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DrMyers PSA Relapse (Indigo)
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DrMyers PSA Relapse (Indigo)

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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......

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.

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  • (A) Kaplan-Meier estimate of the overall progression-free probability after salvage radiotherapy. (B) Progression-free probability after salvage radiotherapy stratified by preradiotherapy 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).
  • 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. The PSA values tend to increase, but the increase rate (slope) decreased. The slope of the mean log PSA of the entire cohort decreased 35%, from 0.066 ± 0.007 (mean λ ± SE) at baseline down to 0.043 (mean λ ± SE) on treatment (P < 0.001).

Transcript

  • 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 RadicalProstatectomyJAMA. 2005;294(4):433-439. doi:10.1001/jama.294.4.433Figure Legend :Biochemical recurrence stratified by all comers vs early biochemical recurrence (within 3 years following surgery) vs latebiochemical recurrence (>3 years following surgery). Copyright © 2012 American MedicalDate of download: 8/12/2012 Association. All rights reserved.
  • 3. From: Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After RadicalProstatectomyJAMA. 2005;294(4):433-439. doi:10.1001/jama.294.4.433Figure Legend :Biochemical recurrence segregated by pathological Gleason Score among patients who experienced a biochemical recurrence. Copyright © 2012 American MedicalDate of download: 8/12/2012 Association. All rights reserved.
  • 4. From: Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After RadicalProstatectomyJAMA. 2005;294(4):433-439. doi:10.1001/jama.294.4.433Figure Legend :Biochemical recurrence segregated by prostate-specific antigen doubling time among patients who experienced a biochemicalrecurrence. PSADT indicates prostate-specific antigen doubling time. Copyright © 2012 American MedicalDate of download: 8/12/2012 Association. All rights reserved.
  • 5. From: Risk of Prostate Cancer–Specific Mortality Following Biochemical Recurrence After RadicalProstatectomyJAMA. 2005;294(4):433-439. doi:10.1001/jama.294.4.433Figure Legend : Copyright © 2012 American MedicalDate 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
  • 8. 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)
  • 9. Patterns of Lymph Node Spread Ganswindt, et al Int. J. Rad. Onc Biol Phys 67:347, 2007
  • 10. 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
  • 11. 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
  • 12. Feraheme MRI
  • 13. 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!
  • 14. 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
  • 15. (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
  • 16. (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
  • 17. Hormonal Therapy
  • 18. Androgen Withdrawal (Two Years Zoladex + Casodex)
  • 19. 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
  • 20. 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
  • 21. 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
  • 22. Agents That Slow PSA-DT• Mediterranean heart healthy diet• Pomegranate• Vitamin D• Celebrex• Avodart• Resveratrol• Curcumin
  • 23. 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.
  • 24. 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
  • 25. Patient DS
  • 26. Patient DS• Testosterone recovered to 600-800 range by March 2010• PSA remains undetectable• Penile implant March 2011• New wife
  • 27. 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
  • 28. 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