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Prostate cancer -what is important and what is new Anette Hylen Ranhoff, MD PhD Ullevaal University Hospital Oslo Norway 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 cancerdeath 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) Etiology a hormon depended cancer Genetic 5-10 % Dominant Early onset PC-gene: HPC1 Susceptibility of male Androgen receptors response and prostate cancer response and prostate cancer Life style Diet Exercise Sexual activity Fat: high risk Antiox.: low risk Exercise: low risk Environmetal Contaminated food and drinking water Environmental oestrogens (DDT, PCB) agrichemicals 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 % 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 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: biopsi Biopsi negative 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 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. 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) 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 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 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 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+) 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;24:37983. • Martin GE. The paradoxes of longevity. Springer-Verlag Ed. Berlin 1999.