1. Prostate cancer -what is important and what is new - Anette Hylen Ranhoff, MD PhD Ullevaal University Hospital Oslo Norway

2. Prostate cancer – epidemiology the old man’s cancer Increase of clinical and subclinical cases with increasing age –5/100 000 at 60 yrs –70/100 000 at 85 yrs –In autopsies: 80 % of men at 85+ yrs have foci of invasive PC Second most frequent cancer in men (after skin cancer) Second leading cause of cancer- death in men > 50 yrs (after lung cancer) More PC patients dies from other causes than from their PC More common among black in USA Incidence pr. 1 000 000 men (USA)

3. Etiology a hormon depended cancer Life style Environmetal Genetic 5-10 % Dominant Early onset PC-gene: HPC1 Diet Exercise Sexual activity Contaminated food and drinking water Susceptibility of male Androgen receptors  response and  prostate cancer  response and  prostate cancer Environmental oestrogens (DDT, PCB) agrichemicals Fat: high risk Antiox.: low risk Exercise: low risk

5. Screening for prostate cancer Digital rectal examination –Sensitivity: 55-69 % –Specificity: 89-97 % PSA: prostate specific antigen (prostate-spesific – not cancer spesific) –Sensitivity: 75-78 % –Specificity: 40 % Novel proetomic tests (protein pattern) J Nat Cancer Inst, 2002;94:1576-8. –95 % of cases of PC correctly identified –Sensitivity 71 %

6. No consensus about whom to screen, when to screen and what to do if cancer is discovered Gambert SR, Geriatrics Jan 2001 Rationale: When detected and treated early – the disease can be cured Useful for families with heriditary PC Not proven that screening reduces mortality ! High number of false positives –Anxiety –Risk of complications to biopsy-taking Many men treated unnecessary with reduced quality of life

8. Algoritm for early detection of prostate cancer Am Urol Ass, Oncology 2000;14:267-86 Candidates for early detection testing Men 50+ yrs Life exp. >10 yrs Afroamerican 40+ yrs PSA and DRE One or both tests abnormal Both tests normal Possible PC, BPH, prostatitis Return regularly for PSA and DRE For diagnosis: biopsiBiopsi negative

9. Diagnosis of prostate cancer Digital rectal examination PSA –<10 is non-spesific –good guide to disease stage Transrectal Ultrasond –Normal does not exclude PC –Guide to biopsy MRI –Localization and distribution of cancer Biopsi –Negative in ¼ of men with PC Assessment for metastasis –Ultrasond, X-ray, CT and MRI –Scintigrafic bone assessment Confirm the diagnosis Localization and distribution: –TNM Histology: –Type of neoplasm –Grading

10. Staging of prostate cancer TNM –Tumor localization and distribution –Nodes –Metastases Gleason system: Histology: glandular architecture –1: close to normal –2-4: well differentiated –5-7: moderate diff. –8-10: poorly diff.

11. Treatment of potentially curable disease – localized disease a controversal matter – particularly in the elderly Watchful waiting Radical prostatectomi (+/- neoadjuvant therapy) –laprascopic –open Radiation therapy (+/- neoadjuvant and adjuvant therapy) –External –Interstitial (brachytherapy) Hormonal therapy –Neoadjuvant therapy with GnRH antagonist (Zoladex) and antiandrogens (Androcur) before surgery and as supplement to radiation therapy (T2/3, N0/X) –Adjuvant therapy with LHRH analog (Procren) after radiation therapy and antiandrogens (T2 and T3, G3 tumor)

12. To treat or not to treat Risk for progressing disease (TNM, grading) Age and life expectancy Quality of life –Adverse effects of treatment (incontinence, sexual dysfunction, osteoporosis) –Symptoms of progressing disease –Psychological factors

13. Palliative care of metastatic disease: to slow progression and releave symptoms First line treatment is castration: Chemical: LHRH analog (+/- antiandrogen) Surgical: Testicular ablation Limited metastasis or isolated elevation of PSA: Antiandrogen monotherapy Hormone-refractory cancer Chemotherapy is not standard treatment, but assessment for trials when hormonresistant metastatic disease Bisfosfonates: experimental, but experience of effect on bone pain

14. New perspectives Better knowledge about etiology of Prostate Cancer can make prevention possible New and better tests for screening Selection for screening from genetic susceptibility More effective treatment with less side effects - to improve quality of life Better palliative therapy: –Bisfosfonates –Radiation

15. Key points Hormon depended cancer and the most important cancer in old men Many undiagnosed cases with unknown disease progression Genetic predisposition and exogenous disposure Screening with PSA and DRE, but no consensus when to screen, whom to screen and what to do if cancer is discovered Palliative treatment most important in old men (75+)

16. References Dearnaley DP, Kirby RS, Kirk D, Malone P, Simpson RJ, Williams G. Diagnosis and management of early prostate cancer. Report of a British Association of Urological Surgeons Working Party. BJU int 1999; 83:18-33. Gambert SR. When to offer screening in the primary care setting. Geriatrics 2001;56:22-31 Kirk D. (ed.): International handbook of prostate cancer, 2nd edition. 2002 Kirby RS, Christmas TJ, Brawer M. Prostate cancer. Mosby, London 1996. Kirk D. Prostate cancer in the elderly. Eur J Surg Oncol 1998;24:379- 83. Martin GE. The paradoxes of longevity. Springer-Verlag Ed. Berlin 1999.