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Algorithms based on PSA, free PSA, DRE result and prostate volume increase specificity of prostate cancer screening
14
13 LOW PSA LEVEL POSSIBLY ASSOCIATED WITH LONG TERM RISK OF PROSTATE CANCER IN YOUNG MEN, AGED 40-49: CORRELATION WITH THE NUMBER OFAFFECTED FIRST DEGREE RELATIVES IN HIGH RISK FAMILIES
Valet-i A.‘, Cannier L.‘. Moineau M.P.‘. ATzouri R.~. Joulin V.‘. Doucet Mangin P.‘. Cusscnot 0.‘. Morin J.F.‘, Fournier G.’
L.‘.
‘Brest University Hospital, Urology, Brest, France, ‘Nancy University Hospital, Ilrology, Nancy, France, ‘Brest University Hospital, Nuclear Medicine, Brest, France, ‘Brest University Hospital, Pathology, Brest. France. ‘Tenon University Hospital Urology, Paris, France & OBJECTIVES: A recent study has shown that the longtenn risk ofprostate cancer (Cap) (I 0 to 25 years). in young men 40-49 years old (yr), unselected for family history, was 3.75 times higher in men with PSA level ‘> = 0.60 ng/ml than for men with PSA level less than this value (Fang et al.Urology, 2001). The aim of this study was to assess the risk of CaP associated with this PSA level, according to the number of affected relatives in high-risk families.
DOES THE AWARENESS OF A POSITIVE PROSTATE CANCER HAVE AN INFLUENCE
Herkommer timversity
FAMILY HISTORY ON SCREENING?
K., Volkmer B.. Paiss T.. Hautmann R.. Cschwend of Uhn, Department
OF
J
of Urology. Uhn. Germany
INTRODUCTION & OBJECTIVES: The clinical presentation of familial prostate cancer is discussed controversial. There is no prospective study about the screening behaviour in prostate cancer families at this time. Thehe data have to be evaluated indirectly by comparison of the clinical data of the patients of a family m chronological order.
INTRODUCTION
MATERIAL & METHODS: We obtained a berum PSA testing. for a CaP screening program, in 337 FDR (brothers or sons). 40-49 yr. of CaPpatients. The proportion of individuals with PSA < or > = 0.6ng/ml was compared according to the familial status of CaP (ICaP vs. 2+CaP). A candidate diagnosed with CaP. after PSA testing, was excluded of the present cohort. A systematic genealogical analysis previously performed. allowed to define the familial CaP status: at least I C‘aP in the family (range: l-7), so the screened men were classified into: familial status (2+ CaP: 3 I .3%), or sporadic (I CaP: 68.7?0). RESULTS: The proportion of individuals having a PSA level > = O.hng/ml was significantly higher (p=O.Ol) in men with 2+ C‘aP vs. I C‘aP in the family (82.5”0 vs. 69.7%) (Table).
Cap/family I CaP 2+ CaP
n 234 103
w
PSA 71 (30.3%) I8 (17.5%)
44.5 +I- 2.x 44.4 +I- 2.7
PSA > =0.6ngiml I63 (69.7%) x5 (82.5%)
MATERIAL & METHODS: All families with at least 3 members with PC were relected from Ihe database of our familial prostate cancer study group at the Umversity of Uhn. The patients in these families were arranged in chronological order of the date of diagnosis. The first case was always the first case with a histological report in the family. The case leadmg to the rcgistratton of the family in our database ic the index case. All memhcrs diagnosed after the index cast \\crc so called post index-cases. The collected data included the age at diagnosis. the TNM stage (WHO 1997) and the grading. Y4Y sporadic patients of the same database were the control group. RESULTS: The age at diagnobla was 63.6 yeari m first casts. 63.0 years in index cases and 63.3 years in post index cast’s, We found a tendency to a higher rate of organ-confined tumours in the post index case:, (41.5%) versus index cases (44.0%) and first cases (47.4%). There were no distant metastases in the post index cases compared to the index case ( 1.2%) and the first cases ( I SO/,). We also found less frequent positive lymph nodes in the post index cases (2.6%) compared to index cases (8.0%) and first cases (14.3%). The Bowker’s test showed a significant increase of the rate ofundifferentiated tumours in post index casts (25.5%) versus index cases (21.0%) (p=O.O2). CONCLUSIONS:
We have shown that FDR aged 40-49, in families with 2+CaP were more likely to have PSA levels higher than O.hng/ml than FDR in sporadic families. This emphasizs the high predictive risk of C‘aP for men with 2+CaP in the family, and may help in identifying high-risk relatives.
There was a tendency towards more organ confined tumours in post index-cases compared to index cases, whllc post index cases present a higher rate of undifferentiated turnours. At the time of diagnosis post index cases show a lower rate of lymph node and distant metastases. Thus the clinical presentation was in accordance with an early detection due to the awareness of a positive family history. Grant support: Deutsche Krebshilfe (70-2179.Vo I).
15
16
CONCLUSIONS:
THE VIENNA NOMOGRAMS VERSUS STANDARD OCTANT BIOPSIES AND REPEAT BIOPSIES: A NOVEL BIOPSY STRATEGY DEFINING THE OPTIMAL NUMBER OF CORES BASED ON PSA. AGE .AND PROSTATE VOLUME SIGNIFICANTLY IMPROVES CANCER
Diavan
Remri M.‘. Settr C’.‘,Anagnostou T.~.D&rob Its M. Hank M.‘. Marbergcr
B.‘.
ALGORITHMS BASED PROSTATE VOLUME CANCER
ON PSA, INCREASE
FREE PSA, DRE RESULT AND SPECIFICITY OF PROSTATE
SCREENING
Finnc P.‘. Finnr R.‘. Bangma (‘.
Hu~os~w~ J:. Au\ incn A.‘. Ctcnman U.11.’
M.’ Um~ersity
of\‘wma,
Urology.
Vienna.
.4ustria.
Iloqral ol’/\thcn\. ljrology.
General
(ireece INTRODUCTION
& OBJECTIVES: We conducted a multiccntcr trial m patients with PSA levels from 2 to IO @ml to validate a newly developed nomogram defining the optimal number of biopsy cores required for prostate cancer detection based on PSA. patient age and prostate volume (VIENNA Nomogram). Thus optimizing not only cancer detection but also eliminating the need for repeat biopslcs. The nomogram was employed and compared to a matched group of patienta undergomg a standard octant biopsy
protocol.
MATERIAL
& METHODS:
A total of 935 patients undcwent the standard octant All underwent tmnsrectal ultrasound guided sextant and 2 transitmn Tone biopsies of the prostate. All patient, with benign disease on imnal biopsy btopsy
protocol.
underwent
repeat
biopsies
within
I to 2 months.
A total
of 394
patients
underwent
prostate biopsy usmg the Vienna Nomogram. Unl- and multivariatc statistical analysts usmg the SAS system (CARY. North Carolina) and ROC curbcs wcrc used to compare both techniques. In addition morbidity v,as evaluated as delined by early and delayed morbidity based on a patient based questionnaire and registered morbidity at follow up.
RESULTS: Of the 935 patients in the stadard group, 263 (28.1%) had PCs, 213 (22.8%) on first and 50 (7.1%) on repeat biopsy. in comparison, cancer detection using the VIENNA nomogram was 38.7% after the first set of biopsies, which was sigmficantly superior (p= 0.002) to the octant biopsy technique and even superior to a combination of first and repeat biopsy. Using the cumulative logistic plot analysis the probability of a positive first/repeat biopsy was analysed. Morbidity was significantly lower in the VIENNA nomogram group as compared to the first + repeat biopsy protocol.
CONCLUSlONS: number detectlon
I-he VIENNA
of prostate
biopsy
is significantly
Early
and delayed
only
in
terms
improved
morbidity
of
cores
improved
Nomogram based
offers
and repeat biopsies
cancer
age,
PSA
therefore
reduced
Urology
Supplements
and
detection
and
economics
2 (2003)
No. 1, pp. 6
volume.
become
suggesting
acceptance and morbidity European
INTRODUCTION
& OBJECTIVES: Prostate cancer screening with prostatespecific antigen (PSA) is being increasingly applied for early detection of prostate cancer. About IO”/ of the screened men hate an elevated serum PSA, but of these only 30% have prostate cancer. The objective of this study was to reduce the number of false positive PSA results by combined use of several variables. MATERIAL & METHODS: The study population was extracted from thr Finnish, Swedish and Dutch par& of the European randomised study of screening for prostate cancer. I964 consccutivc men with a serum PSA of4-IO pg/l in the mltial screening round wpcrr included. To predict prcscncc of cancer in prostate biopsies algorithms based on PSA. free PSA. digital rectal examination (DRE) result, and prostate volume were developed using logistic regression (LR) and a multilayer perceptron (MLP) neural network. Of the patients 70% were used for training and 30% for testing of the algorithms. RESULTS: At 959; sensitivity the LR and MLP algorithms performed equally well (specifictty 26”o and 24”/) and both were more accurate than the proportion of free PSA (I P/u,p
an easy tool to select the optimal
on patient
is also significantly
Ilnncrsity of Hclsinkl. Department of C’limcal C’hcmistry, tlelsinki. Finland, ~Swedish Polytechnic. Department of Automation. Vaasa. Finland. ‘Erasmus University and Academic Hospital. Department of Urology. Rottcrdam. The Netherlands, ‘GGteborg University. Department of Urology, Gtitcborg, Sweden. ‘University of Tampere, Department of Public Health. Tampere, Finland
but
Cancer
unnecessary
an advantage
not
also in patient
CONCL,USIONS: By using diagnostic algorithms based on total PSA, free PSA, DRE result and prostate volume the nwnber of unnecessary prostate biopsies among men with serum PSA 4-10 pgil can be reduced more efftciently than with the proportion of free PSA alone.
13 LOW PSA LEVEL POSSIBLY ASSOCIATED WITH LONG TERM RISK OF PROSTATE CANCER IN YOUNG MEN, AGED 40-49: CORRELATION WITH THE NUMBER OFAFFECTED FIRST DEGREE RELATIVES IN HIGH RISK FAMILIES
Valet-i A.‘, Cannier L.‘. Moineau M.P.‘. ATzouri R.~. Joulin V.‘. Doucet Mangin P.‘. Cusscnot 0.‘. Morin J.F.‘, Fournier G.’
L.‘.
‘Brest University Hospital, Urology, Brest, France, ‘Nancy University Hospital, Ilrology, Nancy, France, ‘Brest University Hospital, Nuclear Medicine, Brest, France, ‘Brest University Hospital, Pathology, Brest. France. ‘Tenon University Hospital Urology, Paris, France & OBJECTIVES: A recent study has shown that the longtenn risk ofprostate cancer (Cap) (I 0 to 25 years). in young men 40-49 years old (yr), unselected for family history, was 3.75 times higher in men with PSA level ‘> = 0.60 ng/ml than for men with PSA level less than this value (Fang et al.Urology, 2001). The aim of this study was to assess the risk of CaP associated with this PSA level, according to the number of affected relatives in high-risk families.
DOES THE AWARENESS OF A POSITIVE PROSTATE CANCER HAVE AN INFLUENCE
Herkommer timversity
FAMILY HISTORY ON SCREENING?
K., Volkmer B.. Paiss T.. Hautmann R.. Cschwend of Uhn, Department
OF
J
of Urology. Uhn. Germany
INTRODUCTION & OBJECTIVES: The clinical presentation of familial prostate cancer is discussed controversial. There is no prospective study about the screening behaviour in prostate cancer families at this time. Thehe data have to be evaluated indirectly by comparison of the clinical data of the patients of a family m chronological order.
INTRODUCTION
MATERIAL & METHODS: We obtained a berum PSA testing. for a CaP screening program, in 337 FDR (brothers or sons). 40-49 yr. of CaPpatients. The proportion of individuals with PSA < or > = 0.6ng/ml was compared according to the familial status of CaP (ICaP vs. 2+CaP). A candidate diagnosed with CaP. after PSA testing, was excluded of the present cohort. A systematic genealogical analysis previously performed. allowed to define the familial CaP status: at least I C‘aP in the family (range: l-7), so the screened men were classified into: familial status (2+ CaP: 3 I .3%), or sporadic (I CaP: 68.7?0). RESULTS: The proportion of individuals having a PSA level > = O.hng/ml was significantly higher (p=O.Ol) in men with 2+ C‘aP vs. I C‘aP in the family (82.5”0 vs. 69.7%) (Table).
Cap/family I CaP 2+ CaP
n 234 103
w
PSA 71 (30.3%) I8 (17.5%)
44.5 +I- 2.x 44.4 +I- 2.7
PSA > =0.6ngiml I63 (69.7%) x5 (82.5%)
MATERIAL & METHODS: All families with at least 3 members with PC were relected from Ihe database of our familial prostate cancer study group at the Umversity of Uhn. The patients in these families were arranged in chronological order of the date of diagnosis. The first case was always the first case with a histological report in the family. The case leadmg to the rcgistratton of the family in our database ic the index case. All memhcrs diagnosed after the index cast \\crc so called post index-cases. The collected data included the age at diagnosis. the TNM stage (WHO 1997) and the grading. Y4Y sporadic patients of the same database were the control group. RESULTS: The age at diagnobla was 63.6 yeari m first casts. 63.0 years in index cases and 63.3 years in post index cast’s, We found a tendency to a higher rate of organ-confined tumours in the post index case:, (41.5%) versus index cases (44.0%) and first cases (47.4%). There were no distant metastases in the post index cases compared to the index case ( 1.2%) and the first cases ( I SO/,). We also found less frequent positive lymph nodes in the post index cases (2.6%) compared to index cases (8.0%) and first cases (14.3%). The Bowker’s test showed a significant increase of the rate ofundifferentiated tumours in post index casts (25.5%) versus index cases (21.0%) (p=O.O2). CONCLUSIONS:
We have shown that FDR aged 40-49, in families with 2+CaP were more likely to have PSA levels higher than O.hng/ml than FDR in sporadic families. This emphasizs the high predictive risk of C‘aP for men with 2+CaP in the family, and may help in identifying high-risk relatives.
There was a tendency towards more organ confined tumours in post index-cases compared to index cases, whllc post index cases present a higher rate of undifferentiated turnours. At the time of diagnosis post index cases show a lower rate of lymph node and distant metastases. Thus the clinical presentation was in accordance with an early detection due to the awareness of a positive family history. Grant support: Deutsche Krebshilfe (70-2179.Vo I).
15
16
CONCLUSIONS:
THE VIENNA NOMOGRAMS VERSUS STANDARD OCTANT BIOPSIES AND REPEAT BIOPSIES: A NOVEL BIOPSY STRATEGY DEFINING THE OPTIMAL NUMBER OF CORES BASED ON PSA. AGE .AND PROSTATE VOLUME SIGNIFICANTLY IMPROVES CANCER
Diavan
Remri M.‘. Settr C’.‘,Anagnostou T.~.D&rob Its M. Hank M.‘. Marbergcr
B.‘.
ALGORITHMS BASED PROSTATE VOLUME CANCER
ON PSA, INCREASE
FREE PSA, DRE RESULT AND SPECIFICITY OF PROSTATE
SCREENING
Finnc P.‘. Finnr R.‘. Bangma (‘.
Hu~os~w~ J:. Au\ incn A.‘. Ctcnman U.11.’
M.’ Um~ersity
of\‘wma,
Urology.
Vienna.
.4ustria.
Iloqral ol’/\thcn\. ljrology.
General
(ireece INTRODUCTION
& OBJECTIVES: We conducted a multiccntcr trial m patients with PSA levels from 2 to IO @ml to validate a newly developed nomogram defining the optimal number of biopsy cores required for prostate cancer detection based on PSA. patient age and prostate volume (VIENNA Nomogram). Thus optimizing not only cancer detection but also eliminating the need for repeat biopslcs. The nomogram was employed and compared to a matched group of patienta undergomg a standard octant biopsy
protocol.
MATERIAL
& METHODS:
A total of 935 patients undcwent the standard octant All underwent tmnsrectal ultrasound guided sextant and 2 transitmn Tone biopsies of the prostate. All patient, with benign disease on imnal biopsy btopsy
protocol.
underwent
repeat
biopsies
within
I to 2 months.
A total
of 394
patients
underwent
prostate biopsy usmg the Vienna Nomogram. Unl- and multivariatc statistical analysts usmg the SAS system (CARY. North Carolina) and ROC curbcs wcrc used to compare both techniques. In addition morbidity v,as evaluated as delined by early and delayed morbidity based on a patient based questionnaire and registered morbidity at follow up.
RESULTS: Of the 935 patients in the stadard group, 263 (28.1%) had PCs, 213 (22.8%) on first and 50 (7.1%) on repeat biopsy. in comparison, cancer detection using the VIENNA nomogram was 38.7% after the first set of biopsies, which was sigmficantly superior (p= 0.002) to the octant biopsy technique and even superior to a combination of first and repeat biopsy. Using the cumulative logistic plot analysis the probability of a positive first/repeat biopsy was analysed. Morbidity was significantly lower in the VIENNA nomogram group as compared to the first + repeat biopsy protocol.
CONCLUSlONS: number detectlon
I-he VIENNA
of prostate
biopsy
is significantly
Early
and delayed
only
in
terms
improved
morbidity
of
cores
improved
Nomogram based
offers
and repeat biopsies
cancer
age,
PSA
therefore
reduced
Urology
Supplements
and
detection
and
economics
2 (2003)
No. 1, pp. 6
volume.
become
suggesting
acceptance and morbidity European
INTRODUCTION
& OBJECTIVES: Prostate cancer screening with prostatespecific antigen (PSA) is being increasingly applied for early detection of prostate cancer. About IO”/ of the screened men hate an elevated serum PSA, but of these only 30% have prostate cancer. The objective of this study was to reduce the number of false positive PSA results by combined use of several variables. MATERIAL & METHODS: The study population was extracted from thr Finnish, Swedish and Dutch par& of the European randomised study of screening for prostate cancer. I964 consccutivc men with a serum PSA of4-IO pg/l in the mltial screening round wpcrr included. To predict prcscncc of cancer in prostate biopsies algorithms based on PSA. free PSA. digital rectal examination (DRE) result, and prostate volume were developed using logistic regression (LR) and a multilayer perceptron (MLP) neural network. Of the patients 70% were used for training and 30% for testing of the algorithms. RESULTS: At 959; sensitivity the LR and MLP algorithms performed equally well (specifictty 26”o and 24”/) and both were more accurate than the proportion of free PSA (I P/u,p
an easy tool to select the optimal
on patient
is also significantly
Ilnncrsity of Hclsinkl. Department of C’limcal C’hcmistry, tlelsinki. Finland, ~Swedish Polytechnic. Department of Automation. Vaasa. Finland. ‘Erasmus University and Academic Hospital. Department of Urology. Rottcrdam. The Netherlands, ‘GGteborg University. Department of Urology, Gtitcborg, Sweden. ‘University of Tampere, Department of Public Health. Tampere, Finland
but
Cancer
unnecessary
an advantage
not
also in patient
CONCL,USIONS: By using diagnostic algorithms based on total PSA, free PSA, DRE result and prostate volume the nwnber of unnecessary prostate biopsies among men with serum PSA 4-10 pgil can be reduced more efftciently than with the proportion of free PSA alone.