management of advanced prostate carcinoma

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. COSTLY2. COMPLIANCE PROBLEMS3. FLARE PHENOMENON4. ESCAPE PHENOMENON5. BREAKTHROUGH PHENOMENON

LHRH AGONIST WORKS BY: *NEGATIVE FEEDBACK *PLUMMETING EFFECT

1. CHEAP2. NO COMPLIANCE PROBLEMS3. PSYCHO EFFECTS OF CASTRATION

MONOTHERAPY MAB

1. DECREASED COMPLICATIONS2. 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

REFERENCES1. 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/targetedtherapies/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-overview7. PRINCIPLES & PRACTICE OF SURGERY INCLUDING PATHOLOGYIN

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