studies have failed to show that androgen suppression improves cancer control outcomes in combination with LDR brachy.

WORKUP/STAGING

What is the purpose of the preimplant volume study in prostate cancer pts being treated with LDR brachy?

A volume study is done prior to implant to assess prostate volume and architecture (presence of median lobe size, assessment for pubic arch interference) and to develop a preliminary seed distribution plan for ordering seeds.

What is pubic arch interference, and how can it be avoided?

Pubic arch interference is when the needle paths are obstructed by the pubic arch. It occurs more frequently in pts with large glands and affects the ant and lat needles. To evaluate for interference, TRUS can be used to compare the largest prostate cross-section with the narrowest portion of the pubic arch. Other than hormonal downsizing, the use of an extended lithotomy position (Trendelenburg) may also alleviate some pubic arch interference.

What sources are typically used in permanent seed prostate brachy?

I-125 and Pd-103 are the sources typically used in prostate brachy. Cesium-131 (Cs-131) has also been utilized more recently.

What are the half-lives of the 3 most common sources used in prostate brachy?

Half-lives of the 3 most common sources:

1. I-125 (60 days)

2. Pd-103 (17 days)

3. Cs-131 (10 days)

What doses are typically prescribed when using monotherapy with I-125, Pd-103, and Cs-131?

Doses typically prescribed for brachy monotherapy:

I-125: 140–160 Gy

Pd-103: 110–125 Gy

Cs-131: 115 Gy

How far outside the prostate gland are Rx IDLs able to reach?

Rx IDLs are able to reach 3 mm outside the prostate gland.

What can be done to place sources into the tissues surrounding the prostate to provide extracapsular coverage?

In order to reliably place sources into tissues surrounding the prostate, a possible technical solution is to place linked seeds embedded in Vicryl sutures in the peripheral portions of the prostate.

Prior to the closed transperineal approach, what other method of seed implantation was used?

Prior to the transperineal approach, an open retropubic laparotomy method of seed implantation was used.

In prostate LDR brachy, to what do D90 and V100 refer and what are the recommended values for these parameters?

In prostate LDR brachy, the D90 refers to the min dose that covers 90% of the postimplant prostate volume (given as a % of the prescribed dose). The goal D90 is >90% of the Rx dose. The V100 refers to the volume of the prostate receiving 100% of the Rx dose. The goal V100 is >90%. Although D90 and V100 are strongly correlated, D90 is used to describe how hot or cold an implant is with respect to the Rx dose and V100 is used to describe how well the implant covers the desired target.

In prostate brachy, why is the D90 parameter used and not the D100?

D90 is used instead of D100 to evaluate postimplant dosimetry b/c retrospective studies have identified D90 as a better predictor of long-term biochemical control. D90 may be a better predictor of outcomes b/c it is less sensitive to small differences in the way a prostate is contoured between users on postimplant CTs. (Potters L et al., IJROBP 2001)

In prostate brachy, to what do RV100 and Ur150 refer?

RV100 is the volume of the rectum in cubic cm receiving 100% of the Rx dose. Ur150 is the volume of the urethra receiving 150% of the Rx dose.

What are the goals for RV100 and Ur150 in prostate brachy planning?

Reasonable goals are to limit RV100 to <0.5 cc and Ur150 to <30% of the urethra.

What isotope is typically used in HDR brachy for prostate cancer?

Ir-192 is typically used for HDR brachy to treat prostate cancer.

What is the half-life for Ir-192?

The half-life for Ir-192 is 73.8 days.

What are the dose/fractionation schedules that have been used with HDR brachy as monotherapy for low-risk prostate cancer?

HDR dose/fractionation schedules for prostate cancer monotherapy (Demanes DJ et al, IJROBP 2011):

1. William Beaumont Hospital schedule: 38 Gy in 4 fx (9.5 Gy/fx) bid (1 implant/day required)

2. California Endocurietherapy Center schedule: 42 Gy in 6 fx (7 Gy/fx) in 2 separate implants 1 wk apart

Have there been any studies comparing EBRT + brachy boost to EBRT alone?

Yes. Hoskin PJ et al. enrolled 218 pts with T1-T3, localized prostate cancer and PSA <50 and randomized to EBRT alone (55 Gy/20 fx [2.75 Gy/fx]) or EBRT + HDR brachy (EBRT 35.75 Gy/13 fx [2.75 Gy/fx] and then 8.5 Gy HDR × 2 over 24h). Median PSA RFS; using the RTOG/ASTRO Phoenix definition) was 9.7 yrs (combined) vs. 6.2 yrs (EBRT alone). No difference in OS. The results of this study are difficult to interpret given the nonstandard fractionation in the control arm. (Radiother Oncol 2012)

TREATMENT/PROGNOSIS

Estimate the long-term (8–10 yrs) biochemical control in low-risk pts treated with LDR brachy.

Estimates of long-term (8–10 yrs) biochemical control vary from 87%–94%. (Koukourakis G et al., Adv Urol 2009)

Does the addition of NHT confer an RFS advantage over brachy monotherapy?

This is uncertain. Retrospective comparisons do not suggest that NHT improves RFS. In a matched pair analysis by Potters L et al., NHT in addition to brachy did not improve 5-yr PSA RFS (87.1% vs. 86.9%, p = 0.935). (JCO 2000)

What are the data comparing the efficacy of I-125 and Pd-103 implantation for prostate brachy?

I-125 and Pd-103 appear similarly efficacious. The Seattle Isotope trial randomized low-risk prostate cancer pts to I-125 vs. Pd-103 and found no difference in 3-yr biochemical freedom from failure (89% vs. 91%, p = 0.76) and no differences in morbidity. (Wallner K et al., IJROBP 2003)

Describe the PSA bounce and its prognostic significance following brachy as monotherapy for prostate cancer.

The PSA bounce is the abrupt rise and fall in the PSA value following brachy Tx. Bounces of ≥0.2 ng/mL may occur in 40% of pts with a median onset of 15 mos and a magnitude of 0.76 ng/mL. Younger pts appear more likely to have a bounce. Bounces of >2 ng/mL (i.e., biochemical failure by Phoenix definition) may occur in 15% of pts. However, PSA bounce does not appear to predict for clinical failure. (Crook J et al., IJROBP 2007)

TOXICITY

What are the most common acute and late side effects from prostate LDR brachy?

Obstructive and irritative urinary Sx and impotence are side effects that are generally experienced due to prostate seed implantation. Rectal toxicity is relatively rare.

Are phosphodiesterase inhibitors effective for prostate brachy–related erectile dysfunction (ED)?

Yes. ∼50% of pts who have ED after prostate brachy can achieve erections useful for intercourse with the use of phosphodiesterase inhibitors.

How does the intensity and timing of urinary irritation differ between men treated with I-125 vs. Pd-103?

Irritative Sx are more intense and occur earlier but resolve more quickly in prostate brachy pts treated with Pd-103 compared to I-125. In the Seattle Isotope trial, at 1-mo postimplant, I-125 implanted pts had a mean morbidity American Urological Association (AUA) score of 14.8 compared with 18.6 for the Pd-103 pts (p = 0.0009). At 6 mos, mean AUA scores were 12 for I-125 implanted pts and 9.9 for Pd-103 pts. (Herstein A et al., Cancer 2005)

Estimate the incidence of late rectal bleeding in prostate cancer pts treated with LDR brachy monotherapy. Is there a difference in the incidence between I-131 vs. Pd-103 brachy?

In the Seattle Isotope trial, the overall incidence of late rectal bleeding was 9%. There was no significant difference between I-125 and Pd-103 pts, though there was a trend toward more radiation proctitis in the I-125 arm. (Herstein A et al., Cancer 2005)

What acute toxicities are associated with HDR brachy?

Similar to LDR therapy, prostate HDR brachy pts experience frequency, urgency, and urinary retention acutely.

What are the late toxicities that have been associated with prostate HDR brachy?

Potential late toxicities associated with prostate HDR brachy: urethral stricture (most common), prolonged dysuria, urinary retention, hematuria, and urinary incontinence. Rectal pain and rectal bleeding can also occur.

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