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DISCUSS THE MANAGEMENT OF A
65 YEAR OLD POLITICIAN WITH
ADVANCED PROSTATE CARCINOMA
DR BASSEY, A. E.
OUTLINE• INTRODUCTION
• DEFINITION
• EPIDEMIOLOGY
• RELEVANT ANATOMY
• RISK FACTORS
• PATHOGENESIS
• PATHOLOGY
• SPREAD
• STAGING/GRADING
• MANAGEMENT
• HISTORY
• EXAMINATION
• INVESTIGATION
• TREATMENT
• COMPLICATIONS
• FOLLOW-UP/PROGNOSIS
• PREVENTION
• CURRENT TRENDS
• CONCLUSION
• REFERENCES
INTRODUCTION
• PROSTATE CARCINOMA IS A MALIGNANT
PROLIFERATION OF THE EPITHELIAL CELLS OF
THE GLANDULAR COMPONENT OF THE
PROSTATE GLAND
EPIDEMIOLOGY
• MOST COMMONLY DIAGNOSED CANCER IN
NIGERIAN MEN1
• IT IS THE LEADING CAUSE OF MALE CANCER
DEATHS
• INCIDENCE IS ON THE RISE
• POST-MORTEM SPECIMENS REVEAL THE
DISEASE IN 14% OF MEN >50YRS & 80%
>70YRS
RELEVANT ANATOMY
RISK FACTORS
• AGE: why? *in older men, though testosterone levels fall, the prostate receptors
become more sensitive to androgen *with aging the estrogen level rises and this increases
prostate sensitivity to androgen as well
• HORMONAL FACTORS: why? *in men castrated before puberty
there’s almost no CaP
• RACE: *in africans testosterone is higher than other races *5-AR levels is also higher so
DHT is higher *black skin reduces UV entry therefore vit D production is less. Vit D is
protective.
• GENETIC FACTORS: *implicated genes are HPCancer gene 1, HPCancer
gene 2, BRCA-2
• HIGH FAT DIET: *due to increased peripheral conversion in adipose
• SMOKING: cadmium exposure
PATHOGENESIS - PATHOLOGY
• IT IS AN ADENOCARCINOMA
• TYPES INCLUDE:
• ORDINARY ADENOCARCINOMA
• MUCINOUS ADENOCARCINOMA
• DUCTAL AGGRESSIVE TYPE
• NEUROENDOCRINE TUMOUR
• SMALL CELL CARCINOMA
PATHOGENESIS - SPREAD
• LOCAL
• PROSTATIC URETHRA
• BLADDER BASE
• EXTERNAL URETHRAL SPHINCTER
• SEMINAL VESICLES
• PELVIC NERVES
• RECTUM
• HAEMATOGENOUS
• BONES
• LIVER
• LUNGS
• BRAIN
• LYMPHATIC SPREAD
STAGING
STAGING
• ADVANCED PROSTATE CARCINOMA IS
THEREFORE2
:
• T3 OR T4, N0, M0
• N1, ANY T, ANY M
• M1, ANY T, ANY N
TUMOUR GRADING
MANAGEMENT - HISTORY
• LUTS
• LOCALLY ADVANCED DISEASE
• METASTATIC DISEASE
• CO-MORBIDITIES
MANAGEMENT - EXAMINATION
• GENERAL – CACHEXIA, PALLOR, JAUNDICE,
LYMPHADENOPATYHY, PEDAL OEDEMA
• ABDOMEN – DISTENDED BLADDER, BALLOTABLE
KIDNEYS, HEPATOMEGALY, PALPABLE MASSES PER
ABDOMEN
• DRE
• NEUROLOGICAL EXAM – PARAPARESIS,
BULBOCAVERNOSUS REFLEX, SENSORY LEVEL
• MUSCULOSKELETAL EXAM – PATHOLOGICAL #
• CHEST – RIB PAIN
• CVS – HYPERTENSION, ARRHYTHMIAS
MANAGEMENT - INVESTIGATION
• TO CONFIRM DGX
• PSA : low in *SqCCa*neuroendocrine tumor*anaplastic Ca
• TRUS/DIGITALLY-GUIDED BIOPSY
• TO DETERMINE EXTENT OF DISEASE
• TRUS PROSTATE:*enlarged prostate*hypoechoic in peripheral
zones*distorted capsule*enlarged seminal vesicles*degree of local
infiltration*bladder findings
• CT/MRI PELVIS
• XRAY SPINE (deposits occur at pedicles becos vertebral plexus runs
along it)
• XRAY PELVIS
• CXR (BONE SCINTIGRAPHY used in early tumors to r/o bone deposits)
• ABDOMINOPELVIC USS :*upper tract dilatation*liver deposits
*ascites*LNs
• LFT
• CT BRAIN
• IVU +/- URETHROCYSTOSCOPY IF THERE’S HEMATURIA
MANAGEMENT - INVESTIGATION
• TO AID MGT
• FBC
• E/U/CR
• FBS
• URINALYSIS
• URINE M/C/S
MANAGEMENT -TREATMENT
• THE AIM IS PALLIATIVE AND APPROACH IS
MULTIDISCIPLINARY – SURGEON, ONCOLOGIST,
PHYSICIAN, PHYSIOTHERAPIST, PSYCHOLOGIST,
RELATIVES
• CORRECT DERANGEMEN
• ANAEMIA
• SEVERE HAEMATURIA (HAEMATURIA COMMONER IN BPH)
• ACUTE URINARY RETENTION
• CLOT RETENTION
• UTI
MANAGEMENT - TREATMENT
• THE CRUX OF TREATMENT IS HORMONAL
MANIPULATION
• ANTIANDROGEN + LHRH AGONIST
• ANTIANDROGEN + BILATERAL ORCHIDECTOMY
• ANTIANDROGEN + DIETHYLSTILBOESTROL
• PATIENT COUNSELLING
• DIAGNOSIS
• TREATMENT OPTIONS
• COMPLICATIONS OF TREATMENT
• PROGNOSIS
MANAGEMENT - TREATMENT
• FOR LOCALLY ADVANCED, NEO-ADJUVANT
HORMONAL THERAPY OR NEO-ADJUVANT
RADIOTHERAPY CAN BE DONE FOLLOWED BY
RADICAL PROSTATECTOMY.
• EXCLUSION CRITERIA - *PTS WITH <10YRS LIFE
EXPECTANCY *PTS WITH SEVERE
COMORBIDITY
• SUCCESS OF SURGERY IS PSA NADIR <0.2ng/ml
LHRH AGONIST BILATERAL ORCHIDECTOMY
1. COSTLY
2. COMPLIANCE PROBLEMS
3. FLARE PHENOMENON
4. ESCAPE PHENOMENON
5. BREAKTHROUGH PHENOMENON
LHRH AGONIST WORKS BY: *NEGATIVE
FEEDBACK *PLUMMETING EFFECT
1. CHEAP
2. NO COMPLIANCE PROBLEMS
3. PSYCHO EFFECTS OF CASTRATION
MONOTHERAPY MAB
1. DECREASED COMPLICATIONS
2. DECREASED COST
1. PREFERABLE FOR THOSE WITH POOR PROGNOSIS AT THE
OUTSET
MANAGEMENT - TREATMENT
• INTERMITTENT HORMONAL THERAPY (DONE
TO SLOW PROGRESSION TO HORMONE-
RESISTANT STATE
• MAB GIVEN FOR 36 WEEKS AND TREATMENT STOPPED
• PSA NADIR NOTED
• TREATMENT RESUMED AFTER 32 WEEKS
• HOWEVER, IF IN THE INTERVAL PSA RISES ABOVE
20NG/ML OR THERE’S A DOUBLING OF NADIR PSA
TREATMENT IS RESUMED
MANAGEMENT - TREATMENT
• PAIN CONTROL
• MAB
• NARCOTICS
• RADIOTHERAPY
• URINE RETENTION
• MAB
• CHANNEL TURP
• RADIOTHERAPY
• STENT
• CHRONIC INDWELLING CATHETER
• CISC
• BONE DESTRUCTION
• BISPHOSPHONATES
• RADIOTHERAPY
• URETERIC OBSTRUCTION 2o
LNs
• URETERIC STENT
• NEPHROSTOMY
• PHYSIOTHERAPY
MANAGEMENT - COMPLICATIONS
• URINE RETENTION
• CLOT RETENTION
• RENAL INSUFFICIENCY
• URINARY INCONTINENCE
• PARAPLEGIA
• ERECTILE DYSFUNCTION
• PATHOLOGIC FRACTURES
• DECREASED LIBIDO
• DEPRESSION
FOLLOW-UP/PROGNOSIS
• FOLLOW UP – THIS IS FOR LIFE
• HISTORY
• EXAMINATION
• DRE
• SERUM PSA, PSA DENSITY, PSA VELOCITY
• PROGNOSIS
• INDICATORS ARE – GLEASON SCORE, TNM STAGE,
HISTOLOGIC TYPE, AGE AT DIAGNOSIS
• VIRTUALLY ALL ADVANCED PROSTATE CARCINOMA
PROGRESS TO A HORMONE-RESISTANT STATE AFTER 12-
18MTHS OF TREATMENT BEYOND WHICH MEDIAN
SURVIVAL IS 2-3 YEARS (BADOE – 24-38WKS i.e 6-9MTHS)
PREVENTION
• PUBLIC AWARENESS
• SCREENING – EARLY DIAGNOSIS = POSSIBLE
CURE
• AVOIDANCE OF KNOWN RISK FACTORS –
SMOKING, HIGH FAT DIET
CURRENT/FUTURE TRENDS
• USE OF 5-ALPHA REDUCTASE INHIBITORS
• TARGETED THERAPY
• ANDROGEN SYNTHESIS INHIBITOR – ABIRATERONE
ACETATE - DROPS TESTOSTERONE TO LEVELS LOWER
THAN ANY PRESENT FORM OF TREATMENT3
• LHRH ANTAGONISTS – DEGARELIX – AVOIDS FLARE
PHENOMENON4
• PSMA-ADC: ANTIBODY + MONOMETHYL
AURISTATIN E5
(DISRUPTS TUBULINS)
CONCLUSION
• DUE TO HIGH PREVALENCE AND RISING
INCIDENCE OF CARCINOMA OF THE PROSTATE
IN OUR ENVIRONMENT, THE NEED FOR
FORMAL SCREENING POLICY AND EFFORTS
TOWARD PREVENTION AND EARLY DIAGNOSIS
CANNOT BE OVER-EMPHASISED, DESPITE
INSPIRING ADVANCES IN MOLECULAR
CHARACTER AND TREATMENT OF THIS
DISEASE.
THANK YOU
REFERENCES
1. Prevalence and characteristics of prostate cancer among
participants of a community-based screening in Nigeria using
serum prostate specific antigen and digital rectal examination.
doi:10.11604/pamj.2013.15.129.2489
2. http://www.cancerresearchuk.org/cancer-help/type/prostate-
cancer/treatment/the-stages-of-prostate-cancer
3. http://www.cancer.gov/cancertopics/understandingcancer/target
edtherapies/prostatecancer_htmlcourse/page2
4. The role of LHRH antagonists in the treatment of prostate cancer.
http://www.ncbi.nlm.nih.gov/pubmed/19626830#
5. http://www.ecco-org.eu/Global/News/ENA-2012-
PR/2012/11/8_11-New-targeted-therapy-for-advanced-prostate-
cancer.aspx
6. http://emedicine.medscape.com/article/1967731-overview
7. PRINCIPLES & PRACTICE OF SURGERY INCLUDING PATHOLOGYIN
THE TROPICS, BADOE ET AL, pp 939 - 952

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Management of advanced prostate carcinoma

  • 1. DISCUSS THE MANAGEMENT OF A 65 YEAR OLD POLITICIAN WITH ADVANCED PROSTATE CARCINOMA DR BASSEY, A. E.
  • 2. OUTLINE• INTRODUCTION • DEFINITION • EPIDEMIOLOGY • RELEVANT ANATOMY • RISK FACTORS • PATHOGENESIS • PATHOLOGY • SPREAD • STAGING/GRADING • MANAGEMENT • HISTORY • EXAMINATION • INVESTIGATION • TREATMENT • COMPLICATIONS • FOLLOW-UP/PROGNOSIS • PREVENTION • CURRENT TRENDS • CONCLUSION • REFERENCES
  • 3. INTRODUCTION • PROSTATE CARCINOMA IS A MALIGNANT PROLIFERATION OF THE EPITHELIAL CELLS OF THE GLANDULAR COMPONENT OF THE PROSTATE GLAND
  • 4. EPIDEMIOLOGY • MOST COMMONLY DIAGNOSED CANCER IN NIGERIAN MEN1 • IT IS THE LEADING CAUSE OF MALE CANCER DEATHS • INCIDENCE IS ON THE RISE • POST-MORTEM SPECIMENS REVEAL THE DISEASE IN 14% OF MEN >50YRS & 80% >70YRS
  • 6. RISK FACTORS • AGE: why? *in older men, though testosterone levels fall, the prostate receptors become more sensitive to androgen *with aging the estrogen level rises and this increases prostate sensitivity to androgen as well • HORMONAL FACTORS: why? *in men castrated before puberty there’s almost no CaP • RACE: *in africans testosterone is higher than other races *5-AR levels is also higher so DHT is higher *black skin reduces UV entry therefore vit D production is less. Vit D is protective. • GENETIC FACTORS: *implicated genes are HPCancer gene 1, HPCancer gene 2, BRCA-2 • HIGH FAT DIET: *due to increased peripheral conversion in adipose • SMOKING: cadmium exposure
  • 7. PATHOGENESIS - PATHOLOGY • IT IS AN ADENOCARCINOMA • TYPES INCLUDE: • ORDINARY ADENOCARCINOMA • MUCINOUS ADENOCARCINOMA • DUCTAL AGGRESSIVE TYPE • NEUROENDOCRINE TUMOUR • SMALL CELL CARCINOMA
  • 8. PATHOGENESIS - SPREAD • LOCAL • PROSTATIC URETHRA • BLADDER BASE • EXTERNAL URETHRAL SPHINCTER • SEMINAL VESICLES • PELVIC NERVES • RECTUM • HAEMATOGENOUS • BONES • LIVER • LUNGS • BRAIN • LYMPHATIC SPREAD
  • 10. STAGING • ADVANCED PROSTATE CARCINOMA IS THEREFORE2 : • T3 OR T4, N0, M0 • N1, ANY T, ANY M • M1, ANY T, ANY N
  • 12. MANAGEMENT - HISTORY • LUTS • LOCALLY ADVANCED DISEASE • METASTATIC DISEASE • CO-MORBIDITIES
  • 13. MANAGEMENT - EXAMINATION • GENERAL – CACHEXIA, PALLOR, JAUNDICE, LYMPHADENOPATYHY, PEDAL OEDEMA • ABDOMEN – DISTENDED BLADDER, BALLOTABLE KIDNEYS, HEPATOMEGALY, PALPABLE MASSES PER ABDOMEN • DRE • NEUROLOGICAL EXAM – PARAPARESIS, BULBOCAVERNOSUS REFLEX, SENSORY LEVEL • MUSCULOSKELETAL EXAM – PATHOLOGICAL # • CHEST – RIB PAIN • CVS – HYPERTENSION, ARRHYTHMIAS
  • 14. MANAGEMENT - INVESTIGATION • TO CONFIRM DGX • PSA : low in *SqCCa*neuroendocrine tumor*anaplastic Ca • TRUS/DIGITALLY-GUIDED BIOPSY • TO DETERMINE EXTENT OF DISEASE • TRUS PROSTATE:*enlarged prostate*hypoechoic in peripheral zones*distorted capsule*enlarged seminal vesicles*degree of local infiltration*bladder findings • CT/MRI PELVIS • XRAY SPINE (deposits occur at pedicles becos vertebral plexus runs along it) • XRAY PELVIS • CXR (BONE SCINTIGRAPHY used in early tumors to r/o bone deposits) • ABDOMINOPELVIC USS :*upper tract dilatation*liver deposits *ascites*LNs • LFT • CT BRAIN • IVU +/- URETHROCYSTOSCOPY IF THERE’S HEMATURIA
  • 15. MANAGEMENT - INVESTIGATION • TO AID MGT • FBC • E/U/CR • FBS • URINALYSIS • URINE M/C/S
  • 16. MANAGEMENT -TREATMENT • THE AIM IS PALLIATIVE AND APPROACH IS MULTIDISCIPLINARY – SURGEON, ONCOLOGIST, PHYSICIAN, PHYSIOTHERAPIST, PSYCHOLOGIST, RELATIVES • CORRECT DERANGEMEN • ANAEMIA • SEVERE HAEMATURIA (HAEMATURIA COMMONER IN BPH) • ACUTE URINARY RETENTION • CLOT RETENTION • UTI
  • 17. MANAGEMENT - TREATMENT • THE CRUX OF TREATMENT IS HORMONAL MANIPULATION • ANTIANDROGEN + LHRH AGONIST • ANTIANDROGEN + BILATERAL ORCHIDECTOMY • ANTIANDROGEN + DIETHYLSTILBOESTROL • PATIENT COUNSELLING • DIAGNOSIS • TREATMENT OPTIONS • COMPLICATIONS OF TREATMENT • PROGNOSIS
  • 18. MANAGEMENT - TREATMENT • FOR LOCALLY ADVANCED, NEO-ADJUVANT HORMONAL THERAPY OR NEO-ADJUVANT RADIOTHERAPY CAN BE DONE FOLLOWED BY RADICAL PROSTATECTOMY. • EXCLUSION CRITERIA - *PTS WITH <10YRS LIFE EXPECTANCY *PTS WITH SEVERE COMORBIDITY • SUCCESS OF SURGERY IS PSA NADIR <0.2ng/ml
  • 19. LHRH AGONIST BILATERAL ORCHIDECTOMY 1. COSTLY 2. COMPLIANCE PROBLEMS 3. FLARE PHENOMENON 4. ESCAPE PHENOMENON 5. BREAKTHROUGH PHENOMENON LHRH AGONIST WORKS BY: *NEGATIVE FEEDBACK *PLUMMETING EFFECT 1. CHEAP 2. NO COMPLIANCE PROBLEMS 3. PSYCHO EFFECTS OF CASTRATION MONOTHERAPY MAB 1. DECREASED COMPLICATIONS 2. DECREASED COST 1. PREFERABLE FOR THOSE WITH POOR PROGNOSIS AT THE OUTSET
  • 20. MANAGEMENT - TREATMENT • INTERMITTENT HORMONAL THERAPY (DONE TO SLOW PROGRESSION TO HORMONE- RESISTANT STATE • MAB GIVEN FOR 36 WEEKS AND TREATMENT STOPPED • PSA NADIR NOTED • TREATMENT RESUMED AFTER 32 WEEKS • HOWEVER, IF IN THE INTERVAL PSA RISES ABOVE 20NG/ML OR THERE’S A DOUBLING OF NADIR PSA TREATMENT IS RESUMED
  • 21. MANAGEMENT - TREATMENT • PAIN CONTROL • MAB • NARCOTICS • RADIOTHERAPY • URINE RETENTION • MAB • CHANNEL TURP • RADIOTHERAPY • STENT • CHRONIC INDWELLING CATHETER • CISC • BONE DESTRUCTION • BISPHOSPHONATES • RADIOTHERAPY • URETERIC OBSTRUCTION 2o LNs • URETERIC STENT • NEPHROSTOMY • PHYSIOTHERAPY
  • 22. MANAGEMENT - COMPLICATIONS • URINE RETENTION • CLOT RETENTION • RENAL INSUFFICIENCY • URINARY INCONTINENCE • PARAPLEGIA • ERECTILE DYSFUNCTION • PATHOLOGIC FRACTURES • DECREASED LIBIDO • DEPRESSION
  • 23. FOLLOW-UP/PROGNOSIS • FOLLOW UP – THIS IS FOR LIFE • HISTORY • EXAMINATION • DRE • SERUM PSA, PSA DENSITY, PSA VELOCITY • PROGNOSIS • INDICATORS ARE – GLEASON SCORE, TNM STAGE, HISTOLOGIC TYPE, AGE AT DIAGNOSIS • VIRTUALLY ALL ADVANCED PROSTATE CARCINOMA PROGRESS TO A HORMONE-RESISTANT STATE AFTER 12- 18MTHS OF TREATMENT BEYOND WHICH MEDIAN SURVIVAL IS 2-3 YEARS (BADOE – 24-38WKS i.e 6-9MTHS)
  • 24. PREVENTION • PUBLIC AWARENESS • SCREENING – EARLY DIAGNOSIS = POSSIBLE CURE • AVOIDANCE OF KNOWN RISK FACTORS – SMOKING, HIGH FAT DIET
  • 25. CURRENT/FUTURE TRENDS • USE OF 5-ALPHA REDUCTASE INHIBITORS • TARGETED THERAPY • ANDROGEN SYNTHESIS INHIBITOR – ABIRATERONE ACETATE - DROPS TESTOSTERONE TO LEVELS LOWER THAN ANY PRESENT FORM OF TREATMENT3 • LHRH ANTAGONISTS – DEGARELIX – AVOIDS FLARE PHENOMENON4 • PSMA-ADC: ANTIBODY + MONOMETHYL AURISTATIN E5 (DISRUPTS TUBULINS)
  • 26. CONCLUSION • DUE TO HIGH PREVALENCE AND RISING INCIDENCE OF CARCINOMA OF THE PROSTATE IN OUR ENVIRONMENT, THE NEED FOR FORMAL SCREENING POLICY AND EFFORTS TOWARD PREVENTION AND EARLY DIAGNOSIS CANNOT BE OVER-EMPHASISED, DESPITE INSPIRING ADVANCES IN MOLECULAR CHARACTER AND TREATMENT OF THIS DISEASE.
  • 28. REFERENCES 1. Prevalence and characteristics of prostate cancer among participants of a community-based screening in Nigeria using serum prostate specific antigen and digital rectal examination. doi:10.11604/pamj.2013.15.129.2489 2. http://www.cancerresearchuk.org/cancer-help/type/prostate- cancer/treatment/the-stages-of-prostate-cancer 3. http://www.cancer.gov/cancertopics/understandingcancer/target edtherapies/prostatecancer_htmlcourse/page2 4. The role of LHRH antagonists in the treatment of prostate cancer. http://www.ncbi.nlm.nih.gov/pubmed/19626830# 5. http://www.ecco-org.eu/Global/News/ENA-2012- PR/2012/11/8_11-New-targeted-therapy-for-advanced-prostate- cancer.aspx 6. http://emedicine.medscape.com/article/1967731-overview 7. PRINCIPLES & PRACTICE OF SURGERY INCLUDING PATHOLOGYIN THE TROPICS, BADOE ET AL, pp 939 - 952