Ca prostate

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lecture by Dr. Ahmed Rehman

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  • Ca prostate

    1. 2. By Dr Ahmed Rehman FCPS (URO) Assistant Professor UROLOGY
    2. 3. CA prostate Incidence and Epidemiology <ul><li>Most common cancer diagnosed in males >65 </li></ul><ul><li>second commonest cause of death from cancer in the western world </li></ul><ul><li>1 in 6 men (FUNCTIONING TESTIS ) will get prostate cancer </li></ul><ul><li>Role of ethnicity & geography </li></ul><ul><li>PSA testing has had a major impact </li></ul>
    3. 4. Mo among Men in the United States
    4. 6. Cancer Incidence Rates* for Men, US, 1975-2000
    5. 7. CA prostate mortality
    6. 8. Risk Factors <ul><li>Age </li></ul><ul><li>Race </li></ul><ul><li>Family history/age of onset </li></ul><ul><li>Diet / fat </li></ul><ul><li>Cadmium, cigarette </li></ul><ul><li>Suspected but Not confirmed </li></ul><ul><ul><ul><li>Vasectomy </li></ul></ul></ul><ul><ul><ul><li>Infections </li></ul></ul></ul><ul><ul><ul><li>sex </li></ul></ul></ul>
    7. 9. Etiology <ul><li>Oncogene </li></ul><ul><ul><li>Familial CAP ----chromosome 1 </li></ul></ul><ul><li>Suppresser gene </li></ul><ul><ul><li>8p,10p,13p,16q,17p, 18p, p53 </li></ul></ul><ul><li>Epithelial stromal interactions/growth factors </li></ul>
    8. 10. Pathology <ul><li>Classification </li></ul><ul><ul><li>>95%------------------ adenocarcinoma </li></ul></ul><ul><ul><li>5%------------------ </li></ul></ul><ul><ul><ul><ul><ul><li>90%-------------- TCC </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>10%--------------neuroendocrine (small cell) CA </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>--------------sarcomas </li></ul></ul></ul></ul></ul>
    9. 11. PROSTATE CANCER Tumor distribution Oesterling J, et al. Cancer: Principles & Practice of Oncology . 5th ed. 1997;1322-1386. Transition zone Central zone Peripheral zone % of glandular tissue in prostate % of cancers in zone 10% 25% 65% 5-10% 70% 20%
    10. 12. Histopathological Grading <ul><li>Gleason grading system </li></ul><ul><ul><li>Grade 1-5 </li></ul></ul><ul><ul><li>Score = primary + secondary grade </li></ul></ul><ul><ul><ul><li>Well diffentiated (G1) 2-4 </li></ul></ul></ul><ul><ul><ul><li>Mod diff (G2) 5-6 </li></ul></ul></ul><ul><ul><ul><li>??? 7(primary ?) </li></ul></ul></ul><ul><ul><ul><li>Poorly dif (G3-4) 8-10 </li></ul></ul></ul><ul><ul><li>Prognosis </li></ul></ul>
    11. 14. <ul><li>Early Disease : asymtomatic </li></ul><ul><li>Peripheral zone : none </li></ul><ul><li>Transition zone : LUTS / UTIs / retention </li></ul><ul><li>Progressive Disease </li></ul><ul><li>Hematuria, Hematospermia, Decreased ejaculate volume </li></ul><ul><li>Impotence </li></ul><ul><li>Advanced Disease </li></ul><ul><li>Bone pain (back) & pathological # </li></ul><ul><li>Cord compression / nerve involvement </li></ul><ul><ul><ul><ul><ul><li>Paraesthesias / weakness </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Urinary / fecal incontinence </li></ul></ul></ul></ul></ul><ul><li>Constitutional symptoms </li></ul><ul><li>Obstructive uropathy </li></ul><ul><li>Bleeding tendencies / DIC, anemia, pancytopenia </li></ul><ul><li>Limb edema, Intestinal obstruction, Lymphadenopathy </li></ul><ul><li>Other manifestations of distant mets </li></ul>SIGNS AND SYMPTOMS / PRESENTATIONS
    12. 15. Detection of cancer: the challenge <ul><li>DRE----- s/s-----------???????? </li></ul><ul><li>PSA------s/s-----------?///////// </li></ul><ul><ul><li>Prostate specific but not cancer specific </li></ul></ul><ul><ul><li>Other causes </li></ul></ul><ul><ul><ul><li>BPH size of prosate </li></ul></ul></ul><ul><ul><ul><li>Acute & CH prostatitis(TB), prostatic abscess </li></ul></ul></ul><ul><ul><ul><li>Manipulation, instrumentation, biopsy </li></ul></ul></ul><ul><ul><li>Poorly diff CA --- not raised </li></ul></ul>
    13. 16. Detection of Prostate Cancer ; The Challenge <ul><li>DRE </li></ul><ul><li>PSA </li></ul>Currently, clinical practice guidelines recommend the use of both PSA and DRE in asymptomatic men
    14. 17. Establishing the diagnosis----- TRUS & Biopsy
    15. 18. Staging <ul><li>Local </li></ul><ul><ul><li>DRE, serum acid phosphatase, </li></ul></ul><ul><ul><li>TRUS,CT / MRI / Endorectal MRI -pelvis </li></ul></ul><ul><li>Skeletal & visceral mets (bone, lung, liver) </li></ul><ul><ul><li>Bone scan , Alkaline phosphatase (asymptomatic,PSA <10, >30) </li></ul></ul><ul><ul><li>CXR, CT scan abdomen </li></ul></ul><ul><li>Nodal </li></ul><ul><ul><li>(high risk----surgery /radiotherapy) </li></ul></ul><ul><ul><li>Involvement <10% </li></ul></ul><ul><ul><li>Sensitivity as low as 22-36% </li></ul></ul><ul><ul><li>CT /MRI (FNA), sampling / frozen sections </li></ul></ul><ul><ul><ul><ul><li>Negative bone scan,PSA>20, T3, gleason ggade (p) 4/5 </li></ul></ul></ul></ul>
    16. 20. PROSTATE CANCER Stage I T1 Clinically inapparent tumor not palpable nor visible by imaging G1 Well differentiated (slight anaplasia) T1a No MO G1 T1a Tumor incidental histologic finding in 5% or less of tissue resected N0 No regional lymph node metastasis M0 No distant metastasis
    17. 21. PROSTATE CANCER Stage II T1a N0 M0 G2, 3-4 T1b N0 M0 Any G T1a Tumor incidental histologic finding in 5% or less of tissue resected T1b Tumor incidental histologic finding in more than 5% of tissue resected N0 No regional lymph node metastasis M0 No distant metastasis T1c N0 M0 Any G T1c Tumor identified by needle biopsy (e.g., because of elevated PSA) T1 clinically inapparent tumor not palpable nor visible by imaging
    18. 23. PROSTATE CANCER Stage II ( Cont’d) T2a N0 M0 Any G T2b N0 M0 Any G T2c N0 M0 Any G T2a Tumor involves one lobe T2b Tumor involves both lobes N0 No regional lymph node metastasis M0 No distant metastasis T2 Tumor confined within prostate* *Note: Tumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by imaging, classified as T1c.
    19. 24. PROSTATE CANCER Stage III T3a N0 M0 Any G T3b N0 M0 Any G T3c N0 M0 Any G T3a Extracapsular extension (unilateral or bilateral) T3b Tumor invades seminal vesicle(s) N0 No regional lymph node metastasis M0 No distant metastasis T3 Tumor extends through the prostate capsule* *Note: Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2.
    20. 25. PROSTATE CANCER Stage IV T4 N0 M0 Any G Any T N1 M0 Any G Any T Any N M1 Any G T4 Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall M1 Distant metastases M1a Nonregional lymph node(s) M1b Bone(s) M1c Other site(s) N1 Metastasis in regional lymph node or nodes
    21. 26. PROSTATE CANCER Distant metastatic spread Lung Bone Liver Epidural space
    22. 30. Natural History of Disease <ul><li>Latent / indolent CA </li></ul><ul><li>Virulent </li></ul><ul><ul><li>Clinically manifested disease </li></ul></ul><ul><ul><ul><li>Time of onset & doagnosis </li></ul></ul></ul><ul><ul><ul><ul><li>Localized </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Locally advanced </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Metastatic </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Hormone refractory (HRCAP/ AICP) </li></ul></ul></ul></ul>
    23. 31. Clinically localized Hormone refractory Local treatment Endocrine Chemotherapy Relapsed and newly diagnosed M+
    24. 32. Treatment: Localized Disease <ul><li>T1-2 </li></ul><ul><li>Options </li></ul><ul><ul><li>Watchful waiting </li></ul></ul><ul><ul><li>Radical prostatectomy ( Young/ Millon / Walsh) </li></ul></ul><ul><ul><ul><ul><ul><li>Margin +ve  adjuvent radiation </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li> radiation at relapse </li></ul></ul></ul></ul></ul><ul><ul><li>Neoadjuvent hormone therapy + surgery </li></ul></ul><ul><ul><li>Radiation </li></ul></ul><ul><ul><ul><li>External beam </li></ul></ul></ul><ul><ul><ul><li>Brachytherapy </li></ul></ul></ul><ul><ul><li>cryosurgery </li></ul></ul>
    25. 33. Treatment: Locally Advance Disease <ul><li>T3-4 </li></ul><ul><li>Options </li></ul><ul><ul><li>Radiaton </li></ul></ul><ul><ul><li>Neoadjuvent hormone therapy  radiation </li></ul></ul><ul><ul><ul><li>2months before & during </li></ul></ul></ul>
    26. 34. Treatment: Recurrent Disease <ul><li>Following RP </li></ul><ul><ul><ul><li>Radiation </li></ul></ul></ul><ul><li>Following RXT </li></ul><ul><ul><ul><li>Salvage RP </li></ul></ul></ul><ul><ul><ul><li>cryosurgery </li></ul></ul></ul>
    27. 35. Treatment: Metastatic Disease <ul><li>Any T,M+N+ </li></ul><ul><ul><li>Options </li></ul></ul><ul><ul><ul><li>Hormone therapy (70-80%) </li></ul></ul></ul><ul><ul><ul><ul><li>Testosterone Pituitary gonadal axis </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>95% testes </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>2% Free  cell  DHT  RECEPTOR  nucleus/transcription </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Surgical ablation </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Bilateral Total orchidectomy </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Bilateral Subcapsular orchidectomy / prosthesis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Medical ablation </li></ul></ul></ul></ul>
    28. 36. Treatment: Metastatic Disease/ Medical ablation <ul><li>Pituitary -------Diethylstilbesterol (Hanovan) </li></ul><ul><ul><li>LHRH Agonists </li></ul></ul><ul><ul><li>Goserelin (zolladex) </li></ul></ul><ul><ul><li>Leuoprolid </li></ul></ul><ul><ul><li>Leuprorelin (Lucrin) </li></ul></ul><ul><li>Adrenals------- Ketoconazole (DIC /cord compression) </li></ul><ul><ul><li>Aminoglutithemide </li></ul></ul><ul><li>Prostate --------Antiandrogens </li></ul><ul><li>Pure Antiandrogens </li></ul><ul><li>Flutamide (Eulexin/Flutamida) </li></ul><ul><li>Nilutamide </li></ul><ul><li>Bicalutamide (Casodex) </li></ul><ul><li>Steridal / Progestational Antiandrogens </li></ul><ul><li>Ceproterone Acetate (Androcur) </li></ul><ul><li>Mesesterol acetate </li></ul>
    29. 37. Treatment: Metastatic Disease <ul><li>Complete androgen blockade </li></ul><ul><ul><li>Testicular +adrenal </li></ul></ul><ul><ul><li>LHRH/ orchedectomy + antiandrogens </li></ul></ul><ul><ul><li>Better initial & prolong response but not confirmed by others. </li></ul></ul><ul><li>Intermittent androgen blockade </li></ul><ul><ul><li>?delays refractory state </li></ul></ul><ul><li>Early versus late blockade </li></ul><ul><ul><li>Veteran’s ----- no survival benefit </li></ul></ul><ul><ul><li>MRC -----better survival + less complication rate </li></ul></ul>
    30. 38. Treatment: HRPC Chemotherapy <ul><li>Why refractory incomplete blockade / resistant cells </li></ul><ul><li>Responsiveness time 18 months-3years </li></ul><ul><li>Logivity 6-9 / 12 months </li></ul><ul><li>No standard chemotherapy regimen has been defined </li></ul><ul><li>Early Management of Endocrine Failure:discontinution / addition of antiandrogrns </li></ul><ul><li>No single agent or combination had improved survival in randomised trials </li></ul><ul><li>Complete remissions were rare </li></ul><ul><li>Physicians were reluctant to use chemotherapy in prostate cancer </li></ul>
    31. 39. Androgen-independent prostate cancer may respond to <ul><li>Withdrawal of anti-androgens </li></ul><ul><li>Ketoconazole </li></ul><ul><li>Corticosteroids prednisolone </li></ul><ul><li>Aminoglutethimide </li></ul><ul><li>Anti-androgens </li></ul><ul><li>Oestrogens </li></ul><ul><li>Progestational agents </li></ul><ul><li>Chemotherapy </li></ul><ul><li>estramustine,mitoxantrone, vinblastine </li></ul><ul><li>etoposide, cyclophosphamide </li></ul><ul><li>Novel agents paclitoxel, Docetaxel </li></ul>
    32. 40. Clinically localized Hormone refractory Local treatment Endocrine Mitoxantrone+P for symptoms Relapsed and newly diagnosed M+ PROSTATE CANCER Treatment Paradigms No survival benefit
    33. 41. Clinically localized Hormone refractory Local treatment Endocrine Taxotere + P q3 wks Relapsed and newly diagnosed M+ PROSTATE CANCER Treatment Paradigms Improves Survival
    34. 42. A multimodal approach to evaluating and treating a patient with androgen – insensitive prostate cancer VOL. 5 SUPPL. 3 2003 REVIEWS IN UROLOGY
    35. 43. PROSTATE CANCER (HRPC / AIPC) Multi-modality Team VOL. 5 SUPPL. 3 2003 REVIEWS IN UROLOGY
    36. 44. Prostate cancer: algorithm <ul><li>(DRE, TRUS, CT + bone scan) </li></ul><ul><li>Surgery </li></ul><ul><li>Radiotherapy </li></ul><ul><li>Adjuvant hormones </li></ul>Presentation Diagnosis Metastatic Localised Locally advanced <ul><li>Hormone therapy </li></ul><ul><li>Surgery + neoadjuvant hormone therapy </li></ul><ul><li>Radiotherapy ± hormone therapy </li></ul><ul><li>Hormone therapy </li></ul>Local control Palliative Curative Observation (symptoms/PSA) (biopsy) Staging CT = computed tomography; DRE = digital rectal examination; PSA = prostate-specific antigen; TRUS = transrectal ultrasound

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