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Ca prostate Ca prostate Presentation Transcript

  •  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)
  • 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)
  • contd…..  b) Inner components– Periurethral glands Transitional zone(TZ) 2.Non glandular portions Prostatic urethra Ant. fibromuscular band
  • Prostate Cancer Facts That Every Man Over 40 Should Know
  • What Is Prostate Cancer? Not Much! What do you know about prostate cancer?
  • • 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.
  • 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.
  • 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.
  • 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
  • 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
  • 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
  • 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.
  • Classification of carcinoma prostate  Primary-  Adenocarcinoma---95% Others—5% .TCC----90% .Neuroendocrine carcinoma .Sarcoma  Secondary- From adjacent organs.
  • 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
  • Possible Levels of Prostate Cancer At Diagnosis Tumor Tumor CAPSULE GLAND PROSTATE Local-Regional Disease Spread Bone Systemic Spread Lymph Node Other Organs
  • 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%
  • 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
  • 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
  • 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)
  • 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
  • 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)
  • Confounding Factors for PSA  Increase  BPH  Age  Prostatitis  Ejaculation  Decrease  Finasteride, dutasteride  Some herbal mixtures  Obesity
  • Establishing a Diagnosis of Prostate Cancer  DRE  PSA/PSA velocity/percent-free PSA  Transrectal U/S  U/S- guided biopsy
  • Staging and grading  Two staging systems- Whitmore –Jewett staging. TNM staging.  Two grading systems- Gleasons grading Mostofis grading
  • 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.
  • 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
  • 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.
  • Prognostic Factors Age Health Race Clinical staging Gleason grading PSA level Predictive models for organ-confined versus non-organ confined disease.
  • 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.
  • 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
  •  Treatment of localized disease  Treatment of locally advanced disease  Treatment of recurrent disease  Treatment of HRPC.  Treatment of metastatic disease
  • Treatment of Localized Disease(T1+T2)  Watchful Waiting & active surveillance .  Radical Prostatectomy.  Definite radiation therapy - External beam radiotherapy (XRT) Brachytherapy  Cryo surgery & HIFU.
  • 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.
  • 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.
  • 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.
  • 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)
  • The Nerve Bundles Cross-Section of Prostate Urethra Rectum Neurovascular Bundles of Walsh Prostate
  • 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
  • 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.
  • 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.
  • 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.
  • External Beam Radiation Goal: Maximize damage to the prostate and minimize damage to surrounding tissues (i.e. bladder and rectum) Prostate Seminal Vesicles
  • Brachytherapy: Distribution Cross-Section of Prostate Urethra Uneven Distribution Ultrasound-guided bead placement for even distribution
  • Image of Prostate With Radioactive Bead Implants
  • 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.
  • 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.
  • 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.
  • 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 .
  • 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.
  • 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
  • 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 %
  • LHRH Analogs  Goserelin  Leuprolide  Triptorelin  Histrelin Available as every 1, 3, or 4 month injections  Castrate levels of testosterone attainable in a few weeks
  • 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
  • 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.
  • Treatment of Symptomatic, Hormone Refractory Metastatic Disease 1.Stop Anti-androgen or Add Anti-androgen. 2. Second line regimen – Aminoglutethimide Ketoconazole Corticosteroid
  • 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.
  • 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. ?
  • 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.
  • 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.
  • 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.
  • Can you guess who can get prostate cancer? Not you? Well, guess again… any male can get prostate cancer Hey, Smart Guy!