Prostate Cancer and the Role of PostOp Radiation

Prostate Cancer
Radiation after Surgery
Robert Miller MD
www.aboutcancer.com

Is there ever a need
for radiation after a
man has already had
his prostate removed
PostOp Radiation (Adjuvant Therapy) if the
pathology report from the surgery raises the
concern: “was the cancer completely removed?”

Salvage Radiation

PostOp Radiation
(Adjuvant Therapy): if
the pathology report
from the surgery raises
the concern: “was the
cancer completely
removed?”

• How likely is it that the cancer will
recur?
• How effective is radiation in
preventing this?

NCCN Advice on PostOp Radiation

RP (radical prostatectomy) PLND (pelvic lymph node dissection) RT
(radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

NCCN Advice on PostOp Radiation

RP (radical prostatectomy) RT (radiation therapy) ADT (androgen
deprivation therapy e.g. Lupron)

Adverse Features
1.Positive Surgical Margins
2.Invasion into the Seminal Vesicles
3.Extracapsular Extension
4.Detectable PSA (after surgery the
PSA should fall to undetectable by a
few weeks)

Prostate-specific antigen as a serum marker for adenocarcinoma of
the prostate. Stamey TA

After radical prostatectomy for cancer, PSA
routinely fell to undetectable levels, with a half-life
of 2.2 days.
N Engl J Med. 1987 Oct 8;317(15):909-16.
Prostate specific antigen in the preoperative and postoperative
evaluation of localized prostatic cancer treated with radical
prostatectomy. Oesterling JE

the half-life of prostate specific antigen was
calculated to be 3.15 days.
J Urol. 1988 Apr;139(4):766-72

PSA Half Life of 3 days
Surgery

6

12

Percentage

3 days
6 days
9 days
12 days
15 days
18 days
21 days
24 days
27 days
30 days
33 days

3
1.5
.75
.375
.1875
.0937
.0468
.0234
.0117
.0059 (<0.01)
.0029 (<0.01)

6
3
1.5
.75
.375
.1875
.0937
.0468
.0234
.0017
.0059 (<0.01)

50%
25%
12.5%
6.25%
3.125%
1.5625%
.0078%
.0039%
.0019%
.00098%
.00049%

Takes 4 to 5 weeks to reach undetectable
(<0.01) so most people wait 6 to 8 weeks
after surgery to check the PSA level

Seminal
Vesicles
PROSTATE
CAPSULE

Impact of Path Reporting
Positive Surgical Margins
Odds of a PSA Relapse
Risk Group

+ Margins - Margins

Low risk
Intermediate
High

5.1%
17%
43%

J Urol. 2010;183(1):145.

0.4%
6.5%
21.5%

Impact of Path Reporting
Positive Surgical Margins
Odds of a PSA Relapse by 3
Years
Solitary Apical Margin
Solitary Non-apical margin
Multiple positive margins

13.0%
18.6%
27.0%

aboutcancer.com/medical_calculators
Adjuvant online has survival and benefit
calculators for breast, colon, lung
Breast cancer calculators here
Cancer Risk: from Harvard, various types of
cancer
Cancer Risk from X-ray Exposure
Colon cancer risk of Lynch syndrome from Dana
Farber
Colon Cancer risk from the NCI here
Head and Neck cancer survival here
Life Expectancy Calculators and Life Expectancy
for the Elderly
Life expectancy lost from smoking here
Lung cancer risk is here
Mayo clinic has calculators for melanoma
MD Anderson (breast, colon , esophagus) here
Melanoma: from the NCI, the risk of getting it
MGH has calculators for breast, melanoma, renal
Prostate cancer calculators are here
Sloan Kettering has nomograms
for bladder,breast,
colorectal,endometrial, gastric,GIST, lung,
melanoma,ovary, pancreas,prostate, renal
(kidney) and sarcoma go here
Fox Chases has many cancer
nomograms here (for kidney, prostate, bladder,
adrenal)

mskcc.org/cancer-care/adult/prostate/predictiontools

http://www.mskcc.org/cancer-care/adult/prostate/prediction-tools

PostOp Radiation…does it work?
SWOG 8794 Trial path (425 men) = extraprostatic extension after surgery

10 Year PSA Cure Rate (seminal vesicle)

Surgery Only
Surgery Plus Radiation

12%
36%

EORTC (1005 men)

5 Year Cure Rate if Positive Margins

Surgery Only

49%
78%

German Study (Wiegel, 268 men)

5 Year Cure Rate all T3

Surgery Only

54%
72%

Is it Better to Treat PostOp for High
Risk Features or to Wait and Treat
later if the PSA starts rising
(salvage)?
8 Year Specific Survival by Group and Therapy
Immediate RT
Positive Margins
91%
Extra-capsular Spread
92%
Gleason 7
88%
Node Metastases
88%

Delayed
67%
75%
72%
68%

Role of postoperative radiotherapy after pelvic lymphadenectomy
and radical retropubic prostatectomy: a single institute experience of
415 patients
Cozzarini. IJROBP 2004;59:674

Survival Benefits from PostOp
Radiation for High Risk
Patients

RT

No RT

RT

No RT

RT

No RT

PSA Cure Rates with Immediate PostOp
Radiation for T3 Prostate Cancers with
Undetectable PSA

Adjuvant Radiotherapy for Pathologically Advanced
Prostate Cancer. A Randomized Clinical Trial.
425 men with pathologically advanced prostate cancer who had
undergone radical prostatectomy. Men were randomly assigned to receive
60 to 64 Gy of external beam radiotherapy delivered to the
prostatic fossa (n = 214) or usual care plus observation (n = 211).
Outcome

Surgery

Metastatic free Survival
Overall Survival

13.2 years
13.8 years

14.7 years
14.7 years

Side Effects
rectal complications
strictures
incontinence

11.9%
0%
9.5%
2.8%

23.8%
3.3%
17.8%
6.5%

Ian M. Thompson, Jr, MD;

Surgery + RT

JAMA. 2006;296:2329-2335

Immediate versus deferred androgen deprivation treatment in
patients with node-positive prostate cancer after radical
prostatectomy and pelvic lymphadenectomy
Lancet Oncology Volume 7, Issue 6, June 2006, Pages 472–479
Eligible patients from 36 institutes in the USA were randomly
assigned in 1988–93 to receive immediate ADT (n=47) or to be
observed (n=51), with ADT to be given on detection of distant
metastases or symptomatic recurrences.

At median follow-up of 11.9 years, men assigned
immediate ADT had a significant improvement in
overall survival (hazard ratio 1.84 p=0.04), prostatecancer-specific survival (4.09 p=0.0004), and
progression-free survival (3.42, p<0.0001).

Is there ever a role
for radiation after a
man has already had
his prostate removed
PostOp Radiation (Adjuvant Therapy): if the pathology report from
the surgery raises the concern: “was the cancer completely
removed?”

Salvage Radiation: if months or
years after surgery the PSA blood
tests starts rising again

NCCN Advice on Salvage Radiation

deprivation therapy e.g. Lupron)

NCCN Advice on Salvage Radiation

deprivation therapy e.g. Lupron) PSADT (PSA doubling time)

Salvage Radiation…does it work?
Depends…
Original Pathology
What was the Gleason?
Where the surgical margins clear?
Did the cancer involve the seminal vesicles or
lymph nodes?
Was there extra-capsular spread?
How long ago was the surgery?
How fast is the PSA rising (doubling time)?
How high the did PSA get before deciding to try
radiation?
How high a dose of radiation will be used?

PSA Cure Rate after Salvage
Radiation Based on Gleason Score

Gleason 2-6

Gleason 7

Gleason 8-10

Time in Months

http://nomograms.mskcc.org/Prostate/SalvageRadiationTherapy.aspx

Cure Rate Based on the PSA Level
at the Time of the Radiation
prostate-specific antigen 0.50 or less
(blue), 0.51 to 1.00 (yellow), 1.01 to 1.50
(gray), and more than 1.50 ng/mL (red)

J Clin Oncol. 2007 May 20;25(15):2035-41.

The Best Results are When the PSA is the
Lowest Possible

Salvage (postOp) radiation works best if
the PSA rise is still very low

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

Does Salvage Radiation Improve
Survival?
Mayo (2657) No improvement in 10 y mortality
(70% versus 69%)
Hopkins (635) Improved cancer mortality at 10
years 86% versus 62%
Duke (519) All cause mortality at 11 years was
reduced by 47%
J Urol. 2009;182(6):2708
JAMA. 2008;299(23):2760.

CT scan is obtained at the time of the
Simulation

CT images are then imported
into the treatment planning
computer

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

Radiation zone

prostate

rectum

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

The most sophisticated technique for image guided IMRT is
Tomotherapy.

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)

There is significant movement of the
prostate gland based on daily gas in
rectum
Planned
target
No Rectal gas

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

Rectal gas

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

Typical Radiation Field for Prostate
Cancer if no Surgery Has Been
Performed

Radiation
Zone

http://www.rtog.org/CoreLab/ContouringAtlases.a
spx

The RTOG has
published
recommended
radiation targets
for patients who
have had surgery
and need postOp
radiation
(purple apex field,
green seminal
vesicles)

Composite MRI showing relapse
sites at the anastomosis (red) or
behind the bladder (green)

PostOp Radiation (after a previous radical
prostatectomy)

rectum
bladder
pubic
Area of
recurrence

Principles of Radiation Therapy PostProstatectomy (NCCN)
• Patients with positive margins and slow PSA
doubling time (>9 months) may benefit the most
from PostOp radiation
• In the salvage setting indications are when an
undetectable PSA becomes detectable on 2
subsequent measurements, treatment is most
effective if slow doubling time and PSA still less
than 1
• The recommended dose is 64 to 70Gy
• The target should include the prostate bed and
may include the nodes, but not the whole pelvis

Side Effects of Prostate Radiation


rectum
bladder

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


rectum
bladder

With IMRT and
image guided
techniques the goal
is to shape the
radiation zone very
precisely based on
the pathology
report and the
location of the
cancer, e.g.
margins or seminal
vesicles or lymph
nodes


rectum
bladder

Radiation
Zone

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

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

Long Term Side Effects:
Irritation of bladder, urethra
and rectum
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 with intact prostate have
problems after radiation, in men with previous
prostatectomy this is even higher

Prostate Cancer and the Role of PostOp Radiation

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