case 8 - prostate cancer Flashcards
what is the function and features of the prostate gland
walnut sized gland located behind the base of the penis, infront of the rectum and below the bladder
Surrounds the urethra
Primary function; produce seminal fluid, the liquid in semen that protects, supports and helps transport sperm
what are the risk factors for prostate cancer
age
Race
Family history
Nationality
Genetics - BRACA1 and 2
Diet, exercise, obesity
1 in 8 men in the UK are diagnosed with prostate cancer
what are the lower urinary tract symptoms for prostate cancer
Obstructive - feel like they can’t empty the bladder etc
Irritative - frequency, discomfort or blood in urine
what are the other symptoms of prostate cancer
metastatic
Pain etc
systemic
Fatigue, weight loss
how is prostate cancer diagnosed
history
DRE
PSA - first three are done in primary care
Multi parametric MRI
Biopsy
when does PSA increase
benign prostatic hypertrophy
Age
Prostatitis
Ejaculation
DRE
when does PSA decrease
drugs - finasteride, dutasteride
Obesity
Herbal preparations
what can screening lead to
Overdiagnosis
Over treatment
consider targeted PSA screening in high risk populations
what are the MRI techniques used
T1 & T2 images
Functional imaging
Dynamic contract enhanced DCE
Diffuse weighted imaging DWI
what are the prostate biopsies used
transrectal ultrasound guided TRUS biopsy
Biopsy taken through the rectal wall under ultrasound guidance
About 12 samples taken
template biopsy
Transperineal
Multiple samples taken
what is the score system used for prostate cancer and what does this tell us
Gleason score - used for prostate cancer
Grading system used to define aggressiveness
Score of 3-5 are considered cancerous
Addition of 2 most common scores = Gleason score
Lowest is 6 and highest Is 10
what is stage 1
cancer confined to prostate T1a-2a
PSA <10
Grade group 1 = 3+3=6
what is stage 2
*Stage IIA
–T1a-2a
–PSA 10-20
–Grade group 2
*Stage IIB
–T1-2
–PSA <20
–Grade group 2
*Stage IIC
–T1-2
–PSA <20
–Grade group 3-4
what is stage 3
*Stage IIIA
–T1-2
–PSA >20
–Grade group 1-4
*Stage IIIB
–T3-4
–Grade group 1-4
*Stage IIIC
–Grade group 5 = 10
what is stage 4
Stage IV prostate cancer - means cancers that have metastasised
- most common place for prostate cancer spread is lymph nodes and bones
what is low risk for prostate cancer
*Low Risk:
–T1-T2a and Gleason score 6 and PSA < 10 ng/ml
what is high risk for prostate cancer
*High Risk:
–T3a or Gleason score 8-10 or PSA > 20
*Gonadotrophin releasing hormone agonists (GnRHa) / Luteinising hormone releasing hormone agonists (LHRHa)
–Stimulate pituitary to produce LH
–LH stimulates testicles to produce testosterone
–Chronic exposure to LHRH leads to desensitisation + ↓LH and subsequent ↓testosterone
–May cause testosterone flare so need to give with androgen blocker
what is intermediate risk for prostate cancer
–T2b-T2c or Gleason score 7 or PSA 10-20
what is the treatment for low/intermediate risk disease
radical prostatectomy
External beam radiotherapy
Brachytherapy
Active surveillance
what is active surveillance of
regular monitoring
PSA
DRE
mpMRI
Biopsy
Constantly monitored and if progresses then active treatment is used
what is brachytherapy
*Low dose rate
–Implanting radioactive source into the prostate
Most of their activity is gone in a few weeks
Have to have a general anaesthetic
*High dose rate (intermediate/high risk disease)
–Used as monotherapy
–Or in combination with EBRT
what is external beam radiotherapy
OP treatment
5-37 fractions (treatments)
No anaesthetic
No catheter
Often in combination with ADT
what is the surgery done
Robotic Assisted Laparoscopic Prostatectomy (RALP)
Surgeon operates from a console with a 3-D screen.
Grasp controls to manipulate surgical tools within the patient.
Robotic arms translate finger, hand, and wrist movements.
Very High-Precision
Less blood loss and less stay in hospital
what is done if intermediate/high risk disease
localised disease with higher risk of disease progression
Important to adequately stage disease
Radiotherapy + ADT
RALP with lymph node dissection
what is androgen depravation therapy
*>95% newly diagnosed prostate cancer will respond to treatment with androgen depravation therapy (ADT).
*2 mechanisms for preventing androgens:
–Reduce the level of androgens
–Block the androgens from binding
Most prostate cancers when they first present are hormone sensitive cancers
what reduces the levels of testosterone and what is the process
*Gonadotrophin releasing hormone agonists (GnRHa) / Luteinising hormone releasing hormone agonists (LHRHa)
–Stimulate pituitary to produce LH
–LH stimulates testicles to produce testosterone
–Chronic exposure to LHRH leads to desensitisation + ↓LH and subsequent ↓testosterone
–May cause testosterone flare so need to give with androgen blocker
what are the LHRH agonists
zoladex
Prostap - 4/52 or 12/52 (every four weeks etc)
Decapeptyl - 4/52, 12/52, 6/12
what are the treatments that reduce the level of testosterone
*GnRH/LHRH antagonists
–Prevent LHRH binding to pituitary gland
–↓LH
–↓Testosterone
–No Testosterone flare
*Degarelix
–240mg initial dose (2x120mg SC)
–80mg 4/52
Is very expensive and has to be given every four weeks
what are the androgen blockers
*Bicalutamide 50mg or 150mg OD
*Cyproterone Acetate 100mg TDS
*Used to reduce testosterone flare
*Directly block androgen receptor on cell surface
*3-4/52 prior to and after LHRHagonist
what are ADT side effects
*Sexual
–Decreased libido
–Erectile dysfunction
*Psychological
–Lack of initiative
–Emotional lability
–Decreased memory and cognitive function
*Metabolic
–Lipid changes
–Diabetes mellitus
Physical
–Hot flushes
–Fatigue
–Weight gain
–Hair changes
–Breast pain
–Decreased muscle mass
–Decreased bone mineral density
–Decreased penile size
what is metastatic prostate cancer and what are the features
*Disease has spread outside the prostate
*Not curable
*Aim of treatment: Disease control
*Median Survival ~ 5years
*Hormone Sensitive
*Castrate Resistant - this is when cancer progresses
*ADT is backbone of treatment
what is given for hormone sensitive metastatic prostate cancers
*ADT
*Chemotherapy – Docetaxel
*Novel Hormones – Abiraterone, Apalutamide, Darolutamide, Enzalutamide
Radiotherapy to the prostate only
STAMPEDE trial - multi-arm, multi-stage stage 3 trial.
what is given for castrate resistant metastatic prostate cancer
*ADT - still carry this on
*Supportive Care – analgesia, antiemetics etc
*Chemotherapy – Docetaxel, Cabazitaxel
*Novel Hormones – Abiraterone, Apalutamide, Darolutamide, Enzalutamide
*Radioisotopes – Radium 223 - preferentially taken into bone and emit alpha particles which act on DNAalpha (best treatment), Lu-PSMA
*Radiotherapy – to painful bone metastases
what is castrate resistant metastatic prostate cancer
*12-18 months post ADT initiation is when cancer becomes resistant to the ADT - this is why its called castrate resistant MPC
*Rising PSA despite castrate levels of testosterone (<0.5nmol/L)
*Androgen receptor amplification
*Androgen receptor mutations
*Intratumoral androgen production
*Other growth signals take over
*Median Survival 3 years
