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Case Presentation

Case Presentation. Emad Shash, M.Sc. Medical Oncology Department National Cancer Institute Cairo University. 20 th December 2010 NCI Grand Round. www.nci.cu.edu.eg. Background. ~ 186,000 new cases and 28,000 prostate cancer –related deaths were predicted in the United States in 2009 [1]

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Case Presentation

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  1. Case Presentation Emad Shash, M.Sc. Medical Oncology Department National Cancer Institute Cairo University 20th December 2010 NCI Grand Round www.nci.cu.edu.eg

  2. Background • ~ 186,000 new cases and 28,000 prostate cancer–related deaths were predicted in the United States in 2009[1] • Prostate cancer cell survival dependent on AR activation[2] • AR expressed in most primary prostate tumors • Over-expression of AR may predict for resistance to ADT • ~ 90% of prostate cancer patients respond to ADT but CRPC typically develops rapidly, especially if PSA nadir is > 4 ng/mL[3,4] • CRPC likely result of AR up-regulation and re-expression of androgen-responsive genes[4,5] 1. American Cancer Society. Available at: http://www.cancer.org. 2. Sharifi N, et al. Clin Cancer Res. 2008;14:4691-4693. 3. Gelmann EP. J Clin Oncol. 2002;20:3001-3015. 4. Hussain M, et al. J Clin Oncol. 2006;24:3984-3990. 4. Holzbeierlein J, et al. Am J Pathol. 2004;164:217-227.

  3. Therapeutic Opportunities Through Prostate Cancer Progression: Androgen Depletion Adjuvant Tumor Burden Biochemical Progression Expectant Hormone Refractory Time

  4. Prostate Cancer Terminology • Castrate-resistant prostate cancer: tumor progression despite castrate levels of androgens • Often responds to second-line hormonal treatment • Hormone-refractory prostate cancer: tumors no longer respond to hormone therapy • Androgen-independent prostate cancer: tumors no longer rely on the androgen receptor or androgen signaling for growth and survival

  5. Definition of CRPC: Progression • CRPC will develop in nearly all patients receiving ADT • Definition: rising PSA with nodal or visceral lesions or growth of measurable disease despite castrate testosterone levels[1] • According to the 2008 guidelines published by the Prostate Cancer Clinical Trials Working Group, several criteria are used to define disease progression[2] • ≥ 2 bone lesions • Reappearance of primary prostate tumor in prostatic fossa after surgery • New lesions at other sites of metastasis 1. Scher HI, et al. J Clin Oncol. 2005;23:8253-8261.2. Scher HI, et al. J Clin Oncol. 2008;26:1148-1159.

  6. What Determines Whether a Patient Is Castrate Resistant? • Has an attempt been made to suppress the patient’s testosterone production through orchiectomy or hormone suppression therapy with an LHRH agonist with or without an antiandrogen (ie, ADT)? • Is the patient’s testosterone level < 50 ng/mL? If the answer to both is yes, the patient is castrate resistant

  7. Criteria Defining CRPC Progression for Clinical Trial Enrollment • Identified by the Prostate Cancer Clinical Trials Working Group 2 Scher HI, et al. J Clin Oncol. 2008;26:1148-1159.

  8. Tumor Progression in CRPC • Tumor progression in CRPC due to AR-associated signaling mechanisms • Receptor over-expression (gene amplification and/or protein over-expression) • AR mutations leading to receptor promiscuity or structure-function activation • Increased AR ligand expression in surrounding tissue • AR activation by co-activators • Ligand-independent receptor activation via other pathways • Ligand hypersensitivity subsequent to AR expression Regardless of event type, the ultimate consequence is activation of the AR signaling cascade and resulting tumor growth, survival, and proliferation despite castrate androgen levels Hsieh AC, et al. J Clin Oncol. 2008;14:11-14.

  9. Our Case

  10. MMK 66 year old gentleman presented to our clinic in March 2009 with dysuria, hematuria and severe peri-anal pain giving a history of prostate cancer of 2 years of diagnosis. • Back to the year 2007, he was seen by his urologist after been suffering of progressive burning micturition and mild hematuria. He was advised to do PSA= 40 ng/ml, TRUS and biopsy were done revealing prostatic carcinoma Gleason score 7 (4+3). • The patient underwent bilateral orchiectomy and received casodex 50mg for about 3 month with marked drop of his PSA, the patient refused to continue treatment and lost follow up for psychological issues.

  11. In February 2009 his urinary symptoms worsened; in addition to the newly developed peri-anal pain, where he decided to seek medical advice. • He is not known to be diabetic or hypertensive with no special habits of medical importance. • Complete physical examination was performed and was completely normal despite hard fixed prostatic mass by DRE. • CBC, KFT, LFT were normal. • PSA 5ng/ml with 19% free PSA. • CXR, bone scan were free. • CT abdomen and pelvis revealed: Gross irregular prostatic enlargement inseparable from the anterior ano-rectal wall and from the thickened enhanced urinary bladder base.

  12. Plan of Management Conformal radiotherapy with marked improvement of both rectal and urinary symptoms. Casodex 50mg per day was initiated again. The patient was followed initially by PSA that was dropped to 1.2 ng/ml and no more urinary symptoms.

  13. Follow Up After 3 month of casodex, CT abdomen and pelvis was done and revealed: • Regressive course of the size of the deep pelvic neoplastic tissues. • Newly developed multiple hepatic nodules and bilateral pulmonary nodules. PET/CT examination was done and revealed widespread metabolically active pulmonary, hepatic, nodal and bone marrow metastases. Hepatic Nodule Biopsy confirmed to be of Prostatic Adenocarcinoma

  14. What do you think? 1- Hormonal Dependent. 2- Hormonal Resistant. 3- Hormonal Refractory. Cazodex was stopped and the patient was shifted to Estracyt 140mg oral 4 times per day and Zoledronic acid 4mg every 28 days

  15. After 4 months of Therapy

  16. Current Situation • The patient maintained response for 6 months till disease progression. • Shifted to Docetaxel + Steroids and he is currently on therapy (not assessed Yet)

  17. European School of Oncology Educational Event www.eso.net

  18. History ESO was founded by Umberto Veronesi and Laudomia Del Dragoin 1982, with the aim of contributing to the reduction of deaths from cancer due to late diagnosis and/or inadequate treatment. www.eso.net

  19. Mission • Is reflected in its motto "Learning to Care", which stresses the concept of studying and learning. • By improving the skills of all health professionals dealing with cancer patients. www.eso.net

  20. Partnership www.eso.net

  21. 9th ESO-ESMO Masterclass in Clinical OncologyMarch 2010 Ermatingen (Lake Constance), Switzerland

  22. THE MASTERCLASS A 5-day residential educational event: • Clinically-oriented • Multidisciplinary • An international faculty of top experts delivering lectures focusing on breast, colorectal, gynaecological, head and neck, urological and lung cancers

  23. ACCREDITATION • Accreditation Council of Oncology in Europe (ACOE). • European Accreditation Council for Continuing Medical Education (EACCME). • European Union of Medical Specialists (UEMS). The Masterclass has been accredited with 25 ESMO-MORA.

  24. IDEAL MASTERCLASS CANDIDATE • Age between 30 and 40 years • At least 2-3 years' experience in medical oncology, radiation oncology or surgical oncology • Involvement in scientific activities • Fluency in English

  25. HOW TO APPLY Interested oncologists should fill in the application form and provide the following documents by the deadline: 1- Letter describing motivation for attending. 2- CV with list of publications. 3- Supporting letter from Head of Department or Mentor. 4- Abstract, relating to one of the subjects of the Masterclass.

  26. The abstract (max. 1 page) should describe a clinical case, not a clinical study, in the form of a clinical grand-round.

  27. Abstract • Diagnostic considerations • Treatment • Results, follow-up • At least three questions proposed for discussion with the faculty

  28. Participant Demographics EUROPEAN JOURNAL OF CANCER 4 6 ( 2 0 1 0 ) 2 1 5 9 –2 1 6 5

  29. EUROPEAN JOURNAL OF CANCER 4 6 ( 2 0 1 0 ) 2 1 5 9 –2 1 6 5

  30. Teaching Material Evaluation EUROPEAN JOURNAL OF CANCER 4 6 ( 2 0 1 0 ) 2 1 5 9 –2 1 6 5

  31. Successful applicants are granted free registration and accommodation Around 60 participants annually

  32. Thank You All Best Of Luck

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