Prostate brachytherapy

Question 1

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

Answer 1

Most common types of prostate BT:

1. LDR using permanently implanted iodine-125 (I-125) or palladium-103 (Pd-103) radioisotopes
2. HDR using temporarily implanted iridium-192 (Ir-192)

Question 2

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

Answer 2

According to the American Brachytherapy Society (ABS) guidelines, lowrisk pts (cT1–2a, GS ≤6, PSA <10) are good candidates for LDR BT monotherapy (Davis et al., Brachytherapy 2012). BT also an option for some
intermediate-risk pts with more favorable Dz (PSA 10–20 or small-volume GS 7, preferably with primary GS 3).

Question 3

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

Answer 3

Seminal vesicle involvement is a relative contraindication to BT 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.

Question 4

List the relative contraindications to prostate LDR BT.

Answer 4

Relative contraindications to prostate LDR BT: (Davis BJ et al., Brachytherapy 2012)
1. Severe pre-existing urinary outlet obstruction Sx (IPSS >20)
2. Previous pelvic RT
3. Transurethral resection defects
4. Large median lobes
5. Prostate gland >60 cc
6. Inflammatory bowel Dz
Other relative contraindications: very small prostates (<20 cc) or active acute prostatitis.

Question 5

Why is a prostate size >60 cc a relative contraindication to LDR prostate BT?

Answer 5

Large prostate volumes >60 cc are considered a relative contraindication to BT b/c they have been associated with a higher rate of post-implant urinary retention and prolonged obstructive urinary Sx. Implantation is
also more technically difficult (Davis BJ et al., Brachytherapy 2012). Size is less of a restriction for HDR BT, and experienced LDR brachytherapists can implant >60 cc prostates.

Question 6

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

Answer 6

Prostate volume may be reduced by 25%–40% after 3 mos of ADT. 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)

Question 7

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

Answer 7

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

Question 8

What are the advantages of prostate BT over EBRT?

Answer 8

Advantages of prostate BT 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
4. Potential radiobiologic advantage from hypofractionation with HDR BT given the low alpha/beta of prostate cancer

Question 9

What is the purpose of ADT prior to BT?

Answer 9

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

1. Decreasing urinary Sx post implant
2. Decreasing operative time and # of seeds/catheters required
3. Decreasing rectal dose d/t smaller gland size
4. Decreasing risk of pubic arch interference

Question 10

Is there an oncologic benefit to adding ADT to BT monotherapy?

Answer 10

Systematic review by Keyes et al. (Brachytherapy 2017) suggested no benefit to adding ADT for low-risk and favorable intermediate-risk pts. Unfavorable intermediate-risk and high-risk pts and those with suboptimal dosimetry may have up to 15% improvement in biochemical recurrence-free survival (bRFS) with 3–12 mos of ADT, although impact on cancer-specific survival is uncertain.

Question 11

Is there a role for prophylactic alpha-blockers?

Answer 11

Prophylactic use of alpha-blockers does not significantly affect retention rates but does result in significantly faster return of urinary Sx to baseline. (Merrick et al., IJROBP 2002)

Question 12

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

Answer 12

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.

Question 13

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

Answer 13

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 pubic arch interference.

Question 14

What sources are typically used in LDR prostate BT?

Answer 14

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

Question 15

What are the half-lives of the 3 most common sources used in LDR BT?

Answer 15

Half-lives of the 3 most common sources:

1. I-125 (60 days)
2. Pd-103 (17 days)
3. Cs-131 (9.7 days)

Question 16

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

Answer 16

Doses typically prescribed for BT monotherapy:

1. I-125: 140–160 Gy
2. Pd-103: 110–125 Gy
3. Cs-131: 115 Gy

Question 17

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

Answer 17

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.

Question 18

What is the post-implant evaluation process for LDR BT?

Answer 18

Generally CT-based study performed immediately after BT or ∼30 days after.
Goals are:
1. Verify that the target volume rcvd Rx dose
2. Establish that normal tissues did not rcv excessive dose
3. Serve as feedback on the quality of the implant process
4. Assess dose within the target volume (Davis et al., Brachytherapy 2017)

Question 19

In prostate LDR BT, what is the D90 and V100 and what are the recommended values for these parameters?

Answer 19

In prostate LDR BT, the D90 refers to the min dose in the hottest 90% of the post-implant prostate volume (given as a % of the Rx 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.

Question 20

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

Answer 20

D90 is used instead of D100 to evaluate post-implant dosimetry b/c retrospective studies have identified D90 as a better predictor of longterm 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 b/t users on post-implant CTs. (Potters et al., IJROBP 2001)

Question 21

In prostate BT, what are the RV100 and the UV150?

Answer 21

RV100 is the volume of the rectum in cc’s receiving 100% of the Rx dose.
UV150 is the volume of the urethra receiving 150% of the Rx dose.

Question 22

What are the goals for RV100 and UV150 in prostate BT planning?

Answer 22

Reasonable goals are to limit RV100 to <1 cc and UV150 to <5%.

Question 23

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

Answer 23

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

Question 24

What is the half-life for Ir-192?

Answer 24

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

Question 25

What are common dose/fractionation schedules for HDR BT monotherapy?

Answer 25

No consensus on dose/fractionation. Common fractionation schemes include:
34 Gy in 4 fx; 36–38 Gy in 4 fx; 31.5 Gy in 3 fx; 26 Gy in 2 fx.

Question 26

What about single-fx HDR monotherapy?

Answer 26

Single-fx HDR monotherapy is investigational but some results are promising. A phase II trial by Hoskin et al. randomized pts to 19–20 Gy × 1, 13 Gy × 2, or 10.5 Gy × 3. There was no difference in bRFS b/t the arms,
with 4-yr bRFS of 94% for single fx (Radiother Oncol 2017). Krauss et al. reported 3-yr bRFS of 93% for 19 Gy × 1 (IJROBP 2017). In the trial by Prada et al., 6-yr bRFS was worryingly low (66%) after 19 Gy × 1, tempering
some enthusiasm for single-fx HDR (Radiother Oncol 2016). Toxicity result sare encouraging. (Morton et al., Radiother Oncol 2017)

Question 27

What studies have compared EBRT + BT boost vs. EBRT + EBRT boost in intermediate- and high-risk prostate cancer?

Answer 27

Several. ASCENDE-RT trial (Morris et al., IJROBP 2017): 398 men, 69% with high-risk Dz, were randomized to ADT + 3D conformal EBRT (46 Gy/23 fx whole pelvis WP), prostate boost to 78 Gy/39 fx) vs. ADT + WP
EBRT + LDR boost (I-125, min peripheral dose 115 Gy). After median f/u of 6.5 yrs, LDR boost associated with significantly lower rates of biochemical failure (7-yr bRFS 86% vs. 75%) than EBRT boost with no difference in OS.
A similar trial by Hoskin et al. also found no difference in OS (Radiother Oncol 2012). In general, the BT boost appears more effective for high-risk pts. A BT boost is allowed on the currently accruing RTOG 0924.

Question 28

What about BT as salvage after EBRT failure?

Answer 28

LR after EBRT occurs in up to 15% (Zumsteg et al., J Urol 2015). Salvage BT is potentially curative Tx. Key selection criteria from RTOG 0526 trial of salvage LDR BT: Bx-confirmed LR with no extraprostatic Dz on imaging,
recurrence >30 mos after EBRT, American Urological Association (AUA) score <15, and pre-salvage PSA <10. Phase II trial of HDR BT at MSKCC reported 5-yr bRFS 68% (Yamada et al., Brachytherapy 2014). The Princeton
Radiation Oncology experience using 4–6 mos of neoadj, concurrent, and adj ADT plus salvage BT (LDR or HDR) reported 5-yr bRFS of 79% and 5-yr freedom from late grade 3 GU toxicity of 85% with no late grade ≥2 GI toxicity. (Baumann et al., Brachytherapy 2017)

Question 29

What is the long-term biochemical control for low-risk pts after LDR monotherapy?

Answer 29

Long-term bRFS rates of 86%–98% have been reported. (Davis et al., Brachytherapy 2017)

Question 30

What is the data comparing the efficacy of I-125 vs. Pd-103 for prostate BT?

Answer 30

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 bRFS (89% vs. 91%, p = 0.76) and no differences in
morbidity. (Wallner K et al., IJROBP 2003)

Question 31

Describe the PSA bounce and its prognostic significance following BT as monotherapy.

Answer 31

The PSA bounce is the abrupt rise and fall in the PSA value following BT. Bounces may occur in 40%–50% of hormone-naïve pts typically 12–30 mos after BT, more commonly in younger pts. Bounces of >2 ng/mL (i.e.,
biochemical failure by Phoenix definition) may occur in 15%. PSA bounce does not appear to predict for clinical failure. (Crook et al., IJROBP 2007) Caution is advised when interpreting PSA levels in the first 30 mos after BT. (Davis et al., Brachytherapy 2017)

Question 32

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

Answer 32

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

Question 33

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

Answer 33

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

Question 34

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

Answer 34

Irritative Sx are more intense and occur earlier but resolve more quickly in pts treated with Pd-103 compared to I-125. (Herstein et al., Cancer 2005)

Question 35

What acute toxicities are associated with prostate BT?

Answer 35

Prostate BT pts experience acute worsening of urinary Sx (frequency, urgency, hesitancy, and weak stream). Acute urinary retention is rare (∼3% require catheterization). Acute irritative and/or obstructive Sx tend to be slightly better with HDR.

Question 36

What late toxicities are associated with prostate BT?

Answer 36

Relatively common: Impotence, mild increased urinary irritative/obstructive Sx, and mild rectal bleeding.
Rare: Significant late GU toxicity (e.g., urethral
strictures), significant rectal bleeding.
Very rare: rectal fistula, seed embolization, 2nd cancers

Question 37

How do QOL outcomes compare for BT monotherapy vs. EBRT?

Answer 37

Short- & long-term QOL comparable (Sanda, NEJM 2008; Prado, JCO 2010). In general, erectile function modestly better with BT. Resolution of urinary irritative Sx is less after BT.