Radiation Therapy for Prostate Cancer

Robert Miller MDwww.aboutcancer.com

NCCN.org

Prostate Guidelines

1. Low risk of extracapsular spread, then external beam or seeds alone

2. Intermediate risk then some (or all) of the radiation should be by external

3. High risk then hormone therapy should be added to the radiation

4. External beam should be daily image guided intensity modulated (IGRT)

5. Need high dose radiation (75 to 81 Gy)

The prostate gland has a capsule around it, and cancers arise close to the capsule, the cancer may invade through the capsule

Age: 67 / Stage T1c / Gleason 6 / PSA 5 =

27.6% risk of extracapsular spread

Age: 67, Stage T2b, Gleason 7/ PSA 12 =

86.2% risk of extracapsular spread

Laparoscopic Prostate Surgery

The surgeon tries to dissect the prostate away from the rectum, bladder, the neurovascular bundle (nerves) and penile urethra

Radiation Fields with Prostate CancerA Low Dose Large Area (Phase 1)

With radiation it is possible to include a wider area around the prostate to cover any cells that may have escaped

After the highest safe dose is reached, the radiation target will be made smaller

Radiation Fields with Prostate CancerA High Dose Large Area (Phase 2)

The final, high dose radiation target will be focused very precisely only on the prostate gland

External beam > 72Gy

External beam < 72Gy

Surgery or Seeds

Prostate Cures Rates by Treatment and Dose

Months

IJROBP 2004; 58:25

Years

Prostate Cancer Relapse Rate by Radiation Dose

< 72Gy

72 - 82Gy

82Gy

Kupelian. IJROBP 2008:71:16

Salvage (postOp) radiation works best if the radiation dose is high

60

65

70

75

80

85

90

95

3+3 3+4 4+4 4+5 5+5

5 year cure rate radiation

radiation plus hormones

Survival Hormone Therapy plus

Radiation by Gleason Score

Gleason Score

Cure Rates for High Risk Prostate Cancer

Months

IJROBP 2006;66:1092

Seeds alone

Surgery

Hormones + External + Seeds

10 Year Cure Rates for Patients with High Risk Prostate Cancer

(PSA >20 or Gleason 8-10 or T3)

Mayo Clinic Study (Cancer Jan 10, 2011)

Treatment Number Cure Rate

Radical Prostatectomy

1,238 92%

Radiation plus Hormones

344 92%

Radiation 265 88%

Typical PSA Decline after External Beam

Months Since Completing Radiation

Declining PSA Levels after Seed Implant

PSA bounce

Years

Evolving Radiation

Technology

CT scan is obtained at the time of the Simulation

Fiducials may be inserted before this step. CT images are then imported into the treatment planning computer

bladder

Radiation zone

prostate

rectum

Goal = radiation zone precisely around the prostate cancer with small margin

IMRT (intensity modulated radiation therapy)

using 7 different beams to target the prostate

The computer can determine the optimal number of beams to deliver the radiation dose to hit the target and avoid other structures

After IMRT was established then IGRT (image guided) was introduced

Lower Risk of Side Effects with Image Guided IMRT compared to IMRT

Better Cure Rates with Image Guided IMRT compared to IMRT for Prostate

Intermediate Risk High Risk

Combine a CT scan and linear accelerator to ultimate in targeting (IGRT) and ultimate in delivery (dynamic, helical IMRT) ability to daily adjust the beam (ART or adaptive radiotherapy)

The most sophisticated technique for image guided IMRT is Tomotherapy.

There is significant movement of the prostate gland based on daily gas in rectum

Planned target

Rectal gas

No Rectal gas

Planned target, missed badly if rectal gas pushes the prostate forward

Significant movement of the prostate gland based on daily gas in rectum

Initial computer target for prostate (red circle) would have badly missed the target if no adjustments were made based on the amount of rectal gas

Importance of daily CT targeting on Tomotherapy and adjusting the treatment daily

Very little bowel gas on initial study and the dose (red) targets the prostate gland closely

large bowel gas on later treatment day and the dose (red) will cover half the rectum if an adjustment is Not made

If no adjustment was made

Actual treatment on Tomotherapy

Using Tomotherapy to tightly target the prostate with very little radiation hitting

the bladder or rectum

Radiosurgery for Cancer

Cyberknife Radiosurgery

Non Isocentric Delivery with CK Beams

Conformality: Dose Painting

SBRT Prostate Cancer / Naples-Tampa Experience

Feb 2005 – Apr 2008 (Naples, FL)• 164 monotherapy, 35 Gy• 168 monotherapy, 36.25 Gy• 59 EBRT + CK boost

Jul 2008 – Dec 2011 (Tampa, FL)• 121 monotherapy, 36.25 Gy

• 10 monotherapy, 38 GY• 12 EBRT + CK boost

PSA Response to CyberKnife

97% biochemical control at 30 months median follow-up

Mean PSAi 6.8ng/mlMean PSAp 0.78ng/ml

Cure Rate after Cyberknife

N = 515, Alan Katz in New York

PSA Response after Cyberknife

Follow-up median 54 months (range, 7 - 78)

Median PSA– 36 m 0.20 ng/ml

– 60 m 0.10 ng/ml By 48 months

– 290 of 329 pts

PSA < 0.5 0 12 24 36 48 60 72

0

1

2

3

4

5

6

735 Gy36.25 Gy

Months

PS

A n

g/m

l

Prostate Seed Implants

A grid or template with holes every 5mm are used to line up the needles

The needles are distributed

The Mick ‘Gun’ is used to push the radioactive seeds into the gland

The seeds are left behind, distributed through the gland and slowly radiate the cancer

CT scans of the prostate will show the seeds and the studies will be used to calculate the radiation dose

Side Effects of Prostate Radiation

Side Effects of Prostate Radiation

Is related to the size and area of normal structures that are over lapped by the radiation zone…the goal is to keep the radiation zone as small as possible

Side Effects of Prostate Radiation

With IMRT and image guided techniques the goal is to shape the radiation zone very precisely , based on the type of cancer (high Gleason might require a larger margin around the gland)

Side Effects of Prostate Radiation

The structures that will get hit by radiation and have inflammation or irritation: bladder, urethra and rectum

Radiationzone

Short Term Side Effects: Irritation of bladder, urethra and rectum

Radiationzone

1. Urinary frequency (getting up at night very few hours, take NSAID’s, or may benefit from medication)

2. Slight burning or stinging with urination (drink cranberry juice)

3. Diarrhea or more frequent, softer bowel movements, rectal soreness (take Imodium)

4. Mild skin irritation is now rarely seen

5. Fatigue is common

Radiationzone

Chronic radiation cystitis or proctitis: about 6% of the men will have occasional episodes of blood in the urine or with bowel movements, this usually responds to medication (e.g. cortisone suppositories) The risk of serious damage to the bladder and rectum is now less than 1%

Impotence: about 30% of men have problems after radiation (see the next slides)

Long Term Side Effects: Irritation of bladder, urethra and rectum

GETUG Dose Trial for Prostate Cancer, Long Term Side Effects

IJROBP 2011:80;1056

Score 70Gy 80Gy

GI grade 3 1.9% 5.9%

GU grade 3,4 2.6% 1.9%

Long Term Side Effects from MD Anderson Dose Trial

IJROBP 2008:70:67

Grade 70Gy 80Gy

GI grade 2 13% 26%

GI grade 3 1% 7%

GU grade 2 8% 13%

GU grade 3 5% 4%

Long Term Side Effects in 9 Trials of SBRT for Prostate Cancer

IJROBP 2012:82:877

Grade Percent

GI Grade 3 0 – 7%

GI Grade 4 0 – 1.5%

GU Grade 3 1.6 – 13%

GU Grade 4 0%

Quality of Life / Medicare Survey Prostate Cancer Patients

Symptom Surgery Radiation

Wear Pads 30% 7%

Potent (< 70y) 11% 33%

Potent (>70y) 12% 27%

More frequent bowel movements

3% 10%

J Clin Oncol 14 (8): 2258-65, 1996

Potency Rates after Prostate Cancer Treatment

Treatment Probability Range

Seeds 80% 64 – 96%

Seeds + External 69% 51 – 86%

External 68% 51 – 95%

Radical Prostatectomy

Nerve Sparing 22% 0 – 53%

Standard 16% 0 – 37%

Cryotherapy 11% 0 - 53%

IJROBP 2002:54:1063

Did they get hormone therapy along with the radiation?

How high was the PSA prior to radiation?

How good was their sexual function before?

Potency Results after External Radiation can range from 16% to 92%

Potency Results after External Radiation can range from 16% to 92%

Patient Age? Race? Obese or thin? How good was their sexual function

before?

Potency Results after Seeds can range from 6% to 98%

Potency Results after Seeds range from 6% to 98%

Responded to Viagra

Surgery: 60%

External Radiation: 63%

Seeds: 85%

JAMA 2011:306:1205

Responded to Viagra

Surgery: 43%

Radiation: 70 – 91%

General Population: 80%

from other studies in the literature

Understanding Prostate Cancer

Robert Miller MDwww.aboutcancer.com