What’s new in PCA... Steven Joniau University Hospitals Leuven, Belgium EAU Guidelines 2010 update

PCA Guideline Panel Axel Heidenreich (Chairman) UrologyGermany Joacqim BellmuntMedical OncologySpain Michel BollaRadiation OncologyFrance Steven JoniauUrologyBelgium Theodor van der KwastPathologyCanada Malcom MasonRadiation OncologyUK Veseled MatveevUrologyRussia Nicolas MottetUrologyFrance Hans Peter SchmidUrologySwitzerland Thomas WiegelRadiation OncologyGermany Francesco ZattoniUrologyItaly

Screening Schröder et al. New Engl J Med 2009 Andriole et al. New Engl J Med 2009 Risk reduction 27% Numbers needed to screen 1410 Numbers needed to treat 48 No significant difference

Screening Risk adapted early detection

Active Surveillance close follow-up examinations under strict rules of guidelines Purpose: Identification & treatment of significant PCA, curative intent Watchful Waiting withhold treatment until development of disease- specific symptoms Purpose: symptom-based therapy, palliative intent

Active Surveillance: why? Because it avoids overtreatment with insignificant or slowly proliferating prostate cancer avoids unnecessary impairment of quality of life Is a viable alternative for elderly and co morbid patients who harbour a higher mortality risk from non-cancer specific causes

Active Surveillance Inclusion Criteria PSA ≤ 10 ng/ml Biopsy Gleason Score ≤ 6 ≤ 2 positive biopsies ≤ 50% cancer per biopsy cT1c – cT2a Intervention required Biopsy Gleason Score > 6 PSA-DT < 3 years cancer volume  patient’s preference

Adjuvant Radiation Therapy Bolla et al. EORTC 22911: 60 Gy vs Wait-and-See pT3a, pT3b, pTxpR1 independent on postop. PSA Wiegel et al. ARO 96-02: 60 Gy vs Wait-and-See pT3a-bpN0, PSA negative ! Swanson et al. SWOG 8794: Gy vs Wait-and-See pT3a, pT3b, pTxpR1 independent on postop. PSA

Adjuvant Radiation Therapy RadiationW & S R076.2%67.4% R177.6%48.5%* R0 + RadR1 + Rad HR Benefit88/ /1000 EORTC 22911

Adjuvant Radiation Therapy 72% 54% ARO/AUO – German Study

Adjuvant Radiation Therapy ARO/AUO – German Study 5 year F-up: 25% benefit for progression-free survival pT3aR1

SWOG 8794 Survellance adj. Radiation Adjuvant Radiation Therapy

SWOG 8794 Wait-and-SeeRadiation PSA≤ – 1.0≤ – 1.0 PSA  59%23%77%34% Local relapse 20%25%7%9% Metastases12%16%4%12% Adjuvant Radiation Therapy

Intermittend Androgen Deprivation Cyclic therapy On-treatment period Off-treatment period IHT aims to Minimise adverse events / improve quality of life (QoL) Delay progression to hormone resistant Pca Reduce costs of care

Intermittend Androgen Deprivation TrialPopulation# patients randomised NCIC/PR7PSA relapse after RT±300 EC 507PSA relapse after RP201 ICELANDPSA relapse/locally advanced±700 SEUGAdvanced PCa626 JapanLocally advanced188 AP 17/95Advanced PCa and M+335 SWOG 9346M+ PCa (PSA > 5 ng/mL)1,345 EC 210M+ PCa (PSA > 20 ng/mL)194 EuropeAdvanced PCa (90% T3)914

Intermittend Androgen Deprivation Calais da Silva FEC et al. ; Eur Urol 2009

Intermittend Androgen Deprivation EC507: IHT does not affect progression-free survival Tunn U. BJU Int 2007;99(Suppl 1)

Intermittend Androgen Deprivation

Follow-up: local

Follow-up: ADT

CAVE: Diabetes mellitus Metabolic Syndrom Cholesterine, Triglyceride Cholesterine/HDL - Ratio Follow-up: cancer specific: PSA, T endocrinologic metabolic cardiovascular