oncoforum 2014 highlights prof. jeroen van moorselaar prof ......68gallium-labelled...
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Oncoforum 2014 highlights
Prof. Jeroen van Moorselaar
Prof. Gert De Meerleer
Dr. Maria De Santis
» Programme to provide specialists with highlights of major
congresses in the form of slide sets in PowerPoint
» Available at www.oncoforum.org
» Used during meetings
» Started in 2001 in France, since 2006 throughout Europe
» Educational programme of (scientific NPO)
What is Oncoforum Urology?
Approach Oncoforum programme
Abstract
presentations at
congresses
Selection of
abstracts by
reporters
Slides rated &
commented by
reviewers
Publication of
slides on
website within
2 mo after
congress
Information
spread at
national /
regional
meetings
Slide libraries
Congresses covered in 2014
» Screening
» Imaging
» Active Surveillance
» Surgery
» Hormonal Therapy
Oncoforum 2014 highlights: Urology
» Population-based study started in 1995; N=20,000 men randomised to:
» Intervention arm: invited for PSA testing every 2nd year until stop age
(average 69 yrs)
» Control arm: not invited for PSA testing but exposed to opportunistic PSA
screening
Hugosson JE. Eur Urol Suppl 2014:13(1):e848
The Gothenburg randomised PCa PSA-based screening trial: 18-yr FU results
8,9
12,9 13,811.5
15,116,2
17,316,2
0
5
10
15
20
50-54 yrs 55-59 yrs 60-64 yrs All
Age at randomisation
Cumulative PCa incidence at 18 yrs of FU (%)
Control arm Screening arm
0,5
1,8
2,7
1,5
0,3
0,9
2,4
1.0
0
1
2
3
50-54 yrs 55-59 yrs 60-64 yrs All
Age at randomisation
Cumulative PCa mortality at 18 yrs of FU (%)
Control arm Screening arm
(1/2)
Data from poster
» Number needed to invite (NNI) and number needed to diagnose (NND)
to prevent 1 PCa death at 18 yrs of FU:
Hugosson JE. Eur Urol Suppl 2014:13(1):e848
Organised PSA-based screening results in a significant decrease in PCa
mortality, however 60 yrs appears to be too late to start organised screening
The Gothenburg randomised PCa PSA-based screening trial: 18-yr FU results
50-54 yrs 55-59 yrs 60-64 yrs All All
(14 yrs of FU)
NNI 500 111 333 200 293
NND 31 4 12 9 12
(2/2)
Data from poster
» German multi-centre registry study; N=942 men with T level ≤12.1 nmol/l who
received T undecanoate injections for up to 16 yrs
Haider A. J Clin Oncol 2014:32(Suppl 4):abs.119
There seems to be no increased risk of PCa in hypogonadal men treated with
long-term testosterone
Effect of testosterone (T) undecanoate injections on PCa incidence in hypogonadal men
1,8
2
0,91,4
1,61,9
0
1
2
3
Baseline After 16 yrs
PSA level (ng/ml)
Centre 1 Centre 2 Centre 3
All P≤0.002
28 3128
37
17 20
0
10
20
30
40
Baseline After 16 yrs
Prostate volume (ml)
Centre 1 Centre 2 Centre 3
All P<0.001
Centre 1 (N=300) Centre 2 (N=261) Centre 3 (N=381)
PCa diagnosis 1.7% of pts 2.3% of pts 0% of pts
PCa incidence 39.4/10,000 pt yrs 54.5/10,000 pt yrs -
» Screening
» Imaging
» PET-CT
» MRI/TRUS
» Active Surveillance
» Surgery
» Hormonal Therapy
Oncoforum 2014 highlights: Urology
» Prospective, single-centre study (2007-2010); N=146 PCa pts who underwent
RP without adjuvant treatments, negative conventional imaging and PSA levels
between 0.2 and 1 ng/ml
» Multivariable analysis: significant predictors of positive 18F-choline PET/CT
Simone G. J Urol 2014:191(4 Suppl):e470(abs.MP42-06)
18F-choline PET/CT might be of value in pts with PSA level <1 ng/ml to
detect PCa recurrence after RP (89% pos in prostatic fossa)
Role of 18F-choline PET/CT in the early (PSA <1 ng/ml) detection of PCa recurrence after RP
Outcome
Median trigger PSA 0.6 ng/ml
Median PSA doubling time 7.9 mo
Median PSA velocity 0.02 ng/ml/mo
Positive PET/CT 76% of pts
18F-choline PET/CT %
Sensitivity 79%
Specificity 70%
Positive predictive value 97%
Negative predictive value 20%
Accuracy 79%
Predictor OR 95% CI P
Trigger PSA ≥0.6 ng/ml 3.13 1.55-6.31 0.001
PSA velocity ≥0.04 ng/ml/mo 4.95 1.65-14.83 0.004
» Single-centre prospective study; N=103 PCa pts with rising PSA values after
RP (N=97) or RT (N=6) who underwent a PET and CT scan
Müller-Mattheis V. Eur Urol Suppl 2014:13(1):e729
A more specific tracer is still needed to detect recurrent disease after RP/RT
Is there a role for 11C-acetate PET/CT imaging in the detection of recurrent disease after RP or RT?
Outcome
Positive PET scan
• PSA 0.5-1.45 ng/ml
• PSA 2.7-9.01 ng/ml
• PSA 13.4-30.5 ng/ml
42 pts
16 pts
16 pts
7 pts
Positive lymph nodes (LNs) on PET scan
• Pathological confirmation
• Treatment with RT for LN metastasis
16/42 pts
10/16 pts
9/16 pts
Additional treatment with hormone therapy 15/42 pts
Additional treatment with chemotherapy 2/42 pts
Pts who underwent RP + RT
• True positives on PET scan
• PSA level <2.0 ng/ml
25 pts
19/25 pts
13/25 pts PPV: 76%
» Retrospective analysis; N=107 PCa pts with biochemical recurrent PCa
(median PSA: 1.9 ng/ml – range: 0.2-45 ng/ml)
» Pathological 68Ga-PSMA uptake on PET/CT (N=57/62) or PET/MR (N=34/45)
Maurer T. Eur Urol Suppl 2014:13(1):e726
68Ga-PSMA PET-imaging seems to be effective to detect recurrent PCa,
even at low PSA levels
68Gallium-labelled prostate-specific membrane antigen (PSMA) PET-imaging: useful to detect biochemical recurrent PCa?
55,6
8,7
11,1
47,8
0
20
40
60
80
100
PET/CT PET/MR
De
tec
tio
n r
ate
(%
)
PSA <1 ng/ml
Highly suggestive lesions
Suspicious lesions
5033,3
41,755,6
0
20
40
60
80
100
PET/CT PET/MR
PSA 1-2 ng/ml
Highly suggestive lesions
Suspicious lesions
12,2 15,4
85,4 84,6
0
20
40
60
80
100
PET/CT PET/MR
PSA ≥2 ng/ml
Highly suggestive lesions
Suspicious lesions
Data from poster
» Single-centre, prospective study (2011-2013); N=216 men (≤cT2c) with
suspicious cancerous lesions on preBx MRI who underwent MRBx (4-cores of
suspicious lesions) and SBx (14 cores) including anterior samplings
Numao N. Eur Urol Suppl 2014:13(1):e949
MRBx appears to have equivalent ability to detect significant PCa compared with SBx
MRI-targeted Bx (MRBx) vs systematic TRUS-guided Bx (SBx) for the detection of significant PCa
Bx results MRBx + SBx: No PCa Indolent PCa* Significant PCa
# of cases: 61 (28%) 21 (10%) 134 (62%)
*PSA <10 ng/ml, cT1-T2a on DRE, Bx GS ≤3+4, maximum cancer length <5 mm
Diagnostic ability SBx MRBx P
Detection rate indolent PCa 18/21 (86%) 11/21 (52%) 0.18
Detection rate significant PCa 125/134 (93%) 120/134 (90%) 0.70
Bx GS 3+3 Bx GS 3+4 Bx GS 4+3 Bx GS 4+4
SBx-missed significant PCa 2 2 4 1
MRBx-missed significant PCa 6 6 2 0
» Single-centre, prospective study; N=154 men (PSA <10 ng/ml) who underwent
a first series of prostate Bx (a standard 12-core Bx followed by a 2 or 3-core
MRI targeted Bx)
» Mean PSA: 6.5 ng/ml; 92% of men had normal DRE
Mozer P. J Urol 2014:191(4 Suppl):e750(abs.MP67-05)
MRI/TRUS fusion targeted Bx seems superior to standard 12-core TRUS-
guided Bx for the diagnosis of significant PCa
MRI/TRUS fusion targeted biopsy (Bx) vs standard TRUS-guided Bx to diagnose clinically significant PCa
Standard Bx Targeted Bx P
% positive Bx cores 14% 37% <0.0001
% clinically significant* Bx cores 7% 28% <0.0001
Average length positive Bx cores 5.4 mm 8.0 mm <0.0001
% of pts with ≥1 positive Bx core 56% 53% 0.503
% of pts with ≥1 clinically
significant* Bx core
35% 42% 0.027
*maximum positive core length >4 mm or Gleason score >6
» Prospective study (2007-2013); N=822 men who underwent systematic 12-core
template TRUS-guided Bx and MRI/US fusion targeted Bx in the same Bx
session; median PSA: 6.6 ng/ml
Rubin R. J Urol 2014:191(4 Suppl):e589(MP53-03)
MRI/US fusion targeted Bx seems more efficient than standard template Bx
for the diagnosis of high-grade PCa
MRI/US fusion targeted biopsy (Bx) vs standard template Bx for the detection of high-grade PCa
Template Bx Targeted Bx
Mean performed Bx/pt 12 5
PCa diagnosis 43% of men 43% of men
High-grade PCa (GS ≥4+3) 24% of tumours 37% of tumours
Bx cores needed to diagnose any PCa 7.6 3.7
Bx cores needed to diagnose high-grade PCa 29.0 10.5
MRI suspicion of lesion: Low Moderate High
Bx cores needed to diagnose any PCa 10.4 3.6 1.5
Bx cores needed to diagnose high-grade PCa 138.4 12.8 2.7
» Single-centre, prospective study; N=223 asymptomatic Bx-naïve men with
elevated PSA who underwent mpMRI:
» PIRADS 1-2: men underwent systematic TRUS-guided Bx (SBx, 12 cores)
» PIRADS 3-5: men underwent MRI-guided Bx (MRBx, 2-4 cores) followed by SBx
» Missed intermediate/high-risk PCa by MRBx but found by SBx: 15
» Missed intermediate/high-risk PCa by SBx but found by MRBx: 29
Pokorny MR. Eur Urol Suppl 2014:13(1):e947
In asymptomatic men with an elevated PSA, targeted MRBx following mpMRI
might reduce overdiagnosis and increase the detection of significant PCa
Use of MRI in the diagnostic strategy of asymptomatic men with suspicion of PCa
Bx outcomes SBx MRBx Difference
Number of men 223 142 -36%
Bx cores sampled 2,672 417 -84%
Detection PCa
• Low risk*
• Intermediate + high-risk
126 cases
47 cases (21%)
79 cases (35%)
99 cases
6 cases (4%)
93 cases (65%)
-87%
+18%
Data from poster
*low-volume Gleason 3+3 or very low volume Gleason 3+4
» Screening
» Imaging
» Active Surveillance
» Surgery
» Hormonal Therapy
Oncoforum 2014 highlights: Urology
» Prospective single-centre study; N=993 men (median age 68 yrs) with T1b-2b
N0 M0 PCa selected for AS (PSA ≤10 ng/ml or ≤15 ng/ml if ≥70 yrs old,
Gleason score 3+3 or 3+4 if ≥70 yrs old)
» Median FU: 8.1 yrs
» 3.1% of pts developed metastases; 1.5% of pts died of PCa
» Cumulative hazard ratio for non-prostate to PCa mortality: 9.2:1
Klotz L. Eur Urol Suppl 2014:13(1)e26
AS for favourable or selected early intermediate risk PCa appears safe in a
15-20 yr time frame
Active surveillance (AS) for favourable or selected early intermediate risk PCa: long-term FU results
Data from poster
98 9483
0
25
50
75
100
10-yr 15-yr 20-yr
Can
cer-
sp
ecif
ic
su
rviv
al 64
55 55
0
25
50
75
100
10-yr 15-yr 20-yr
Pts
sti
ll o
n A
S (
%)
Klotz et al, JCO 33: 272, 2015
» Prospective, single-centre study; N=191 men with favourable-risk PCa
» Significant predictors of QoL outcomes :
Parker PA. J Clin Oncol 2014:32(Suppl 4):abs.135
Both increased anxiety and illness uncertainty are associated with poorer
general and disease-specific QoL in PCa pts on AS
Quality of life (QoL) of men with PCa on active surveillance (AS): outcomes over 2.5 yrs
Baseline characteristics
Average age 67 yr Gleason score 6 98% of pts
Mean PSA 3.3 ng/ml cT1c 85% of pts
Predictor EPIC summary
scores
PCS
scores#
MCS
scores#
Illness uncertainty* P<0.05 P<0.05 P<0.05
Anxiety** P<0.05 P=0.08 P<0.05
EPIC: Expanded Prostate Index Composite; PCS: Physical Health Component; MCS: Mental
Health Component; *Mishel Uncertainty in Illness Scale; **State-Trait Anxiety Inventory; #SF-12
» Single-centre study; N=245 pts referred for RP (2010-2013)
» Comparison Bx pathology reports between referral and specialised pathologists
» Uro-pathologist reports: based on ISUP 2005 criteria including GS, tumour
volume and site, and number of positive cores with PCa
» Concordance for GS between referring and specialised pathologists: 69%
» Upgrading: 23% - Downgrading: 8% of cases (P<0.0005)
» GS change resulted in upgrading (14% of cases) and downgrading (4%) of risk
stratification groups (all would have altered treatment advice)
Al-Itejawi HHM. Eur Urol Suppl 2014:13(1):e734
Compared with uro-pathologists, referring pathologists are prone to downgrade PCa
Prostate Bx pathology reports of referring pathologists vs specialised uro-pathologists
Referring pathologist report %
Absence of tumour volume in both mm and %
• In mm
• In %
26%
82%
40%
Not correctly reporting on number of positive cores 51%
Errors in use of WHO classification 36%
Data from poster
» SEER analysis (2010); N=7,004 cT1-2 N0 M0 PCa pts with bGS 6 who
underwent RP
» Multivariable analysis: factors associated with Gleason upgrading *:
Caster JM. Int J Radiat Oncol Biol Phys 2014:90(1S):S154-
5(abs.342)
GS upgrading seems common in PCa pts with bGS 6 who underwent RP
Pathological outcomes in PCa pts with biopsy Gleason score (bGS) 6 and high PSA
RP outcome PSA
<10 ng/ml
(N=6,291)
PSA
10-19.9 ng/ml
(N=596)
PSA
20-29.9 ng/ml
(N=76)
pT2 SM+ or pT3-4 17% 29% 38%
pGS 7 42% 54% 54%
pGS 8-10 1% 4% 7%
Age (vs <60) OR 95% CI P
60-64 1.27 1.13-1.43 <0.001
65-69 1.28 1.12-1.50 <0.001
>70 1.59 1.32-1.50 <0.001
PSA (vs <10) OR 95% CI P
10-19.9 1.71 1.44-2.03 <0.001
20-29.9 1.92 1.21-3.07 0.006
Data from oral presentation
*bGS6 pGS7-10
» Single-centre, retrospective analysis (2010-2013); N=330 PCa pts who fulfilled
all PRIAS* criteria and N=36 PCa pts who fulfilled all PRIAS criteria with the
exception of bGS (3+4)
» Pts underwent extended Bx sampling (≥10 cores; mean number of cores: 16)
and RP
Gandaglia G. J Urol 2014:191(4 Suppl):e814(abs.MP69-01)
Pts with limited involvement of GS 3+4 at extended Bx sampling who fulfil all
other PRIAS criteria appear not to have an increased risk of unfavourable
disease and biochemical recurrence after surgery
Limited involvement of Bx Gleason score (bGS) 3+4: reason to exclude pts from active surveillance (AS)?
pGS 8-10
N (% of pts)
ECE
N (% of pts)
SVI
N (% of pts)
LNI
N (% of pts)
PRIAS pts (N=330) 6 (2%) 19 (6%) 5 (2%) 4 (1%)
All pts (N=366) 8 (2%) 22 (6%) 7 (2%) 6 (2%)
PRIAS pts All pts P
5-yr BCR-free survival 96.1% 95.7% 0.9
*PSA ≤10 ng/ml, PSA density <0.2 ng/ml/cc, bGS=6, ≤2 positive biopsy cores, ≤cT2
BCR:
PSA detection ≤0.2 ng/ml
» Screening
» Imaging
» Active Surveillance
» Surgery
» Hormonal Therapy
Oncoforum 2014 highlights: Urology
Positive surgical margin due to capsular incision
Chuang and Epstein, Am J Surg Pathol 32:1201, 2008
» SEER analysis; N=13,434 non-metastatic PCa pts treated with RARP or ORP
(2004-2009)
Hu JC. J Clin Oncol 2014:32(Suppl 4):abs.51
RARP seems associated with improved SM status among men with
intermediate- and high-risk disease
Robot-assisted (RARP) vs open (ORP) radical prostatectomy: surgical margin (SM) status
RARP
(N=5,556)
ORP
(N=7,878)
Absolute
difference
OR (95% CI) P
SM+ (%) 13.7 18.4 4.7 0.68 (0.63-0.73) <0.001
• 6.6% lower absolute incidence in intermediate- and high-risk PCa
• 15.4% lower absolute incidence in men with ECE
Lower incidence of SM+ for RARP vs ORP OR (95% CI)
T-stage pT2 0.67 (0.61-0.74)
pT3a 0.72 (0.60-0.85)
Risk group Intermediate 0.66 (0.58-0.74)
High 0.69 (0.64-0.75)
» Retrospective, single-centre study (1978-2009); N=1,053 PCa pts with SM+
after RP (27%); N=107 pts included in study (received no hormone therapy)
» Median FU: 18 yr
» Multivariable analysis: independent predictors for survival outcomes:
Djaladat H. J Clin Oncol 2014:32(Suppl 4):abs.98
Positive surgical margins (SM+) after RP: effect on oncological outcomes
Pathological characteristics % of pts
Intraprostatic incision vs
extracapsular extension
59% vs 41%
SM+ length: <3 mm vs >4 mm 38% vs 62%
Maximum GS at SM+: <6 vs >7 66% vs 34%
60
81
60
0
20
40
60
80
100
10
-yr
outc
om
es
(%)
bRFS Clinical RFS OS
bRFS Clinical RFS OS
HR P HR P HR P
SM+ length >4 mm 2.6 0.011 6.1 0.157 - -
Extracapsular extension 2.8 0.002 7.5 <0.001 2.7 0.002
Age - - 1.1 0.009
» Retrospective, single-centre study (2002-2010); N=205 PCa pts who underwent
RP with pT2, pN0/Nx and SM+ and who did not receive adjuvant RT
» Median FU: 64 mo
Nguyen JN. J Clin Oncol 2014:32(Suppl 4):abs.103
Length of SM+, extracapsular extension and highest Gleason grade at SM+
might be predictors of biochemical failure after RP for PCa
Positive surgical margins (SM+) after RP: effect on oncological outcomes
69
0
20
40
60
80
5-yr bFFS*
%
*biochemical failure free survival i.e. 2
sequential PSA values ≥0.2 ng/ml or any
detectable PSA prompting adjuvant RT
Variable HR (95% CI) P
SM+ length
>1 mm vs ≤1 mm
1.9 (1-3.7) 0.05
Gleason grade at SM+
>3 vs 3
7.1 (1.7-30) 0.007
Multivariable analysis: predictors for bFFS
» Retrospective, single-centre study; N=2,908 pts with localised PCa who
underwent open or robot-assisted RP (2002-2013), 46% had high-risk features
» Median FU: 28 mo
Nguyen H. J Clin Oncol 2014:32(Suppl 4):abs.138
Further data are needed to determine which pts benefit from immediate adjuvant RT
or a strategy of surveillance followed by selective salvage RT
Adjuvant RT (aRT) or salvage RT (sRT) after RP: functional and oncological outcomes
4-yr outcomes No postop.
RT (N=1,086)
aRT
(N=109)
sRT
(N=156)
P
Sexual function (SHIM score)* 11.1 5.2 5.2 0.01
Voiding function* - - - Not sign.
bRFS (overall) 92% 82% 55% 0.01
bRFS (pts with pT2/3a, SM+, neg. LNs) 86% 90% 63% -
Combined BMFS/CSS 98% Not sign.
OS 98% Not sign.
*Comparable pretreatment sexual and voiding function between groups
BMFS: bone metastasis-free survival; SHIM: Sexual Health Inventory for Men (higher=better)
» Retrospective, single-centre study; N=15,901 PCa pts who underwent RP,
734 pts received aRT (<6 mo) and 1,405 pts received sRT (>6 mo, median time
22 mo) (1992-2012); median FU: 48 mo
» Annual assessment of continence rate (number of pads) by questionnaire
» Multivariable analysis: no correlation of RT with long-term continence status:
» No sign. difference pre- and post-RT (N=248 analysed pts, P>0.05)
» No sign. difference between pts receiving aRT vs matched cohort of RP-only
pts (P>0.05) (adjusted for age, prostate volume, extent of nerve sparing, yr of surgery)
Adam M. J Clin Oncol 2014:32(Suppl 4):abs.100
aRT and sRT do not to negatively affect urinary continence
Adjuvant RT (aRT) or salvage RT (sRT) after RP: impact on long-term urinary continence
Variable OR P
RT (adjusted for age, prostate volume, extent of nerve
sparing, yr of surgery)
1.2 Not sign.
RT (adjusted for pT, pN, Gleason, PSA, margin status) - Not sign.
aRT 1.7 Not sign.
sRT 1.2 Not sign.
» Canadian retrospective cohort study; N=32,465 PCa pts who underwent
RP (15,870) or RT (16,595) alone (2002-2009)
Nam R. J Urol 2014:191(4 Suppl):e348-9(abs.PD12-06)
Complications other than urinary incontinence and erectile dysfunction after RP or RT for PCa
5-yr cumulative rate in different outcome categories % 95% CI
Admission to hospital for treatment-related complication 22% 22-23%
Risk of requiring urological procedure 32% 31-33%
Risk of requiring rectal/anal procedure 14% 13-14%
Risk of requiring open surgical procedure 0.9% 0.8-1.1%
Risk of second primary malignancy 3.0% 2.6-3.5%
(1/2)
40-65 yrs 65-90 yrs
RT 3.5 (2.3-4.7) 0.8 (0.7-1.0)
RP 1.3 (0.9-1.8) 0.4 (0.3-0.6)Standardised incidence ratio
per treatment and age group
Data from oral presentation
» Predictors for complications:
» Age and comorbidity at time of treatment (in all outcome categories)
» Type of treatment: strongest predictor
• Pts treated with RT experienced higher rates of complications for hospital
admission, rectal/anal procedures, open surgical procedures and secondary
malignancies at 5 yrs
Nam R. J Urol 2014:191(4 Suppl):e348-9(abs.PD12-06)
Complications after RT or RP for PCa are frequent and seem dependent on
age, comorbidity and the type of treatment
Complications other than urinary incontinence and erectile dysfunction after RP or RT for PCa
(2/2)
Data from oral presentation
Open surgical procedure RT RP
Ureteric re-implant 9% 0%
Cystotomy 20% 71%
Open bladder neck repair 30% 0%
Gu/GI fistula repair 40% 22%
Cystectomy and conduit 7% 0%
Open lymphocoele drainage 1% 0%
» SEER analysis (2008-2009); N=5,804 non-metastatic PCa pts (mean age 69
yrs) who underwent open RP (ORP) vs RARP
» 58% of pts underwent a PLND
» Multivariable analysis:
Gandaglia G. J Urol 2014:191(4 Suppl):e414(abs.PD14-09)
RARP seems associated with the absence of PLND and suboptimal extent
when extended PLND is performed, even in pts with high-risk tumours
Impact of robotic-assisted RP (RARP) on the use and extent of pelvic lymph node dissection (PLND)
ORP RARP P
Pts treated with PLND 71% 49% <0.001
Median number of removed LNs 5 4 <0.001
OR (ORP vs RARP) P
Treated with PLND 2.7 <0.001
Treated with extended PLND 1.3 <0.001
» Retrospective, multi-centre study; N=1,338 LN+ PCa pts treated with RP and
ePLND (1998-2010); median FU: 72 mo
» Median number LN 14 (IQR 10-20), median number pos LN 1 (IQR 1-2)
Touijer K. Eur Urol Suppl 2014:13(1):e262
Assessment of the optimal postoperative management of LN+ PCa
Postoperative management P
Observation
(N=387)
ADT
(N=676)
ADT+RT
(N=325)
Median age at RP (yrs) 62 66 65
<0.0001PSA at RP (ng/ml) 8.5 14.1 14.8
pT2/pT3a (%) 56 37 22
Pos. surgical margins (%) 33 55 72
83 85798890 94
0
20
40
60
80
100
7-yr OS 7-yr CSS
Observation
ADT
ADT+RT
P=0.02 for OS
P=0.002 for CSS
Data from poster
(1/2)
» Multivariable analysis: impact of postoperative management on mortality
Touijer K. Eur Urol Suppl 2014:13(1):e262
Multimodal treatment seems to have the best cancer control with the least
impact on other-cause mortality in LN+ PCa pts treated with RP + ePLND
Assessment of the optimal postoperative management of LN+ PCa
(2/2)
Data from poster
HR (95% CI)
(Treatment vs
observation)
P
Overall mortality ADT 0.90 (0.65-1.24) Not sign.
ADT+RT 0.41(0.27-0.63) <0.0001
Cancer-specific
mortality
ADT 0.63 (0.42-0.95) 0.03
ADT+RT 0.26 (0.15-0.44) <0.0001
Other-cause
mortality
ADT 3.04 (1.45-6.40) 0.003
ADT+RT 2.02 (0.84-4.89) Not sign.
» Retrospective, single-centre study; N=59 pts with biochemical recurrence (BR)
after RP and nodal pathologic 11C-choline PET/CT scan who underwent sLND
(2002-2008)
» Mean PSA at sLND: 3.95 ng/ml; median FU after sLND: 6 yr
Di Trapani E. Eur Urol Suppl 2014:13(1):e267
sLND seems a therapeutic option for PCa pts with biochemical recurrence
after RP and nodal pathologic uptake at 11C-choline PET/CT scan
Salvage LND (sLND) for clinically recurrent PCaafter RP: 8-yr FU results
22 27
81
0
20
40
60
80
100
BR-freesurvival*
CR-freesurvival**
CSS
8-y
r outc
om
es (
%)
*BR: PSA ≥0.2 ng/ml at 40 d after salvage LND; **CR: positive imaging in presence of rising PSA
Predictor HR (95% CI) P
PSA at sLND 1.08 (1.00-1.15) 0.03
Biochemical
response after sLND
0.42 (0.20-0.87) 0.02
Pos. vs no pos.
retrop. LNs at sLND
2.48 (1.04-7.05) 0.04
Multivariable analysis: independent
predictors of clinical recurrence (CR)
Data from poster
» Observational study based on National PCa register in Sweden (PCBaSe)
» Matched* study of advanced PCa pts (PSA >50 ng/ml or T4 or M+ disease) initially
treated by ADT alone or radical tx (RT or RP) of the primary tumour
» Multivariable analysis: ADT vs radical tx:
Sooriakumaran P. Eur Urol Suppl 2014:13(1):e974
In pts with advanced PCa, initial radical tx of the primary tumour might be
beneficial in survival compared with initial tx with ADT alone
ADT alone vs radical treatment (tx) in pts with advanced PCa: mortality outcomes
*matched for grade, T-stage, M-stage and Charlson comorbidity index
**adjusted for baseline differences between the groups
Mortality outcome (14 yr FU) ADT (N=699) Radical tx (N=699)
Death due to PCa 33% of pts 13% of pts
Death due to other causes 13% of pts 9% of pts
Mortality outcome HR** 95% CI
PCa mortality 2.89 2.25-3.71
Other cause mortality 1.41 1.01-1.98
Data from poster
ADT alone vs radical treatment (tx) in pts with advanced PCa: mortality outcomes
Sooriakumaran P. Eur Urol Suppl 2014:13(1):e974
» Screening
» Imaging
» Active Surveillance
» Surgery
» Hormonal Therapy
Oncoforum 2014 highlights: Urology
» Population-based cohort study in areas covered by SEER programme
» N= 66,717 men (≥66 years) with localised PCa who did not receive definitive
local tx within 180 d of diagnosis (1992-2009); median FU: 9.2 yr
Lu-Yao G. J Clin Oncol 2014:32(15S):331s(abs.5033)
Primary ADT is not associated with improved long-term overall or cancer-
specific survival in pts with localised PCa
Primary ADT for localised PCa: 15 yr survival outcomes
20%
91%
9%
79%
21%
91%
9%
79%
0%25%50%75%
100%
15-yr OS 15-yr CSS 15-yr OS 15-yr CSS
% o
f p
ts High-use regions
Low-use regions
Survival outcomes depending on primary ADT use and disease differentiation
Primary ADT vs conservative managementAdj. HR 95% CI
PCa-specific mortality 1.01 0.90-1.14
Overall mortality 1.04 0.99-1.09
Data from poster
Moderately differentiated PCa Poorly differentiated PCa
» CaPSURE database analysis; N=2,012 men with ≤cT3aN0M0 PCa
treated with RP or RT who had PSA-only relapse* and did not receive
ADT 12 mo before inclusion
» Pts assigned to immediate ADT** or deferred ADT***
» In absence of correcting for bias: immediate ADT worse survival
» Statistical analysis (inverse probability weighting)
Confounding factors included in adjusted analysis
Garcia-Albeniz X. J Clin Oncol 2014:32(15S):323s(abs.5003)
Immediate vs deferred ADT in PCa pts with PSA-only relapse
(1/2)
Data from oral presentation
** start within ≤3 mo of relapse
*** start ≥2 yr after inclusion or at progression: metastasis (on imaging),
severe cancer-related symptoms, PSA DT <12 mo if PSA ≥10 ng/ml or
PSA DT ≤6 mo based on 3 measurements
Baseline factors Time-varying factors
Gleason score PSA
T-stage Performance status
Primary treatment (RP or RT) Fatigue
% of positive biopsies Bone pain
Time from tx relapse
Calender yr of relapse
Age
*>0.2 ng/ml (RP) or 3 rising
determinations 1 mo apart (RT)
PSA-only: no symptoms, no
metastasis
» Analysis adjusted for baseline and time-varying confounding
after correcting for bias, there is no difference between immediate ADT and
deferred ADT
Garcia-Albeniz X. J Clin Oncol 2014:32(15S):323s(abs.5003)
Delaying ADT until rapid PSA DT or development of metastasis is NOT
associated with adverse outcome for the pts. When to start and how to guide
both pts and investigators is still unresolved
Immediate vs deferred ADT in PCa pts with PSA-only relapse
(2/2)
Data from oral presentation
All cause mortality PCa-specific mortality
Immediate
ADT
Deferred
ADT
Immediate
ADT
Deferred
ADT
HR (95%CI) 0.94
(0.51-1.73)
Ref 1.15
(0.33-3.97)
Ref
5-yr survival (%) 85 87 93 96
10-yr survival (%) 72 72 89 90
» Secondary analysis NCIC/SWOG/UKCCR PR7 trial; N=626 M0 PCa pts on
continuous ADT for biochemical failure after RT ± surgery; assessment T level
every 3 mo
» Median T level during 1st year of ADT is associated with higher risk of
developing hormone resistance:
» Maximum T >0.7 nmol/L (breakthrough): trend to more rapid progression to
hormone resistance (P=0.17)
Klotz L. J Urol 2014:191(4 Suppl):e855-6(abs.MP74-01)
In PCa pts treated with continuous ADT for biochemical failure, a serum nadir
T <0.7 nmol/L seems associated with a longer duration of response to ADT
Serum nadir testosterone (T) on ADT: does it predict time to castrate resistant progression?
Median T (nmol/L) during 1st yr: <0.7 0.7-1.7 ≥1.7 P
Time to hormone resistance* NR 6.4 yr 4.2 yr 0.009
*rising PSA >4 ng/ml and T <3.0 nmol/L; NR: not reached
Factor HR 95% CI
Median T 0.7-1.7 nmol/L 1.41 1.07-1.84
Median T >1.7 nmol/L 1.91 1.11-3.29
Klotz L. J Urol 2014:191(4 Suppl):e855-6(abs.MP74-01)
Serum nadir testosterone (T) on ADT: does it predict time to castrate resistant progression?
» French phase III RCT; N=413 men with high-risk* localised PCa were
randomised to 3 yr ADT alone or 3 yr ADT + D (4 cycles 70 mg/m2 q3 wk) + E
(10mg/kg/d d1-5) ; local tx (mostly RT) was administered at 3 mo in both groups
» Median FU: 7.6 yr
Fizazi K. J Clin Oncol 2014:32(15S):324s(abs.5005)
Docetaxel-estramustine was not associated with improved PFS in men with
high-risk localised PCa
Docetaxel-estramustine (DE) in localised high-risk PCa: updated results from GETUG 12
Data from oral presentation
*T3-T4 (67%) and/or GS ≥8 (42%) and/or PSA ≥20 ng/ml (59%) and/or pN+ (29%)
DE + ADT
(N=207)
ADT
(N=208)
HR (95%CI)
8-y
r P
FS Total group 62% 53% 0.75 (0.55-1.01)
GS≤7 69% 51% 0.55 (0.36-0.84)
GS≥8 No difference 1.1 (0.71-1.74)
8-y
r O
S
Total group 83% 0.94 (0.60-1.49)
GS≤7 94% 85% 0.40 (0.17-0.91)
GS≥8 No difference
Primary endpoint; P=0.06
Gr ≥2 toxicity
(GU, GI)
%
DE + ADT 21
ADT 18