Prostate cancer treatment in localised prostate cancer

Prostate cancer treatment in localised prostate cancer Renske Postma Prostate cancer • • • • • Most common non-cutaneous cancer > 50 years; incidence is highest in men > 75 years life time risk 1 in 6 men in USA prostate cancer is a slow growing cancer Screening for prostate cancer • PSA screening is recommended by the AUA in men 50 years and older and in men at high risk (i.e. African-American, positive family history) • Introduction of PSA led to increase in prostate cancer incidence PSA testing • To date no evidence of randomised clinical trials that prostate cancer mortality is lowered due to PSA screening • Lower stage and grade due to introduction of PSA screening • Lead time Jemal cancer statistics 2006, USA Treatment of localised prostate cancer • • • • • Surgery radiotherapy hormone therapy active surveillance other Radical prostatectomy • Advantages: -full pathologic assessment of the tumour (Gleason grading, staging, resection margins) -PSA measurement -curative Radical prostatectomy • Disadvantages - long operation time (complications) - comorbidity - side effects urinary leakage impotence Laparoscopic (LRP) vs. open radical prostatectomy (RRP) • Less invasive (hospital stay, postoperative pain, intra-operative bleeding are improved, less blood transfusions) • oncologic and surgical margins comparable • urinary incontinence comparable and erectile dysfunction (hard to compare) • biochemical recurrence is comparable Disadvantages laparoscopic prostatectomy • Higher urethral complications compared to open radical prostatectomy • steep learning curve Laparoscopic radical prostatectomy vs. Robotic-assisted laparoscopic prostatectomy • The limited follow-up available do not provide long-term functional data • Rapid recovery of continence and potency • Robotic prostatectomy has a short learning curve • promise of shorter operative time • Joseph et al reported similar percentages of positive surgical margins, comparing robotic assisted with laparoscopic prostatectomy Disadvantages robotic laparoscopic prostatectomy • high costs (purchase and maintenance) • limited to a few academic centres Radiotherapy:External beam radiotherapy • advantages -no anaesthesia, postoperative complications -no in-hospital stay -can be used despite extensive co-morbidity -curative External beam radiotherapy • Disadvantages -recruitment by clinical staging -posttreatment monitoring difficult side effects -urinary incontinence, bother -bowel complications -erectile dysfunction brachytherapy • Implantation of radioactive seeds • advantages -effective dose planning -low patient morbidity -favourable long-term PSA outcomes. brachytherapy • disadvantages -urinary toxicity -PSA monitoring Hormone therapy • Well known in metastatic disease • survival benefit of adjuvant therapy for radiation therapy for high-risk localised disease. Rationale for active surveillance • side-effects of radical prostatectomy and radiotherapy • natural slow course of prostate cancer • lead time • overdiagnosis • ethical aspects and costs Active surveillance • Definition: selected men are managed expectantly with the intention to apply curative treatment if signs of progression occur Recent* Prostate-Specific Antigen (PSA) Test Prevalence (%), by Educational Attainment and Health Insurance Status, Men 50 Years and Older, US, 2001-2004 70 60 Prevalence (%) 58 2001 55 52 46 42 39 2002 2004 50 40 30 20 10 0 Total 30 28 25 Less than a high school education No health insurance *A prostate-specific antigen (PSA) test within the past year. Source: Behavioral Risk Factor Surveillance System Public Use Data Tape (2001, 2002, 2004), National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 2002, 2003, 2005. PSA testing 2001/2005 in the Netherlands PSA testing Clinical stage 1st screening round (%) n=1014 2nd screening round (%) n=550 Control group (%) n=373 T1c T2 T3-4 35.3 45.6 18.5 61.1 34.7 0.7 25.2 24.1 25.4 PSA testing Gleason score 1st screening round (%) n=1014 2nd Control screening group (%)* round (%) n=373 n=550 <7 7 >7 63.8 27.4 8.1 79.3 17.5 3.2 0 41.0 33.8 5.2 na unknown 0.7 * TURP and cystoprostatectomy excluded (n=54) Five-year Relative Survival (%) during Three Time Periods By Cancer Site Site 1974-1976 1983-1985 1995-2001 • All sites • Breast (female) • Colon • Leukaemia • Lung and bronchus • Melanoma • Non-Hodgkin lymphoma • Ovary • Pancreas • Prostate • Rectum • Urinary bladder 50 75 50 34 12 80 47 37 3 67 49 73 53 78 58 41 14 85 54 41 3 75 55 78 65 88 64 48 15 92 † 60 45 5 100 65 82 Active surveillance • Advantages -no side effects -almost no complications -prevent overtreatment -deferred (curative) treatment possible Active surveillance • disadvantages -psychological effect -unsuspected fast growing beyond cure -No test to distinguish between indolent and aggressive prostate cancer Active surveillance • Eligibility criteria • monitoring disease • definitions of disease progression and cutoff points for deferred treatment Active surveillance: eligibility criteria • • • • • • PSA-level at diagnosis <= 10 ng/mL PSA density (PSA D) less than 0.2 ng/ml/cc Clinical stage T1C or T2 Appropriate biopsy sampling Gleason score 3+3=6 (or less) One or 2 biopsy cores invaded with prostate cancer • Participants must be willing to attend the followup visits Active surveillance: monitoring disease and continuation criteria • PSA test (every 3 months) / PSA (kinetics) • DRE (every 6 months) • Biopsy (every 1,4,7, and 10 years, according to biopsy scheme) • Patient content to continue active surveillance Randomised clinical trial (holmberg et al NEJM 2002 and 2005) • Radical prostatectomy vs. Watchful waiting n=695 • Localized prostate cancer T1-T2 • Well-moderately differentiated tumour • Negative bone scan • PSA <50 ng/ml • Follow-up was monitored by clinical examination, lab. tests and bone scan Prospective trial watchful waiting (Johansson et al. JAMA 1997 and . 2004) • • • • • • 223 men where selected Population-based, cohort study Observation time 21 years Stage: (T0-T2 NX M0 classification) No screening performed Folow-up was monitored by clinical examination, lab. tests and bone scan • Patients with tumour progression were hormonally treated Trial Johansson et al. Cause-Specific Survival by Stage of Disease and Tumour Grade at Diagnosis Johansson, J.-E. et al. JAMA 2004;291:2713-2719. Copyright restrictions may apply. 20-year outcomes following conservative management of clinically localized prostate cancer (Albertsen et al. JAMA, 2005) • • • • retrospective population-based cohort study 55-74 years (n=767) clinically localized prostate cancer TURP, open prostatectomy, needle biopsy of the prostate, other • Gleason score was used • Median Observation period was 24 years Survival and Cumulative Mortality From Prostate Cancer and Other Causes Up to 20 Years After Diagnosis, Stratified by Age at Diagnosis and Gleason Score Albertsen, P. C. et al. JAMA 2005;293:2095-2101. Copyright restrictions may apply. Dicussion Holmberg, Johansson, Albertsen • Men with Gleason high grade Gleason pattern 4 and 5 included • The prostate cancer survival in both studies is high after a 15 years follow up • These studies are performed before PSA era • monitoring disease was more difficult in that days • deferred curative treatment was not given Active surveillance might be safe • Long lead time of prostate cancer • low-grade and low stage prostate cancers are diagnosed • low progression rates and high survival rates in low-grade prostate cancer • better disease monitoring • curative treatment possible Conclusions • An increasing number of prostate cancers is detected due trough PSA screening • an increasing number of prostate cancers is staged in lower stage and grade • The lead time afforded by PSA screening is is 1015 years. • overdiagnosis of prostate cancer • Due to overdiagnosis, there is a risk of overtreatment Conclusions • No randomised clinical trials for prostate cancer treatments • Due to overtreatment active surveillance is a safe and ethical treatment in men with eligible selection criteria • However, there is still no marker for aggressive prostate cancer and active surveillance needs to be carried out with care Acknowledgements • • • • Prof. dr. F.H. Schröder Prof. dr. Th.H. van der Kwast Prof. dr. C.H. Bangma All members of the ERSPC (stijn roemeling and monique Roobol)