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123PSA and the future risk of prostate cancer
122 A S I N G L E M E A S U R E M E N T O F P R O S T A T E - S P E C I F I C A N T I G E N AND HUMAN KALLIKREIN 2 COULD PREDICT TUMOUR
A G G R E S S I V E N E S S UP T O 20 Y E A R S B E F O R E P R O S T A T E C A N C E R DIAGNOSIS Uhnert D. 1, Becker C. 1, Berglund G. 2, Abrahamsson P.A?, Lilja H.4, Bjork Y.3 1Clinical Chemistry, Laboratory Medicine, Malmo, Sweden, 2Medicine, Surgery Orthopedics, Medicine, Malmo, Sweden, 3Medicine, Surgery Orthopedics, Urology, Malmo, Sweden, 4Memorial Sloan-Kettering Cancer Centre, Clinical Laboratories, New York, United States INTRODUCTION & OBJECTIVES: We studied concentrations of hK2, free, eomplexed and total PSA in plasma samples obtained from 406 prostate cancer patients up to 20 years prior to diagnosis. The measured levels were linked to disease information retrieved from patient records. MATERIAL & METHODS: Concentrations of the analytes were measured in plasma samples that originate from a large population based study performed between 1974-86 in Malm6, Sweden. Out ofthe19.439 men that contributed at baseline were 515 men diagnosed with prostate cancer up to December 31st 2000. Patient charts were retrievable from 406/515 (79%) patients. The median age among these men was 47 years (range; 33-60). Information regarding tumour grade, lymph node and skeletal involvement and disease progression after treatment was collected. RESULTS: Patients that later succumbed due to their prostate cancer had significantly higher concentrations of all analytes compared to men that died from other causes or are still alive. Significantly higher concentrations of all analytes but hK2 were seen in men with progressive disease. Also, significantly higher concentrations of free, total and complexed PSA were found in men with a positive bone scan at the time of diagnosis. Median (0.25;0.75) tPSA cPSA fPSA hK2
Stable disease 1.05(0.63;1.79) 0.72(0.42;1.3) '0.32(0.2;0.5) 0.04(0.03;0.055)
Dead from PCa
Progressive
1.58(0.76;4.11) 1.38(0.65;2.78) 1.23(0.54;2.78) 0.97(0.43;2.08) 0.47(0.20;1.01) 0.35(0.20;0.74) 0.054(0.03;0.08) 0.045(0.03;0.07)
P R E D I C T I O N O F C L I N I C A L L Y I N S I G N I F I C A N T PROSTATE C A N C E R P R I O R TO R A D I C A L P R O S T A T E C T O M Y - FACT O R F I C T I O N ? Alschibaia M. 1, Massmann j.z, Funk A. 2, Van Randenborgh H. 1, Hartung R. l, Paul R ? ITechnische Universitaet Munich, Department of Urology, Munich, Germany, 2Pathological Institute Massmann-Funk-Dettmar, Department of Pathology, Munich, Germany I N T R O D U C T I O N & O B J E C T I V E S : A significant subset of patients who undergo radical prostatectomy are regarded as insignificant disease. Several models to predict insignificant cancers have been proposed. In our study we evaluated the use of such models in a large cohort of patients. M A T E R I A L & M E T H O D S : 515 consecutive radical prostatectomy specimens from a single surgeon were evaluated according to the Stanford protocol. Tumour areas were marked by the same pathologist, scanned and digitally rendered (PicEd Corn 7.0®-Software). Turnout volume was calculated as the sum of all tumour areas multiplied by the mean thickness of sections (3mm). Tumour volume was corrected by the shrinking factor, which was calculated at 1.5. Insignificant PC was defined as low volume (<0.5cc) and low grade (
M+ 1.42(0.71;3.77) 1.05(0.47;2.79) 0.38(0.22;1.01) 0.052(0.03;0.08)
CONCLUSIONS: Patients that later die from their PCa have significantly higher concentrations of PSA and hK2 up to twenty years prior to diagnosis compared to men with a more stable disease. Our results show that even the early processes of cancer development are reflected in elevated concentrations of analytes. These findings may be of clinical importance since it may be possible to identify men with a high risk of developing aggressive, potentially lethal turnouts at an early curable stage. This strongly implies that screening programmes should be carried out early, with regular follow-ups and measurements of analytes for men with initially elevated hK2 and PSA.
RESULTS: From a total of 515 specimen n=52 (10.1%) were scored as insignificant prostate cancers. According to the binary logistic regression model preoperative PSA-value, Gleason Score and patients age revealed best results in predicting insignificant mmours. This model obtained a sensitivity of 75% and a specificity of 90.6%. The positive predictive value of only 15.8% demonstrates that 9.4% of clinically significant cancers would be missed. C O N C L U S I O N S : About 10 % of patients undergoing radical prostatectomy may inherit insignificant tumours in our patient cohort. Models to predict insignificant disease however will miss a substantial proportion of clinically relevant tumours. Our result emphasize that we should not rely on algorhythms predicting insignificant prostate cancer.
124
123 P S A AND T H E F U T U R E R I S K O F P R O S T A T E C A N C E R
Aus G.~, Damber J.E.1, Khatami A.1 Lilja H. 2, Stranne J.1 Hugosson j.1
PROSTATE CANCER DETECTION WITH MR SPECTROSCOPIC I M A G I N G IN T H E P E R I P H E R A L AND T R A N S I T I O N A L Z O N E S IN PATIENTS WITH ELEVATED PSA AND PREVIOUS NEGATIVE BIOPSIES
1Sahlgrens University Hospital, Department of Urology, G6teborg, Sweden, ~University Hospital UMAS and Memorial Sloan-Kettering Cancer Centre, Department of Clinical Chemistry, Malmr, Sweden and New York, United States I N T R O D U C T I O N & O B J E C T I V E S : The aim of the present study is to evaluate the median- to long-term cumulative risk to be diagnosed with prostate cancer in relation to a single PSA measurement. This information may be used to counsel patient individually about follow-up based on the finding at their first PSA measurement. M A T E R I A L & M E T H O D S : From our ongoing, population-based, randomized screening study, we evaluated the 5855 men (aged 50-66 years) who participated in our first screening round in 1995-96. They have now been followed for a median of 7.6 years (until June 2003). PSA has been analyzed every second year and in every occasion when the PSA was >3 ng/ml, the men were invited for prostate biopsy. The risk to be diagnosed with prostate cancer was related to the initial PSA value from 1995-96. RESULTS: In total has 539 men (9.2%) been diagnosed with prostate cancer. The risk to be diagnosed with prostate cancer in relation to the initial PSA value from 1995-96 was: 0-0.49 ng/ml - 0% (0/958);); 0.5-0.99 ng/ml - 0.85% (17/1992); 1-1.49 ng/ml 4.8% (54/1138); 1.5-1.99 ng/ml - 12.6% (70/571); 2-2.49 ng/ml - 21.4% (67/313); 2.5-2.99 ng/ml - 25.2%(56/222); 3-3.99 ng/ml - 33.3% (89/267); 4-6.99 ng/ml - 38.7% (103/265); 7-9.99 ng/ml - 50% (30/60) samt >10 ng/ml 76.8% (53/69). Not a single case of prostate cancer was diagnosed among the 2950 men (50.4% of the population) who had an initial PSA of <1 ng/ml within the first three years after blood sampling. C O N C L U S I O N S : It is possible to estimate the future risk of being diagnosed with prostate cancer with the aid of a single PSA measurement. Men with a PSA value o f < l ng/ml (half of the population in actual age groups) may safely wait for three years before next test is necessary. Patients with PSA values within the normal range but >2 ng/ml may warrant a closer follow-up due to comparatively high risk of being diagnosed with prostate cancer within the next years.
Comet Batlle j.1, Vilanova Busquets j.2, Areal Calama j.3 Maroto Genover A. 4, Osorio Fernandez M.4, Barcelo j.a, Lopez Bonet E. s, Torrent Quer N?, Ordis Dalmau M. ~, Agencia d'Avaluaci6 de Tecnologia per la Recema M~dica (AATRM), Girona, Spain 1Hospital Universitari Dr. J. Trueta, Dept. of Urology, Girona, Spain, 2RessonSncia Magnrtica Girona, Dept. of Radiology, Girona, Spain, SHospital Germans Trios I Pujol, Dept. of Urology, Badalona, Spain, 4Hospital Universitari Dr. J. Trueta, Dept. of Radiology, Girona, Spain, 5Hospital Universitari Dr. J. Trueta, Dept. of Pathology, Girona, Spain INTRODUCTION & OBJECTIVES: To evaluate the role of magnetic resonance spectroscopic imaging (MRSI) in prostate cancer detection in the transition and peripheral zones, in patients with elevated PSA levels and negative biopsy results for prostate cancer; analyze and compare the metabolic changes between prostate cancer and BPH in each zonal area. MATERIAL & METHODS: Endorectal MR and 3D MRSI were performed in 27 patients with elevated PSA levels with previous negative biopsy results for prostate cancer. Patients had PSA levels >4ng/ml but progressively higher. All studies were performed on a 1.5 Tesla GE Signa MR using an endorectal coil in combination with an ADT torso coil. MRSI consisted of point resolved spectroscopy (PRESS) voxel excitation with 3D phase encoding (16x8x8) of the whole prostate. The Choline+Creatine/Citrate (CC/Ci) ratio and the Choline/Creatine (Ch/Cr) ratio were evaluated in each voxel. A transrectal sextant biopsy was performed after the endorectal MR exam with additional biopsies in the transitional zone and in the area/s suspected by MR imaging. RESULTS: 10 patients (37%) had positive results for prostate cancer, 4 in the transitional zone and 6 in the peripheral gland. The overall accuracy, sensitivity and specificity of tumour detection, using MRSI in the transition zone was 85%, 75% and 87% respectively. The CC/Ci ratio and Ch/Cr ratio for cancer voxels (2.13+/-1.21, 3.51+/-1.32) were significantly different from the ratios in the voxels with BPH (0.79+/-0.32, 1.32+/-0.38 respectively) (p<0.01) in the transitional zone. For the peripheral gland the CC/Ci ratio and Ch/Cr ratio for cancer voxels (1.81+/-1.01, 2.53+/-1.12) were significantly different from the ratios in the voxels of the normal gland (0.53+/-0.31, 1.02+/-0.32 respectively) (p<0.01). Accuracy, sensitivity and specificity for tumour detection was 92%, 83% and 95% respectively, for the peripheral gland. CONCLUSIONS: The combination of MR imaging and MRSI may be of benefit for patients with previous negative biopsies and increasing PSA levels. Assessment of this patient population on MRSI should include the entire gland, transitional and peripheral zone, as the benign and malignant prostatic tissues might be differentiated and located on 3D MRSI.
European Urology Supplements 4 (2005) No. 3, pp. 33
A G G R E S S I V E N E S S UP T O 20 Y E A R S B E F O R E P R O S T A T E C A N C E R DIAGNOSIS Uhnert D. 1, Becker C. 1, Berglund G. 2, Abrahamsson P.A?, Lilja H.4, Bjork Y.3 1Clinical Chemistry, Laboratory Medicine, Malmo, Sweden, 2Medicine, Surgery Orthopedics, Medicine, Malmo, Sweden, 3Medicine, Surgery Orthopedics, Urology, Malmo, Sweden, 4Memorial Sloan-Kettering Cancer Centre, Clinical Laboratories, New York, United States INTRODUCTION & OBJECTIVES: We studied concentrations of hK2, free, eomplexed and total PSA in plasma samples obtained from 406 prostate cancer patients up to 20 years prior to diagnosis. The measured levels were linked to disease information retrieved from patient records. MATERIAL & METHODS: Concentrations of the analytes were measured in plasma samples that originate from a large population based study performed between 1974-86 in Malm6, Sweden. Out ofthe19.439 men that contributed at baseline were 515 men diagnosed with prostate cancer up to December 31st 2000. Patient charts were retrievable from 406/515 (79%) patients. The median age among these men was 47 years (range; 33-60). Information regarding tumour grade, lymph node and skeletal involvement and disease progression after treatment was collected. RESULTS: Patients that later succumbed due to their prostate cancer had significantly higher concentrations of all analytes compared to men that died from other causes or are still alive. Significantly higher concentrations of all analytes but hK2 were seen in men with progressive disease. Also, significantly higher concentrations of free, total and complexed PSA were found in men with a positive bone scan at the time of diagnosis. Median (0.25;0.75) tPSA cPSA fPSA hK2
Stable disease 1.05(0.63;1.79) 0.72(0.42;1.3) '0.32(0.2;0.5) 0.04(0.03;0.055)
Dead from PCa
Progressive
1.58(0.76;4.11) 1.38(0.65;2.78) 1.23(0.54;2.78) 0.97(0.43;2.08) 0.47(0.20;1.01) 0.35(0.20;0.74) 0.054(0.03;0.08) 0.045(0.03;0.07)
P R E D I C T I O N O F C L I N I C A L L Y I N S I G N I F I C A N T PROSTATE C A N C E R P R I O R TO R A D I C A L P R O S T A T E C T O M Y - FACT O R F I C T I O N ? Alschibaia M. 1, Massmann j.z, Funk A. 2, Van Randenborgh H. 1, Hartung R. l, Paul R ? ITechnische Universitaet Munich, Department of Urology, Munich, Germany, 2Pathological Institute Massmann-Funk-Dettmar, Department of Pathology, Munich, Germany I N T R O D U C T I O N & O B J E C T I V E S : A significant subset of patients who undergo radical prostatectomy are regarded as insignificant disease. Several models to predict insignificant cancers have been proposed. In our study we evaluated the use of such models in a large cohort of patients. M A T E R I A L & M E T H O D S : 515 consecutive radical prostatectomy specimens from a single surgeon were evaluated according to the Stanford protocol. Tumour areas were marked by the same pathologist, scanned and digitally rendered (PicEd Corn 7.0®-Software). Turnout volume was calculated as the sum of all tumour areas multiplied by the mean thickness of sections (3mm). Tumour volume was corrected by the shrinking factor, which was calculated at 1.5. Insignificant PC was defined as low volume (<0.5cc) and low grade (
M+ 1.42(0.71;3.77) 1.05(0.47;2.79) 0.38(0.22;1.01) 0.052(0.03;0.08)
CONCLUSIONS: Patients that later die from their PCa have significantly higher concentrations of PSA and hK2 up to twenty years prior to diagnosis compared to men with a more stable disease. Our results show that even the early processes of cancer development are reflected in elevated concentrations of analytes. These findings may be of clinical importance since it may be possible to identify men with a high risk of developing aggressive, potentially lethal turnouts at an early curable stage. This strongly implies that screening programmes should be carried out early, with regular follow-ups and measurements of analytes for men with initially elevated hK2 and PSA.
RESULTS: From a total of 515 specimen n=52 (10.1%) were scored as insignificant prostate cancers. According to the binary logistic regression model preoperative PSA-value, Gleason Score and patients age revealed best results in predicting insignificant mmours. This model obtained a sensitivity of 75% and a specificity of 90.6%. The positive predictive value of only 15.8% demonstrates that 9.4% of clinically significant cancers would be missed. C O N C L U S I O N S : About 10 % of patients undergoing radical prostatectomy may inherit insignificant tumours in our patient cohort. Models to predict insignificant disease however will miss a substantial proportion of clinically relevant tumours. Our result emphasize that we should not rely on algorhythms predicting insignificant prostate cancer.
124
123 P S A AND T H E F U T U R E R I S K O F P R O S T A T E C A N C E R
Aus G.~, Damber J.E.1, Khatami A.1 Lilja H. 2, Stranne J.1 Hugosson j.1
PROSTATE CANCER DETECTION WITH MR SPECTROSCOPIC I M A G I N G IN T H E P E R I P H E R A L AND T R A N S I T I O N A L Z O N E S IN PATIENTS WITH ELEVATED PSA AND PREVIOUS NEGATIVE BIOPSIES
1Sahlgrens University Hospital, Department of Urology, G6teborg, Sweden, ~University Hospital UMAS and Memorial Sloan-Kettering Cancer Centre, Department of Clinical Chemistry, Malmr, Sweden and New York, United States I N T R O D U C T I O N & O B J E C T I V E S : The aim of the present study is to evaluate the median- to long-term cumulative risk to be diagnosed with prostate cancer in relation to a single PSA measurement. This information may be used to counsel patient individually about follow-up based on the finding at their first PSA measurement. M A T E R I A L & M E T H O D S : From our ongoing, population-based, randomized screening study, we evaluated the 5855 men (aged 50-66 years) who participated in our first screening round in 1995-96. They have now been followed for a median of 7.6 years (until June 2003). PSA has been analyzed every second year and in every occasion when the PSA was >3 ng/ml, the men were invited for prostate biopsy. The risk to be diagnosed with prostate cancer was related to the initial PSA value from 1995-96. RESULTS: In total has 539 men (9.2%) been diagnosed with prostate cancer. The risk to be diagnosed with prostate cancer in relation to the initial PSA value from 1995-96 was: 0-0.49 ng/ml - 0% (0/958);); 0.5-0.99 ng/ml - 0.85% (17/1992); 1-1.49 ng/ml 4.8% (54/1138); 1.5-1.99 ng/ml - 12.6% (70/571); 2-2.49 ng/ml - 21.4% (67/313); 2.5-2.99 ng/ml - 25.2%(56/222); 3-3.99 ng/ml - 33.3% (89/267); 4-6.99 ng/ml - 38.7% (103/265); 7-9.99 ng/ml - 50% (30/60) samt >10 ng/ml 76.8% (53/69). Not a single case of prostate cancer was diagnosed among the 2950 men (50.4% of the population) who had an initial PSA of <1 ng/ml within the first three years after blood sampling. C O N C L U S I O N S : It is possible to estimate the future risk of being diagnosed with prostate cancer with the aid of a single PSA measurement. Men with a PSA value o f < l ng/ml (half of the population in actual age groups) may safely wait for three years before next test is necessary. Patients with PSA values within the normal range but >2 ng/ml may warrant a closer follow-up due to comparatively high risk of being diagnosed with prostate cancer within the next years.
Comet Batlle j.1, Vilanova Busquets j.2, Areal Calama j.3 Maroto Genover A. 4, Osorio Fernandez M.4, Barcelo j.a, Lopez Bonet E. s, Torrent Quer N?, Ordis Dalmau M. ~, Agencia d'Avaluaci6 de Tecnologia per la Recema M~dica (AATRM), Girona, Spain 1Hospital Universitari Dr. J. Trueta, Dept. of Urology, Girona, Spain, 2RessonSncia Magnrtica Girona, Dept. of Radiology, Girona, Spain, SHospital Germans Trios I Pujol, Dept. of Urology, Badalona, Spain, 4Hospital Universitari Dr. J. Trueta, Dept. of Radiology, Girona, Spain, 5Hospital Universitari Dr. J. Trueta, Dept. of Pathology, Girona, Spain INTRODUCTION & OBJECTIVES: To evaluate the role of magnetic resonance spectroscopic imaging (MRSI) in prostate cancer detection in the transition and peripheral zones, in patients with elevated PSA levels and negative biopsy results for prostate cancer; analyze and compare the metabolic changes between prostate cancer and BPH in each zonal area. MATERIAL & METHODS: Endorectal MR and 3D MRSI were performed in 27 patients with elevated PSA levels with previous negative biopsy results for prostate cancer. Patients had PSA levels >4ng/ml but progressively higher. All studies were performed on a 1.5 Tesla GE Signa MR using an endorectal coil in combination with an ADT torso coil. MRSI consisted of point resolved spectroscopy (PRESS) voxel excitation with 3D phase encoding (16x8x8) of the whole prostate. The Choline+Creatine/Citrate (CC/Ci) ratio and the Choline/Creatine (Ch/Cr) ratio were evaluated in each voxel. A transrectal sextant biopsy was performed after the endorectal MR exam with additional biopsies in the transitional zone and in the area/s suspected by MR imaging. RESULTS: 10 patients (37%) had positive results for prostate cancer, 4 in the transitional zone and 6 in the peripheral gland. The overall accuracy, sensitivity and specificity of tumour detection, using MRSI in the transition zone was 85%, 75% and 87% respectively. The CC/Ci ratio and Ch/Cr ratio for cancer voxels (2.13+/-1.21, 3.51+/-1.32) were significantly different from the ratios in the voxels with BPH (0.79+/-0.32, 1.32+/-0.38 respectively) (p<0.01) in the transitional zone. For the peripheral gland the CC/Ci ratio and Ch/Cr ratio for cancer voxels (1.81+/-1.01, 2.53+/-1.12) were significantly different from the ratios in the voxels of the normal gland (0.53+/-0.31, 1.02+/-0.32 respectively) (p<0.01). Accuracy, sensitivity and specificity for tumour detection was 92%, 83% and 95% respectively, for the peripheral gland. CONCLUSIONS: The combination of MR imaging and MRSI may be of benefit for patients with previous negative biopsies and increasing PSA levels. Assessment of this patient population on MRSI should include the entire gland, transitional and peripheral zone, as the benign and malignant prostatic tissues might be differentiated and located on 3D MRSI.
European Urology Supplements 4 (2005) No. 3, pp. 33