Diagnosis and management of

prostate cancer in the

Jeremy Teoh (張源津)

Assistant Professor, Department of Surgery,

The Chinese University of Hong Kong.

Email: jeremyteoh@surgery.cuhk.edu.hk

Estimated age-standardised rates per 100,000

Prostate-specific antigen (PSA)

• Glycoprotein secreted by prostatic ductal epithelial cells

which liquefy seminal coagulum

• Organ-specific but NOT tumour-specific marker

• Overall half-life of 2-3 days

• Higher PSA level -> Higher chance of prostate cancer

• First prospective clinical trial on the use

of PSA in early prostate cancer

detection 20 years ago

• Indications of TRUS-PB

– PSA >4.0ng/ml

– Abnormal digital rectal examination

• In patients with PSA 4-9.9ng/mL,

22% had prostate cancer

Prostate cancer detection rates in patients with PSA 4-10ng/mL.

PSA screening

• ERSPC trial (Schorder et al. Lancet 2014)

– 27% relative risk reduction in prostate cancer-specific mortality

(RR 0.73, 95% CI 0.61-0.88)

– No difference in all-cause mortality

• PLCO trial (Andriole et al. JNCI 2012)

– No difference in prostate cancer-specific mortality

– No difference in all-cause mortality other than PLCO cancers

(RR 0.96, 95% CI 0.93-1.00)

Guidelines on PSA screening

• Men who are younger than 40 years old

– Advised against PSA screening

• Men aged 40-55 years old

– Recommended to have PSA screening only if they are at high

risk of cancer development

• Men aged 55-77 years old

– Recommended to have a shared decision making for PSA

screening after pros and cons have been discussed

• Men who are older than 77 years old or have less than

10-year life expectancies

– Advised against PSA screening

Shared decision making?

• Reduction of prostate cancer related mortality and quality of

life impairment due to advanced or metastatic prostate cancer

with early detection and treatment of prostate cancer

• Possibility of increased PSA and the options of management if

PSA result is abnormal

• Limitations of screening tests

• Risk of prostate biopsy

• Chance of over-diagnosis, over-treatment and treatment

related morbidities

• Option of active surveillance to reduce over-treatment

Any there any better markers?

Prostate health index

• US FDA approved test for men aged 50 years and older,

with PSA 4-10ng/mL and normal DRE

• A score derived from total PSA, free PSA and [-2]pro-PSA

• Better delineate between benign prostatic hyperplasia

and prostate cancer

• Better delineate between significant and insignificant

prostate cancer

PHI range Probability of cancer(Catalona series)

Probability of cancer(HK series)

Probability of significantcancer (HK series)

0-24.9 11.0% 3.6% 0.5%

24.0-34.9 18.1% 7.6% 0.9%

35.0-54.9 32.7% 22.9% 6.9%

55.0+ 52.1% 38.1% 19.0%

Adaptation and External validation of

ERSPC risk calculator for Chinese men

in Hong Kong

• Collaborative project between PWH, Erasmus University

Medical Centre (Rotterdam) and QMH

• PWH cohort- development cohort for adaptation to the

ERSPC risk calculator

• QMH cohort- validation cohort for external validation of

the adapted risk calculator

PK Chiu et al. Prostate Cancer Prostatic Dis. 2017

Table 1. Baseline characteristics of the development and validation cohorts

Median

IQR

All

n=5305

Developmentcohort

Hospital1

n=3091

Validationcohort

Hospital2

n=2214

Age(years)68

62-73

67

62-72

68

62-73

PSA(ng/mL)7.3

5.2–11.3

7.3

5.3–11.5

7.2

5.2–11.0

TRUS-PV(ml)43.1

31.0–60.0

46.4

33.0–63.3

39.5

29.5–54.9

AbnormalTRUSfindings 260(8.4%) N/A

AbnormalDRE 825(15.6%) 437(14.1%) 388(17.5%)

TRUSbiopsycores

<6cores

6-8cores

9-10cores

11-12cores

>12cores

Missing

10(0.2%)

1275(24.0%)

3516(66.3%)

493(9.3%)

2(0.04%)

9(0.2%)

6(0.19%)

1153(37.3%)

1911(61.8%)

13(0.4%)

1(0.03%)

7(0.2%)

4(0.2%)

122(5.5%)

1605(72.5%)

480(21.7%)

1(0.05%)

2(0.09%)

Anygradeprostatecancer 970(18.3%) 523(16.9%) 447(20.2%)

Highgradeprostatecancer 461(8.7%) 247(8.0%) 214(9.7%)

PK Chiu et al. Prostate Cancer Prostatic Dis. (In press)

Multi-parametric MRI

• T2 weighed imaging

• Diffusion weighted imaging

• Dynamic contrast enhanced imaging

PI-RADS

• 1- Clinically significant cancer is highly unlikely to be present

• 2- Clinically significant cancer is unlikely to be present

• 3- The presence of clinically significant cancer is equivocal

• 4- Clinically significant cancer is likely to be present

• 5- Clinically significant cancer is highly likely to be present

T2W in Peripheral Zone

PI-RADS 1 PI-RADS 2 PI-RADS 3

PI-RADS 4 PI-RADS 5

DWI in Peripheral Zone

PI-RADS 1 PI-RADS 2 PI-RADS 3

PI-RADS 4 PI-RADS 5

ADC

PI-RADS 1 PI-RADS 2 PI-RADS 3

PI-RADS 4 PI-RADS 5

High b value

DCE in Peripheral Zone

Transrectal ultrasound-guided

prostate biopsy

• Peripheral zone of prostate

gland is located just anterior to

rectum

• Most prostate cancers are

located at the peripheral zone

• Prostate biopsy through the

transrectal route is the most

direct approach

• Systematic biopsy is needed

MRI fusion targeted biopsy

Cancer detection rate

• PI-RADS 2 – 0% (0/33)

• PI-RADS 3 – 11.4% (4/35)

• PI-RADS 4 – 29.2% (7/24)

• PI-RADS 5 – 50% (3/6)

92.9% (13/14) of the detected cancers are clinically significant cancers!

Treatment of Prostate Cancer

Localised prostate cancer

• Radical prostatectomy

• Radiotherapy

• Active surveillance

Surgical Outcomes Monitoring and

Improvement Program (SOMIP)

0%10%20%30%40%50%60%70%80%90%

100%

Open

Laparoscopic

Robotic

SOMIP peri-operative results

• July 2015 – June 2016

• 329 radical prostatectomies

• Median hospital stay - 4 days

• Complications

– 2.4% bleeding requiring transfusion (8/329)

– 1.8% sepsis (6/329)

– 0.9% anasmotic leakage (3/329)

– 0.3% pulmonary embolism (1/329)

– 0.3% tissue injury (1/329)

Active surveillance

• Regular PSA blood taking

• Regular DRE

• Repeated prostate biopsy for Gleason score

• If any of the parameters worsen

– offer radical surgery or radiotherapy!

• No difference in 10-year survival when compared to

radical surgery or radiotherapy in PSA screened

prostate cancersHamdy et al. NEJM 2016.

Localized disease

To treat or not to treat?

• Patient factors

– Age

– Comorbidities

• Disease factors

– Clinical T stage

– PSA

– Gleason score

Metastatic prostate cancer

• Hormonal therapy

– Bilateral orchidectomy

– LHRH agonist (3-monthly or 6-monthly injection)

Need short-term anti-androgen coverage

– LHRH antagonist (Monthly injection)

Less CVS adverse events in patients with pre-existing

ischemic heart disease

Metastatic prostate cancer

• Chemohormonal therapy

i.e. Hormonal therapy + docetaxel

Survival benefit in particular for patients with high volume

metastatic disease (up to 17 months!)

Always consider this, especially for young and fit patients

with reasonable renal function!

Castration resistant prostate cancer

Chemo? Symptoms Median overall survival benefit

Hazard ratio(95% CI)

Abiraterone(COU-AA-301)

Post-chemo BPI-SF 0-10 4.6 months 0.74 (0.64-0.86)

Abiraterone(COU-AA-302)

Pre-chemo BPI-SF 0-3 4.4 0.81 (0.70-0.93)

Enzalutamide(AFFIRM)

Post-chemo BPI-SF 0-10 4.8 months 0.63 (0.53-0.75)

Enzalutamide(PREVAIL)

Pre-chemo BPI-SF 0-3 2.2 months 0.71 (0.60-0.84)

Carbazitaxel(TROPIC)

Post-chemo - 2.4 months 0.70 (0.59-0.83)

Radium(ALSYMPCA)

Both pre- and post-chemo

Analgesic or EBRT for cancer-related bone pain

3.6 months 0.70 (0.58-0.83)

Sipuleucel-T Both pre- and post-chemo

Asymptomatic or minimally symptomatic

4.1 months 0.78 (0.61-0.98)

Summary

• Prostate cancer detection rate with reference to PSA

level is much lower in Chinese men

• PSA screening (HKUA recommendation)

– Men aged 40-55 years old

Only if they are at high risk of cancer development

– Men aged 55-77 years old

Shared decision making after the potential benefit and

harm are discussed

Summary

• Prostate health index is a good marker for detecting

prostate cancer/ significant prostate cancer

• The Chinese Prostate Cancer Risk Calculator may help

guide patients and doctors to decide on prostate biopsy

• MRI should be considered in patients with clinical

suspicion of prostate cancer with prior negative biopsy

• Perform systematic biopsy and targeted biopsy of lesion

being identified on MRI

Summary

• Radical prostatectomy, radiotherapy and active

surveillance can be considered in localized prostate

cancer

• Each treatment options has its pros and cons

Need to consider both patient and disease factors

Summary

• Hormonal therapy should be given in metastatic prostate

cancer

• Concurrent chemotherapy should always be considered,

especially in young and fit patients with reasonable renal

function

Thank you!

Jeremy Teoh (張源津)

Assistant Professor, Department of Surgery,

The Chinese University of Hong Kong.

Email: jeremyteoh@surgery.cuhk.edu.hk