Prostate Cancer.pptx for healthcare professionals

this slide is about prostate cancer

1. Prostate Cancer Zikria, Ph.D.

2. Anatomy

3. Anatomy Blood supply – Inferior vesical artery • Derived from the internal iliac artery • Supplies blood to the base of the bladder and prostate • Capsular branches of the inferior vesical artery – Help identify the pelvic plexus Nerve supply – Neurovascular bundle • Lies on either side of the prostate on the rectum – Derived from the pelvic plexus , arising from the S2-4 (pelvic splanchnic nerves) and T10-12 nerve roots – thoracic spinal nerves – Important for erectile function.

4. Peripheral zone (PZ) – 70% of cancers • Transitional zone (TZ) – 20% • TZ prostate cancers are relatively nonaggressive • PZ cancers are more aggressive – Tend to invade the peri-prostatic tissues.

5. Regional Lymph nodes Pelvic • Hypogastric • Obturator • Iliac (internal, external) • Sacral Metastatic Lymph nodes Distant lymph nodes lie outside the confines of the true pelvis. • The distant lymph nodes include the following: • Aortic ( paraaortic lumbar) • Common iliac • Inguinal, deep • Superficial inguinal (femoral) • Supraclavicular • Cervical • Scalene – neck region • Retroperitoneal – abdominal cavity

6. Epidemiology Family history: 2-3 fold increased risk in men with a first degree relative. • Hereditary association: Early onset of disease and a Mendelian autosomal dominant inheritance– accounting for <10% of all cases but 40% in younger men in <55 years. • Racial Factors: Striking differences in incidence and mortality between the Black and White population, more common in blacks. • Environmental Factors: also responsible for ethnic differences, as Asians migrating to USA have higher incidence of prostate cancer.

7. Diet: one of the most important modifiable risk factors -- high fat intake increases risk whereas diets rich in carotenoids (tomato based products containing lycopene) and vitamin-E are protective. • No association with cigarette smoking, alcohol use, height and weight and blood group. • No data regarding viral origin. • No convincing evidence that Vasectomy increases risk of prostate cancer

8. Pathology Adenocarcinoma 95% of prostate cancers - Developing in the acini of prostatic ducts Rare histopathologic types of prostate carcinoma - Occur in approximately 5% of patients – Include • Small cell carcinoma • Mucinous carcinoma • Endometrioid cancer (prostatic ductal carcinoma) • Transitional cell cancer • Squamous cell carcinoma • Basal cell carcinoma • Adenoid cystic carcinoma ( basaloid ) • Signet-ring cell carcinoma • Neuroendocrine cancer

9. Pathophysiology In prostate cancer, the cells of these prostate glands mutate into cancer cells. Mutation is majorly in p53 gene, BCL2 and ERK5 or alteration in Akt kinase signaling contribute toward the development of prostate cancer. The prostate glands require hormones, known as androgens that are involved in cell survival and apoptosis. Androgens include testosterone, dehydroepiandrosterone and dihydrotestosterone.

10. Initially, small clumps of cancer cells remain confined to prostate glands, a condition known as carcinoma in situ or prostatic intraepithelial neoplasia (PIN). Over time, these cancer cells begin to multiply and spread to the surrounding prostate tissue forming a tumor. Eventually, the tumor may grow large enough to invade nearby organs such as the nearby lymph nodes or the rectum, or metastasize to bone, lymphatic system and bladder.

11. Risk Factors

12. Clinical Manifestation EARLY STAGE • Asymptomatic • Cancer is in the peripheral zone • LOCALLY ADVANCED DISEASE • Obstructive / irritative voiding  Hesitancy  Intermittent urinary stream  Decreased force of stream --May have growth into the urethra or bladder neck • Retention of urine •Hematuria • Hematospermia • Renal failure • Pelvic pain ADVANCED DISEASE (spread to the regional pelvic lymph nodes) • Edema of the lower extremities • Pelvic and perineal discomfort • METASTATIC DISEASE • Bone pain • Spinal cord compression symptoms • Paraperesis (partial paralysis of both legs)

13. Sign and Symptoms Chronic pain in back, pelvis and hips Weakness and numbness in legs

14. Diagnosis Laboratory – Complete blood cell count, blood biochemistry – Serum PSA (total, free, percentage free) – prostate specific antigen – Plasma acid phosphatases (prostatic/total) • Radiographic imaging – Transrectal ultrasonography (for biopsy guidance) – Biopsy/Needle biopsy of prostate ( transrectal , transperineal ) – Chest radiograph (high risk for metastatic disease) – Computed tomography of pelvis. – Radioisotope bone scan – Magnetic resonance imaging. – PET CT Scan for metastasis in high

15. Abnormal DRE : although correlates poorly with the volume and extent of cancer, an integral part of the algorithm. • Serum PSA : usually > 4 ng/ml With increasing PSA level, chance of getting cancer increases, but less likely to be organ confined. • TRUS guided Biopsy : - Trans-rectal ultrasonography 1) to establish the diagnosis. 2) to report extent and grade of cancer in each core. 3) to document presence of PNI ( perineural invasion ) or ECE (extracapsular extension).

16. PROSTATE SPECIFIC ANTIGEN – Serine protease glycoprotein secreted by prostatic epithelium – Carcinoma specific – Normal : 0.4 - 4 ng/ml (upper limit 2.6 ng/ml) – t1/2 : 2.2― 3.2 ±0.1 days – Mild elevation 4 ― 10 ng/ml – Significant elevation >10 ng/ml – Sensitivity ― 85% – Specificity – 65-70% – Estimated rate of cancer detection by PSA screening ― 1.8- 3.3% – Carcinoma with normal PSA ― 25%

17. Age specific PSA : – Age PSA 40-50 0-2.5 60-70 0-4.5 70-80 0-6.5 Pretreatment serum PSA is also predictive of EPE (extra prostatic extension) and SVI ( seminal vesicle invasion ): PSA Rate of organ-confined disease – 4 -10 ng/ml 53% - 70% 10 -20 ng/ml 31% - 56% Roach’s Probability of ECE, SVI and LNI : The risk of positive seminal vesicles (SV+) was calculated using the equation; SV+ = (PSA) + [10 * {(Gleason score) – 6}]. The risk of positive lymph nodes (LN+) was calculated using the equation; LN+ = (0.667 * (PSA)) + (10 * ((Gleason score) - 6)) The risk of positive capsular penetration (CP+) was calculated using the equation; CP+ = (1.5 * (PSA)) + (10 * ((Gleason score) - 3))

18. Gleason Scores Typical Gleason Scores range from 6-10.  The higher the Gleason Score, the more likely that the cancer will grow and spread quickly. It is recommended that the primary and secondary pattern as well as the score be reported, e.g. Gleason score 3+4=7. • If the tumour only has one pattern, Gleason score is obtained by doubling that pattern, e.g. Gleason score 3+3=6.

19. A score of 7 suggests and intermediate risk for aggressive cancer.  Scoring a 7 means that the primary score (largest section of the tumor) scored a 3 or 4.  Tumors with a primary score of 3 and a secondary score of 4 have a fairly good outlook, whereas cancers with a primary Gleason Score of 4 and a secondary score of 3, are more likely to grow and spread. Scores of 8 or higher describe cancers that are likely to spread more rapidly, these cancers are often referred to as poorly differentiated or high grade.  Scores of 6 or less describe cancer cells that look similar to normal cells and suggest that the cancer is likely to grow slowly.

20. Grading Gleason X:  The Gleason score cannot be determined. Gleason 6 or lower:  The cells are well differentiated, meaning they look similar to healthy cells. Gleason 7:  The cells are moderately differentiated, meaning they look somewhat similar to healthy cells. Gleason 8, 9, or 10:  The cells are poorly differentiated or undifferentiated, meaning they look very different from healthy cells. Gleason scores are often grouped into simplified Grade Groups: Grade Group 1 = Gleason 6 Grade Group 2 = Gleason 3 + 4 = 7 Grade Group 3 = Gleason 4 + 3 = 7 Gleason Group 4 = Gleason 8 Gleason Group 5 = Gleason 9 or 10 Cancer stage grouping

21. Digital Rectal Examination Cornerstone of the physical examination/ instrumental in staging • Sim’s lateral position. – Organ palpation: • Craniocaudal and transverse dimension • Consistency / Mobility • Any firm/ elevated area and its size.

22. Typical finding a prostate- Hard, nodular, asymmetrical, may or may not be raised above the surface of gland and is surrounded by compressible prostatic tissue. – Prostatic induration - BHP nodule/ calculi/ infection/granulomatous prostatitis / infarction – Specificity- 50% and Sensitivity- 70% – Only 25-50% of men with an abnormal DRE have cancer. – DRE + PSA specificity 87%

23. Staging

24. Staging

25. Stage III:  PSA levels are high, the tumor is growing, or the cancer is high grade. These all indicate a locally advanced cancer that is likely to grow and spread. Stage IIIA:  The cancer has spread beyond the outer layer of the prostate into nearby tissues. It may also have spread to the seminal vesicles. The PSA level is high. Stage IIIB:  The tumor has grown outside of the prostate gland and may have invaded nearby structures, such as the bladder or rectum. Stage IIIC:  The cancer cells across the tumor are poorly differentiated, meaning they look very different from healthy cells. Stage IV:  The cancer has spread beyond the prostate. Stage IVA:  The cancer has spread to the regional lymph nodes. Stage IVB:  The cancer has spread to distant lymph nodes, other parts of the body, or to the bones.

26. TRANRECTAL ULTRASONOGRAPHY (TRUS) Most commonly used to perform an  ultrasound -guided needle biopsy evaluation of the prostate gland in men TRUS of the prostate, first described by Wantanabe (1968) • TRUS-guided systematic sextant biopsy protocol by Hodge • Normal adult prostate : Symmetric, triangular, relatively homogenous structure with an echogenic capsule The paired seminal vesicles are positioned posteriorly at the base of the prostate. They have a smooth, saccular appearance and should be symmetrical. Normal SV measures 4.5 to 5.5 cm(l) and 2 cm (w) Hypoechoic mass – PSA 100ng/mL

27. – Sensitivity-66% Specificity- 46% Accuracy- 58% • Seminal vesicle invasion – Echogenic abnormalities – Ant. displacement and enlargement of SV TRUS-directed prostate needle biopsy remains the gold standard for diagnosis of prostate cancer – Guided biopsy of the prostate

28. • Recommendation: TRUS guided Bx in patients with PSA> 4 ng/ml • To establish the diagnosis • To report extent and grade of each core • To document presence of Pelvic LN involvement and ECE – Staging of clinically localized prostate cancer – Guidance during the seed/interstitial brachytherapy – Monitoring prostate cryotherapy – Evaluation and aspiration of prostate abscess – Monitoring the response to prostate cancer treatment

29. Imaging CXR – chest X-ray – Pulmonary metastasis – Miliary pattern • Axial skeletal survey : Specific sites of bony pain – Osteoblastic secondaries • USG abdomen-pelvis:  hydroureteronephrosis - dilatation of the renal pelvis, calyces and ureter  large post void residual urine volume – ≥ 50mL  retroperitoneal lymphadenopathy -  located in a specific part of the abdominal cavity immediately behind the intestine that is closer to backbone  Liver mets.

30. CT Scan Primary role – Size determination of the gland – Assess pelvic LN metastasis – Treatment planning in RT – Extra Prostatic Extension: • Loss of peri-prostatic fat planes • Bladder base deformity • Obliteration of the normal angle b/w the SV and post. aspect of UB – LN involvement • Abnormality in size • Sensitivity 25% • Reserved for patients with higher PSA values (>20-25 ng/ml) • CT guided FNAC

31. MRI Scan Superior to CT in defining prostate apex, NVB (neurovascular bundle) and anterior rectal wall • Better delineation of periprostatic fat involvement – T1w- provides high contrast b/w water density structures i.e. Prostate, SV and fat, NVB, perivesical tissue and LNs – T2w fast spine echo- zonal anatomy, architecture of SV • Ca Prostate: A focal, peripheral region of decreased signal intensity surrounded by a normal(high intensity) peripheral zone • BHP: centrally located nodules of similar signal • Primary staging sensitivity- 69% • Endo-rectal surface coil MRI- accuracy of 54-72% staging the primary and detects SVI and ECE – extra capsular extension

32. Indications: High likelihood of capsular invasion and LN metastasis – Abnormal DRE – PSA>20 – Poorly differentiated ca • Sensitivity to locate gland tumor- 79% and specificity- 55% • LN detection- Low sensitivity but high specificity

33. MRSI – magnetic resonance spectroscopy imaging Improved diagnostic accuracy of MRI both in localizing and staging and risk stratifying patients – Specificity for tumor location (MRI + MRSI) ~ 91%. – Accurate localization of prostate tumors and improved guided biopsy – Combined MRI/MRSI enhances the assessment of both ECE and SVI and capsular breech – Predict tumor aggressiveness – Distinguishing b/w tumor and post biopsy hemorrhage – Detect residual cancer following t/t and follow-up – Development of more focused therapy

34. 99 Tc BONE SCAN • Clinically apparent metastatic disease limited to bone in 80-85% of patients of metastatic ca prostate • Osteoblastic secondaries • Most common sites of metastasis – Vertebral column- 74% – Ribs- 70% Indications Pre-therapy – Early stage disease-T1-T2 with • PSA > 20 ng / ml • GS≥ 8 • Bony pain – T3-T4 –Symptomatic patients – High grade tumor

35. Treatment 1. Prostatectomy: Removal of Prostate gland.   2. Radiotherapy : External Beam Radiotherapy: Radiation directed towards the whole pelvis externally. Brachytherapy (radioactive seeds): Tiny radioactive seeds are placed in the body close to tumor. 3 . Hormone Therapy : The goal is to reduce levels of hormones, called androgens, in the body, or to prevent them from reaching prostate cancer cells. There are different types of drugs that lower testosterone levels. Luteinising Hormone (LH) Blockers : Luteinising hormone blockers stop the pituitary gland making the hormone. So the testicles don't receive the message telling them to make testosterone.

36. Chemotherapy Chemotherapy is sometimes used if prostate cancer has spread outside the prostate gland and hormone therapy isn't working. For prostate cancer, chemo drugs are typically used one at a time. Some of the chemo drugs used to treat prostate cancer include: Docetaxel Cabazitaxel

37. Doxorubicin Etoposide Vinblastine Paclitaxel Carboplatin In most cases, the first chemo drug given is docetaxel, combined with the steroid drug prednisone. If this drug does not work (or stops working), a newer drug called cabazitaxel is given specially in cases when cancer has stopped responding to hormone therapy and chemotherapy.

38. Principles of Radiation Therapy (PROS-C) External Beam Radiation Therapy External beam radiation therapy (RT) is one of the principle treatment options for clinically localized prostate cancer. A dose of 75.6-79 Gy in to the prostate (with or without seminal vesicles) is appropriate for patients with low-risk cancers. Intermediate-risk and high-risk patients should receive doses between 75 and 80 Gy. For higher doses (above 75 Gy), daily prostate localization using daily image-guided radiation therapy (IGRT) is essential for target margin reduction and treatment accuracy.

39. Brachytherapy Brachytherapy involves plaCing radioactive sources into the prostate tissue. Most centers use permanent implants, where the sources are implanted into the prostate and gradually lose their radioactivity. Prostate brachytherapy as monotherapy has become a popular treatment option for early, clinically organ-confined prostate cancer (cT1c-T2a, Gleason grade 2-6, PSA < 10 ng/mL).

40. Proton Therapy Proton beams can be used as an alternative radiation source. Theoretically, protons may reach deeply-located tumors with less damage to surrounding tissues. Palliative Radiation Is an effective means of palliating bone metastases from prostate cancer. A short course of 800 cGy x 1 is as effective and less costly than 3000 cGy in 10 fractions. Most patients should be managed with a single fraction of 800 cGy for non-vertebral metastases based on therapeutic guidelines from the American College of Radiology

41. Sipuleucel -T ( Provenge ®) is a cancer vaccine used to treat advanced prostate cancer. Most vaccines are designed to prevent diseases, but this vaccine is aimed at treating prostate cancer, not preventing it. This vaccine is not mass produced. It has to be made special for each patient from his own blood cells. To make it, white blood cells are removed from the patient's blood and sent to a lab, where they are exposed to a certain protein from prostate cancer cells. These cells are given back to the patient into a vein (IV). Vaccination

42. Prevention

43. Any Question Special thanks to Prof Dr Hamid Saeed for graciously allowing the use of their insightful PowerPoint slides