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© Copyright 2007, 2008, 2009 ProstateCancerTopics.com – All Rights ReservedTOPICS NEXT ►
Topic 001 - UltraSensitive PSA Testing – One Example
UltraSensitive PSA assays (blood tests) are capable of both higher resolution and lower thresholds of detection than
standard PSA “screening tests.” Although multiple laboratories have offered UltraSensitive PSA “monitoring tests” for years,
both Prostate Cancer (PC) specialists and policy makers at major medical centers do not universally embrace UltraSensitive
PSA testing for post treatment monitoring of PC patients following their initial surgery and/or radiation.
Significant confusion today is found among PC patients resulting from this ongoing dispute within the PC industry.
PC physicians and patients do not always speak the same language. There is no better example than discussions regarding the
UltraSensitive PSA test. Physicians frequently are quoted as saying “there is NO clinical significance in the use of the
Ultrasensitive PSA test.” It is important for patients to realize that this physician-assertion actually translates as “at our
institution, we would not make treatment decisions differently based on results of PSA UltraSensitive testing.”
Some physicians falsely imply to patients that the UltraSensitive test is somehow “not a valid assay.” Some go so far as to
assert that “there is no science supporting the use of UltraSensitive PSA Testing.” Such assertions are purely uninformed.
This dispute is not really over the validity of UltraSensitive PSA testing, but instead, this is a dispute among physicians over
which disease model should be used for prostate cancer. Physicians who do not support the use of UltraSensitive PSA testing,
by definition, simply do not themselves believe that recurrent prostate cancer CAN be forced into remission IF treated
APPROPRIATELY AND treated EARLY ENOUGH. These physicians are actually saying that “this test is not important
because early detection of residual disease is not important because early treatment is not important.”
Several notable PC Oncologists believe that prostate cancer does follow normal “cancer rules” and that UltraSensitive PSA
testing is critical to early detection which increases their success in obtaining durable remissions through “early treatment.”
Topic 001.1 - UltraSensitive PSA Testing Example – The Pre-Surgical History
Topic 001.2 - Pre-Surgery PSADT Estimated by Exponential Curve Fit
Topic 001.3 - UltraSensitive PSA Testing – The Basics
Topic 001.4 - Post-Treatment PSADT Initial Estimate by Exponential Curve Fit
Topic 001.5 - Post-Treatment PSADT Estimated w/o Nadir
Topic 001.6 - Estimating the True Nadir – Intercept of Decay and Growth Curves
Topic 001.7 - Post-Treatment PSADT Estimate Improved Using Estimated Nadir
Topic 001.8 - UltraSensitive PSA Testing – Remission Protocol Performance
Topic 001.9 - UltraSensitive PSA Testing – Protocol Performance vs. PSA Estimate w/o Intervention @ 12 Months
Topic 001.10 - UltraSensitive PSA Testing – Protocol Performance vs. PSA Estimate w/o Intervention @ 16 Months
Topic 001.11 - UltraSensitive PSA Testing – Protocol Performance vs. PSA Estimate w/o Intervention @ Two Years
Reference: Clinical Significance of UltraSensitive PSA Test Results in Post Operative Monitoring
Reference: Using UltraSensitive PSA Testing To Potentially Gain Years of Earlier Warning of Recurrence
Reference: Rising PSA in Nonmetastatic Prostate Cancer - Judd Moul and Stephen Freedland
June 2009
This example demonstrates
the use of UltraSensitive PSA
testing in early recurrence
PC detection and intervention.
http://www.prostatecancertopics.com/http://www.aacc.org/events/expert_access/2003/prostate/Pages/qanda.aspxhttp://www.prostate-cancer.org/education/preclin/McDermed_Using_PSA_Intelligently2.htmlhttp://www.cancernetwork.com/display/article/10165/63133
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Pre-Surgery PSA
(PSADT - approx 4.7 months)
0
5
10
15
20
25
30
35
40
45
50
10/8
/200
5
11/8
/200
5
12/8
/200
5
1/8/
2006
2/8/
2006
3/8/
2006
4/8/
2006
5/8/
2006
6/8/
2006
Radical Retropubic
Prostatectomy
Open Procedure
05/09/2006
Gleason 7 ( 3 + 4 )
pT3a : ECE pos left 0.8cm
Perineural invasion – pos
Margins – all neg
Nodes 4 + 5 – all neg
Seminal vesicles – neg
Bladder neck – neg
Quest PSA Tests
Biopsy at a Top 10 USA Med Center
2 of 12 cores positive (10 of 35 mm)
Right transitional zone only
02/13/2006 Gleason 5 ( 3 + 2 )
16.1
19.1
20.8
31.3
45.6
Final Pre-Surgery
PSA Test
PSA Sampling
“Blackout Period”
( Post-biopsy )
Topic 001.1 - UltraSensitive PSA Testing Example – The Pre-Surgical History
4.0Maximum Value
of “Roche ECLIA”
UltraSensitive PSA
Assay Results
(now at LabCorp)
ng/ml
April 09
http://www.prostatecancertopics.com/
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PSADT EstimatePre-Surgery / Pre-IMRT
Exponential Curve fit to the
Five Measured PSA Readings
Doubling Time of PSA Level from Five PSA Assays
Preoperative patient's nickname: Example 1
The best fit to the doubling time is 0.39 years 4.7 months.
The doubling time lies within the interval (0.35, 0.45) years.
The precision of the fit is fair with chi^2 per DOF = 1.72.
Without treatment the PSA could reach the life-threatening level
of 4,000 in the year 2009 or within the interval (2008, 2009).
The input data were:
On 8 October 2005 his PSA was 19.10 (ng/ml).
On 11 October 2005 his PSA was 16.10 (ng/ml).
On 30 November 2005 his PSA was 20.80 (ng/ml).
On 17 January 2006 his PSA was 31.40 (ng/ml).
On 27 April 2006 his PSA was 45.60 (ng/ml).
Topic 001.2 - Pre-Surgery PSADT Estimated by Exponential Curve Fit
Jan 30
http://www.prostatecancertopics.com/http://kevin.phys.unm.edu/psa/5formgn.html
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UltraSensitive PSA at initiation of Complete Androgen Blockade (CAB)
Post-Surgery PSA Doubling Time: Estimate 5.4 months (quite aggressive)
0.00
0.05
0.10
0.15
0.20
0.25
0.30
5/9
/2006
6/9
/2006
7/9
/2006
8/9
/2006
9/9
/2006
10/9
/2006
11/9
/2006
12/9
/2006
1/9
/2007
2/9
/2007
3/9
/2007
4/9
/2007
5/9
/2007
6/9
/2007
7/9
/2007
8/9
/2007
9/9
/2007
10/9
/2007
11/9
/2007
12/9
/2007
Last Quest
“high-scale”
PSA Test
Surgery
60 Gy
Secondary
Radiation
Treatment
IMRT
on
21EX
All UltraSensitive Results are from
“Immulite 2000” LabCorp PSA Tests
0.070.06
0.13
0.3
45.6
Final
PSA Test
pre-surgery
0.05
Screening
& LabCorp
PSA Tests
Both 0.1Post-Radiation
“Baseline” and
Measured Nadir
?
“UltraSensitive UNDETECTABLE”
Topic 001.3 - UltraSensitive PSA Testing – The Basics
ng/ml
0.12
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PSADT Estimate #1Post-Surgery / Post-IMRTExponential Curve fit to the
Four Measured PSA Readings
Starting with Measured Nadir:
( 0.05 on 9/27/2006 )
Measured
Nadir
♦
Doubling Time of PSA Level from Four PSA Assays
Postoperative patient's nickname: Example 1
The best fit to the doubling time is 0.45 years 5.4 months.
The doubling time lies within the interval (0.41, 0.50) years.
The precision of the fit is good with chi^2 per DOF = 0.47.
Without treatment the PSA could reach the life-threatening level
of 4,000 in the year 2014 or within the interval (2013, 2015).
The input data were:
On 27 September 2006 his PSA was 0.05 (ng/ml).
On 11 January 2007 his PSA was 0.07 (ng/ml).
On 20 March 2007 his PSA was 0.10 (ng/ml).
On 18 April 2007 his PSA was 0.12 (ng/ml).
Topic 001.4 - Post-Treatment PSADT Initial Estimate by Exponential Curve Fit
?
Jan 30
http://www.prostatecancertopics.com/http://kevin.phys.unm.edu/psa/4formg.html
-
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PSADT Estimate #2Post-Surgery / Post-IMRTExponential Curve fit to the
Three Measured PSA Readings
Recorded After but
Excluding the Measured Nadir:
( 0.05 on 9/27/2006 )
Doubling Time of PSA Level from Three PSA Assays
Postoperative patient's nickname: Example 1
The best fit to the doubling time is 0.35 years 4.2 months.
The doubling time lies within the interval (0.31, 0.41) years.
The precision of the fit is good with chi^2 per DOF = 0.04.
Without treatment the PSA could reach the life-threatening level
of 4,000 in the year 2013 or within the interval (2012, 2014).
The input data were:
On 11 January 2007 his PSA was 0.07 (ng/ml).
On 20 March 2007 his PSA was 0.10 (ng/ml).
On 18 April 2007 his PSA was 0.12 (ng/ml).
Topic 001.5 - Post-Treatment PSADT Estimated w/o Nadir
?
Jan 30
http://www.prostatecancertopics.com/http://kevin.phys.unm.edu/psa/3formg.html
-
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PSADT - Estimating True Nadir During Sparse Sampling Interval
0.01
0.1
1
8/11/06 9/11/06 10/11/06 11/11/06 12/11/06 1/11/07 2/11/07 3/11/07 4/11/07
Measured
Nadir
0.05 on
9/27/2006
0.02
0.07
0.03
0.04
0.050.06
Estimated
True Nadir
0.044 on
10/26/2006
Best Estimate of the True Nadir is the Exponential Intersection of the Decay Curve with the Reemergence Growth Curve
♦
Topic 001.6 - Estimating the True Nadir – Intercept of Decay and Growth Curves
ng/ml
Jan 30
http://www.prostatecancertopics.com/
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PSADT Estimate #3Post-Surgery / Post-IMRTExponential Curve fit to the
Three Measured PSA Readings
Plus the Estimated Nadir:
( 0.044 on 10/26/2006 )
Estimated
Nadir
Measured
Nadir
♦♦
Doubling Time of PSA Level from Four PSA Values
Postoperative patient's nickname: Example 1
The best fit to the doubling time is 0.33 years 4.0 months.
The doubling time lies within the interval (0.30, 0.36) years.
The precision of the fit is good with chi^2 per DOF = 0.06.
Without treatment the PSA could reach the life-threatening level
of 4,000 in the year 2012 or within the interval (2012, 2013).
The input data were:
On 26 October 2006 his PSA was estimated to be 0.044 (ng/ml).
On 11 January 2007 his PSA was 0.07 (ng/ml).
On 20 March 2007 his PSA was 0.10 (ng/ml).
On 18 April 2007 his PSA was 0.12 (ng/ml).
√
Topic 001.7 - Post-Treatment PSADT Estimate Improved Using Estimated Nadir
Jan 30
http://www.prostatecancertopics.com/http://kevin.phys.unm.edu/psa/4formg.html
-
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UltraSensitive PSA at initiation of Complete Androgen Blockade (CAB)
Post-Surgery PSA Doubling Time: Estimate 4 months (quite aggressive)
0.00
0.05
0.10
0.15
0.20
0.25
0.30
5/9
/06
6/9
/06
7/9
/06
8/9
/06
9/9
/06
10/9
/06
11/9
/06
12/9
/06
1/9
/07
2/9
/07
3/9
/07
4/9
/07
5/9
/07
6/9
/07
7/9
/07
8/9
/07
9/9
/07
10/9
/07
11/9
/07
12/9
/07
1/9
/08
2/9
/08
3/9
/08
4/9
/08
Last Quest
“high-scale”
PSA Test
Surgery
60 Gy
Secondary
Radiation
Treatment
IMRT
on
21EX
All UltraSensitive PSA Tests
Were Performed by LabCorp
Before 4/1/08 “Immulite 2000”
After 4/1/08 “Roche ECLIA”
Screening Test
& LabCorp
PSA Tests
Both 0.1
Post-Radiation
“Baseline”and
Measured Nadir
0.07
0.06
0.13
0.3
Example Graph Showing Necessity of UltraSensitive PSA Testing – From Surgery / IMRT through 11 months of CAB “ON Cycle”
45.6Final
PSA Test
pre-surgery Eligard Injection #1 Added
Remission Diet Started
Remission Supplements Added
Casodex + Avodart Added
0.03
0.02
-
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UltraSensitive PSA at Initiation of Complete Androgen Blockade (CAB) vs.
Projected PSA Expotential Growth Curve w/o Remission Protocol (Red Curve)
Post-Surgery PSA Doubling Time (PSADT): Estimate 4 months
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
5/9
/06
6/9
/06
7/9
/06
8/9
/06
9/9
/06
10/9
/06
11/9
/06
12/9
/06
1/9
/07
2/9
/07
3/9
/07
4/9
/07
5/9
/07
6/9
/07
7/9
/07
8/9
/07
9/9
/07
10/9
/07
11/9
/07
12/9
/07
1/9
/08
2/9
/08
3/9
/08
4/9
/08
5/9
/08
6/9
/08
Topic 001.9 - UltraSensitive PSA Testing – Remission Protocol Performance
ng/ml
April 09
Projected PSA
Exponential
Growth Curve
w/o Intervention
12 Month
PSA Estimate
0.12 x 2 x 2 x 2
0.96 ng/ml
AUA Official Recurrence Threshold
“PSA > 0.2 ng/ml AND rising”
At 11 months - PSA remains < 0.01 ng/ml
“UNDETECTABLE” via UltraSensitive Testing
Max 0.12
4 months4 months 4 months
http://www.prostatecancertopics.com/http://www.cancernetwork.com/display/article/10165/63133http://www.cancernetwork.com/display/article/10165/63133
-
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UltraSensitive PSA Results (Green Curve) from Complete Androgen Blockade (CAB)
vs. 16 Month Projected PSA Recurrence Curve w/o Remission Protocol (Red Curve)
Post-Surgery PSA Doubling Time (PSADT): Estimate = 4 months
0.00
0.100.20
0.300.40
0.500.60
0.700.80
0.901.00
1.10
1.201.30
1.401.50
1.601.70
1.801.90
2.00
5/9
/2006
6/9
/2006
7/9
/2006
8/9
/2006
9/9
/2006
10/9
/2006
11/9
/2006
12/9
/2006
1/9
/2007
2/9
/2007
3/9
/2007
4/9
/2007
5/9
/2007
6/9
/2007
7/9
/2007
8/9
/2007
9/9
/2007
10/9
/2007
11/9
/2007
12/9
/2007
1/9
/2008
2/9
/2008
3/9
/2008
4/9
/2008
5/9
/2008
6/9
/2008
7/9
/2008
8/9
/2008
9/9
/2008
10/9
/2008
Topic 001.10 - UltraSensitive PSA Testing – Remission Protocol Performance
ng/ml
Sept 28
Projected PSA
Exponential
Growth Curve
w/o Intervention
16 Month
PSA Estimate
0.12 x 2 x 4
= 1.92 ng/ml
AUA “Official” Recurrence Threshold
“PSA > 0.2 ng/ml AND rising” At 16 months - PSA remains < 0.01 ng/ml
“UNDETECTABLE” via UltraSensitive Testing
Max 0.12
4 months4 months 4 months 4 months
2 3 51 4
http://www.prostatecancertopics.com/http://www.cancernetwork.com/display/article/10165/63133http://www.cancernetwork.com/display/article/10165/63133
-
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UltraSensitive PSA Results (Green Curve) from Complete Androgen Blockade (CAB)
vs. Projected PSA Recurrence Curve w/o Remission Protocol (Red Curve)
Post-Surgery PSA Doubling Time (PSADT): Estimate = 4 months
0.00
0.01
0.10
1.00
10.00
100.00
Apr-
06
Jun-0
6A
ug-0
6
Oct-06
Dec-
06
Feb-0
7
Apr-
07
Jun-0
7A
ug-0
7
Oct-07
Dec-
07
Feb-0
8
Apr-
08
Jun-0
8A
ug-0
8
Oct-08
Dec-
08
Feb-0
9
Apr-
09
Jun-0
9
Topic 001.11 - UltraSensitive PSA Testing – Remission Protocol Performance
ng/ml
June 2009
Projected
PSA
Exponential
Growth w/o
Intervention
Without CAB Treatment, the Apr-2009, 24 Month
PSA Estimate 0.12 x 2 x 2 x 2 x 2 x 2 x 2 = 7.68 ng/ml
AUA “Official”
Recurrence Threshold
“PSA > 0.2 ng/ml AND rising”
Max 0.12
4 months4 months 4 months 4 months
2 3 61 4 5
4 months4 months
At two years - PSA remains < 0.01 ng/ml
“UNDETECTABLE” via UltraSensitive Testing
http://www.prostatecancertopics.com/http://www.cancernetwork.com/display/article/10165/63133http://www.cancernetwork.com/display/article/10165/63133http://www.cancernetwork.com/display/article/10165/63133
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