PSA - Worlds Favourite Tumour Marker

Question 1

Why do you measure serum tumour markers?

Answer 1

1) Detect malignancy and possibly identify the organ involved - screening/ diagnostic

2) establish tumour burden and predict response - prognosis/prediction

3) monitor in response to therapy and need for further therapy - follow up

Question 2

What are general limitations of serum tumour markers?

Answer 2

1) lack of clinical specificity for cancer
- most markers are present in normal tissue
- many are elevated in benign disease

2) lack of clinical sensitivity for early cancers - only rarely elevated in early malignancy

3) rarely raised in all cancers of a particular type
- exception hCG

4) often raised in different cancers
Exception - PSA

Question 3

What are some important consideration of tumour markers?

Answer 3

• Tumour markers should only be requested after considering the likelihood that the test result will improve patient outcome, increase quality of life, or reduce overall cost of care.
• inappropriately used tumour markers can cause patients additional anxiety and distress
• There is significant inappropriate requesting of tumour markers

Question 4

What are the two prostatic diseases?

Answer 4

BPH - benign prostatic hyperplasia and prostate cancer

Question 5

Symptoms of BPH?

Answer 5

Frequency, urgency, nocturia, dysuria, dribbling, incontinence, poor stream, hesitancy, retention, infection

Enlarged but smooth ad symmetrical gland on DRE

Question 6

Symptoms of prostate cancer

Answer 6

Frequency, urgency, nocturne, dysruia, retention, back pain, weight loss, anaemia, obstruction, altered bowel movement.

Modular and stony hard prostate

Question 7

What is the ideal prostate bio marker?

Answer 7

• in screening of symptomatic men is would identify men with cancer or premalignant disease likely or progress to aggressive prostatic cancer.
• Diagnosis / case finding - In symptomatic men it Would differentiate prostatic cancer from benign prostatic hyperplasia (BPH) and Would differentiate aggressive from indolent diseases
• monitoring - in patients with prostate cancer it would realisable confirm stable disease or indicate disease progression requiring intervention.

Question 8

What is PSA?

Answer 8

Prostate specific antigen

Question 9

What does PSA do as a bio marker?

Answer 9

Dissolves seminal coagulum to increase sperm motility

Circulates in free and bound forms in serum

decrease in free PSA is malignant prostate disease

Question 10

How do you use PSA?

Answer 10

Screening/early detection
- population screening isn’t recommended and so an informed decision has to be made on whether or not to test.

Diagnostic aid - prostatic biopsy required one definitive diagnosis. Risk stratification - assessing the need for biopsy

Monitoring - active surveillance - should remain stable, post total prostatectomy (get rid of prostate) (undetectable), radiotherapy/endocrine therapy - rate of fall relevant to therapy

Question 11

Establish quality requirements - what are the preanalytic requirements?

Answer 11

• Appropriate reason for request / prior discussion.

• Awareness of specimen requirements – e.g. stability

Question 12

Establish quality requirements - what are the analytical requirements?

Answer 12

Well-standardized methods - acceptable specificity,sensitivity, precision, bias, stability etc

Question 13

Established quality requirements - what is the post analytical requirements?

Answer 13

Consensus about reference intervals/decision pointsand interpretation.

Excellent communication between lab & clinic.

Question 14

What are some other conditions that can raise PSA?

Answer 14

Benign prostatic hyperplasia, urinary tract infection, prostatitis and after catheterisation

Question 15

Is there a guideline for men wanting to take a PSA test if they are unsymptomatic?

Answer 15

Yes

Question 16

What are the timing requirements for the specimen once taken?

Answer 16

• Not in men with a urinary tract infection
• Prior to digital rectal examination or 1 week after
• At least 48 hours after ejaculation
• At least 6 weeks after prostate massage
• before or 1 week after ultrasound
• Before or 1 week after rigid cytoscopy

Question 17

What are the storage requirements for a specimen?

Answer 17

• Up to 7 days at 4 degrees for total PSA / up to 2 years at -70 degrees
• For <2 days at 4 degrees for freePSA / up to 2 years at -70 degrees
• early separation of specimens desirable for free PSA
• stable for 5 freeze thaw cycles

Question 18

Does catherisation increase PSA?

Answer 18

Yes

Question 19

Immunoassay - analytical quality requirements?

Answer 19

Immunoassay for PSA must be accurately calibrated in terms of the international standard for PSA and must be equimolar

Independent assessment of both calibrations and equimolarity should be carried annually for all PSA assay used in the UK and for new PSA assays as they become available.

Question 20

What are the lab responsibility for a PSA specimen?

Answer 20

• Ensure that rigorous internal quality control and external quality assessment systems are in place for PSA especially around decision limits
• State the name of the method used on the laboratory report
• Provide fully cumulated results to enable interpretation of trends in PSA results
• Confirm increases in PSA results as appropriate

Question 21

Internal quality control?

Answer 21

You need to run a known value sample along with your sample and compare - make sure your doing it right.

Question 22

Post analytic - intelligent reporting?

Answer 22

This includes highlighting trends and changes, interventions, clinical details and interpretative pitfalls.

Question 23

What would a raised PSA result lead to?

Answer 23

Increased PSA Doesn’t necessarily indicate there is prostatic disease but a normal result doesn’t mean there is no malignancy