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Carcinoma Of The Prostate

  1. Features
    1. Commonest malignant condition in men over 65 years. It usually originates from lateral lobes (Lowsley) / peripheral zone (Mcneal).
    2. Porsterior lobe (peripheral zone) 70% (Most common site for ca prostate), central lobe – 15-20%, Transitional lobe – 10-15%.
    3. Histologically commonest type is Adenocarcinoma. Q
    4. Although there is no proof that Prostatic Intraepithelial Neoplasia (PIN) is a cancer precursor, it is closely associated with cancer.
    5. Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum, or the tumor cells may develop the ability to travel in the bloodstream and lymphatic system.
    6. The route of metastasis to bone is thought to be venous as the prostatic venous plexus draining the prostate connects with the vertebral veins.
    7. Early prostate cancer usually causes no symptoms.
    8. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as benign prostatic hyperplasia like frequent urination, nocturia , difficulty starting and maintaining a steady stream of urine, hematuria , and dysuria.
    9. Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. 
    10. prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.  
    11. Spread: Local: initially capsule and the denonvillier’s fascia prevents its spread. Later on there is spread to SV, ureter, bladder base, urethra or rectum.
    12. Hematogenous: Ca prostate spreads to bones through periprostatic venous plexus. Prostate is the most common site of origin to bone metastasis. Secondary is mostly to Pelvic bone, lower vertebra, Femur, ribs and skull.
    13. Other than bones, breast, kidney, lungs or thyroid may be secondarily involved.
    14. Lymphatic: to internal iliac nodes, external iliac nodes, and later on to retroperitoneal node, mediastinal and supraclavicular node. 
    15. Common presenting symptoms are: Features of bladder outlet obstruction, retention, haematuria or incontinence.
    16. This may be an incidental finding found by raised PSA, palpable nodule in PR examination, histologically detected Ca in TURP chips. Occasionally bone mets. (Pain, neurological symptoms due to cord compression, or pathological fracture) may be a presenting symptom.
    17. PR examination reveals hard irregular enlarged prostate with loss of median sulcus.
    18. Diagnosis is confirmed by ultrasound guided needle biopsy of mass lesion (Carcinoma appear as hypoechoic lesion in USG).
    19. Other important investigations are complete hemogram, LFT, acid phosphatase (raised in 70% cases of bone mets), PSA (other then diagnosis it is also helpful in detecting recurrence after radical prostatectmy), x-ray chest and pelvis (to rule out mets, bone secondary in Ca prostate is sclerotic: D/D; pegets disease), CT scan (to see the extent of disease in advanced cases) MRI (to locate the neuro-vasculer bundle, if nerve sparing prostatectomy is to be done), Bone scan (Technitiun 99-m labeled methylene diphosphonate is used).
Prostate Specific Antigen (PSA)
  • It is a glycoprotein, serine protease.
  • Free: 10-40%; complexed to antiprotease: 60-90%
  • Formed in prostate, secreted in seminal fluid
  • Causes liquefaction of seminal coagulum.
    Normal value: ≤4 ng/ml (in >50 years); Value >20 ng/ml is diagnostic of CA prostate.
    PSA is the single test with highest positive predictive value for CA prostate.
    PSA is prostate specific, not the cancer specific.
    Level of PSA is directly related to tumor burden.
Uses of PSA:-
  1. Screening of prostate cancer
  2. Post treatment monitoring
  3. Forensic identification of semen
  4. Biomarker of semen, useful of identify semen from vasectomized and azos permic males.
  • Grading system for prostate cancer
  1. Gleason grading system is most widely used grading system.
  2. Primary gleason score 1-5.
  3. Secondary gleason score 1-5.
  4. Gleason score is arrived at through addition of the predominant and secondary grade patterns to yield range of tumor total Gleason score from 2 to 10.
  5. If score is more prognosis is poor.
All are true about Gleason’s staging except? (AIIMS Nov 08/May 2011)
A. Score from 1-10                                                                        
B. High score is associated with bad prognosis
C. Helps in grading of tumour                                                      
D. Helps to decide about treatment modality
Ans: A. Score from 1-10
  1. Staging systems for prostate cancer.
  • Primary tumor clinical (T)
    TX  Primary tumor cannot be assessed
    T0  No evidence of primary tumor
    T1  Clinically inapparent tumor not palpable or visible by imaging.
    T1a: Tumor incidental histologic finding in 5% or less of tissue resected.
    T1b: Tumor incidental histologic finding in more than 5% of tissue resected.
    T1c: Tumor indentified by needle biopsy because of increased PSA.
    T2  Tumor confined within the prostate gland
    T2a: Tumor involves one-half of one lobe or less.
    T2b: Tumor involves more than one-half of one lobe, but not both lobes
    T3c: Tumor involves both lobes
    T3  Tumor extends through the prostate capsule.
    T3a:  Extracapsular extension (unilateral or bilateral)
    T3b: Seminal vesicle invasion.
    T4  Invasion of bladder neck, rectum, external spincter, levator muscles, or pelvic side wall.  

Diagnostic tools under investigation.

  1. PCA-3m RNA
  2. EPCA-2
  3. Prostasomes (Epithelial cells of prostate secrete, Prostasomes surround sperm & protect it from  attach by female immune system
  1. Treatment
    1. Surgery: radical prostatectomy is surgical option of choice for CA prostate. Complications of surgery include: Haemorrhage, injury to obturator nerve, ureter, or rectum, incontinence and impotency.
    2. Radiation Therapy: A: External beam radiotherapy of 6800-7000 rads to prostate and 4500-5000 rads to pelvic nodes. B: Intrestitial implants: I 125 is used to deliver high dose (10,000 to 17,000 rads) to prostate without damaging surrounding tissue.
    3. Complications of radiotherapy are: Inestinal sequelae (rectal bleed, tenesmus, mucous discharge, diarrhoea, fecal incontinence, intestinal obstruction, and rectal stricture), Urological (frequency, dysuria, cystitis, hematuria, and urethral stricture, and recto-vesical fistula) and other rare complications like; impotency, pedal edema.
    4. Hormone ablation therapy which include GnRH analogue Leuprolide is hormonal therapy of choice:
    5. Along with GnRH analogue peripheral testrone synthesis blocker Callutamide is required.
    6. Estrogen: DES has comparable efficacy with orchidectomy, but complication rate is higher.
    7. Orchidectomy – bilateral sub capsular orchidectomy.
    8. LHRH agonist: Complications are like DES e.g. hot flashes, gynacomastia etc.
    9. Antiandrogens.Inhibitors of androgen synthesis includes aminoglutethimide, ketokonazole and spironolactone. Ketoconazole is a P450 inhibitor, which inhibits both adrenal and testicular androgen synthesis. Side effects are severe; GI intolerance, hepatotoxicity, gynacomastia and hypocalcemia. It is rapid acting and is useful in bone pains or impending spinal cord compression.
    10. Chemotherapy: It is a relatively chemoresistant tumour. Some agents (e.g. adramycin, 5-FU) have shown some effects (about 10% objective response). Suramin, by blocking growth factors (Beta FGF, EGF), direct cytotoxicity and adrenocorticolytic activity has shown 40 % response rate.
    11. Palliative therapy: Painful Bone mets are managed with RT (2000-3000 rads). Strontium 89 (a beta emoting compound) has a affinity for new bone activity and is effective in bone secondary. TURP is done to relieve outflow obstruction.
    12. No treatment required for incidental CA prostate after the age of 80 year.
Extra Edge: 
Most common lymph nodes involved
CA Penis Inguinal LN
CA testis On right; inter – aortocaval LN
On left: Para aortic LN
CA bladder Obturator LN
CA prostate Obturator LN

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