case 8 - prostate cancer

Question 1

what is the function and features of the prostate gland

Answer 1

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

Question 2

what are the risk factors for prostate cancer

Answer 2

age
Race
Family history
Nationality
Genetics - BRACA1 and 2
Diet, exercise, obesity

1 in 8 men in the UK are diagnosed with prostate cancer

Question 3

what are the lower urinary tract symptoms for prostate cancer

Answer 3

Obstructive - feel like they can’t empty the bladder etc
Irritative - frequency, discomfort or blood in urine

Question 4

what are the other symptoms of prostate cancer

Answer 4

metastatic
Pain etc
systemic
Fatigue, weight loss

Question 5

how is prostate cancer diagnosed

Answer 5

history
DRE
PSA - first three are done in primary care
Multi parametric MRI
Biopsy

Question 6

when does PSA increase

Answer 6

benign prostatic hypertrophy
Age
Prostatitis
Ejaculation
DRE

Question 7

when does PSA decrease

Answer 7

drugs - finasteride, dutasteride
Obesity
Herbal preparations

Question 8

what can screening lead to

Answer 8

Overdiagnosis
Over treatment
consider targeted PSA screening in high risk populations

Question 9

what are the MRI techniques used

Answer 9

T1 & T2 images
Functional imaging
Dynamic contract enhanced DCE
Diffuse weighted imaging DWI

Question 10

what are the prostate biopsies used

Answer 10

transrectal ultrasound guided TRUS biopsy
Biopsy taken through the rectal wall under ultrasound guidance
About 12 samples taken
template biopsy
Transperineal
Multiple samples taken

Question 11

what is the score system used for prostate cancer and what does this tell us

Answer 11

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

Question 12

what is stage 1

Answer 12

cancer confined to prostate T1a-2a
PSA <10
Grade group 1 = 3+3=6

Question 13

what is stage 2

Answer 13

*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

Question 14

what is stage 3

Answer 14

*Stage IIIA
–T1-2
–PSA >20
–Grade group 1-4

*Stage IIIB
–T3-4
–Grade group 1-4

*Stage IIIC
–Grade group 5 = 10

Question 15

what is stage 4

Answer 15

Stage IV prostate cancer - means cancers that have metastasised
- most common place for prostate cancer spread is lymph nodes and bones

Question 16

what is low risk for prostate cancer

Answer 16

*Low Risk:
–T1-T2a and Gleason score 6 and PSA < 10 ng/ml

Question 17

what is high risk for prostate cancer

Answer 17

*High Risk:
–T3a or Gleason score 8-10 or PSA > 20

Question 18

*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

Answer 18

–T2b-T2c or Gleason score 7 or PSA 10-20

Question 19

what is the treatment for low/intermediate risk disease

Answer 19

radical prostatectomy
External beam radiotherapy
Brachytherapy
Active surveillance

Question 20

what is active surveillance of

Answer 20

regular monitoring
PSA
DRE
mpMRI
Biopsy
Constantly monitored and if progresses then active treatment is used

Question 21

what is brachytherapy

Answer 21

*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

Question 22

what is external beam radiotherapy

Answer 22

OP treatment
5-37 fractions (treatments)
No anaesthetic
No catheter
Often in combination with ADT

Question 23

what is the surgery done

Answer 23

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

Question 24

what is done if intermediate/high risk disease

Answer 24

localised disease with higher risk of disease progression
Important to adequately stage disease
Radiotherapy + ADT
RALP with lymph node dissection

Question 25

what is androgen depravation therapy

Answer 25

*>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

Question 26

what reduces the levels of testosterone and what is the process

Answer 26

*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

Question 27

what are the LHRH agonists

Answer 27

zoladex Prostap - 4/52 or 12/52 (every four weeks etc) Decapeptyl - 4/52, 12/52, 6/12

Question 28

what are the treatments that reduce the level of testosterone

Answer 28

*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

Question 29

what are the androgen blockers

Answer 29

*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

Question 30

what are ADT side effects

Answer 30

*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

Question 31

what is metastatic prostate cancer and what are the features

Answer 31

*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

Question 32

what is given for hormone sensitive metastatic prostate cancers

Answer 32

*ADT *Chemotherapy – Docetaxel *Novel Hormones – Abiraterone, Apalutamide, Darolutamide, Enzalutamide Radiotherapy to the prostate only STAMPEDE trial - multi-arm, multi-stage stage 3 trial.

Question 33

what is given for castrate resistant metastatic prostate cancer

Answer 33

*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

Question 34

what is castrate resistant metastatic prostate cancer

Answer 34

*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