1. Prostate cancer As. MUDr. Jan Pokorný, FEBU Head: Doc. MUDr. Robert Grill, Ph.D. Vice-head: As. MUDr. Lukáš Bittner, FEBU Urologická klinika 3. LF UK a FNKV

2. Prostate cancer Epidemiology:  Incidence: ČR 80/100 000 USA 120/100 000  Mortality: ČR 15/100 000

3. Prostate cancer Epidemiology: ČR

4. Prostate cancer Epidemiology: Prostate cancer: EU – 2 nd in men mortality for cancer (1 st lung cancer) USA – 1 st in men mortality for cancer

5. Prostate cancer Epidemiology:  Risk factors: Increasing age, race (afroamericans), heredity  Exogenous factors: Diete, UV radiation, alcohol consumption, risk sexual behavior, infection (HPV?)

6. Prostate cancer Epidemiology:  Increasing age: The prostate cancer incidence in per cent generaly correlates to the patient´s age

7. Prostate cancer Epidemiology: Basic check-up: Discussion about the mass screening  Expenses  Unapparent (asymptomatic) tumors treatment

8. Prostate cancer Epidemiology: Basic check-up: Recommended:  Screening in risk population – positive family history  Positive clinical symptoms  In patients who actively visit doctor and ask for check-up

9. Prostate cancer Epidemiology: Basic check-up: Recommended:  Digital rectal examination in all men in all time  PSA only in recommended case (previous slide)

10. Prostate cancer Epidemiology: Basic check-up: Recommended:  Start PSA test between 45-50 years  Start PSA test in the positive family history case between 40-45 years

11. Prostate cancer Epidemiology: Basic check-up: Recommended: In patient unfit for treatment (age, co-morbidity, weak life prognosis) there is NO INDICATION FOR PSA TESTING !!!

12. Prostate cancer Diagnosis: Basic exams:  Digital rectal exam (DRE)  Prostate specific antigen (PSA)

13. Prostate cancer Diagnosis: DRE:

14. Prostate cancer Diagnosis: DRE:  Prostate shape, volume, consistence, demarcation  Semen vesicules examination  Bimanual palpation (in anesthesia)

15. Prostate cancer Diagnosis: DRE:  95 % of cancer originates from the peripheral zone of prostate  Suitable for palpation

16. Prostate cancer Diagnosis: Prostate specific antigen (PSA):  33 kD molecular weigh glycoprotein (Proteases enzyme)  Gene in 19 th chromosome  Half-life period 3-5 days

17. Prostate cancer Diagnosis: Prostate specific antigen (PSA):  Produced almost exclusively by the epithelial cells of the prostate  Prostate-specific marker, no cancer-specific  High sperm concentration

18. Prostate cancer Diagnosis: Prostate specific antigen (PSA):  Venous blood sample  The exact cut-off level of what is considered to be a normal PSA value has yet to be determined  Generally used cut-off level: 4-4.2 ng/ml  Values of approximately < 2-3 ng/ml are often used for younger men

19. Prostate cancer Diagnosis: Prostate cancer diagnosis:  PSA elevation or DRE suspicion  Prostate biopsy – Transrectal USG (TRUS biopsy)  PCA3 (Prostate Cancer Antigen 3)

20. Prostate cancer Diagnosis: TRUS prostate biopsy:  Prostate morphology  Peripheral zone biopsy  Min. of 12 samples, according to prostate volume correction  In case of negative first biopsy repet one is needed

21. Prostate cancer Diagnosis: TRUS prostate biopsy: Biopsy gun

22. Prostate cancer Diagnosis: Prostate Cancer Antigen 3 (PCA3):  Genetic marker  Cancer - specific  Urine sampled after DRE  Additional test, no standard

23. Prostate cancer Diagnosis: Prostate Cancer Antigen 3 (PCA3): Indications:  PSA elevation and negative prostate biopsy  Decision on re-biopsy  No treatment in PCA3 elevation only

24. Prostate cancer Diagnosis: Prostate Cancer Antigen 3 (PCA3):  Some studies present the PCA3 level and Gleason Score correlation (tumor aggressiveness)

25. Prostate cancer Diagnosis: Morphology: Histological types:  Acinar adenocarcinoma  Papilar (ductal) carcinoma  Small cell carcinoma  Ring cell carcinoma  Sarcomatoid carcinoma (No PSA production)

26. Prostate cancer Diagnosis: Grading: Gleason grade

27. Prostate cancer Diagnosis: Grading: Gleason score:  The Gleason score is the sum of the most dominant and second most dominant (in terms of volume) Gleason grade. If only one grade is present, the primary grade is doubled.  Examples include: GS 2+2, GS 3+4, GS 4+3 etc.

28. Prostate cancer Diagnosis: Grading:  Gleason scoce correlates to the tumor dedifferentiation (aggressiveness)

29. Prostate cancer Diagnosis: Staging:  DRE  TRUS  CT scan and bone scan in PSA value > 20 ng/ml (in case of GS ≥ 7 even in PSA value > 10 ng/ml)  MRI

30. Prostate cancer Diagnosis: Staging: TNM classification:  T1 – Clinically unapparent tumour not palpable or visible by imaging  T2 – Tumour confined within the prostate  T3 – Tumour extends through the prostatic capsule  T4 – Tumour is fixed or invades adjacent structures other than seminal vesicles

31. Prostate cancer Diagnosis: Staging: TNM classification:  N1 – Lymph nodes involvement  M1 – Distant metastases (non-regional lymph nodes, bones, liver, lungs)

32. Prostate cancer Diagnosis: Staging:

33. Prostate cancer Diagnosis: Staging:

34. Prostate cancer Diagnosis: Prognotic factors:  Gleason score (Tumor aggressiveness)  PSA level  Age and biological condition

35. Prostate cancer Treatment: Localised prostate cancer (T1-T2):  Watchful Waiting / Active Monitoring  Surgery – Radical Prostatectomy  Radiation therapy (Tele, Brachy)  Experimental – Kryosurgery, HIFU ( High Intensity Focused Ultrasound)

36. Prostate cancer Treatment: Watchful waiting (WW):  Deferred treatment  Treatment starts in case of clinical symptoms developement  No cure intention  Suitable for patients with shorter life expectancy

37. Prostate cancer Treatment: Active surveillance or monitoring (AS):  Deferred treatment with cure intention  Active monitoring of tumor activity (PSA, repet TRUS biopsy – progression of number of positive samples, Gleason Score progression etc.)  Treatment starts at the moment of progression  Well-informed patient only

38. Prostate cancer Treatment: Radical prostatectomy:  Complete prostate, prostate capsule, vesicles and prostate part of urethra removal  Lymphadenectomy only in indicated cases

39. Prostate cancer Treatment: Radical prostatectomy:  Retropubic access  Open surgery  Laparoscopy  Robot - assisted

40. Prostate cancer Treatment: Radical prostatectomy:  T1-2 stages  „Younger“ patients – life expectancy > 10 years

41. Prostate cancer Treatment: Radical radiation therapy: Teleradiotherapy:  External beam of radiation of prostate, vesicles and surrounding tissues, in special cases of regional lymph nodes

42. Prostate cancer Treatment: Teleradiotherapy:  Linear accelerators  Three-dimensional conformal radiotherapy (3D- CRT) and intensity modulated external beam radiotherapy (IMRT)  Dose escalation  Adverse events minimalization

43. Prostate cancer Treatment: Teleradiotherapy: Innovative techniques:  Proton beam accelerators  Carbon ion beam accelerators

44. Prostate cancer Treatment: Teleradiotherapy:  T1-2 stages and no plan of radical prostatectomy  T3-T4, N1 stages

45. Prostate cancer Treatment: Transperineal Brachytherapy:  Effective technique in T1-2 stages, PSA ≤ 10 ng/ml, GS ≤ 6 and prostate volume ≤ 50-60 ml

46. Prostate cancer Treatment: Transperineal Brachytherapy:  Transperineal access, USG guided technique  Permanent radioactive implats application (Palladium-103)

47. Prostate cancer Treatment: Transperineal Brachytherapy:  Local anesthesia only  One-shot application

48. Prostate cancer Treatment: Local advanced prostate cancer (T3-T4, N1):  Watchful waiting  Radiation therapy (Teleradiotherapy)

49. Prostate cancer Treatment: Metastatis prostate cancer:  Watchful waiting  Hormonal therapy  Chemotherapy  Palliative therapy

50. Prostate cancer Treatment: Hormonal therapy:  Stage M1 Endogeneous androgen production:  Testicles 90 – 95 %  Adrenal glands 5 – 10 %

51. Prostate cancer Treatment: Hormonal therapy: Testosterone is essential for the prostate tissue growth and prostate cancer growth as well http://www.oncoprof.net

52. Prostate cancer Treatment: Hormonal therapy:  LHRH analogs – central blocade  Antinadrogens – peripheral blocade  Ketokonazole – adrenal production blocade  Surgical– bilateral orchiectomy  Combinations

53. Prostate cancer Treatment: Chemotherapy:  Taxans – Docetaxel, Cabazitaxel  Estramustin Treatment of relapse after hormonal therapy in stage M1

54. Prostate cancer Treatment: Palliative therapeutic options: Bone metastases: (Bone resorption inactivation)  Bisphosphonates  Denosumab Painful bone metastases – i.v. aplication of radionuclides (Stroncium)

55. Prostate cancer Treatment: Palliative therapeutic options: Urinaty retention:  TURP (Transurethral Prostate Resection)  Urethral catheter, epicystostomia  Ureteral stents  Nephrostomy tube

56. Prostate cancer Treatment: Palliative therapeutic options:  Opoids  Blood supplementation  Corticosteroids  Surgical treatment of pathological bone fractures and vertebral compression

57. Prostate cancer Follow-up : Basic periodic exam.:  PSA  DRE

58. Prostate cancer Follow-up : PSA elevation - restaging  CT  Bone scan

59. Prostate cancer Follow-up : In special cases:  PET – CT  MRI

60. Prostate cancer Prognosis:  Generally excellent (in T1-N1 stage generally complete cure)  Majority of patients in M1 stage survive years!  Prognosis estimation: Entering Gleason score, PSA, biological condition

61. Prostate cancer Contact: jan.pokorny@fnkv.cz