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Diagnosis
and impact of
pathology on prognosis
Novelties with clinical impact
Universitat Autónoma de Barcelona
F.Algaba
Unit of Pathology
No Conflict of Interest
PROSTATE CANCER PATHOLOGY
What´s the morphologic
aspect of
prostate carcinoma?
Normal prostate acini
Prostate cancer
Prostate cancer low proliferative rate
Prostate cancer high proliferative rate
Gleason
• 1966
PSA had not yet been discovered
• 1974
86% advanced disease
• Only 2 core biopsies
• Radical prostectomy: infrequent
• No immunohistochemistry
1966 1974 1977
The same
biological
significance
Fused
Cribriform
Glomeruloid
ill defined
Cribriform pattern worse prognosis?
ISUP 2014
WHO 2016
Gleason WHO 2016
Biopsy
Pattern 3
4
3+4
Pattern 4
3
4+4
Pattern 3
Pattern 4
5
3+5
Am. J. Surg. Pathol. 2005; 29: 1228-1242
4
3
4
5
Gleason 4+5
4
4
WHO 2016
BIOPSY
Grade Group
ISUP / WHO 2016
recommendation
The Johns Hopkins University
System (J. Epstein)
6
1
3 +4
2
4 +3
3
4 +4
sG 9 to 10
4
5
4+4=8
3+5=8 (0.2%)
5+3=8 (0.02%)
“Recurrence-free progression”
Post prostatectomy according grade groupr in biopsy
5 hospitals 20845 patients
Follow-up 3 years, 6008 patients 5 years
1
2
3
4
5
Años
Biochemical recurrence PSA 0.2 ng/ml,
Eur Urol 2016; 69: 428 – 435
“Recurrence-free progression”
Post prostatectomy according grade groupr in prostatectomy specimen
5 hospitals 20845 patients
Hazard
Follow-up 3 years, 6008 patients 5 years No
recurrence
ratio
1
96%
1
2
88%
2.2
3
4
63%
48%
7.3
12.3
5
26%
23.9
Años
Eur Urol 2016; 69: 428 – 435
Recurrence-free progression following radical prostatectomy
stratified by pre-prostatectomy biopsy grade
1
2
3
4
5
20845 patients
3694 patients
1
2
4
3
5
4325 patients
Eur. Urol. 2015 doi: 10.1016
Eur. Urol. 2016; 69: 428 – 435
BJU Int 2016 doi:10.111
Eur. Urol. 2016; 69: 557
Grade
group 1
Grade
group 2
Grade
group 3
Grade
group 4
Grade
Group 5
426 prostatectomías
2016
Very low risk prostate cancer
Needle biopsy
Low grade
Low volume
Low PSA
No invasion
T1c
PSA density ≤ 0.15 Gs 6 (group 1)
≤ 2 cores ≤ 50% in every core
Very low risk prostate cancer
Grading
WHO 2016
Needle biopsy Low grade
Recurrence-free progression following radical prostatectomy
stratified by pre-prostatectomy biopsy grade (20845patients)
3+3
Recurrence
1
4%
2
3
4
5
12%
Very low risk prostate cancer
Kweldam CF et al Eur. J. Cancer en prensa
Recurrence-free progression in radical prostatectomy
according to grade 6 versus 7 (with or without cribriform pattern)
No cribriform
Cribriform
Similar approach for Gs 6 and 3+4 without cribriform pattern ?
NO CONSENSUS ABOUT PERCENTAGE
BILATERALITY CORRELATE
Percentage
Insignificant PCa
in Radical Pr.
PCa
Bilaterality
70.1%
No Prostate
73%
23% ?
PCa
High probability of
cancer between them
80% ?
Very low risk prostate cancer
Definitions in needle biopsies
T1c
PSA density ≤ 0.15 Gs 6 (Grade group 1)
Gs7 (3+4 no cribriform)(group 2)?
≤ 2 cores ≤ 50% in every core
≤ 2 cores , Unilateral ?
J. Urol 2013; 190: 1218
Urology 2014; 83: 869
PROSTATE CANCER PATHOLOGY STAGE
2016
PROSTATE CANCER PATHOLOGY STAGE
Pathological stage versus 10-years
biochemical recurrence–free survival.
Eur Urol. 2015; 67:342–346.
pT3a
AJSP 2007; 31: 311
Biochemical recurrence
2 years
4 years
< 0.75 mm
38%
65%
> 0.75 mm
65%
82%
NEGATIVE MARGIN
POSITIVE MARGIN
Positive margins
Positive focal margin ≤ 3mm
Positive non-focal margin > 3mm.
pT2
Negative
margin
Positive 1
focal
Positive
1 non focal
Positive
mNon focal
Patients
1065
84.3%
62
4.9%
104
8.2%
33
2.6%
5years
Free survival
90%
83.4%
pT2
pT3a
Positive margins
pT2
PSA recurrence
Smooth margin
30.6%
Irregular margin
65.5%
Ojea CA et al., Actas Urol Esp. 2005;29:641-56
PROSTATE CANCER PATHOLOGY
Cellular transformation
afther non-surgical treatment
Castration resistance
Secretory cells (AR+)
Indifferentiated or
intermedate
phenotype
Stem and
Neuroendocrine
Cells (AR-)
Intermediate
cells (AR+/-)
Neuroendocrine
phenotype
PROSTATE CANCER PATHOLOGY
artificial selection
Chromogranine A score
(neuroendocrine)
No hormonal treatment
0.4± 07
3-6 m. hormonal treatment
0.7 ± 0.7
1 year hormonal treatment
1.4 ± 1.1
Staining of prostatic carcinoma was scored as
0 = no staining;
1 = staining cells <10%;
2 = staining cells 10–20%;
3 = staining cells >20%.
Köllerman et al Eur. Urol. 2001; 40: 313
Hirano et al Eur.Urol. 2004; 45: 586
PROSTATE CANCER PATHOLOGY
How can we improve
the prediction of the
biology of prostate cancer ?
PROSTATE CARCINOMA BIOMARKERS
Choudhury et al. Eur. Urol. 2012; 62: 577
50%
6%- 13%
27-79%
20%- 40%
Histopathology 60:187–198, 2012
PTEN & ERG/ETV1
PTEN loss
Br. J. Cancer 2010; 102: 678
Diagnosis and impact of
pathology on prognosis
Refinement grading criteria and
new groups (WHO- TNM 2016)
Quantification
Number and mm of PCa in core biopsies
Radial growth in extraprostatic invasion
Focal vs non-focal positive margins
MRI
PTEN+ERG…