crpc

1,131 views
973 views

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,131
On SlideShare
0
From Embeds
0
Number of Embeds
61
Actions
Shares
0
Downloads
52
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide
  • Good morning Mr. President, Mr. Secretary, Members and Guests. Today I will present to you the newly developed CRPC Guidelines. I will point out that this is the first time the AUA has addressed the management of this disease state, and given the current state of health care it is both timely and imperative for our memberswho treat men with APC to be familiar with this information.
  • Prostate cancer is the most commonly diagnosed malignancy in American men and remains the second leading cause of cancer deaths. In 2012, approximately 240,000 men were diagnosed and over 28,000 died of the disease. Prostate cancer deaths are typically the result of metastatic castration resistant prostate cancer (mCRPC), and historically the median survival for men with mCRPC was < 2 years.
  • The treatment of CRPC has undergone a dramatic change over the past decade. Prior to 2004, once patients failed primary androgen deprivation, all treatments were palliative. Landmark studies in demonstrated that docetaxel improved survival for these patients. Since then, 4 additional agents that show a survival benefit have been FDA approved on the basis of randomized clinical trials. These agents have been tested in multiple disease states to determine which patients benefit from each treatment. While greater availability of effective agents benefits patients, multiple options and sequencing may complicate decision-making
  • 1.TheAUA conducts rigorous systematic reviews in accordance with the Institute of Medicine’s standards for trustworthy guidelines.2. The systematic review encompassed publications from January 1, 1996 to February 14 20133. This yielded 5376 potentially relevant studies of which 303 qualified through inclusion/exclusion criteria and were included in the final analysis.4.The multidisciplinary expert panel then developed Guideline statements and a treatment algorithmbased on this literature review.
  • The quality of the evidence was assessed according to standard methodology,and studies were categorized by Grade based on the certainty of the results as a High, Moderate or Low.
  • The AUA nomenclature system explicitly links statement types to the body of evidence according to Grade and the Panels judgment regarding the balance between the benefits risk or harms of the treatment.
  • These Guidelines were developed to provide a rational basis for treatment of patients with CRPC based on our current understanding of the data. To this end, six index patients were developed representing the most common clinical scenarios that are encountered based on:the presence or absence of metastatic disease,the degree and severity of symptomsthe patients’ performance status, and the pretreatment with docetaxel-based chemotherapy.
  •  8. Based on our current understanding of the data, 6 index patients were developed representing the most common clinical scenarios that are encountered.
  • This rationale based on the most common clinical presentations of men with CRPC were used as the rationale for development of a user friendly management algorithm.
  • In men with non-metastatic CRPC, no treatment has been shown to prolong overall survival. As all agents have potential side effects, we must first do no harm. As such, it was the panel judgment that observation be the recommended. There was a strong panel judgment that patients should be encouraged to enter clinical trials when available. However, some patients may still choose to forego this approach in favor of first generation anti-androgens or first generation androgen synthesis inhibitors.
  • While multiple agents have been shown to prolong survival for men with metastatic CRPC, none of the agents are FDA-approved in the non-metastatic setting. Thus, the panel strongly recommended against this practice for multiple reasons, clinicians should NOT offer systemic chemotherapy or immunotherapy to patients outside the context of a clinical trial.
  • As a standard, Abiraterone and docetaxel (both with prednisone) and sipuleucel-T are currently the only agents that have an FDA indication for use in men with mCRPC who have not yet received docetaxel chemotherapy. For each agent, there is a randomized clinical trial that has shown a benefit for the drug. Unfortunately, there are no direct studies comparing the agents that can be used to inform optimal sequencing. As a general principle, it is preferable to give the least toxic agent first, particularly given the lack of head-to-head data, but this must be considered in light of other considerations, including convenience of administration. As such, patients should be informed of all options and be allowed to make an informed decision based upon their own preferences and goals related to therapy.
  • In patients who elect not to receive the standard therapies for whatever reason, there are a number of other options available. Data to support the use of these options in the setting of asymptomatic or minimally symptomatic prostate cancer is limited and generally of lesser strength than the standard treatments. Some have suggested that the removal of anti-androgen therapy may have a beneficial effect on mCRPC.Manipulation with existing first generation anti-androgen agentscan only be considered an option in this setting, if only because they offer patients who do not want or cannot have one of the standard therapies (for whatever reason) a relatively simple, non-toxic therapeutic option.
  • In Index Patient 3, the symptomatic, metastatic CRPC with good performance status and no prior docetaxel chemotherapy, the Panel recommendedAs a Standard,clinicians should offer Docetaxel+Prednisone should be offered Based on results of 2 RCT’s (TAX 327 and SWOG 9916)As a Recommendation, clinicians may offer abiraterone + prednisone to these patients prior to docetaxel chemotherapy.
  • As an Option, clinicians may offer ketoconazole + steroid, mitoxantrone or radionuclide therapy to patientswho do not want or cannot have one of the standard therapies.Finally, it it recommended by the Panel that clinicians should NOT offer treatment with either estramustine or sipuleucel-T in this setting.
  • In Index Patient 4, symptomatic, mCRPC with poor performance status and no prior docetaxel chemotherapy, the Panel recommendedAs an option, clinicians may offer treatment with abiraterone+prednisoneAnd, clinicians may offer as an option treatment with ketoconazole + steroid or radionuclide therapy for those who are unable or unwilling to receive abiraterone + prednisone.
  • Also in Index Patient 4, it was the Expert Opinion of the Panel that clinicians may offer docetaxel or mitoxantrone chemotherapy to patients in select cases, specifically when the performance status is directly related to the cancer. The Panel recommended that clinicians should NOT offer sipuleucel-T to patients in this clinical scenario based on the fact that patients with very symptomatic disease and poor performance status would be unlikely to gain significant survival benefit from use of immunotherapy.______________________
  • Index Patient 5, the Symptomatic, metastatic CRPC with good performance status and prior docetaxel chemotherapy, The Panel recommended:As a Standard, clinicians should offer treatment with abiraterone + prednisone, cabazitaxel or enzalutamide. If the patient received abiraterone + prednisone prior to docetaxel chemotherapy, he should be offered cabazitaxel or enzalutamide.
  • In Index Patient 5, the Symptomatic, metastaticCRPC with good performance status and prior docetaxel chemotherapy   As an Option, clinicians may offer ketoconazole + steroid if abiraterone + prednisone, cabazitaxel or enzalutamide is unavailable.Also as an Option, clinicians may offer retreatment with docetaxel to patients with mCRPC with good performance status who were benefitting at the time of discontinuation (due to reversible side effects) of docetaxel chemotherapy.
  • Palliative care is an interdisciplinary, holistic approach to managing advanced disease such as prostate cancer with a limited prognosis. It can include controlling symptoms that are physical, psychological, spiritual and social. The goal of palliation is to prevent and relieve suffering and to support the best possible quality of life for the patient and family.As such, for Index Patient 6 Symptomatic, metastatic CRPC with poor performance status and prior docetaxel chemotherapy, the Panel felt that based on expert opinion, clinicians should offer palliative care.Alternatively, for selected patients, clinicians may offer treatment with abiraterone + prednisone, enzalutamide, ketoconazole + steroid or radionuclide therapy is selected cases.
  • The Guideline also includes statements on bone health that apply to all index patients with CRPC. These include the recommendation that clinicians should offer supplemental calcium, Vitamin D for preventative treatment of fractures and skeletal related events. As an Option, clinicians may choose either denosumab or zoledronic acid when selecting a preventative treatment for skeletal related events for metastatic CRPC patients with bony metastases.
  • This demonstrates the Clinical Algorithm that was based on the Panel’s methodology and approach to patients with CRPC and will be available via Internet and Pocket Guide.
  • I wish to acknowledge the dedication and determination of my esteemed panel. This was truly a group project that could not have been completed without the cooperation of all involved. This included not only Urologists, Urologic Oncologists, Medical Oncologists with special expertise in GU Oncology and Palliative care, Nursing and Methodologist. Special thanks to Dr. Adam Kibel, Vice Chair, who’s contribution was especially impactful.
  • crpc

    1. 1. Castration-ResistantProstate Cancer (CRPC):AUA GuidelineMichael S. Cookson, MD, MMHCVice Chairman and Hart Professor of Urologic SurgeryVanderbilt University Medical CenterNashville, Tennessee
    2. 2. Header. Arial 48.Prostate cancer remains the 2nd leading cause of cancer deaths inAmerican menThis year alone, more than 28,000 men will die from prostate cancerHistorically, the median survival for men with mCRPC was less than2 years…but, we are beginning to impact on this and extend survivalThe recent surge of new treatment agents for men with mCRPC hasimproved survival, but unfortunately it remains an incurable diseaseScope of the ProblemSiegel R, et al: CA Cancer J Clin 2012; 62:10.
    3. 3. Header. Arial 48.Treatment Evolution2004:DocetaxelTannock et al.(TAX 327)2010:Cabazitaxelde Bono et al.(TROPIC)2010:Sipuleucel-TKantoff et al.(IMPACT)2011:Abirateronede Bono et al.(COU-AA-301)2012:EnzalutamideScher et al.(AFFIRM)2013:AbirateroneRyan et al.(COU-AA-302) Since the FDA approval of docetaxel, fouradditional agents with survival benefit have beenFDA approved based on RCT’s While greater availability of effective agentsbenefits patients, multiple options andsequencing may complicate decision-making2003 2005 2007 2009 2011 2013
    4. 4. Header. Arial 48.Consistent with the AUA guideline methodology, acomprehensive systematic review of the publishedliterature on therapies for CRPC from January 1996through February 2013:5376 potential studies303 qualified included in the final analysisGuideline statements and a treatment algorithm wereformed based on this literature review.Systematic Review
    5. 5. Methodology: Rating of EvidenceStrength and QualityA• Well conducted RCT’s• Exceptional observational studiesB• RCT’s and/or observationalstudies with some weaknessesC• Observational studies that areinconsistent -difficult to interpret
    6. 6. • Standard• Benefits are >or< than the harms• Level of evidence A or B• Recommendation• Benefits are >or< than the harms• Level of evidence C• Option• Benefits = harms• Level of evidence A, B, or CMethodology: Linking of Evidence toStatement Type
    7. 7. Header. Arial 48.To assist in clinical decision-making, six index patients weredeveloped representing the most common clinical scenarios thatare encountered in clinical practiceThese index patients were created based on the following:1. Presence or absence of metastatic disease2. Degree and severity of symptoms3. Patients’ performance status (ECOG scale)4. Prior docetaxel chemotherapyIndex Patients
    8. 8. Header. Arial 48.1. Asymptomatic non-metastatic CRPC and a rising PSA2. Asymptomatic or minimally symptomatic, metastatic (mCRPC)without prior docetaxel chemotherapy3. Symptomatic, mCRPC and no prior docetaxel chemotherapy withgood performance status4. Symptomatic, mCRPC and no prior docetaxel chemotherapy withpoor performance status5. Symptomatic, mCRPC and prior docetaxel chemotherapy withgood performance status6. Symptomatic, mCRPC and prior docetaxel chemotherapy withpoor performance statusIndex Patients
    9. 9. Header. Arial 48.Clinical AlgorithmStaging/ H&P/ImagingIndex Patient 1Index Patient 2Index Patient 3 Index Patient 4Index Patient 5Index Patient 6Non-metastatic CRPC and rising PSAMetastatic CRPCNo prior docetaxel Prior docetaxelAsymptomatic or mildlysymptomaticSymptomaticGood performance statusPoor performance statusGood performance statusPoor performance status
    10. 10. Header. Arial 48.Asymptomatic non-metastatic CRPCClinicians should recommend observation with continuedandrogen deprivation.(Recommendation; Evidence Level Grade C)Clinicians may offer treatment with first- generation anti-androgens (flutamide, bicalutamide and nilutamide) or first-generation androgen synthesis inhibitors (ketoconazole +steroid) to select patients who are unwilling to acceptobservation. (Option; Evidence Level Grade C)Index Patient 1
    11. 11. Header. Arial 48.Asymptomatic non-metastatic CRPCClinicians should NOT offer systemic chemotherapy orimmunotherapy to patients outside the context of a clinical trial.(Recommendation; Evidence Level Grade C)Index Patient 1
    12. 12. Header. Arial 48.Asymptomatic or minimally symptomatic,mCRPC without prior docetaxel chemotherapyClinicians should offer abiraterone + prednisone, docetaxel orsipuleucel-T to patients with good performance status. [Standard;Evidence Level Grade A (abiraterone) / B (docetaxel) /B (sipuleucel-T)]Clinical Principle: As there are no direct studies comparing the agentsto inform optimal sequencing, it is preferable to give the least toxicagent first and other considerations including ease of administrationIndex Patient 2
    13. 13. Header. Arial 48.Asymptomatic or minimally symptomatic,mCRPC without prior docetaxel chemotherapyClinicians may offer first-generation anti-androgen therapy,ketoconazole + steroid or observation to patients with goodperformance status and no prior docetaxel chemotherapy who donot want or cannot have one of the standard therapies.(Option; Evidence Level Grade C)Index Patient 2
    14. 14. Header. Arial 48.Symptomatic, mCRPC with good performancestatus and no prior docetaxel chemotherapyClinicians should offer docetaxel to patients with symptomatic,mCRPC with good performance status and no prior docetaxelchemotherapy. (Standard; Evidence Level Grade B)Clinicians may offer abiraterone + prednisone to patients withsymptomatic, mCRPC with good performance status and no priordocetaxel chemotherapy.(Recommendation; Evidence Level Grade C)Index Patient 3
    15. 15. Header. Arial 48.Symptomatic, mCRPC with good performancestatus and no prior docetaxel chemotherapyClinicians may offer ketoconazole + steroid, mitoxantrone orradionuclide therapy to patients who do not want or cannot have oneof the standard therapies. [Option; Evidence Level Grade C(ketoconazole) /B (mitoxantrone) / C (radionuclide therapy)]Clinicians should NOT offer treatment with either estramustine orsipuleucel-T. (Recommendation; Evidence Level Grade C)Index Patient 3
    16. 16. Header. Arial 48.Symptomatic, mCRPC with poor performancestatus and no prior docetaxel chemotherapyClinicians may offer treatment with abiraterone + prednisone topatients with symptomatic, mCRPC with poor performance status andno prior docetaxel chemotherapy. (Option; Evidence Level Grade C)Clinicians may offer treatment with ketoconazole + steroid orradionuclide therapy who are unable or unwilling to receiveabiraterone + prednisone. (Option; Evidence Level Grade C)Index Patient 4
    17. 17. Header. Arial 48.Symptomatic, mCRPC with poor performancestatus and no prior docetaxel chemotherapyClinicians may offer docetaxel or mitoxantrone chemotherapy topatients in select cases, specifically when the performancestatus is directly related to the cancer. (Expert Opinion)Clinicians should NOT offer sipuleucel-T to patients withsymptomatic mCRPC with poor performance status and no priordocetaxel. (Recommendation; Evidence Level Grade C)Index Patient 4
    18. 18. Header. Arial 48.Symptomatic, mCRPC with good performancestatus and prior docetaxel chemotherapyClinicians should offer treatment with abiraterone + prednisone,cabazitaxel or enzalutamide. If the patient received abiraterone +prednisone prior to docetaxel chemotherapy, he should beoffered cabazitaxel or enzalutamide. [Standard; Evidence LevelGrade A (abiraterone) /B (cabazitaxel) /A (enzalutamide)]Index Patient 5
    19. 19. Header. Arial 48.Symptomatic, mCRPC with good performancestatus and prior docetaxel chemotherapyClinicians may offer ketoconazole + steroid if abiraterone +prednisone, cabazitaxel or enzalutamide is unavailable.(Option; Evidence Level Grade C)Clinicians may offer retreatment with docetaxel to patients withmCRPC with good performance status who were benefitting at thetime of discontinuation (due to reversible side effects) ofdocetaxel chemotherapy. (Option; Evidence Level Grade C)Index Patient 5
    20. 20. Header. Arial 48.Symptomatic, mCRPC with poor performancestatus and prior docetaxel chemotherapyClinicians should offer palliative care to patients with mCRPC withpoor performance status who received prior docetaxel chemotherapy.Alternatively, for selected patients, clinicians may offertreatment with abiraterone + prednisone, enzalutamide,ketoconazole + steroid or radionuclide therapy.(Expert Opinion)Index Patient 6
    21. 21. Header. Arial 48.The following statements apply to all indexpatients:Clinicians should offer preventative treatment (e.g., supplementalcalcium, Vitamin D) for fractures and skeletal related events to CRPCpatients. (Recommendation; Evidence Level Grade C)Clinicians may choose either denosumab or zoledronic acid whenselecting a preventative treatment for skeletal related events formCRPC patients with bony metastases.(Option; Evidence Level Grade C)Bone Health
    22. 22. Staging/ H&P/ImagingIndex Patient 1Index Patient 2Index Patient 3 Index Patient 4Index Patient 5Index Patient 6• Clinicians should recommendobservation with continuedandrogen deprivation• Clinicians may offer treatmentwith first- generation anti-androgens (flutamide,bicalutamide and nilutamide) orfirst-generation androgensynthesis inhibitors(ketoconazole+steroid) to selectpatients unwilling to acceptobservation• Clinicians should NOT offersystemic chemotherapy orimmunotherapy outside thecontext of a clinical trialNon-metastatic CRPCMetastatic CRPCNo prior docetaxel Prior docetaxel• Clinicians should offerabiraterone + prednisone,docetaxel systemicchemotherapy or sipuleucel-Timmunotherapy• Clinicians may offer first-generation anti-androgentherapy, ketoconazole + steroidor observation to patients whodo not want or cannot have oneof the previously listed standardtreatments.Asymptomatic or mildlysymptomaticSymptomaticGood performance status• Clinicians should offerpalliative care• Clinicians may offertreatment withabiraterone + prednisone,enzalutamide,ketoconazole + steroid orradionuclide therapy• Clinicians should NOT offersystemic chemotherapy orimmunotherapyGood performance statusPoor performance status• Clinicians should offer docetaxel• Clinicians may offer abiraterone+ prednisone• Clinicians may offerketoconazole + steroid,mitoxantrone or radionuclidetherapy to patients who do notwant or cannot have one of thepreviously listed treatments• Clinicians should NOT offertreatment with eitherestramustine or sipuleucel-T• Clinicians may offer treatment withabiraterone + prednisone• Clinicians may offer treatment withketoconazole + steroid orradionuclide therapy to patientswho are unable or unwilling toreceive abiraterone + prednisone• Clinicians may offer docetaxel ormitoxantrone chemotherapy inselect cases, specifically whenperformance status is directlyrelated to the cancer• Clinicians should NOT offersipuleucel-T• Clinicians should offertreatment with abiraterone+ prednisone, cabazitaxel orenzalutamide; if the patientreceived abiraterone +prednisone prior todocetaxel chemotherapy,cabazitaxel or enzalutamideshould be offered• Clinicians may offerketoconazole + steroid ifone of the previously listedstandard treatments isunavailable• Clinicians may offerretreatment with docetaxelto patients who werebenefitting at the time ofdiscontinuation (due toreversible side effects) ofdocetaxel treatmentGuideline Statements on Bone Health for all Index Patients• Clinicians should offer preventative treatment (e.g. supplemental calcium, VitaminD) for fractures and skeletal related events to CRPC patients• Clinicians may choose either denosumab or zoledronic acid when selecting apreventative treatment for skeletal related events for CRPC patients with bonymetastasesPoor performance status
    23. 23. AcknowledgementsCRPC PanelMichael S. Cookson, MD (Chair)Adam S. Kibel, MD (Vice Chair)Philipp Dahm, MD, MHScChristine Engstrom, PhD, CRNP, AOCNStephen J. Freedland, MDMaha Hussain, MD, FACPDaniel W. Lin, MDWilliam T. Lowrance, MDWilliam K. Oh, MDDavid F. Penson, MDBruce J. Roth, MDMethodologyHassan Murad, MD, MPHOsama Altayar, MDMohammed Nabhan, MDAUA Guidelines Staff.AcknowledgementsFOR MORE INFORMATION, PLEASE ATTEND:Detection of Prostate Cancer & Castration-Resistant Prostate Cancer CourseMay 6, Noon-130pm San Diego Convention Center 6C

    ×