Unfortunately, many patients develop an increasing PSA after surgery or radiation therapy. Because standard imaging techniques are so inadequate, it has been impossible to find the cancer until PSA levels exceed 20 ng/ml. In our talk, we will first review what are the current standard treatment options: prostate bed radiation therapy and hormonal therapy. We will then discuss new imaging techniques that have dramatically improved our ability to locate the cancer. These imaging techniques allow radiation to be highly focused on actual sites of disease and both increase cancer control and reduce side effects. Finally, we talk about approaches that can arrest the progression of the cancer and can thus avoid both radiation and hormonal therapy.

1. PSA Only Recurrence After
Surgery or Radiation
Charles E Myers, MD
Foundation for Cancer Research and Education
&
American Institute Diseases of Prostate
Earlysville, VA

2. From: Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After Radical
Prostatectomy
JAMA. 2005;294(4):433-439. doi:10.1001/jama.294.4.433
Figure Legend :
Biochemical recurrence stratified by all comers vs early biochemical recurrence (within 3 years following surgery) vs late
biochemical recurrence (>3 years following surgery).
Copyright © 2012 American Medical
Date of download: 8/12/2012
Association. All rights reserved.

3. From: Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After Radical
Prostatectomy
JAMA. 2005;294(4):433-439. doi:10.1001/jama.294.4.433
Figure Legend :
Biochemical recurrence segregated by pathological Gleason Score among patients who experienced a biochemical recurrence.
Copyright © 2012 American Medical
Date of download: 8/12/2012
Association. All rights reserved.

4. From: Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After Radical
Prostatectomy
JAMA. 2005;294(4):433-439. doi:10.1001/jama.294.4.433
Figure Legend :
Biochemical recurrence segregated by prostate-specific antigen doubling time among patients who experienced a biochemical
recurrence. PSADT indicates prostate-specific antigen doubling time.
Copyright © 2012 American Medical
Date of download: 8/12/2012
Association. All rights reserved.

5. From: Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After Radical
Prostatectomy
JAMA. 2005;294(4):433-439. doi:10.1001/jama.294.4.433
Figure Legend :
Copyright © 2012 American Medical
Date of download: 8/12/2012
Association. All rights reserved.

6. DO NOT PANIC!
Take Time to Review Treatment
Options

7. How and Where the Cancer Spreads

9. Metastatic Pattern
• Lymph Nodes in Pelvis
• Lymph Nodes in Lower Abdomen
• Bone (NaF18 PET/CT Bone Scan will help this)
• Liver
• Adrenal Gland
• Lung (Special Case)

10. Patterns of Lymph Node Spread
Ganswindt, et al Int. J. Rad. Onc Biol Phys
67:347, 2007

11. Advances in Imaging
• Bone scan: Technetium-m99 vs NaF18-PET/CT bone scan
• MRI-based: Combidex vs Feraheme as iron based imaging
– For now, Combidex is unavailable
– Difficult with a pacemaker
– Only sees lymph node disease
– Will see any cancer in nodes: being evaluated for ca Pancreas
• Carbon-11 PET/CT: Choline vs Acetate
– Pacemaker is not a problem
– Sees cancer everywhere
– Depends on the cancer being metabolically active
– Choline is prostate specific
– Unclear to me if PET imaging can ever match MRI for resolution

12. Pathologic Confirmation of Feraheme
MRI
• Twenty-nine cases biopsied
• Twenty-five were confirmed prostate cancer
• Two showed lymphoma
• Two showed no cancer
• Pathologic confirmation of 3-4 millimeter
resolution

13. Feraheme MRI

14. Opportunity?
• If we can see the cancer, why not get rid of it?
• Possible outcomes:
– We get all the cancer and patient is cured
– Smaller, slower growing cancer is present and will
re-emerge over time: progress of cancer is slowed
– Cancer is in the process of exploding and no
benefit results
• But we already showed that exploding cancer
is uncommon!

15. Salvage Radiation Therapy
• Standard treatment is limited to the prostate
bed
• Increases risk of incontinence and impaired
sexual function
• Likely increase risk of colorectal and bladder
cancer
• Radiation damage to testes can cause drop in
testosterone production

16. (A) Kaplan-Meier estimate of the overall progression-free probability after salvage
radiotherapy.
Stephenson A J et al. JCO 2007;25:2035-2041
©2007 by American Society of Clinical Oncology

17. (A) Pretreatment nomogram predicting 6-year progression-free probability after salvage
radiotherapy for prostate-specific antigen (PSA) recurrence after radical prostatectomy.
Stephenson A J et al. JCO 2007;25:2035-2041
©2007 by American Society of Clinical Oncology

18. Hormonal Therapy

19. Androgen Withdrawal
(Two Years Zoladex + Casodex)

20. ADT
• NCC/SWOG intergroup trial (JPR7): intermittent
versus continuous ADT
• Men with rising PSA (greater than 3) after
external beam radiation therapy with a time
to castrate resistant disease endpoint
• It showed no inferiority
• Not published yet, so details missing

21. Growth Arrest
• PSA doubling times are easy to measure
• Growing list of agents reported to slow PSA DT
• Quite a few are nontoxic or have mild side effects
• Combinations can be easily tailored to the
patient

22. Each individual thin line represents the log PSA by time for one subject, pretreatment and
posttreatment (month 0 = baseline treatment), with the average slope of the entire cohort
plotted in thick black line.
Pantuck A J et al. Clin Cancer Res 2006;12:4018-4026
©2006 by American Association for Cancer Research

23. Agents That Slow PSA-DT
• Mediterranean heart healthy diet
• Pomegranate
• Vitamin D
• Celebrex
• Avodart
• Resveratrol
• Curcumin

24. Our Current Approach
• Start an individualized growth arrest program
• When PSA is 2-4 ng/ml, sent to Sand Lake Imaging for
Feraheme MRI
• On same patients, NaF18 PET/CT bone scan
• If cancer is found, advantages and disadvantages of
radiation are discussed
• If radiation is not done, intermittent hormonal therapy is
used.

25. Patient DS
• Diagnosed April 2003 with PSA 6.0
• Radical Prostatectomy June 2003
• PSA recurrence at 12 months with PSA 0.1
• Prostate bed radiation
• PSA doubling time 12 months growth arrest
failed
• June 2008 recommended androgen
withdrawal and IMRT to Combidex detected
nodes

26. Patient DS

27. Patient DS
• Testosterone recovered to 600-800 range by
March 2010
• PSA remains undetectable
• Penile implant March 2011
• New wife

28. Conclusions: 1
• Cancer recurrent after surgery or radiation is
still often slow to grow, spread and kill
• PSA doubling time is the most important
prognostic factor
• Best modern imaging detects residual cancer
in these patients and allows effective
radiation to residual cancer

29. Conclusions: 2
• Radiation to the prostate bed misses nodal metastases
and is of limited benefit
– Risks include rectal and bladder cancer
– May impair urine control and sexual function
• Hormonal therapy is very effective, but compromises
quality of life
• Many men can arrest progression of their cancer with
a healthy life style and medications with minimal or
modest risk