Prostate Cancer -Radiation Therapy For Prostate Cancer - 100

Front 1

What two technological advances since the early 80s have improved the results of radiation therapy for the treatment of prostate cancer in terms of both quality of life and cancer control?

Back 1

The development of linear accelerators and conformal techniques that allow for deeper penetration of tissues within the pelvis while simultaneously respecting the normal tissue

tolerance of the anterior rectal wall, prostatic urethra, femoral heads, and bladder neck.

ii. The development image-guided techniques for insertion of radioactive sources directly into the prostate gland (i.e. brachytherapy)

Front 2

The chapter describes three risk groups for predicting PSA or clinical recurrence after treatment with external-beam RT. What are the criteria for each group and what are the stated 5-year PSA failure-free survival rates for each after RT?

Back 2

1. Low risk: clinical stage T1c-T2a, PSA < 10 ng/ml, and Gleason grade of 6 or less;

5-year PSA failure-free survival 85%

2. Intermediate risk: T2b, PSA 10 -20, or Gleason of 7.

5-year PSA failure-free survival 50%

3. High risk: T2c, PSA > 20, or Gleason 8 or more

5-year PSA failure-free survival 33%

Front 3

What other pretreatment factor along with clinical stage, PSA, and Gleason score does the book state as having important prognostic significance for low-risk and favorable, intermediate risk patients?

Back 3

The percentage of positive prostate biopsies (e.g. positive cores/total cores sampled).

Front 4

Is PSA expected to go to zero after RT? How then is biochemical failure after RT defined?

Back 4

No.

Three consecutive increases in PSA with PSA determinations spaced 3 to 4 months apart in the first 2 years post RT and every 6 months thereafter (old ASTRO definition)

Front 5

Does a rapid time to PSA nadir after RT bode poorly or well for a patient?

Back 5

1. Poorly. The time to nadir and disease-free survival have been shown to be inversely related.

The median time to nadir in patients who remain with no evidence of disease is 22 to 34 months.

92% of men who reached nadir greater at 36 months or longer remain disease free compared to

30% of men who nadir at 12 months or less.

Front 6

Does the absolute level of the PSA nadir have prognostic significance? What about PSA doubling time after nadir?

Back 6

- Yes. In fact the level of the nadir may also reflect the type of clinical recurrence. The median

PSA nadir for men who remain disease free is 0.4 to 0.5. For those who later exhibit local failure,

PSA nadir usually is greater than 1.0. Finally, patients who later exhibit distant failure, PSA nadir

is often greater than 2.0.

- Likewise post-nadir doubling times also correlate with the type of failure with distant failures

having doubling times of 3 to 6 months and local failures having doubling times of 11 to 13 months.

Front 7

How dose the use of neoadjuvant and concurrent androgen deprivation with RT affect the interpretation of post-RT PSA?

Back 7

- In this setting, patients often start radiotherapy with an already undetectable PSA. If hormone

therapy is continued after RT, the PSA will likely remain undetectable and a true PSA nadir

can never be determined. If the hormone therapy is only given neoadjuvantly or concurrently,

rapid recovery of serum T may cause a temporary increase in PSA shortly after completion of RT.

As the effects of the RT then begin to manifest, PSA declines once again. Likely, the secondary

nadir has the same prognostic significance as PSA nadir in the absence of hormonal therapy.

Front 8

What is the “benign bounce” phenomenon?

Back 8

- fluctuation or even an increase in PSA around the time of RT followed by a durable decline due

to the presence of residual benign epithelium. This is especially common after bracy and may

occur as late as 9 to 30 months after treatment and reach a maximum PSA of up to 10 ng/ml.

Currently, there is no way to distinguish a benign bounce from a true biochemical failure in the

first 3 years post RT other than to just continue to monitor PSA for a durable declince after the spike.

Front 9

What is the main reason to perform post-radiation prostate needle biopsies and when does the book indicate is the optimal time to perform them?

Back 9

- Post-RT biopsies are fraught with problems of timing, interpretation, and sampling error. However, they may help distinguish between local and distant recurrence of disease when considering post-RT salvage prostatectomy. The book states the optimal time to perform the biopsies is 30 to 36 months after RT.

Front 10

What is conformal radiation therapy and what are its main advantages compared to conventional RT?

Back 10

- conformal radiation therapy refers to the use of CT imaging in the design of patient specific

radiation plans that conform to the shape and location of the prostate within the pelvis.

- the advent of CRT over traditional XRT has allowed higher dosages of radiation to be applied to

the prostate while simultaneously minimizing the dose to the surrounding normal tissue.

(CRT is now the gold standard modality for RT for prostate cancer).

Front 11

Have the theoretical advantages of CRT compared to traditional RT in terms of reducing side effects been bourn out in the literature?

Back 11

- Yes, but not dramatically so. Two randomized trials completed in Europe comparing side effects

from CRT against traditional RT showed statistically significant improvement in GI side effects in the conformal arms of each. Interestingly, no difference was seen in the patient reported GU side effects in either study likely due to the small numbers of patients who encountered GU problems after either form of RT.

- Sexual side effects are generally improved with CRT compared to traditional whole-pelvis RT.

However, again, the studies mentioned in the chapter showed trends toward but not statistically

significant improvements in sexual side effects.

Front 12

Does dose escalation of radiation applied to the prostate make a difference in terms of cancer control? What groups of patients tend to benefit the most from the higher doses used in CRT compared to traditional RT?

Back 12

- Yes, dose escalation does improve recurrence rates for localized disease. Historically (before the

advent of CRT), 70 Gy was considered the maximum dose that could be safely delivered. With

CRT, however, doses of up to 78 Gy are now routinely being administered. While long-term data

on the efficacy of these higher doses is still forthcoming, it appears that has improved recurrence rates at least in the intermediate term (8 years).

- The patients that benefit most from this are the intermediate risk patients (PSA 10 – 20, Gleason 6).

Lower risk patients do equally well at the lower doses of radiation. Higher risk patients do equally poorly even at higher doses of radiation.

Front 13

What is IMRT and what are its main advantages compared to CRT?

Back 13

- Intensity-modulated radiotherapy. Whereas conformal RT was a step forward in terms of

pretreatment planning, IMRT is a step forward in terms of the actually delivery of the radiation.

It uses sophisticated software and mechanical adaptations to linear accelerators to allow for

delivery of a precise non-uniform radiation beam. The outcome is a set of radiation beams with

varying intensities across the field.

- Again, this newer technology allows for even higher doses to the prostate while minimizing the

dose applied to the rectum and bladder.

Front 14

Is movement of the prostate within the pelvis a concern for radiation oncologist? What two strategies have been designed to minimize the effect?

Back 14

-Yes it is a big deal. The prostate can change anatomic position within the pelvis not only from

one treatment to the next but even over the course of a single treatment.

- 1) rectal balloon immobilization device that pins the prostate against the pubic bone;

2) placement of radiopaque beacons (Calypso) within the prostate what can then be used prior

to each treatment to precisely identify the prostate.

Front 15

What other forms of radiation can be used to treat prostate cancer? What is the state of these other forms of RT currently in terms of clinical applicability?

Back 15

- Heavier particle beams such as neutrons and protons have been used and studied in the treatment of prostate cancer. These other particles do offer some theoretical advantages compared to electrons in that they are more densely destructive to tissue and they offer a sharp cutoff of dose at the end of the particle’s range.

- These other particle beams are difficult to produce and control and therefore have limited

applicability currently. However, efforts are continuing to develop particle beams that are safe and inexpensive.

Front 16

What two isotopes are most commonly used for Brachytherapy? Has any difference in terms of clinical outcome been shown for either?

Back 16

- 125Iodine and 103Palladium

- there are differences in terms of radiation admitted and half-life, but no prospective study has

shown any difference in terms of clinical outcome.

Front 17

Describe the most commonly used method for seed implantation.

Back 17

- The most common technique is closed tranperitoneal implantation with the aid of TRUS. In

this approach, the patient is in high lithotomy. A transrectal ultrasound probe is placed and

fixed to a stabilizer attached to a stepper. A template with a predrilled pattern of parallel holes

is then attached to the stepper and used to guide the needle placement. The seeds are deployed using 17- or 18- guage needles.

Front 18

How long does it typically take for brachytherapy to take full effect after implantation based on the rate of PSA decline?

Back 18

- at least 18 months.

Front 19

What have recent studies shown the rate of post-brachy positive biopsies to be? What is the clinical significance of these positive biopsies after brachytherapy?

Back 19

- 3% - 20%

- The clinical significance is unclear particularly when the biopsies are performed within the first 2 years after seed implantation.

Front 20

In what patient population is brachytherapy combined with external beam radiation “boost” typically performed? What is the rationale for this practice? When it is performed, how does the dose of the radiation used compare to that used for brachy or EBRT monotherapy?

Back 20

- Patients choosing brachytherapy with higher risk disease typically get the EBRT boost.

- The rationale is to treat the periprostatic tissues which are left relatively untreated by brachy

alone.

- The brachy therapy dose is reduced to 70 to 80% of that used for monotherapy; the EBRT dose is reduced to 60% of that used as monotherapy.

Front 21

Summarize the chapters discussion of the side-effect profile of brachytherapy including urinary toxicity, rectal toxicity, and potency.

Back 21

- Urinary toxicity: symptoms as measured by IPSS dramatically increase at first but then tend to

get better overtime. 2 – 3% have symptoms refractory to medical mgmt in long-term f/u. Pre-treatment symptoms are most important prognostic indicator of post treatment side-effects.

- Rectal toxicity: usually self-limited proctitis. Rarely requires intervention.

- Potency: better results for brachy compared to EBRT. Potency rates range from 50-76% at five years for brachy alone in patients initially fully potent.

Front 22

What is High-dose brachytherapy and how is it currently being used?

Back 22

- High-Dose Brachytherapy (HDR) as opposed to permanent seed placement uses temporary

transperineal needles to deliver gamma-radiation from 192Iridium which is significantly more

penetrating than either 125I or 103P.

- Its currently being used as a boost to EBRT for patients with intermediate or high risk features.

Front 23

Has the addition of androgen suppression to RT proven to make a difference in clinical outcomes compared to RT alone? What is the ideal type, timing, and duration for adjuvant androgen ablation combined with RT?

Back 23

- Yes, hormonal manipulation around the time of RT has consistently demonstrated improvement

in local/regional control, disease-free survival, and freedom-from-failure survival. However, the

ultimate impact on overall and cause-specific survival remains to be fully defined.

- the optimal regimen in terms of timing, duration, and type of adjuvant hormonal manipulation
around RT has not been defined.

Front 24

When should prophylactic surgical fixation be considered prior to RT in treatment of prostatic mets to wt bearing bones?

Back 24

- 1) intramedullary lytic lesion equal to or greater than 50% of the cross-sectional diameter of the

bone

2) lytic lesion involving a length of cortex equal to or greater than the corss-sectional diameter of the bone or greater than 2.5 cm in axial length.

Front 25

What is the typical initial presenting symptom of spinal cord compression due to metastatic spinal lesion? What is the first move when spinal cord compression is suspected.

Back 25

- Boney spinal pain which precedes neurologic symptoms by up to for months but can also rapidly advance in a number of hours to days.

- Steroids: specifically decadron 4 to 10 mg initially followed by 4 to 24 mg q 6 hours

Front 26

What are the RTOG acute radiation scoring schema for early lower GI radiation side effects?

Back 26

columns are 0 through 4

Front 27

What are the RTOG acute radiation scoring schema side effects for GU?

Back 27

columns are 0-4

Front 28

What are the late radiation side effects for GI EORT/RTOG schema?

Back 28

Front 29

What are the late radiation side effects on the bladder EORTC/RTOG?

Back 29