1. Current Guidelines in the treatment of Prostate Cancer: what is most appropriate for Nigerian patients?
Dr Emmanuel Ajibola Jeje
BSc. M. B. Ch.B; FMCS; FWACS; FICS; FACS
Consultant Urologist, Lagos University Teaching Hospital
President Nigeria Association of Urological Surgeons

2. Which Guidelines do you think Prostate Specialists in Nigeria refer to?
EAU Guidelines
AUA Guideline
BAUS Guideline
ESMO guidelines
NCCN or other US
Internal Guidelines from HCPs institution
National Guidelines
Other guidelines
At the Faculty Update meeting held in Nice in May 2011 the delegates (~ ) were asked which guidelines do they refer to. They were allowed to select only one option

3. Which Guidelines do Prostate Specialists in SSA refer to?
These are the answers
As expected the EAU guidelines were the most popular and this is not surprising given that it was an EMEA audience

4. Review of Guidelines
Compare the following guidelines for similarities and differences on the key issues:
EAU
ESMO
NCCN
AUA
We have undertook a review of the top 3 guidelines to look for similarities and the differences and then given an overall conclusion for each topic
NCCN Guidelines Version Accessed December 2014
ESMO Prostate Cancer :Clinical Practice Guidelines, 2013
EAU Guidelines 2014; Accessed December 2014

5. Screening EAU ESMO NCCN
At present widespread mass screening for PCa is not appropriate
Rather, early
detection (opportunistic screening) should be offered to the well-informed man
No guidance
Early detection when applied properly should reduce PCa mortality. However the reduction comes at the expense of over treatment that may occur in as many as 50% of men treated for PSA detected PCa
No clear guidance
Overall
No clear guidance on the use of routine screening of PSA for detection of prostate cancer (PCa)
Due to the contradictory evidence on the usefulness of screening, all of the guidelines either do not recommend or do not give any clear guidance on the use of mass screening to detect prostate cancer

6. General agreement between the guidelines on the diagnosis of PCa
EAU
ESMO
NCCN
Serum PSA, DRE & transrectal ultrasnography (TRUS)
Need for prostate biopsy made on results from: PSA, DRE, age, co-morbidities.
Number of cores: minimum 10
Commonest and the worst Gleason grades should be reported
Serum PSA & DRE
Need for prostate biopsy made on results from:
PSA (3 ng/mL cut off), DRE, age, symptoms, co-morbidities, patient values and family history, TRUS results
Number of cores: minimum 8
Biopsy recommended but no guidance given
Number of cores: not stated
Overall
General agreement between the guidelines on the diagnosis of PCa

7. Staging Stage EAU ESMO NCCN Overall
Very Low
Not defined
T1c
Gleason score ≤6
PSA <10 ng/mL
Fewer than 3 positive biopsy cores, ≤50% cancer in each core
Low Risk
T1-T2a
Gleason ≤ 6
PSA<10 ng/mL
Gleason <7
T1-2a
Gleason 2-6
Intermediate
T2b-T2c or
Gleason score 7 or
PSA ng/mL
All others not fitting into low or high categories
High
T3a or
Gleason score 8-10 or
PSA >20 ng/ml
T3-4
Gleason >7
PSA >20 ng/mL
Very High
T3b-T4
N0 or any T, N1
Metastatic M1
Any T, N1 or Any T, Any N, M1
Overall
Consistency between definitions for low, intermediate and high but additional stages at the extremes for EAU and NCCN

8. Treatment Protocol

9. Consistency between the guidelines on management of low-risk PCa
EAU
ESMO
NCCN
Watchful waiting or
Active Surveillance
Radiotherapy
Low dose Brachytherapy
Radical prostatectomy
Active surveillance
external beam radiotherapy, brachytherapy with
permanent implants or high-dose rate brachytherapy with temporary implants
Radical prostatectomy (RP)
Hormone therapy (HT) alone or adjuvant to RP
Watchful waiting with delayed HT at symptomatic progression (those unwilling to receive radical treatment)
PSA every 6 months (min)
DRE every 12 months (min)
Repeat biopsy every 12 months
Radiotherapy (external beam radiotherapy or brachytherapy)
Radical prostatectomy ± pelvic lymph node dissection
If adverse features then radiotherapy or observation
If lymph node positive then observation or ADT
Overall
Consistency between the guidelines on management of low-risk PCa

10. Intermediate Risk EAU ESMO NCCN Overall
Watchful waiting or
Radiotherapy
Radical prostatectomy
Brachytherapy
Hormonal
Combination
External beam radiotherapy or brachytherapy with permanent implants
If moderate dose of radiotherapy (<60 Gy), ADT for 6 months should be given
Watchful waiting with delayed hormone therapy at symptomatic progression (those unwilling to receive radical treatment)
Active Surveillance
PSA every 6 months (min)
DRE every 12 months (min)
Repeat biopsy every 12 months
Radiotherapy ± short-term ADT (4-6 months) ± brachytherapy
Radical prostatectomy ± pelvic lymph node dissection
If adverse features then radiotherapy or observation
If lymph node positive then observation or ADT
Overall
Consistency between the guidelines on management of intermediate-risk PCa

11. Consistency between the guidelines on management of high-risk PCa
EAU
ESMO
NCCN
Watchful waiting
External Beam Radiotherapy + long-term ADT (3 years) or
Radiotherapy + short-term ADT
Radical prostatectomy + pelvic lymph node dissection
Radical prostatectomy (for N1 disease post-operative ADT)
Radiotherapy (external beam) plus (neo)adjuvant treatment (LHRH for 3-6 months)
Radiotherapy + long term ADT (≥24 months years or ≥6 months for locally advanced disease, ≥T2b)
Watchful waiting with delayed hormone therapy at symptomatic progression (those unwilling to receive radical treatment)
Intermittent HT can be offered for locally advanced disease
External Beam Radiotherapy ± long-term ADT (2-3 years) (category 1)
Radiotherapy + brachytherapy ± long-term ADT (2-3 years)
If adverse features then radiotherapy or observation
If lymph node positive then observation or ADT± pelvic EBRT
Overall
Consistency between the guidelines on management of high-risk PCa

12. ? Less acceptance of this category within EMEA
Very High Risk
EAU
ESMO
NCCN
Watchful waiting or
Radical Prostatectomy
Radiotherapy + long-term ADT (3 years)
Hormonal
Combination
No guidance
External Beam Radiotherapy ± long-term ADT (2-3 years) (category 1)
Radiotherapy + brachytherapy ± long-term ADT (2-3 years)
Radical prostatectomy + pelvic lymph node dissection
If adverse features then radiotherapy or observation
If lymph node positive then observation or ADT ± pelvic EBRT
ADT in selected patients
Overall
NCCN guidelines have more detail guidance on management of very-high risk PCa.
? Less acceptance of this category within EMEA

13. M0 or M1 ADT-Naïve Patients
EAU
ESMO
NCCN
Watchful waiting or
Radical prostatectomy
Radiotherapy
Hormonal
Orchiectomy
Lifelong ADT
LHRH agonist alone ± anti-androgen to prevent testosterone flare
Any T, N1
ADT
EBRT +ADT (2-3 y) (category 1) Or
Any T,N,M1
Overall
Guidelines provide similar recommendations for management of M0 and M1 PCA

14. Asymptomatic mCRPC Chemotherapy-Naïve Patients
EAU
ESMO
NCCN
Performans Status 0 or 1 with no visceral metastasis
Abiraterone
Enzalutamide
Sipuleucel T or
Second-line hormone therapy (antiandrogen, antiandrogen withdrawal, estrogen, steroids)
Performans Status 2+
Monitoring
Anti- androgens
Second-line hormone therapy (antiandrogen, antiandrogen withdrawal, estrogen, ketoconazole, steroids)
Sipuleucel-T
Clinical trial
Docetaxel (should be discussed with asymptomatic patients)
No Visceral Metastases
Enzalutamide (category 1)
Abiraterone acetateX with prednisone (category 1)
Docetaxel + prednisone (category 1)
Radium-223 for symptomatic bone metastases (category 1)
Secondary hormone therapy
Antiandrogen
Antiandrogen withdrawal
Ketoconazole
Corticosteroids
Clinical trials
X For patients who are not candidates for docetaxel-based regimens
Overall
In NCCN Guidelines Replaced «syptomatic» with «visceral disease». Abiraterone and enzalutamide are recommended by EAU and NCCN Guidelines.

15. Symptomatic mCRPC EAU ESMO NCCN Overall
Androgen suppression should therefore be continued indefinitely in these patients
First line options include PS 0-1 no visceral mets:
Docetaxel
Alpharadin (Radium-223)
First line options include PS 0-1 visceral mets:
Performans Status 2+
Docetaxel using a 3-weekly schedule should be considered for Symptomatic CRPC
Second-line options include:
Abiraterone (post-docetaxel)
Cabazitaxel (post docetaxel)
Docetaxel rechallenge
Mitoxantrone
Enzalutamide (if available)
Radium-223 (if available)
Visceral Metastases
Docetaxel + prednisone (category 1)
Enzalutamide (categoty 1)
Abiraterone acetatex with prednisone
Alternative chemox (mitoxantrone)
Clinical trial
X For patients who are not candidates for docetaxel-based regimens
Overall
Docetaxel is the preferred chemotherapy. 2nd line options post-docetaxel are cabazitaxel and abiraterone, enzalutamide

16. Subsequent therapy for mCRPC with no visceral metastases
EAU
ESMO
NCCN
Second line options include:
(dependent on previous treatment)
Docetaxel
Abiraterone
Enzalutamide
Cabazitaxel
Radium-223 no visceral mets. NA
Prior therapy enzalutamide/abiraterone:
Docetaxel + prednisone (category 1)
Abiraterone acetate or enzalutamide
Radium-223 (category 1) If bone-predominant disease
Sipuleucel-T If asymptomatic or minimally symptmatic,no liver metastases,life expectancy >6 mo,ECOG 0-1
Clinical trial
Other secondary hormone therapy
Antiandrogen
Antiandrogen withdrawal
Ketoconazole
Corticosteroids
DES or other Estrogen
Best supportive care
Prior therapy Docetaxel:
Enzalutamide (categoty 1)
Abiraterone acetate with prednisone(categoty 1)
Cabazitaxel with prednisone (category 1)
Alternative chemo (mitoxantrone)
Docetaxel rechallenge
Other secondary hormone therapy and Best supportive care(see above)
Overall
2nd line options post-docetaxel are cabazitaxel and abiraterone, enzalutamide, 2nd line options post- abi/enza are docetaxel,radium 223,abiraterone or enzalutamide,sipuleucel-T

17. Subsequent therapy for mCRPC with visceral metastases
EAU
ESMO
NCCN
Second line options include:
(dependent on previous treatment)
Docetaxel
Abiraterone
Enzalutamide
Cabazitaxel
Radium-223 no visceral mets. NA
Prior therapy enzalutamide/abiraterone:
Docetaxel + prednisone (category 1)
Clinical Trial
Abiraterone acetate or enzalutamide
Other secondary hormone therapy
Antiandrogen
Antiandrogen withdrawal
Ketoconazole
Corticosteroids
DES or other Estrogen
Best supportive care
Prior therapy Docetaxel:
Enzalutamide (categoty 1)
Abiraterone acetate with prednisone(categoty 1)
Radium-223 (category 1) If bone-predominant disease
Cabazitaxel with prednisone (category 1)
Docetaxel rechallenge
Alternative chemo (mitoxantrone)
Clinical trial
Other secondary hormone therapy and Best supportive care (see above)
Overall
2nd line options post-docetaxel are cabazitaxel and abiraterone, enzalutamide, 2nd line options post- abiraterone/enzalutamide are docetaxel,abiraterone or enzalutamide

18. Use of Bisphophonates EAU ESMO NCCN Overall
The optimal regimen for zoledronic acid is unclear
One study recommends treatment every 3 weeks, while another trial has produced similar results with an annual
injection
The initial BMD could be used to guide the choice of regimen
Denosumab may prevent further SREs
Benefit vs risk must be carefully weighed
Denosumab or zoledronic acid to delay SREs
In CRPC patients with bone metastases, denosumab and zoledronic acid have been shown to prevent disease-related skeletal complications
Optimal duration of therapy of either drug remains uncertain
Overall
Bisphosphonates are recommended only for patients with bone metastases. Both zoledronic acid and denosumab are equally recommended

19. Which of these Guidelines do you think is best suited for our patients in Nigeria?
EAU Guidelines
AUA Guideline
BAUS Guideline
ESMO guidelines
NCCN or other US
Internal Guidelines from HCPs institution
National Guidelines
Other guidelines
At the Faculty Update meeting held in Nice in May 2011 the delegates (~ ) were asked which guidelines do they refer to. They were allowed to select only one option

20. Conclusion
General consistency between the guidelines on prostate cancer
EAU are the most comprehensive of the European guidelines
NCCN guidelines provide most in-depth and up to date information on the management of prostate cancer
Novel agents (abiraterone, cabazitaxel, enzalutamide, radium-223) are now being included in the guidelines
Urgent need for National guideline

21. Thank you for listening