• Save
DrBlasko Low/IntermediateRiskProstateCancer(Sky/Teal)
Upcoming SlideShare
Loading in...5
×
 

Like this? Share it with your network

Share

DrBlasko Low/IntermediateRiskProstateCancer(Sky/Teal)

on

  • 1,010 views

It is important to understand that prostate cancer is not a single disease but a spectrum of diseases. Treatment considerations, therefore, must be individualized to each person’s particular ...

It is important to understand that prostate cancer is not a single disease but a spectrum of diseases. Treatment considerations, therefore, must be individualized to each person’s particular situation. Patients diagnosed with Low or Intermediate Risk disease are faced with multiple choices for management. Low Risk (SKY in the Shades of Blue classification scheme) is usually defined as stage T1 – T2a, Gleason score < 6 and PSA < 10. Intermediate Risk (TEAL in the Shades of Blue classification) is defined as having one of the following: stage T2b, Gleason score 7, PSA 10 – 20. Additional diagnostic information such as percent positive biopsy cores, perineural invasion and modern imaging results are useful in further refining the status of the disease. . What is unique for Low and most Intermediate Risk is that treatment may be either unnecessary or delayed because the disease can be so small and slow growing that it does not threaten the life of the patient. Further, there is data to suggest that death from prostate cancer at this stage is rare even if it is not eradicated. The question is how can you be sure of this and are you comfortable with this idea of not treating a cancer?
Many men are not comfortable with no treatment in these risk groups and opt for some form of definitive treatment at the time of diagnosis such as surgery, brachytherapy, or external beam radiation. . Lacking airtight randomized studies comparing treatments, a great deal of work has gone into analyzing the available literature for outcomes and complications of these three approaches. It is this author’s opinion that review of the literature supports brachytherapy as offering the highest probability of cure with the least long-term complications in patients who are suitable for this approach.
For patients who wish to avoid or at least delay the risks of definitive treatment, they may wish to consider some form of disease monitoring such as Active Surveillance. . There is exciting research being done with multi-parametric MRI scanning that in the future may allow us to accurately monitor prostate cancer without the invasiveness of biopsies. If disease does advance, some studies show that treatment at that time is as effective as treatment would have been initially.
Patients with Low or Intermediate Risk prostate cancer are faced with many decisions and choices that can be confusing and anxiety provoking. It is important to work with a knowledgeable physician to help guide you through this labyrinth. The good news is that patients with this category of disease very rarely die of prostate cancer no matter what choices are made and if definitive treatment is done, the chances of complete cure is over 90%.

Statistics

Views

Total Views
1,010
Views on SlideShare
1,010
Embed Views
0

Actions

Likes
0
Downloads
0
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment
  • 1 st Group References: Bahn, D et al. Targeted Cryo-Ablation of the Prostate:7 yr Outcomes in Primary Treatment of Prostate Cancer. Urology 2002 ; 60(Supp 2A):3-11. Boorjian, S et al. Mayo Clinic Validation of the D&apos;Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy . J Urology 2008;179:1354-1361. 3 Critz, F et al. 10-Year Disease Free Survival Rates after Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation and Methodology. J Urology 2004;172:2232-2238. 4 Galalae, R et al . Long-term Outcome by Risk Factors Using Conformal high Dose Brachytherapy Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer. Int J Radiat Oncol Bio Phys 2004; 58(4):1048-1055. 5 Klein E , et al . Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy . Urologic Oncology 2009;27(1):67-71. (RP) 6 Klein E , et al . Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy . Urologic Oncology 2009;27(1):67-71. (Seeds) 7 Kupelian, P et al. Imporved biochemial Relapse-Free Survival With Increased External Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in patients in 1994 and 1995. Int J Radiat Oncol Bio Phys 2005;61(2):415-419. 8 Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Bio Phys 2003;57(4):915-928. 9 Kupelian, P et al . Radical Prostatectomy, External Beam Radiotherapy &lt;72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1):25-33. (EBRT & Seeds) 27. Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185:495-500. 28 Zelefsky, M et al . Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J Urology 2006;176:1415-1419. 29 Zelefsky, M et al. Multi Institutional Analysis of Long term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation . Int J Radiat Oncol Biol Phys 2007;67(2):327-333 30. Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. 31 (Open) 32 Dattoli, M et al . Long-term Outcomes after Treatment with Brachytherapy and Supplemental Conformal Radiation for Prostate Cancer Patients having Intermediate and High-risk Features. Cancer 2007;110(3):551-555. Moyad, M et al . Statins, Especially Atorvastatin, May Favorably Influence Clinical Presentation and Biochemical Progression-free Survival after Brachytherapy for Clinically Localized Prostate Cancer. Urology 2005;66(6):1150-1154. Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1):16-22. (Seeds & EBRT) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1):16-22. (Seeds & ADT) 36. Galalae, R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer: Is Escalation to Very High Biologically Equivalent Dose Beneficial in All Prognostic Risk Groups? Strahlenther Onkol 2006;182(3):135-141. 37. Taira, A et al . Natural History of Clinically Staged Low and Intermediate risk Prostate Cancer Treated with Monotherapeutic Permanent Interstitial Brachytherapy Int J Radiat Oncol Bio Phys 2010; 76(2):349-354. Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5):1336-42. 38. Demanes, J et al . Excellent Results from HDR Brachytherapy and EBRT for PCA are not Improved by Androgen deprivation Am er J Clin Oncology 2009;32(4):342-347. 39. Stone, N et al. Local Control Following Permanent Prostate Brachytherapy: Effect of High Biologically Effective Dose on Biopsy Results and Oncologic Outcomes Int J Radiat Oncol Bio Phys 2010; 76(2):355-360. Dattoli, M et al . Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Radiation and Brachytherapy J Oncology 2010; 2010(Art. Id 471375): 6 pages. Menon, M et al. Biochemical Recurrence Following Robot Assisted RP: Analysis of 1384 patients with a median 5 year Follow-up. Eur Urol 2010; 58:838-846. (Robot) Munro, N et al. ( Leeds) Outcomes for Gleason Score 7, intermediate risk Localized Prostate Cancer Treated with I-125 monotherapy over 10 years. Radiother Oncol 2010;96(1):34-37. Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010; 76(5):1251-1257 (RP) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Proatate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5):1251-1257 (Seeds) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5):1251-1257 (EBRT) Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients treated with I-125 Permanent Prostate Brachytherapy. Int J Rad Onc Biol Phys 2010;76(5):1433-1438. 47.. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol. 2011 18; 2980-87.
  • 1. Morris et al BC Cancer Center Presented Seattle Annual Mtg 2006 2. Merrick et al Androgen Deprivation Does not Impact Cause Specific or Overall Survival after PPB Int J Radiat Oncol Biol Phys 65:669-677,2006 (Results -All Hormone naïve Not stated how many received EBRT + seeds) 3, Blasko Grimm Sylvester 2007 4. Hernandez, D Nielsen, Partin,A ( Johns Hopkins) Contemporary Evaluation of the D&apos;Amico Risk Group Classification of Prostate Cancer Urology 70: 931-935 2007 5. Kupelian,P ( Cleveland Clinic) Int J Rad Onc Biol. Vol 58 p 25-33, 2204 6. Potters NY Prostate Institute Monotherapy ofr Stage T1-2 prostate Cancer : radical prostatectomy external beam radiation or permanent seed implantation Radio ad Oncology 71: 29-33 2004 7. Stock, Stone J Urol 169, 2003 8. Sharkey et al Brachytherapy Sharkey et al Brachytherapy vs RP in Pts with Clinically Localized PCa Brachytherapy Current Urology Reports 2002, p1-5 Brachytherapy 2005;4(1):34-44 9. Cohen J, Reviews in Urology Vol 6 Supl 4 p20-26. 2004. 10. Ellis, R et al 4 year Biochemical Outcome after Radio-immunoguided Transperineal Brachytherapy for patients with Prostate Adenocarcinoma Int J Radiat Oncolo Biol Phs 57: p 362-370, 3003 11. Livsey, J et al Hypofractionated Conformal Radiotherapy in Carcinoma of the prostate: Five year outcome analysis Int J Radiat Oncol Biol Phys 57: p 1254-1259, 2003 12. Stokes, Comparison of Biochemical Disease Free Survival of patients ,,, Int J Radiat Oncolo Biol Phys 47 p 129-136, 2000. 13. Thames, H et al Increasing External Beam Dose for t1-2 Prostate Cancer Effect on Risk Groups Int J Radiat Oncol Biol Phys 65: p975-981, 2006 Low intermediate and intermediate Average 72Gy 14. Zelefsky et al High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the outcome of localized prostate Cancer J Urol. 166: 0 876-881, 2001 15. Zelefsky et al Five Year Outcome of Intraoperative Conformal Permanent Interstitial Implantation for Patients with Clinically Localized Prostate Cancer Int J Radiat Oncol Biol Phys 67: p 65-70, 2007. Zelefsky et al Multi-insitutional Analysis of Long term Outcome for T1-2 Prostate Cancer Treated with Permanent Seed Implantation with Int J Radiat Oncol Biol Phys 67: p 327-333, 2007. .Martin Q. et al Permanent Prostate Implant Using High activity Seeds and Inverse Planning with Fast simulated annealing Algorithm: 12 Year Canadian Experience Int J Radiat Oncol Biol Phys 67: p 334-341, 2007 18. Khan et at Expectant management of Localized Prostate Cancer Urology 62: p 793-799, 2003. Intermediate Risk = Mod differentiated Only 21 % PFS at10 years 19. Kuban et al Long Term Multi-institutional Analysis of Stage T1-2 Prostate cancer Treated with Radiotherapy in the PSA ERA Int J Radiat Oncol Biol Phys 57: p915-928, 2003 All pts > 72 Gy 20.Zelefsky, M et at al Improved Biochemical DFS of men younger than 60 yeas with PCa Treated with High Dose Conformal EBRT J Urol. Vol 170 1828-1832,2003 Dose > 80 Gy 21. Zietman et al Comparison of Conventional Dose vs High Dose Conformal Radiation Therapy in Clinically Localized PCa JAMA Vol 294 p 1233-1276. 2005 High Dose EBRT 79 Gy Photons and Protons ( Mixed intermediate with some High Risk) 22. Grimm et al 10 year Biochemical PSA control of PCa with I-125 Brachytherapy Int J Radiat Oncol Biol Phys 51: p31-40, 2001 23. Blasko, Grimm Sylvester et al Pd 103 Brachytherapy for Prostate carcinoma Int J Radiat Oncol Biol Phys 46: 839-850 2000 24.Merrick et al Impact of Supplemental EBRT and/or ADT on Biochemical outcome after Permanent Prostate Brachytherapy Int J Radiat Oncol Biol Phys 61 32-43 Majority 25. Sylvester Grimm Blasko et al 15 year RFS in Clinical Stage T1-3 PCa following combined EBRT and Brachytherapy: Seattle Experience Int J Radiat Oncol Biol Phys 67: p 57-64 26. Symon et ( U Mich) Dose Escalation for Localized PCa: Substantial Benefit Observed with 3D conformal TX Int J Radiat Oncol Biol Phys 57 384-390 2003 27. Bahn et al Targeted Cryoablation of the prostate:7 yr outcomes in primary Tx of Pca Urology 60 3-11 2002 28. Rossi, C et al ( Loma Linda) Conformal Proton Beam RT for PCa Community Oncology 235-240 April 2007 28.Uchida et al Treatment of Localized PCa with High intensity Ultrasound BJU 97 55-61 2006 Uchida et al 5 Year experience with High Intensity Focused Ultrasound using the Sonoblate Device in the treatment of Localized PCa Int J Urol 13, 228-233, 2006 29. Rossi, C et al ( Loma Linda) Conformal Proton Beam RT for PCa ( 79 Gy) Community Oncology 235-240 April 2007 30 Bolla et al Long Term Results with Immediate Androgen Suppression and EBRT in Pts with locally advanced PCa (EORTC study) Lancet 360: 103-108 2002. note low ebrt doses 31. Roupert et al. (France) Outcome after RP in young men with and without a family History of PCa. Urology 67 , 1028-1032. 2006. Very small study of only 36 pts 32. Berglund et al. (CAPSURE) Limited Pelvic LND at time of RP Does not affect 5yr Failure Rates for low intermediate and High Risk PCA Results from Capsure J Urology 177: 526-530, 2007 33. Galalae et al. Long Term Outcome by Risk Factors using HDR Brachytherapy Boost with and without Neoadjuvant androgen suppression for Localized PCA. Int J Radiat Oncol Biol Phys 58. 1048-1055,2004 34. Lee, L. Stock, stone. Role of HT in the management of Int to High risk PCa Treated with Permanent seed implant alone Int J Radiat Oncol Biol Phys 52 444-452 ,2002 35. Lederman et al Retrospective Stratification of a Consecutive cohort of PCa Pts Treated with Combined EBRT and Brachytherapy. Int J Radiat Oncol Biol Phys 49 1297-1303 ,2001 36. Kwok et al ( U Maryland) Risk group Stratification in Pts undergoing permanent I-125 Prostate Brachytherapy as Monotherapy. Int J Radiat Oncol Biol Phys 53 ,588-594 ,2002 37. Potters, L et al 12 year Outcomes Following permanent Prostate Brachytherapy in Patients with clinically Localized Prostate Cancer J Urol 173;1562-1566,2005 38. Zelefsky et al Comparison of 7 Year Outcome Between LDR Brachytherapy and High Dose IMRT with Clinically Localized Prostate Cancer Proceedings of ASTRO Abstract # 1074, 2007 39. Kuban D., Tucker, S,. Et al Long Term Results of the MD Anderson Randomized Dose Escalation Trial for Prostate Cancer IJROBP 2006; 70:67-74,2004 40. Vassil .D et al. (Cleveland Clinic, Kaiser) A comparison of bRFS and Initiation of Salvage Therapy in Pts with Intermediate risk PCa Tx with RP , EBRT or Permanent Seed implantation ASTRO 2007 abstract # 2225 43. Chun et al Anatomic Retropubic prostatectomy Long term recurrence free survival rates for localized PCA. World J Urol 24: 273-280. 2006
  • Author Journal and Yr 1 Kupelian P, Kuban D, Thames H, et al. Radical Prostatectomy, External Beam Radiotherapy &lt;72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int’l J. Oncology Biology Physics, 2004;58(1):25-33 2 Thames H, Kuban D, DeSilvio M, et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups. Int’l J. Oncology Biology Physics, 2006;65(4):975-981 3 Zelefsky Zelefsky M, , Kuban D, Levy L, et al. Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation. Int’l J.Oncology Biology Physics, 2007;67(2):327-333 4 Martin Martin AG, Roy J, Beaulieu L, at al. Permanent Prostate Implant Using High Activity Seeds & Inverse Planning With Fast Simulated Annealing Algorithum: A 12-Year Canadian Experience. Int’l J. Oncology Biology Physics, 2007;67(2):334-341 5 Potters Potters L, Morgenstern C, Calugaru E, et al. 12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients With Clinically Localized Prostate Cancer. J. Urology, 2005;173:1562-1566 6 Potters Potters L, et al. External Radiotherapy and Permanent Prostate Brachytherapy in Patients with Localized Prostate Cancer. Brachytherapy, 2002;1:36-41 7 Zelefsky Zelefsky M, Chan H, Hunt M, et al. Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J. Urology, 2006;176:1415-1419 8 Zelefsky Zelefsky M, Yamda Y, Cohen, G, et al. Five-Year Outcome of Intraoperative Conformal Permanent I-125 Interstitial Implantation for Patients With Clinically Localized Prostate Cancer. Int’l J. Oncology Biology Physics, 2007;67(1):65-70 9 Boorjian Boorjian S, et al. Mayo Clinic Validation of the D&apos;Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J. Urology, 2008;179:1354-1361 10 Critz Critz J, et al. 10-Year disease free survival rates after simultaneous irradiation for prostate cancer with a focus on calculation and methodology. J. Urology, 2004;172:2232-2238 11 Kuban D, et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int’l J. Oncology Biology Physics, 2003;57(4):915-928 12 Weight C, Reuther A, Gunn P, et al. Limited pelvic lymph node dissection does not improve biochemical relapse free survival at 10-years after radical prostatectomy in patients with low risk prostate cancer. J. Urology, 2008;71:141-145 13 Kupelian Kupelian P, et al. Improved Biochemical Relapse-Free Survival With Increased Radiation Doses in Patients With Locaized Prostate Cancer: The Combined Experience of Nine Institutions in 1994 and 1995. Int’l J. Oncology Biology Physics, 2005;61(2):415-419 14 Merrick G, et al. Androgen deprivation therapy dose not impact cause specific overall survival after permanent prostate brachytherapy. Int’l J. Oncology Biology Physics, 2006;65(3):669-677 15 Rossi C, et al. Conformal Proton Beam Radiation Therapy for Prostate Cancer: Concepts & Clinical Results. Community Oncology, 2007;4:235-240 16 Sharkey J, et al. PD-103 Brachytherapy Versus Radical Prostatectomy in Patients With Clinically Localized Prostate Cancer: A 12-Year Experience From a Single Group Practice. Brachytherapy, 2005;4:35-44 17 Sharkey J, et al. PD-103 Brachytherapy Versus Radical Prostatectomy in Patients With Clinically Localized Prostate Cancer: A 12-Year Experience From a Single Group Practice. Brachytherapy, 2005;4:35-44 18 Zelefsky M, Yamada Y, Fuks Z, et al. long-term results of conformal radiotherapy for prostate cancer: impact of dose escalation in biochemical tumor control and distant metastases-free survival outcomes. Int’l J. Oncology Biology Physics, 2008;71(4):1028-1033 19 Zelefsky J of Urology 2001 20 Peters implant Peters C, et al. Effect of family History on Outcomes in Patients Treated With Definitive Brachytherapy for Clinically Localized Prostate Cancer. Int’l J. Oncology Biology Physics, 2009;73(1):24-29 21. Bittner Bittner N, et al. Primary causes of death after permanent prostate brachytherapy. Int’l J. Oncology Biology Physics, 2008;72(2):433-440 22. Stone Stone N, et al. Customized dose Prescription for Permanent Prostate Brachytherapy: Insights From a Multicenter Analysis of Dosimetry Outcomes. Int’l J. Oncology Biology Physics, 2007;69(5):1472-1477 23.Moyad et al Statins especially Atorvastatin may favorably influence clinical presentation and Biochemical PFS after brachytherapy of Clinically Localized PCa Urology 66, 1150-1154,2005. 24. Bhatta Dhar et al No Difference in 6 year Biochemical Failure rates with or without pelvic LND during RP in Low Risk Patients with PCa Urology 63: 528-531, 2004 25. Zietman et al Comparison of Conventional Dose vs High Dose Conformal Radiation Therapy in CLincially Localized PCa JAMA Vol 294 p 1233-1276. 26. Nguyen Biochemical recurrence after RP for prevalent vs incident cases of Pca Cancer 113, 3146-3152, 2008
  • Kaplan-Meier analysis of return to 90% baseline HRQOL score over time, with p values comparing return to baseline curves from log rank test. A, urinary function. B, urinary bother. C, sexual function. D, sexual bother. E, bowel function. F, bowel bother.
  • (A) Cumulative hazard ratio for non–prostate cancer to prostate cancer mortality. (B) Cumulative hazard ratio for mortality by cause and age, stratified around age 70 years.
  • (A) Likelihood of remaining alive and on surveillance. (B) Prostate-specific antigen (PSA) failure in 117 patients treated with surgery or radiation after a period of surveillance.
  • Kaplan-Meier estimates of recurrence-free survival after surgery and radiation therapy. Time zero was defined as the time of intervention.

DrBlasko Low/IntermediateRiskProstateCancer(Sky/Teal) Presentation Transcript

  • 1. TREATMENT CONSIDERATIONS FORLOW INTERMEDIATE RISK / PROSTATE CANCER John Blasko MD
  • 2. Diagnosing a Shade of Blue * One core > 50% replaced with cancer bumps to Teal ** Two yellow boxes bumps Teal to Azure*** Any rising PSA with a low testosterone bumps to RoyalECE = Extra-capsular Extension, SV = Seminal Vesicle, PN = Pelvicnode
  • 3. Shades: The Question of TreatmentWith occasional exceptions, men below the blue dottedline always require treatment. Men above the bluedotted line may or may not require treatment Low Risk Sky Treatment vs.Intermediat Teal no treatment? e High Azure Relapsed Indigo Treatment Advanced Royal
  • 4. Treatments for Prostate Cancer Surgery- robotic or not (studies show no difference) Radiation  Seed implantation  Permanent Seeds  Iodine  Palladium  Cesium  Temporary High Dose Rate (HDR) Seeds  Beam Radiation  IMRT (conventional, accelerated, hypofractionated)  Proton
  • 5. Surgery
  • 6. The Prostate is “Built In” Surgical Access is Difficult Pubic BoneUrethra BladderIntestines
  • 7. Robotic Prostatectomy  Computer enhanced  Surgeon operates at the console within a 3D view  Bedside surgical assistant is next to the patient  Instruments move like a human wrist (↑ dexterity and precision)
  • 8. Surgeon Directs Instruments  The surgeon’s hands are placed in special devices that direct the instrument movement
  • 9. BladderAnatomy of the Neurovascular BundlesTo preserve sexual potency, the goal is toavoid cutting the nerves
  • 10. Surgery Pros and ConsPros Learn more about cancer status Some men feel better about “having it out” Long experienceCons Major operation Greater chance of incontinence and
  • 11. Radiation- Brachytherapy: Permanent Seeds High-Dose Rate Afterloading- Beam Radiation: IMRT (conventional and accelerated) Hypofractionated (cyberknife)- Protons
  • 12. Seeds
  • 13. Seed Implant ProcedurePreloaded Needles Mick Applicator
  • 14. Implant Procedure
  • 15. X-Ray of Patient after Completing a SeedImplant
  • 16. prostate urethraPeripheral Placement of Seeds to AvoidUrethra
  • 17. High-Dose-Rate Afterloading: Temporary Iridium-192 Brachytherapy1. HDR afterloader; Ir-192 source on cable 2. Needle insertion by TRUS guidance3. Implant completed; CT planning 4. Implant needles attached to HDR afterloader
  • 18. Catheters in place for hours to days
  • 19. Brachytherapy Pros and ConsPros Delivers highest biologic dose of radiation Most convenient and least disruptive Less chance of long term complicationsCons Requires expertise and experience Short term urinary side effects
  • 20. Linear AcceleratorExternal Beam Radiation(IMRT and Accelerated IMRT)
  • 21. Intensity Modulated Radiation Therapy (IMRT)
  • 22. “Cut Away” View of IMRT Showing DoseDistribution
  • 23. External Beam Radiation Pros andConsPros Widely available Technical advances Generally easy treatmentCons Radiation dose is limited Standard treatment is time consuming Risk of rectal injury
  • 24. Goals of Treatment- Cure the disease- Prevent suffering- Minimize impact on quality of life
  • 25. Cure: What is its significance?Cure does not necessarily mean longersurvival. The majority of men with prostatecancer who have a relapse after treatment dieof causes unrelated to prostate cancer.
  • 26. Summary of >100 Studies Looking at 5-year Cure Rates of Different Treatments 18,000 prostate studies published between 2000 and 2010 848 studies reported treatment results 140 of those studies met the following criteria: 1. Reported on 100 or more patients 2. Results reported for Low, Intermediate and High- Risk 3. Minimum of five years of follow up
  • 27. Cure Rates with Seed Monotherapy Intermediate Risk: Teal 100 33 33 23 13 14 14 23 13 37 37 90 44 44 16 16 39 39 6 12 6 12 42 42 80 17 17 BrachyAlone Seeds Surgery 70 29 29 EBRT 11 11 46 CRYO 60 46 HIFUs ecc u St ne maer T 50er gor P ASP % ← Years from Treatment → t 40 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 •Numbers within symbols refer to references
  • 28. Seed Monotherapy vs. Surgery*: Teal (Intermediate Risk) 1 0.9 24 1540 8 Brachy 23 0.8 2 17 37 12 22 Brachy 4 40Percentage 0.7 16 Relapse 3612 Surgery 0.6 34 32 Surg Free 31 43 8 0.5 no ss er gor P % 0.4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years after Treatment i *Grimm, BJU Int, 2012, Vol. 109(Supp 1)
  • 29. Cure Rates Intermediate Risk: Teal 14 33 14 33 13 13 EBRT + Seeds 37 37 Robot RP 31 31 35 35 34 34 90 1544 1544 + + Seeds + HT 38 40 Seeds Alone 3240 36 45 36 45 4 4 38 EBRT & Seeds 32 77 39 39 12 16 12 16 42 42 80 43 43 3 3 17 17 Hypo EBRT 18 18 28 Brachy Seeds Alone EBRT 6 5 28 6 5 9 9 70 7 25 7 4125 29 41 1 29 Surgery Surgery 1 2 2 10 10 11 46 11 46 60 EBRT 20 8 20 8s ecc u St ne maer T HDR 50er gor P ASP % ← Years from Treatment → t 21 21 40 22 22 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 29
  • 30. 100 21 8 8 14 21 14 20 20 23 23 Brachy 4 4 17 10 17 10 90 19 19 16 5 EBRT & 16 5 26 12 26 24 12 Seeds 24 7 7 22 22 Robot RP Surgery 3 3 9 9 18 Brachy 80 25 25 18 15 13 15 13 11 11 Surgery 13 13 EBRT 2 2 EBRT CRYO 70 HIFU Protonsgor P ASP % ← Years → No TX 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 • Prostate Cancer Results Study Group 3/31/09 • Numbers within symbols refer to references09/14/12 30
  • 31. Conclusion on Cure Rates:Modern seed implants result incure rates that appear slightlybetter than surgery
  • 32. Comparing Long-Term SideEffectsWhat percentage of men recovernormal urinary and sexual function(similar to before treatment) aftersurgery or radiation?
  • 33. Return to Baseline Urinary Function Schellhammer, J Urol 183:1822, 2010 Brachytherapy or Cryotherapy Robotic or Open Surgery Months after Treatment
  • 34. Return to Baseline Sexual Function Schellhammer, J Urol 183:1822, 2010 Brachytherapy Surgery or Cryotherapy
  • 35. Return to Baseline Urinary Control Gore , JNCI 101:888, 2009
  • 36. Return to Baseline Sexual Function Gore , JNCI 101:888, 2009
  • 37. Sexual Distress of 625 Spouses Sanda, NEJM 358:1250, 2008 Type of Median Age of % of PartnersTreatment Patient DistressedSurgery 59 44%Radiation 69 22%Seed 65 13%Implants
  • 38. QOL after 5 years: Surgery vs. Seeds Crook J Clin Onc 29:362, 2010 Compared to surgery, seeds implants showed significantly better:  Urinary function  Sexual function  Overall patient satisfaction There was no difference in bowel function between seeds and surgery
  • 39. Study of Side Effects: IMRT vs. Proton Sheets, JAMA 307:1611, 2012 Study evaluated the incidence of GI, urinary, sexual function in 6600 men treated with IMRT and 684 men with Proton between 2002 and 2007 IMRT was associated with a lower incidence of gastrointestinal morbidity compare to Proton There was no difference between the two treatments in sexual or urinary function
  • 40. Accelerated IMRT 2.5 Gy in 5 weeks (Kupelian, IJROBP 68:1424, 2007)  3.1% grade 2 rectal toxicity  5.1% grade 2 urinary toxicity 3.1 Gy in 4 weeks (Lock, IJROB 80:1306, 2011)  25% grade 2 and 3% grade 3 rectal toxicity  14% grade 2 and 5% grade 3 urinary toxicity
  • 41. Conclusion: Quality of Life Chances for complete recovery of sexual function are better after seed implantation than they are after surgery Chances for complete recovery of urinary function are better after seed implantation than after surgery Chances for normal bowel function are better after seeds than after external beam
  • 42. Comparison of Treatments “The Gold Standard” Surgery was the “Gold Standard” in the 1990s when radiation was ineffective and toxic  Surgical cure rates were better  The side effects of surgery were less Seed implantation is the new “Gold Standard” in the modern era. Compared to surgery:  Cure rates from seeds are at least as good  Side effects of seed implantation are less than surgery
  • 43. Cure Rates = Mortality RatesProstate cancer tends to be an indolentdisease, even if it isn’t cured. The majorityof men who develop a relapse after surgeryor radiation die of causes other thanprostate cancer (mainly heart disease).
  • 44. Cancer Specific Survival after Treatment (I rm e d ia te -Ris k: Teal) nte 8 years: 1019 men (Zelefsky, JCO 28:1508, 2010)  Surgery: 98.1%  External beam 95.5%* 10 years: 10,500 men (Kibel, J Urol 187:1259, 2012)  Surgery: 98.2%  External beam: 97.1%  Seed implant: 97.7% *In the Zelefsky study, patients initially treated with radiation and who subsequently relapsed had delayed salvage treatment compared to patients who relapsed after surgery
  • 45. Dangerous Types of Prostate Cancer Can be Indentified in Advance Eggener, Journal of Urology 185:869, 2011 Different Types of PC 15-Yr. MortalityGleason 6 0.2-1.2%Gleason 8 - 10 26-37%Seminal Vesicle Invasion 15-27%Lymph Node Metastases 22-30%Only 3 men of 10,000 who had Grade 6, organ-confined disease died of prostate cancer
  • 46. Predicting Prostate Cancer Mortality(PCSM) Stephenson, Journal of Clinical Oncology 2009“Only 4% (1 in 25) of contemporary patients have a PCSM risk greater than 5%”
  • 47. To Treat or Not To Treat Low/Interm. RiskWhitmore’s Conundrum“The quandary in prostatecancer: is cure necessary inthose for whom it is possible,and is cure possible in thosefor whom it is necessary?”1988 Willet Whitmore, Jr, MD Father of Urologic Oncology
  • 48. Management Choices for Low/ Interm Risk MonitoringObservation Active Surveillance Definitive TreatmentWatchful WaitingNo testing. Periodic testing. Treat to eradicateTreat only when and Definitive treatment the disease.if symptoms develop. if progression.
  • 49. “Watching” Palpable Disease Connecticut study: 20-year death rate of men diagnosed in the 1970’s was 7%  JA A2 0 0 5 M Swedish study: 15-year death rate of men with well-differentiated prostate cancer was 2.5%  JA A1 9 9 7 M
  • 50. PIVOT Trial: Surgery vs. “Observation” Wilt, NEJM 367:203, 2012 731 men randomized between1994 to 2002 Cancer detected by PSA testing Average age = 67, median PSA = 7.8 Half the men had Gleason 7 or above Half the men had a palpable nodule Two-thirds were I nte rm e d ia te -Ris k or Hig h-Ris k
  • 51. Outcome Ten Years Later Wilt, NEJM 367:203, 2012 # Men Cancer Cancer Severe Potenc Dead Death Death Loss y from Rate Rate Urinary Gone Cancer Overall (PSA>10 Control ) Surgery 21 5.8% 5.6% 17% 81% 364 men Observ. 31 8.4% 12.8% 6% 44% 367 menAdditional side effects of surgery: 1 death, 2 blood clots, 1 stroke,2 lung emboli, 3 heart attacks, 1 on kidney dialysis, 10 requiredadditional surgery, 5 had serious infections, 17 had wound infectionsor UTI, 6 had a urinary catheter for > 1 mo. and 6 blood transfusions.
  • 52. Scandinavian Trial: Surgery vs. No Treatment Bill-Axelson, NEJM 364:1708, 2011  695 men randomized between1989 & 1999  Cancer detected by rectal examination (DRE)  88% had a palpable abnormality on DRE  Average age 65, average PSA was 13  One-third of the men had Gleason 7 or more  Death rate @ 15 years 6% lower in men
  • 53. Scandinavian Trial: Surgical Complications Bill-Axelson, NEJM 364:1708, 2011Complication in 289 Number Incidence 1 YearMen of Events after SurgeryUrinary Leakage or 99 34.3%BlockageImpotence 168 58.1%Leg or Lung Blood 7 2.4%ClotsDeath from Surgery 1 0.3%
  • 54. “Observation” = Active Surveillance Observation Active Surveillance Aim Avoid treatment Individualize therapy Monitoring Lax Aggressive Indications for Cancer symptoms PSA increase, treatment such as bone pain changes on ultrasound or biopsy Treatment timing Late Early Treatment intent Symptom control Cure
  • 55. The Advantage of Active Surveillance: Accurate Selection of Men Who Need Treatment At initial diagnosis, treatment decisions are made by looking at a “single frame” from the whole movie Changes in predictive factors such as Gleason, PSA and imaging o ve r tim e enable treatment decisions to be tailored to the tumor biology in e a c h ind ivid ua l
  • 56. Study of Active Surveillance Klotz, JCO 28:126, 2010 450 men monitored from 1 to 13 years Median age 70; Median PSA between 5 to10 71% Lo w-Ris k; 29% I rm e d ia te -Ris k nte 10-year cancer survival was 97.2%--5 men died of prostate cancer. Four of the five were treated within 2 years of initial diagnosis 117 patients had surgery or radiation and their cure rate was 50%
  • 57. Non–Prostate Cancer Mortality vs. Prostate Cancer Mortality. Ratio was 18.6 to 1 Klotz, JCO 28:126, 2010XXX
  • 58. X XCure Rates with Surgery or Radiation X after X Active Surveillance X Xx Klotz, JCO 28:126, 2010 X #35 p = n.s. #90
  • 59. Study of Active Surveillance Tosoian , JCO 29:2185, 2011 769 men monitored from 1 to 15 years Median age 66; Median PSA was 5 All Gleason six; most with 2 or fewer cores positive No cancer deaths, no occurrence of metastases 192 had surgery or radiation of whom 18 (9.4%) have had a PSA relapse
  • 60. Cure Rates with Surgery orRadiation after Active Surveillance Tosoian , JCO 29:2185, 2011
  • 61. For Whom is Surveillance a Safe Option?Slide Provided by Laurence Klotz
  • 62. National Comprehensive Cancer Network (NCCN) Practice Guidelines Mohler et al, J Natl Compr Canc Netw. 2010ECURRENCE RISK EXPECTED INITIAL RISK SURVIVAL THERAPY Very Low Active <20yr Surveillance (Epstein Criteria) Preferred Low Risk 1) Active Surveillance >10yr 2) Radiotherapy (D’Amico Criteria) 3) Radical Prostatectomy Slide Provided by Laurence Klotz
  • 63. Monitoring Protocols of Different Centers  Klotz  DRE/PSA every 3 months for 2yrs, then every 6 months  Biopsy 6-12 months after enrollment, then every 3-4yrs  Multi-institutional (Univ Miami, Univ British Columbia; MSKCC; Cleveland Clinic)  DRE/PSA every 6-12 months  Biopsy 18 months after enrollment, then every 1- 3yrs  Johns HopkinsSlide Provided by Laurence Klotz  DRE/PSA at 6 month intervals
  • 64. Surveillance vs. Surgery vs. IMRT vs. BrachytherapyComparative Effectiveness and Value Institute for Clinical and Economic Review Massachusetts General Hospital
  • 65. Results of Surgery after Active Surveillance Duffield, J Urol 182:2274, 2009 100% of men with tumor volume > 1.0 cm were located in the anterior portion of the prostate, “out of reach” to a standard 8-12 core biopsy MRI directedStandard or Color Doppler Biopsy ultrasound directed biopsy can Prostate Prostate diagnose anterior tumors Rectum Rectum
  • 66. Future Directions: Monitoring with Imaging Instead of Repeated Biopsy? AUA Abstracts 2012  Abstract #2051: 179 men diagnosed with a 14- core biopsy. Multi-parametric MRI prior to the biopsy only missed one case of low volume high grade disease (Case was low volume 4 + 4 = 8)  Abstract #1444: 64 men evaluated with multi- parametric MRI prior to a template mapping biopsy. MRI predicted the absence of Gleason above 3 + 4 = 7 with 95% accuracy
  • 67. Individual Factors Affecting Treatment Choice, But Not Addressed in this Talk Patient factors:  Advanced age  Comorbidity health issues  Previous abdominal surgery Sexual factors:  Baseline Potency  Libido and sexual interest  Partner’s sexual availability and libido Prostate factors:  Prostate size  Preexisting urinary symptoms  Previous history of transurethral resection (TURP)
  • 68. Conclusions RegardingTreatment for Low/Intermediate Risk Since mortality rates are low, treatment selection should be influenced much more by quality of life considerations than by survival concerns The pros and cons of all the different alternatives need to be evaluated in light of each individual’s priorities and unique clinical profile Delaying immediate treatment and taking time to learn about all the various options is usually a wise initial course of action.