This document provides an overview of localized prostate cancer, including: 1. It describes the anatomy of the prostate and surrounding structures. 2. It discusses diagnosis and imaging for prostate cancer including DRE, PSA testing, multiparametric MRI, and prostate biopsy. 3. It covers risk stratification for prostate cancer based on factors like Gleason score, PSA, and tumor stage to determine appropriate management strategies.

1. LOCALIZED PROSTATE
CANCER
​Dr Mayank Mohan Agarwal
MBBS, MS, MRCS(Ed), ​DNB, MCh (PGIMER, Chandigarh)
VMMF and IAUA Fellowships Uro-Oncology, Pelvic Floor Reconstruction
(MSKCC, NY; UCLA, LA; WFUBMC, NC)​
Formerly, Associate Professor of Urology (PGIMER, Chandigarh)
Formerly, Consultant & Head of Urology (NMCSH, Abu Dhabi)
Consultant and Head of Urology
(Aster) Dr. Ramesh Cardiac and Multispecialty Hospitals Pvt. Ltd.
Guntur (AP), India

2. Introduction
• Anatomy
• Diagnosis
• Imaging
• Risk stratification
• Management strategies

3. Anatomy
4cm
3cm
2cm

4. Vascular anatomy

5. Muscular structures

6. NERVE BUNDLES

8. CONTINENCE
ERECTION
LGI FUNCTION
LUT FUNCTION

9. DIAGNOSIS AND IMAGING
• DRE
• PSA
• MULTIPARAMETRIC MRI
• TRUS guided prostate biopsy
UROLOGIST

10. Population based PSA screening
• Population based RCT n = 182000
0
0.2
0.4
0.6
0.8
1
1.2
50-54 55-59 60-64 65-69 70-74
CAP specific deaths per 1000 person-year
screening control
Schroder FH et al. N Engl J Med 2009;360:1320-8.

11. PSA (human Kallikrein peptidase 3)
• Serine protease, member of a family of 15 hkp’s
• preproPSA  proPSA  PSA  _mg/ml into semen
A millionth (_ng/ml)
unprocessed
Processed
in prostate
(70-80%)
(90-95%)
(5-10%)
(1-2%)
(20-30%)

12. PSA (human Kallikrein peptidase 3)
• Serine protease, member of a family of 15 hkp’s
• preproPSA  proPSA  PSA  _mg/ml into semen
A millionth (_ng/ml)
unprocessed
Processed
in prostate
(70-80%)
(90-95%)
(5-10%)
(1-2%)IN
CANCER
(<20-30%)

13. PSA (human Kallikrein peptidase 3)
• Organ specific (almost)
– breast tissue, breast milk, breast/kidney/adrenal cancer, parotid
• Disease non-specific
– prostatic hyperplasia, prostatitis, prostate manipulation, prostate cancer

14. Risk of CAP based on PSA
• PSA is a continuous variable
• There is actually no “normal” value
• “probability” of having CAP proportional to PSA
0
20
40
60
80
100
0.0-0.5 0.6-1.0 1.1-2.0 2.1-3.0 3.1-4.0 4.1-10.0 10.1-20.0 >20.1
% risk of CAP
Thompson, I.M., et al. N Engl J Med 2004; 350: 2239.

15. NCCN 2018

17. HOW TO IMPROVE SPECIFICITY OF PSA 4-10
• PSA > 3ng/ml – indication for biopsy ~25% PPV
• Can we avoid biopsies in some of these patients?

18. Percent free PSA
• “more the merrier”
0
20
40
60
80
100
8 10 11 12 13 14 15 17
perc free PSA
sensitivity specificity
unprocessed
Processed
in prostate
(70-80%)
(90-95%)
(5-10%)
(1-2%)IN
CANCER
(<20-30%)

19. PSA density
• PSA per unit volume (PSAD) 0.10 – 0.15
• PSA per unit TZ volume (PSAD-TZ) ?? 0.20 – 0.30
0
20
40
60
80
100
0.1 0.15 0.2 0.3
sensitivity specificity
PSAD-TZ
0
20
40
60
80
100
0.075 0.1 0.15 0.2 0.25
sensitivity specificity
PSAD

20. PSA velocity
• Various cutoffs sensitivity – specificity balance poor
• Valid only in long term follow up (at least 3 values, at least 18m duration)
• For PSA 4-10 cutoffs 0.35-0.75 ng/ml/yr have been used with relatively
high specificity but low sensitivity
Mettlin C. Cancer 1994; 74:1615-20; Lee SC. Korean J Urol 2004;45:747-752

21. TRUS GUIDED PROSTATE BIOPSY
• Proper preparation
- Control of sugar
- Urine culture (+/_ stool culture to detect MDR / ESBL)
- Reduce anticoagulation (max aspirin 75mg/d)
- Bowel preparation
- Antibiotic prophylaxis
• Counseling for complications
- Sepsis
- Retention
- Hematuria
• At least 12 cores
+ lesion guided (if applicable)
+ more cores for larger prostates

22. Multiparametric MRI
• T1
• T2
• DWI / ADC
• CEMRI
• spectroscopy
PIRADS. American College of Radiology. 2015

23. Risk stratification
Very low
low
Int. favorable
Int. unfavorable
Intermediate high
low Very high
high
REGIONAL (N1)
METASTATIC (M1)

24. Risk stratification
Factors to consider –
1. TNM staging
2. Gleason scoring
3. PSA
4. PSAD
5. No. of biopsy cores (+)
6. % of a core (+)
T1
T2
T3
T4

25. Risk stratification
Factors to consider –
1. TNM staging
2. Gleason scoring
3. PSA
4. PSAD
5. No. of biopsy cores (+)
6. % of a core (+)
1-3
4
5

26. Risk stratification
Factors to consider –
1. TNM staging
2. Gleason scoring
3. PSA < 10 – 20 <
4. PSAD
5. No. of biopsy cores (+)
6. % of a core (+)

27. Risk stratification
Factors to consider –
1. TNM staging
2. Gleason scoring
3. PSA < 10 – 20 <
4. PSAD
5. No. of biopsy cores (+)
6. % of a core (+)
Minor factors for
‘fine tuning’

28. Management strategies for localized cancer
Determinants –
• Risk-group
• Patient’s physiological status
 Charlson’s comorbidity index
 Life expectancy
• Availability and affordability
• Patient’s preferences
RADICAL
PROSTATECTOMY
RADICAL
RADIOTHERAPY
ACTIVE
SURVEILLANCE

29. ACTIVE SURVEILLANCE
Diagnosis progression metastasis Death by disease
Natural Death
Very low
low
Int. favorable
Int. unfavorable
Intermediate high
low Very high
high
• Gleason score 6
• PSA <10
• T1 – 2a

30. ACTIVE SURVEILLANCE
• Is not watchful waiting
• Actively monitoring disease status throughout
• Suitable for very low risk and low risk patients
• Monitoring by
• PSA velocity
• MRI
• Re-biopsy
Diagnosis progression metastasis Death by disease
Natural Death

31. Radical prostatectomy vs radiotherapy

32. Radical prostatectomy vs radiotherapy
CURE
PROS
CONS
PROS
CONS

33. Radical prostatectomy vs radiotherapy

34. Radical prostatectomy
• Open
• Laparoscopic
- Without
- With robotic assistance
Retropubic transperitoneal
radical prostatectomy
retropubic retroperitoneal
radical prostatectomy
laparoscopic
transperitoneal radical
prostatectomy
extraperitoneoscopic radical
prostatectomy robotic
assisted transperitoneal
radical prostatectomy
robotic assisted
extraperitoneoscopic radical
prostatectomy intrafascial
prostatectomy, transfascial
prostatectomy extrafascial
prostatectomy partial
prostatectomy sexuality
preserving prostatectomy
open perineal radical
prostatectomy robotic
perineal radical
prostatectomy veil of
Aphrodite procedure
complete posterior
reconstruction complete
anterior reconstruction
Rocco’s stitch
• Most effective local
clearance of localized
disease
• Most accurate biopsy to
design further treatment
• Incontinence
• Erectile dysfunction
• LUT dysfunction

35. Radical Radiotherapy
• 3d-CRT
• IMRT
• With or without IGRT ** - preferred
• Non-invasive
• Incontinence
• Erectile dysfunction
• LUT dysfunction
• LGI dysfunction

36. Admissions MIS urology Rectal proceduresOpen surgery
Radical prostatectomy vs Radical Radiotherapy
• 32465 men with CAP almost 1:1 open RP and RT
• 32465 men without CAP comparator
Nam et al. Lancet Oncol 2014

37. Radical prostatectomy vs Radical Radiotherapy
• 68665 men with CAP almost 1:2 RP and RT
Abdollah et al. Int J Urol 2012

38. Adjuvant therapy
RADICAL
PROSTATECTOMY
RADICAL
RADIOTHERAPY
ADT
LHRH antagonist
LHRH agonist
Orchidectomy

39. THANK YOU