Diagnosis and management of prostate cancer in the

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1 Diagnosis and management of prostate cancer in the Jeremy Teoh ( 張源津 ) Assistant Professor, Department of Surgery, The Chinese University of Hong Kong. jeremyteoh@surgery.cuhk.edu.hk

2 Estimated age-standardised rates per 100,000

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4 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

5 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

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

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12 PSA screening ERSPC trial (Schorder et al. Lancet 2014) 27% relative risk reduction in prostate cancer-specific mortality (RR 0.73, 95% CI ) 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 )

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14 Guidelines on PSA screening Men who are younger than 40 years old Advised against PSA screening Men aged years old Recommended to have PSA screening only if they are at high risk of cancer development Men aged 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

15 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

16 Any there any better markers?

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19 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

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22 PHI range Probability of cancer (Catalona series) Probability of cancer (HK series) Probability of significant cancer (HK series) % 3.6% 0.5% % 7.6% 0.9% % 22.9% 6.9% % 38.1% 19.0%

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28 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

29 Median IQR Age (years) PSA (ng/ml) TRUS-PV (ml) All n= Development cohort Hospital 1 n= Table 1. Baseline characteristics of the development and validation cohorts Validation cohort Hospital 2 n= Abnormal TRUS findings 260(8.4%) N/A Abnormal DRE 825 (15.6%) 437 (14.1%) 388 (17.5%) TRUS biopsy cores <6 cores 6-8 cores 9-10 cores cores >12 cores 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%) Any grade prostate cancer 970 (18.3%) 523 (16.9%) 447 (20.2%) High grade prostate cancer 461 (8.7%) 247 (8.0%) 214 (9.7%) PK Chiu et al. Prostate Cancer Prostatic Dis. (In press)

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33 Multi-parametric MRI T2 weighed imaging Diffusion weighted imaging Dynamic contrast enhanced imaging

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35 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

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37 T2W in Peripheral Zone

38 PI-RADS 1 PI-RADS 2 PI-RADS 3 PI-RADS 4 PI-RADS 5

39 DWI in Peripheral Zone

40 ADC PI-RADS 1 PI-RADS 2 PI-RADS 3 PI-RADS 4 PI-RADS 5

41 High b value PI-RADS 1 PI-RADS 2 PI-RADS 3 PI-RADS 4 PI-RADS 5

42 DCE in Peripheral Zone

43 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

44 MRI fusion targeted biopsy

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47 Cancer detection rate PI-RADS 2 0% (0/33) PI-RADS % (4/35) PI-RADS % (7/24) PI-RADS 5 50% (3/6) 92.9% (13/14) of the detected cancers are clinically significant cancers!

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49 Treatment of Prostate Cancer

50 Localised prostate cancer Radical prostatectomy Radiotherapy Active surveillance

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52 Surgical Outcomes Monitoring and Improvement Program (SOMIP) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Open Laparoscopic Robotic

53 SOMIP peri-operative results July 2015 June 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)

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59 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 cancers Hamdy et al. NEJM 2016.

60 Localized disease To treat or not to treat? Patient factors Age Comorbidities Disease factors Clinical T stage PSA Gleason score

61 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

62 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!

63 Castration resistant prostate cancer

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65 Chemo? Symptoms Median overall survival benefit Hazard ratio (95% CI) Abiraterone (COU-AA-301) Abiraterone (COU-AA-302) Enzalutamide (AFFIRM) Enzalutamide (PREVAIL) Carbazitaxel (TROPIC) Post-chemo BPI-SF months 0.74 ( ) Pre-chemo BPI-SF ( ) Post-chemo BPI-SF months 0.63 ( ) Pre-chemo BPI-SF months 0.71 ( ) Post-chemo months 0.70 ( ) Radium (ALSYMPCA) Both pre- and post-chemo Analgesic or EBRT for cancer-related bone pain 3.6 months 0.70 ( ) Sipuleucel-T Both pre- and post-chemo Asymptomatic or minimally symptomatic 4.1 months 0.78 ( )

66 Summary Prostate cancer detection rate with reference to PSA level is much lower in Chinese men PSA screening (HKUA recommendation) Men aged years old Only if they are at high risk of cancer development Men aged years old Shared decision making after the potential benefit and harm are discussed

67 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

68 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

69 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

70 Thank you! Jeremy Teoh ( 張源津 ) Assistant Professor, Department of Surgery, The Chinese University of Hong Kong. jeremyteoh@surgery.cuhk.edu.hk