Localized Prostate Cancer Have we finally got it right? Shingai Mutambirwa Professor & Chair-Division Urology DGMAH & SMU Pretoria SOUTH AFRICA ESMO Cape Town 14 Feb 2018
Disclosures Advisory boards/lecturer/consultant- Aspen Astellas Astra-Zeneca Bayer Ferring Lilly Pfizer Sanofi
The male reproductive system Vas deferens Urethra Urinary bladder Seminal vesicle Prostate Rectum Penis Testicle Epididymis Scrotum
Incidence of cancer in males Prostate Lung Colorectal Bladder Kidney-renal Mouth Pharynx Stomach Percentage incidence of cancer in males.
Predicted increase in incidence n over 65 years. PROBABLY 50% DON T NEED TREATMENT!
Worldwide variation in prostate cancer incidence rates US Black 102 US White 60 Sweden Norway Switzerland 40 44 50 UK 23 Japan India China 7 1.2 6.6 0 20 40 60 80 100 120 Rates per 100,000 population
Diagnosis Diagnosis of prostate cancer The diagnosis of prostate cancer may comprise three steps, incorporating a range of diagnostic and imaging tests Early detection of prostate cancer is performed through DRE and PSA testing TRUS-guided prostate biopsy is performed to confirm the diagnosis and grade the tumour Imaging studies CT, MRI and radionuclide bone scan may be conducted if metastases are suspected CT=computed tomography; DRE=digital rectal examination; MRI=magnetic resonance imaging; PSA=prostate-specific antigen; TRUS=transrectal ultrasound. American Cancer Society. http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-diagnosis. Last accessed June 2014. 9
Rate per 100,000 Impact of PSA screening on incidence and mortality Epidemiology 250 200 Change in prostate cancer incidence and mortality in the USA Incidence The introduction of PSA screening in the early 1990s has led to a rise in the detection of prostate cancer across Europe, particularly among men aged <75 years 1,2 150 This was most significant in the USA which had the highest uptake of screening 1,2 100 50 Mortality Prostate cancer-related mortality has declined since the 1990s, with the exception of Eastern European countries, although the role of PSA testing in this trend has not been confirmed 2,3 0 1975 1980 1985 1990 1995 2000 2005 Year PSA=prostate-specific antigen. 1. Wolf AMD, et al. CA Can J Clin 2010;60:70 98. 2. Neppl-Huber C, et al. Ann Oncol 2012;23:1325 34. 3. SEER PSA Testing. Available from: http://seer.cancer.gov/studies/surveillance/study6.html. Last accessed January 2013. 10
Diagnosis Prostate biopsy Transrectal TRUS or a transperineal laterally-directed core biopsy is the standard way to obtain material for histopathology 1 A 10 12 core systematic biopsy targeting the far lateral aspect of the peripheral zone is standard practice for initial biopsy 2 The transrectal approach has limitations in sampling the anterior regions of the gland 2 The transperineal approach employing a mapping scheme, allows for more accurate sampling of the entire gland 2 MRI-guided biopsy may be used to investigate anterior located prostate cancer 1 Saturation biopsy is the preferred option after initial negative sampling 2 Transperineal MRI=magnetic resonance imaging; TRUS=TransRectal UltraSound. 1. Heidenreich A, et al. Eur Urol 2011:59;61 71. 2. Dominguez-Escrig JL, et al. Prostate Cancer 2011;2011:386207. 13
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Clinical staging N+ N1-N3 Nx = loco-regional lymph nodes cannot be evaluated N0 = no lymph node involvement = regional lymph metastasis = no metastasis can be evaluated M0 = no distant metastasis M+Mx M1 = distant metastasis present 1a = lymph nodes other than regional nodes 1 b = skeletal 1c = other sites D3 Resistant to hormonal therapy
Characterising the tumour Imaging techniques Radionuclide bone scan Used to determine spread of prostate cancer to the bones A small amount of radioactive material is injected into a vein and settles in damaged areas of bone, viewed as hot spots on the skeleton Hot spots are suggestive of cancer in the bone, but may also arise due to arthritis or other bone diseases The detection of possible cancer needs to be confirmed with other imaging tests such as X-rays, CT or MRI scans Please see Module 3: CRPC and its treatment for further information on metastatic spread CT=computed tomography; MRI=magnetic resonance imaging. ACS prostate cancer: Detailed guide. Available from: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostatecancer-diagnosis. Last accessed June 2014. 20
Characterising the tumour Imaging techniques Computed tomography Combines X-rays and computer technology to give images of the soft tissues and bones in the body 1 Can determine spread of cancer into the lymph nodes, or other organs/structures 1 Not as useful as MRI for looking at the prostate gland itself 1 With addition of a radionucleotide tracer, PET-CT is the preferred technique for recurrence detection 2 MRI/diffusion-weighted MRI Uses radio waves and strong magnets instead of X-rays to produce 3D images of the prostate and show whether the cancer has spread to nearby structures 1 MRI is the most accurate technique for staging cancer 2 Diffusion-weighted MRI detects free water diffusion: the greater the density of tissues, e.g. tumours, the more water restriction 2 CT=computed tomography; MRI=magnetic resonance imaging; PET=positron emission tomography. 1. ACS prostate cancer: Detailed guide. Available from: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostatecancer-diagnosis. Last accessed June 2014. 2. Mayans AR, et al. Arch Esp Urol 2011;64:746 64. 21
Treatment Options Localised Active Surveillence Curative Prostatectomy Radiotherapy HIFU/Cryo? Hormonal therapy? Locally advanced Watchful waiting Local control Hormonal therapy Radiotherapy Combinations Metastatic Palliation - Hormonal therapy
Androgens & the prostate gland
Radical Prostatectomy- Retropubic,Perineal,Laparoscopic or Robotic?
Radiotherapy Alternative to radical prostatectomy EBRT (external beam radiation therapy) Old EBRT(<70Gry) vs Conformal radiation therapy(up to 80Gry) Neo-adjuvant hormonal? Brachytherapy (permanent vs temporary?) Radioactive Iodine or Palladium seeds(mixed?) Higher levels of radiation than EBRT(BED 160+) Fewer rectal & bladder side effects? Sandwich Therapy
Radical prostatectomy for localised/ locally advanced prostate cancer % patients progressionfree 100 90 80 p<0.0001 p=0.001 70 60 50 40 30 20 10 0 Localised Focal capsular penetration Established capsular penetration Seminal vesicle invasion Lymph node metastases Epstein et al 1996
Focal therapy?
Conclusion Today 170 000 new cases/year in the US, 343 000 in Europe 70 % undergo radical treatment 20% have active surveillance which can be stressful Around 35% patient have overtreatment: they are the target for focal therapy Active Surveillance Focal treatment Whole gland treatment Agressive radical treatment Surgery + radiotherapy Radiotherapy + hormonal therapy G 6 G7 (3+4) G7 (4+3) G8 G9/T3
ABI Chemo MDV-3100 Hormonal Management Local Therapy 10,000,000 men at risk Death 34,000 CRP Fail Local Treatme (30%) Incidenc 240,000
PET +/-MRI vs CT
Why are biomarkers needed for prostate cancer? i) for reliable diagnosis of significant prostate cancer and making therapy decisions; ii) for early prediction of prognosis of the future course of disease, which may lead to adjusted monitoring and optimized therapy iii) for prediction of therapy response and thus stratifying potential treatment benefit iv) the identification of alternative therapeutic targets based on molecular analyses (eg. target expression and mutational status) v) developing individualized treatment options and thus improve patient outcomes vi) standardization of study/cohort design, permitting standardized reporting
Organisation of Follow Up and Multidisciplinary Uro-oncology Panel Patient Urologist Follow- Up Medical Oncologist Follow-Up Radiotherapist Radiologist Full Panel members Urologist Medical Oncologist Radiologist Radiotherapist Additional: Neurosurgeon General Surgeon Thoracic Surgeon Pathologist Neurosurgeon