Ca prostate


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Ca prostate

  3. 3.  The prostate is part of the male reproductive system  Its major function is to secrete a fluid to nourish semen during intercourse  The prostate is about the size of a walnut but it can grow with age  It is located below the urinary bladder, in front of the rectum surrounding the urethra (the canal for the discharge of urine that extends from the urinary bladder to the outside)
  4. 4. Anatomy of the prostate gland A) Capsules - True capsule False capsule B) Glandular and non glandular elements- 1.Glandular prostate a) outer components- Central zone(CZ) peripheral zone(PZ)
  5. 5. contd…..  b) Inner components– Periurethral glands Transitional zone(TZ) 2.Non glandular portions Prostatic urethra Ant. fibromuscular band
  6. 6. Prostate Cancer Facts That Every Man Over 40 Should Know
  7. 7. What Is Prostate Cancer? Not Much! What do you know about prostate cancer?
  8. 8. • Cancer is a cellular disease • It is a disordered and abnormal cell growth • In prostate cancer, as in other types of cancer, cells grow out of control and form tumors • If the tumor is within the gland, the cancer is said to be localized and curable  If the cancer escapes the gland it is considered advanced and incurable • Early detection before the cancer escapes the gland becomes very important.
  9. 9. Distribution of prostate cancer  Tumor location— .70% in peripheral zone(PZ) .20% in transitional zone (TZ) .10% in cental zone( CZ)  Central gland most difficult to localize carcinoma, because of overlaping signal intensity with normal gland / hypertrophy.
  10. 10. How much threat of PROSTATE CANCER?  Most common malignancy of men in US after skin cancer.  At autopsy ,CaP is found in 30% of men in age 50. 90% of men in age 90.  Despite the long latent period, 2nd most common cause of cancer death in American men over age 55.  About 1 in 6 men will be diagnosed with carcinoma prostate during life time.
  11. 11. Aging and Prostate Cancer • As men age, prostate cells are increasingly likely to turn cancerous Bad News: American male has a 16.7% risk of being diagnosed with prostate cancer Good News: In most cases, the cancer cells are slow growing and occur late in life – only 3.5% of U.S males die from prostate cancer
  12. 12. Prostate cancer risk factors:  Age: The risk increases with age, but 25% of diagnoses are made under age 65.  Race: African-Americans have a rate of incidence double that of Caucasian men  Family history of prostate cancer: Men with a family history have two- to three-fold increase in the risk of prostate cancer
  13. 13. Risk Factors DIET  Eating red meat increases the risk of developing prostate cancer 2.64 times  Total fat intake and animal fat intake are associated with prostate cancer.  Vitamin D and calcium also increase risk.  Vegetable oil is rich in alpha linolenic acid (a fatty acid)  By-products of these fats promote the growth and seriousness of prostate cancer
  14. 14. So what CAN WE eat?  A balanced diet rich in fruits and vegetables!  Lower your intake of red meat, processed and fried foods. Eat more plant-based food like soy protein.  Eat foods with lycopene (tomatoes, watermelon and red grapefruit) which may be associated with a decreased risk of prostate cancer.  Vitamin E, selenium, and omega -3 fatty acids(fish) have been shown to be protective.
  15. 15. Classification of carcinoma prostate  Primary-  Adenocarcinoma---95% Others—5% .TCC----90% .Neuroendocrine carcinoma .Sarcoma  Secondary- From adjacent organs.
  16. 16. What are the symptoms of prostate cancer?  You might not have any at all!  Often there are none, or they are not recognized  Major symptoms:  Urinary frequency  Slow urinary flow  Painful urination  Blood in urine or semen  Impotence  Lower back or thigh pain
  17. 17. Possible Levels of Prostate Cancer At Diagnosis Tumor Tumor CAPSULE GLAND PROSTATE Local-Regional Disease Spread Bone Systemic Spread Lymph Node Other Organs
  18. 18. How does early detection help?  Survival rate at 5 years is 99% for those whose cancer is still just in the prostate gland (localized).  Survival rate at 5 years for those whose cancer has spread beyond the gland (late diagnosis) is only 31%
  19. 19. Early detection and screening  Digital rectal exam – Feel for nodules  PSA – How high?  Transrectal ultrasound – not for screening First two tests are convenient and inexpensive, but consequences may not be
  20. 20. Why do I have to have a DRE?  In the DRE the doctor examines you by feeling the prostate gland through the rectum with his finger (digit)  DRE improves the value of PSA testing in early disease detection  DRE and PSA together are often able to detect prostate cancer better and sooner than either test alone
  21. 21. When do I need to start getting tested?  DRE: 40 years and older every year (American Cancer Society guidelines)  PSA: 50 years and older every year (American Cancer Society guidelines)  If family history of prostate cancer and/or African-American: 45 years and older every year (American Cancer Society guidelines)
  22. 22. What You Should Know About the PSA Test PSA is a glycoprotein .  It exists in two form- complexed & bound form.  Its normal value is <4ng/ml & raises wth increasing age & size of the prostate gland.  The real value of the PSA test is in testing year to year and observing the rate of change  Medical opinion is divided about the usefulness of a single PSA  One test out of range could be caused by other problems  PSA is not prostate cancer specific
  23. 23. Under investigation: PSA Density, PSA Velocity, % free PSA  PSA Density - Normalized to prostate volume  PSA Velocity - Change in PSA over time (e.g., more than 15% per year)  Free PSA/Total PSA - lower ratio suggests cancer, since more free PSA from normal prostate is degradated (< 10% - biopsy)
  24. 24. Confounding Factors for PSA  Increase  BPH  Age  Prostatitis  Ejaculation  Decrease  Finasteride, dutasteride  Some herbal mixtures  Obesity
  25. 25. Establishing a Diagnosis of Prostate Cancer  DRE  PSA/PSA velocity/percent-free PSA  Transrectal U/S  U/S- guided biopsy
  26. 26. Staging and grading  Two staging systems- Whitmore –Jewett staging. TNM staging.  Two grading systems- Gleasons grading Mostofis grading
  27. 27. TNM Staging T= Tumor T1a and T1b (Incidental, early) T1c --Confirmed by needle biopsy T2a—Tumor involved one lobe T2b –Tumor involved both lobes . T3a—Extracapsular extension. T3b—Tumor invades seminal vesicles T4 –Tumor invaded adjacent structures. N= Regional Lymph nodes involvement M= Distant metastasis.
  28. 28. Gleason score  Characterize the degree of glandular differentiation under microscope.  It grades two most representative areas of tumor (primary grade & secondary grade).  Adds two values together—Gleason score (2—10).  Gleason score- 2—4 well differentiated 5—6 moderately differentiated 8—10 poorly differentiated
  29. 29. Chemoprevention for Prostate Cancer  Finasteride = 5-alpha reductase inhibitor, blocks intracellular conversion of testosterone to dihydrotestosterone  Based on solid evidence, chemoprevention with finasteride reduces the incidence of prostate cancer (6% absolute; 25% relative risk reduction), but the evidence is inadequate  Harms: erectile dysfunction, loss of libido, gynecomastia, higher grade cancers.
  30. 30. Prognostic Factors Age Health Race Clinical staging Gleason grading PSA level Predictive models for organ-confined versus non-organ confined disease.
  31. 31. In Case of a Diagnosis With a Positive Biopsy…  Do not panic,  Get a second opinion on the biopsy sample by a pathologist specializing in prostate cancer. Your treatment decision depends on a good assessment of the biopsy material.  Get a second opinion about your diagnosis and treatment options from an unbiased specialist in prostate cancer treatment.
  32. 32. Prostate Cancer Survival  Related to  Stage  Grade  Extent of tumor at diagnosis  Local disease - Median Survival > 5 years  Metastatic disease Median Survival 1-3 years, but individuals may survive 10 or more years
  33. 33. TREATMENT
  34. 34.  Treatment of localized disease  Treatment of locally advanced disease  Treatment of recurrent disease  Treatment of HRPC.  Treatment of metastatic disease
  35. 35. Treatment of Localized Disease(T1+T2)  Watchful Waiting & active surveillance .  Radical Prostatectomy.  Definite radiation therapy - External beam radiotherapy (XRT) Brachytherapy  Cryo surgery & HIFU.
  36. 36. Watchful Waiting  Life expectancy less than 10 years.  Diagnosis of an early-stage (T1-T2), low-grade tumor.  No medical treatment is provided.  Patient receives regular follow-up to monitor tumor.
  37. 37. Why Wait?  PSA and DRE can detect prostate cancer at a very early stage.  Average doubling time of a prostate tumor is quite slow (2-4 years).  Immediate radical therapy may constitute over-treatment and an introduce unnecessary urinary and potency risks.  May be appropriate if the patient is elderly and/or in poor health, and will live out their life spans without the cancer causing problems.  May also be appropriate for a younger patient who is willing to be vigilant and accept the risk of the cancer spreading.
  38. 38. Radical Retropubic Prostatectomy (RRP)  “Nerve Sparing” procedure developed by Walsh consisted of modified surgical technique to control blood and enhance visibility within surgical site.  Allowed for the identification and potential preservation of the nerves that control erectile function (potency).  Two neurovascular bundles that lie behind & on either side of the prostate that control erectile function.
  39. 39. RRP: The Surgical Approach Bladder Prostate Urethra Rectum 1.5-4 hours, usually epidural anesthesia. Incision: Begins just below navel and extends to pubic bone. Remaining Urethra is sewn to bladder neck over a catheter. Surgical Approach Pelvic Bone (Pubis)
  40. 40. The Nerve Bundles Cross-Section of Prostate Urethra Rectum Neurovascular Bundles of Walsh Prostate
  41. 41. RRP: Advantages  Whole prostate - and thus the entire tumor - can be examined histologically.  Surgeon has access to regional lymph nodes to test if prostate cancer cells have left the tumor.  Surgical margin can be examined. TT Negative Surgical Margin Positive Surgical Margin Not all of tumor removedOR
  42. 42. RRP: Complications  Severe or life-threatening complications are rare.  Incontinence (Urinary Control): complete incontinence is uncommon, although a significant number of patients experience some stress-incontinence. Usually improves with time.  Impotence (Erectile Dysfunction): if both neurovascular bundles were spared, potency rates range from 30-86%, depending on institution. Usually improves over time, and other ED treatments can work.
  43. 43. Radiation Therapy (RT)  High-Powered X-Rays that damage DNA and kill prostate cancer cells. 1. External Beam Radiation Therapy (EBRT): X-rays aimed at prostate. 2. Brachytherapy: Radioactive seed implants into prostate.
  44. 44. General Procedure: EBRT and Brachytherapy  EBRT: 1. Map precise area that will receive radiation. 2. Multiple treatments ~5 days/week for ~8 weeks. Each treatment takes about 10 minutes and no anesthesia is required.  Brachytherapy 1. 40-100 rice-sized radioactive seeds are implanted into the prostate via ultrasound-guided needles. Anesthesia is required. 2. All radiation inside the pellets is generally exhausted within a year.
  45. 45. External Beam Radiation Goal: Maximize damage to the prostate and minimize damage to surrounding tissues (i.e. bladder and rectum) Prostate Seminal Vesicles
  46. 46. Brachytherapy: Distribution Cross-Section of Prostate Urethra Uneven Distribution Ultrasound-guided bead placement for even distribution
  47. 47. Image of Prostate With Radioactive Bead Implants
  48. 48. RT: Complications Brachytherapy  High initial dose of radiation that slowly fades over 1 year.  Prostate inflammation and swelling, sometimes with severe urinary symptoms.  Other, more rare symptoms include persistent urinary and bowel frequency and urgency.  Erectile dysfunction: similar to EBRT.
  49. 49. RT: Complications EBRT  Most symptoms occur during treatments and subside after completion.  Diarrhea, rectal irritation, fatigue, frequent and painful urination, blood in the urine.  Erectile dysfunction: less common than radical prostatectomy following treatment but slower recovery.
  50. 50. Cryotherapy  Destroys prostate cells by freezing tissue.  Old idea that is making a comeback due to greater precision and better methods of imaging and temperature monitoring.  Method: insertion of sub-zero cryoprobes into prostate perineally (between scrotum and anus).  As yet unresolved how effective cryotherapy is compared to surgery or radiation.
  51. 51. Treatment of locally advanced disease:  Most Pt with T3 (T3a+ T3b ) CaP are at the present time treated with neoadjuvent hormone therapy followed by external beam radiotherapy .
  52. 52. Treatment of Recurrent Disease :  Following radical prostatectomy – Salvage radiation .  Following radiation therapy – Androgen ablation therapy If disease is local recurrence only— Bracy therapy, Cryo surgery ,Salvage prostatectomy.
  53. 53. Treatment of Symptomatic Metastatic Disease 1 . Hormonal Therapy - initial therapy for locally advanced or metastatic disease  Orchiectomy  Estrogens (No longer used)  LHRH analogs (+/- anti-androgens)  Antiandrogens + finasteride  Second line therapies consist of one of therapies not used before, e.g., anti- androgens if used only LHRH analogs
  54. 54. Hormone Therapy  Prostate cells and prostate cancer cells are dependant upon androgens (male sex hormones) for survival and growth.  Removal of androgens kills a majority of prostate cancer cells. Testes Prostate Growth and Function Testosterone 95% Adrenal Androgen 5 %
  55. 55. LHRH Analogs  Goserelin  Leuprolide  Triptorelin  Histrelin Available as every 1, 3, or 4 month injections  Castrate levels of testosterone attainable in a few weeks
  56. 56. Antiandrogens  Flutamide  Bicalutamide  Nilutamide  Combined androgen blockade not superior to LHRH therapy alone  Higher cost and more side effects than LHRH therapy alone  Primary value when starting LHRH to limit the flare reaction
  57. 57. Hormone-Refractory Prostate Cancer (HRPC)  Despite initial response rates of 80-90%, nearly all men with advanced prostate cancer develop hormone-resistant prostate cancer after 18-36 months.  These “hormone-refractory” (HR) prostate cancer cells can grow in the absence of androgens.  The behavior of HR prostate cancers differ widely between patients.
  58. 58. Treatment of Symptomatic, Hormone Refractory Metastatic Disease 1.Stop Anti-androgen or Add Anti-androgen. 2. Second line regimen – Aminoglutethimide Ketoconazole Corticosteroid
  59. 59. Contd…… 3. Cytotoxic chemotherapy  Docetaxel (every three weeks) and prednisone improves pain and reduces need for analgesic agents  Docetaxel with estramustine  Mitoxantrone  Other agents have had limited effectiveness  Continue hormone therapy to prevent flare with rising testosterone levels 4. Bisphosphonates - decreases skeletal complications. 4. 5. Gene threapy.
  60. 60. Management of Prostate Cancer Bone Metastases  Goal: prevent pain, improve mobility, prevent complications such as fractures or compression, maintain acceptable quality of life.  Methods: bis-phosphonates, radiation of detected metastatic lesions, surgery. ?
  61. 61. Emerging Therapy: Laparoscopic Radical Prostatectomy  Eliminates the need for a large incision by using a telescopic instruments called a laparoscopes.  Small camera attached to the laparoscope allows the surgeon to view inside the abdomen.
  62. 62. Laparoscopic Prostatectomy  Advantages:  Less blood loss.  No large incision.  Shorter hospital stay and earlier return to activities.  Disadvantages:  Longer procedure  Variable surgical margins rates.  Slower return of urinary continence.  Variable potency rates.
  63. 63. Conclusions  Risk factors are age, family history, race, and possibly diet .  Overall survival excellent (many years)  Early detection can find localized cancer, but survival benefits still uncertain  Treatment depends on grade, extent and location of disease  Surgery and radiation are equivalent therapeutic tools for localized prostate cancer  Hormonal therapy is effective for metastatic prostate cancer  Hormone refractory prostate cancer responds to chemotherapy, with occasional long term improvement.
  64. 64. Can you guess who can get prostate cancer? Not you? Well, guess again… any male can get prostate cancer Hey, Smart Guy!