116 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Sunday, April 27,2003 450 SURGICAL RENAL DENERVATION EFFECTS RAT POLYCYSTIC KIDNEY DISEASE Arieh L Shalhav*, Chicago, IL; Tiberio Siqueira, Recife, Brazil; Chad Trambaugh, Indianapolis, IN; Cr Powell, Chicago, IL; Vincent Gattone, Indianapolis, IN INTRODUCTION AND OBJECTIVE: The kidney has both afferent (sensory) and efferent (sympathetic) nerves which can function together in arenorenal reflex. Sympathetic renal innervation is known to contribute to the hypertension in adult dominant poly cystic kidney disease (PKD). The present study in male Han: SPRD-cy rats (which is the best animal model for PKD) was aimed to evaluate the possible contribution of renal innervation to the progression of hypertension, renal failure and cystic change in PKD. METHODS: At 4 weeks of age, male rats were randomized as either: l)denervation; a midline laparotomy and bilateral surgical renal denervation with physical stripping of the nerves and immersing the artery with phenolfalcohol (Denervated), 2)sham operated control; anesthesia with a midline laparotomy only (Sham Op) or 3) non-operated control; similarly handled but not anesthetized or subjected to surgery (Non Op) groups. Blood pressure (tail cuff method), renal function (BUN) and renal histology were assessed at 8 weeks of age. RESULTS: Bilateral renal DeNx in cystic rats reduced cystic kidney size (total kidney weight and kidney weight as % of body weight), reduced cyst volume density, normalized systolic blood pressure and improved renal function as compared to Non Op control cystic rats. Compared to sham Op control cystic rats, the denervated cystic rats exhibited a reduced blood pressure only(see table). CONCLUSIONS: Bilateral renal denervation was efficacious in slowing PKD progression in the rat model. The most significant effect noted was on hypertention. However, sham operation appears to also have some effect on PKD progression, possibly through afferent nerves since the skin at the same spinal levels that innervate the kidney was incised during laparotomy. Renal innervation plays a role in the hypertension and possibly in disease progression in the rat model of PKD. Further studies to assess the clinical aplicability of this approach are underway. 448 URINARY NITRITE EXCRETION AND URINARY VARIABLES IN PATIENTS WITH NOCTURNAL FREQUENCY OF MICTUR- ITION: EFFECTS OF INDOMETHACIN Noori S Al-Waili*, Dubai, UAE INTRODUCTION AND OBJECTIVE: Nitric oxide(NO) playa role in renal physiology and pathology. We found that NO increased in primary enuresis and indomethacin could reduce frequency of micturition and urinary nitrite excretion.Urinary nitrite excretion and urinary variabels were measured in patients with primary nocturnal frequency of micturition (PNFM) and compared with normal individuals before and after indomethacin treatment. METHODS: The study comprised seven patients with PNFM and seven normal control. Nitrite was assayed in spot morning urine samples; urine volume, urine osmolality and electrolytes, serum osmolality and electrolytes and functional bladder capacity (FBC) were assayed. Both groups were then given 100 mg of indomethacin suppository daily for ten days and urinary variables were re- evaluated during day ten. RESULTS: Inodmethaicn significantly reduced frequency of voiding in patients with PNFM.Urinary nitrite excretion of patients with PNFM was greater than that of normal subjects (230+/-62 umolll versus 42 +/-30 umolll, p<0.05). The mean (SD) 24 hr urine volume and osmolality, the night urine volume and osmolality, serum osmolality, FBC, creatinine clearance, fractional excretion of sodium (FENa,fractional excretion of potassium(FEK),and urinary excretion of glucose and potassium were lower in patients with PNFM as compared with normal individuals, although not statistically significantly so, except for FEC that was significantly lower in the patients. Urinary excretion of electrolytes, day; night urinary volume ratio, spot morning osmolality, nocturnal index, and nocturnal polyuria index were higher in patients with PNFM. Indomethacin decreased 24 hr urinary volume, creatinine clearance, osmolar clearance and urinary protein excretion in the patients and control except for 24 hr urinary protein excretion that was increased mildly in the conrol. Indomethacin increased day: night urinary volume ratio in the normal subjects. CONCLUSIONS: Urinary nitrite excretion and urinary excretion of electrolytes increased and FBC decreased in patients with PNFM;Indomethacin decreased urinary volume, FENa, FEK, osmolar clearance, and free water clearance in patients and normal control. This might explain the mechanism of effect of indomethacin on frequency of voiding. Possible interaction of prostaglandin and NO in the pathogenesis of PNFM is discussed. Source of Funding: None. Group Denervated ShamOp Non Op Phenotype Kidney Wgt as Cyst Vd (%) BUN (mg/dl) Systtllte BP 0/0 Body Wgt (mmHg) Normal (4) 1.07:1:0.05 19.6:1:2,6 134:1:6.3 Cystic (8) 2.00±0.20' 17.2±5.2" 23.0±2.6' 123±8.S't Normal (4) l.oo±0.07 20.5:1:1,2 127±13 Cystic (8) 2,34:1:0.20 29.6±3.9 33.1:1:3.7' 1SS±6,0 Normal (2) 1.05±0.02 22.5 130±4.3 Cystic (6) 3.11+0,22 45,1:1:7.0 45.0±1.3 161+8.3 449 CRYSTAL LOCALIZATION AND OSTEOPONTIN IMMUNO· STAINING IN GENETIC HYPERCALCIURIC STONE FORM- ING RATS Andrew P Evan*, Sharon Bledsoe, Indianapolis" IN; Susan Smith, David Bushinsky, Rochester, NY INTRODUCTION AND OBJECTIVE: In some experimental models calcium oxalate (CaOx) stone formation has been reported to induce severe proximal tubular damage. The inbred genetic hypercalciuric stone forming (GHS) rats develop calcium phosphate (apatite) stones when fed a normal 1.2% calcium diet. The addition of I% hydroxyproline (OHP) to this diet does not alter the type of stone formed while rats fed this diet with 3% OHP form mixed apatite and CaOx stones and those with 5% OHP added form only CaOx stones. The present study was designed to determine the localization of stone formation and if the crystals resulted in pathological changes to the kidneys. METHODS: GHS rats were fed IS gm of the control diet or the diet supplemented with 1%, 3% or 5% OHP for 18 wks. A separate group of Sprague-Dawley rats (the parental strain of the GHS rats) served as the controls. At that time all kidneys were perfusion-fixed for structural analysis and detection of crystalline deposits using the Yasue silver substitution method and immunostaining for osteopontin. RESULTS: Crystal deposits were found in the kidneys of all animals in all groups and this Yasue stained material was detected only in the urinary space. No crystalline deposits were noted within the cortical or medullary segments of the nephron. There was no evidence for tubular damage in any group. The only pathological changes occurred in 3% and 5% OHP groups with the 5% group showing the most severe changes. In these rats, which form only CaOx stones, focal sites along the urotheliallining of the papilla and fornix of the urinary space demonstrated a proliferative response characterized by increased density of urothelial cells that always surrounded the crystalline deposits. At the fornix some crystals appeared to be lodged within the interstitium deep to the proliferative urothelium. Osteopontin innunostaining was similar for all groups. CONCLUSIONS: Thus in the GHS rat, the initial stone formation occurred solely in the urinary space. Tubular damage was not observed with either apatite or CaOx stones. The apatite stones do not appear to cause any pathological change while those rats forming CaOx stones have a proliferative response of the urothelium around the crystalline material in the fornix. Source of Funding: NIH POI DK56788. *Presenting author. , p<0.05 fordifference from Non-Op CtrI, t p<O,OS fordifference from op Clrl, Vd-Volume density, Op-Operated, Mean ± SEM Source of Funding: Methodist institute of Stone disease, Indianapolis IN. Prostate Cancer: Detection and Screening (I) Moderated Poster Sunday, April 27, 2003 3:30-5:30 PM 451 COMPLEXED PSA REDUCES UNNECESSARY BIOPSIES IN THE 2.6-4.0 NGIML PSA RANGE Michael K Brower", Seattle, WA; Carol Cheli, Tarrytown, NY; Alan W Partin, Baltimore, MD; Bob Djavan, Vienna, Austria INTRODUCTION AND OBJECTIVE: Complexed PSA reduces unnecessary biopsies in the 2.6-4.0 ng/mL PSA range MK Brawer, C. Cheli, A. Partin, B. Djavan Objectives: Catalona et al (J Urol, vol 168,922-925) recently reported that the use of a 25% free PSA cutoff detected 85% of cancers and avoided 19% of biopsies in a biopsy confirmed population of men within the 2.6-4.0 ng/mL PSA range. We, therefore, sought to evaluate the diagnostic performance of cPSA relative to total PSA and % free PSA within this clinically relevant PSA range. METHODS: We evaluated the performance of cPSA within the 2.6 ng/rnL-4.0 ng/rnL PSA range to discriminate benign and malignant disease from data derived from 2 multicenter studies within the US and Europe. A total of 316 consecutive men scheduled for prostate biopsy were enrolled prospectively and were tested with total PSA and cPSA methods and a sub-population of 205 men were tested with free PSA. ROC analysis was performed for PSA and cPSA and % free PSA. RESULTS: A total of 316 men were evaluated of which 82 (25.9%) were diagnosed with prostate cancer. ROC analysis performed from results of all samples showed that the AUC of cPSA was statistically greater than total PSA of 0.625, and 0.560, respectively (p<0.008). Using cutoff values for cPSA of 2.3 ng/mL, and total PSA of 2.73 ng/rnL provided specificities of 20.1%, and 9.8%, respectively at sensitivities of 95%. ROC analysis performed from results of the
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116 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Sunday, April 27,2003
450SURGICAL RENAL DENERVATION EFFECTS RATPOLYCYSTIC KIDNEY DISEASE Arieh L Shalhav*, Chicago, IL;Tiberio Siqueira, Recife, Brazil; Chad Trambaugh, Indianapolis, IN; CrPowell, Chicago, IL; Vincent Gattone, Indianapolis, IN
INTRODUCTION AND OBJECTIVE: The kidney has both afferent (sensory)and efferent (sympathetic) nerves which can function together in arenorenal reflex.Sympathetic renal innervation is known to contribute to the hypertension in adultdominant poly cystic kidney disease (PKD). The present study in male Han:SPRD-cy rats (which is the best animal model for PKD) was aimed to evaluate thepossible contribution of renal innervation to the progression of hypertension, renalfailure and cystic change in PKD.
METHODS: At 4 weeks of age, male rats were randomized as either:l)denervation; a midline laparotomy and bilateral surgical renal denervation withphysical stripping of the nerves and immersing the artery with phenolfalcohol(Denervated), 2)sham operated control; anesthesia with a midline laparotomy only(Sham Op) or 3) non-operated control; similarly handled but not anesthetized orsubjected to surgery (Non Op) groups. Blood pressure (tail cuff method), renalfunction (BUN) and renal histology were assessed at 8 weeks of age.
RESULTS: Bilateral renal DeNx in cystic rats reduced cystic kidney size (totalkidney weight and kidney weight as % of body weight), reduced cyst volumedensity, normalized systolic blood pressure and improved renal function ascompared to Non Op control cystic rats. Compared to sham Op control cystic rats,the denervated cystic rats exhibited a reduced blood pressure only(see table).
CONCLUSIONS: Bilateral renal denervation was efficacious in slowing PKDprogression in the rat model. The most significant effect noted was on hypertention.However, sham operation appears to also have some effect on PKD progression,possibly through afferent nerves since the skin at the same spinal levels thatinnervate the kidney was incised during laparotomy. Renal innervation plays a rolein the hypertension and possibly in disease progression in the rat model of PKD.Further studies to assess the clinical aplicability of this approach are underway.
448URINARY NITRITE EXCRETION AND URINARY VARIABLESIN PATIENTS WITH NOCTURNAL FREQUENCY OF MICTURITION: EFFECTS OF INDOMETHACIN Noori S Al-Waili*, Dubai,UAE
INTRODUCTION AND OBJECTIVE: Nitric oxide(NO) playa role in renalphysiology and pathology. We found that NO increased in primary enuresis andindomethacin could reduce frequency of micturition and urinary nitriteexcretion.Urinary nitrite excretion and urinary variabels were measured in patientswith primary nocturnal frequency of micturition (PNFM) and compared withnormal individuals before and after indomethacin treatment.
METHODS: The study comprised seven patients with PNFM and sevennormal control. Nitrite was assayed in spot morning urine samples; urine volume,urine osmolality and electrolytes, serum osmolality and electrolytes and functionalbladder capacity (FBC) were assayed. Both groups were then given 100 mg ofindomethacin suppository daily for ten days and urinary variables were reevaluated during day ten.
RESULTS: Inodmethaicn significantly reduced frequency of voiding in patientswith PNFM.Urinary nitrite excretion of patients with PNFM was greater than that ofnormal subjects (230+/-62 umolll versus 42 +/-30 umolll, p<0.05). The mean (SD) 24hr urine volume and osmolality, the night urine volume and osmolality, serumosmolality, FBC, creatinine clearance, fractional excretion of sodium (FENa,fractionalexcretion of potassium(FEK),and urinary excretion of glucose and potassium werelower in patients with PNFM as compared with normal individuals, although notstatistically significantly so, except for FEC that was significantly lower in the patients.Urinary excretion of electrolytes, day; night urinary volume ratio, spot morningosmolality, nocturnal index, and nocturnal polyuria index were higher in patients withPNFM. Indomethacin decreased 24 hr urinary volume, creatinine clearance, osmolarclearance and urinary protein excretion in the patients and control except for 24 hrurinary protein excretion that was increased mildly in the conrol. Indomethacinincreased day: night urinary volume ratio in the normal subjects.
CONCLUSIONS: Urinary nitrite excretion and urinary excretion ofelectrolytes increased and FBC decreased in patients with PNFM;Indomethacindecreased urinary volume, FENa, FEK, osmolar clearance, and free waterclearance in patients and normal control. This might explain the mechanism ofeffect of indomethacin on frequency of voiding. Possible interaction ofprostaglandin and NO in the pathogenesis of PNFM is discussed.
Source of Funding: None.
Group
Denervated
ShamOp
Non Op
Phenotype Kidney Wgt as Cyst Vd (%) BUN (mg/dl) Systtllte BP0/0 Body Wgt (mmHg)
449CRYSTAL LOCALIZATION AND OSTEOPONTIN IMMUNO·STAINING IN GENETIC HYPERCALCIURIC STONE FORMING RATS Andrew P Evan*, Sharon Bledsoe, Indianapolis" IN; SusanSmith, David Bushinsky, Rochester, NY
INTRODUCTION AND OBJECTIVE: In some experimental models calciumoxalate (CaOx) stone formation has been reported to induce severe proximaltubular damage. The inbred genetic hypercalciuric stone forming (GHS) ratsdevelop calcium phosphate (apatite) stones when fed a normal 1.2% calcium diet.The addition of I% hydroxyproline (OHP) to this diet does not alter the type ofstone formed while rats fed this diet with 3% OHP form mixed apatite and CaOxstones and those with 5% OHP added form only CaOx stones. The present studywas designed to determine the localization of stone formation and if the crystalsresulted in pathological changes to the kidneys.
METHODS: GHS rats were fed IS gm of the control diet or the dietsupplemented with 1%, 3% or 5% OHP for 18 wks. A separate group ofSprague-Dawley rats (the parental strain of the GHS rats) served as the controls. Atthat time all kidneys were perfusion-fixed for structural analysis and detection ofcrystalline deposits using the Yasue silver substitution method and immunostainingfor osteopontin.
RESULTS: Crystal deposits were found in the kidneys of all animals in allgroups and this Yasue stained material was detected only in the urinary space. Nocrystalline deposits were noted within the cortical or medullary segments of thenephron. There was no evidence for tubular damage in any group. The onlypathological changes occurred in 3% and 5% OHP groups with the 5% groupshowing the most severe changes. In these rats, which form only CaOx stones,focal sites along the urotheliallining of the papilla and fornix of the urinary spacedemonstrated a proliferative response characterized by increased density ofurothelial cells that always surrounded the crystalline deposits. At the fornix somecrystals appeared to be lodged within the interstitium deep to the proliferativeurothelium. Osteopontin innunostaining was similar for all groups.
CONCLUSIONS: Thus in the GHS rat, the initial stone formation occurredsolely in the urinary space. Tubular damage was not observed with either apatite orCaOx stones. The apatite stones do not appear to cause any pathological changewhile those rats forming CaOx stones have a proliferative response of theurothelium around the crystalline material in the fornix.
Source of Funding: NIH POI DK56788.
*Presenting author.
, p<0.05 fordifference from Non-Op CtrI, t p<O,OS fordifference from op Clrl, Vd-Volume density,Op-Operated, Mean ± SEM
Source of Funding: Methodist institute of Stone disease, Indianapolis IN.
Prostate Cancer: Detection andScreening (I)
Moderated PosterSunday, April 27, 2003 3:30-5:30 PM
451COMPLEXED PSA REDUCES UNNECESSARY BIOPSIES INTHE 2.6-4.0 NGIML PSA RANGE Michael K Brower", Seattle, WA;Carol Cheli, Tarrytown, NY; Alan W Partin, Baltimore, MD; Bob Djavan,Vienna, Austria
INTRODUCTION AND OBJECTIVE: Complexed PSA reduces unnecessarybiopsies in the 2.6-4.0 ng/mL PSA range MK Brawer, C. Cheli, A. Partin, B.Djavan Objectives: Catalona et al (J Urol, vol 168,922-925) recently reported thatthe use of a 25% free PSA cutoff detected 85% of cancers and avoided 19% ofbiopsies in a biopsy confirmed population of men within the 2.6-4.0 ng/mL PSArange. We, therefore, sought to evaluate the diagnostic performance of cPSArelative to total PSA and % free PSA within this clinically relevant PSA range.
METHODS: We evaluated the performance of cPSA within the 2.6 ng/rnL-4.0ng/rnL PSA range to discriminate benign and malignant disease from data derivedfrom 2 multicenter studies within the US and Europe. A total of 316 consecutivemen scheduled for prostate biopsy were enrolled prospectively and were testedwith total PSA and cPSA methods and a sub-population of 205 men were testedwith free PSA. ROC analysis was performed for PSA and cPSA and % free PSA.
RESULTS: A total of 316 men were evaluated of which 82 (25.9%) werediagnosed with prostate cancer. ROC analysis performed from results of allsamples showed that the AUC of cPSA was statistically greater than total PSA of0.625, and 0.560, respectively (p<0.008). Using cutoff values for cPSA of 2.3ng/mL, and total PSA of 2.73 ng/rnL provided specificities of 20.1%, and 9.8%,respectively at sensitivities of 95%. ROC analysis performed from results of the
Vol. 169, No.4, Supplement, Sunday, April 27, 2003 THE JOURNAL OF UROLOGY@ 117
Source of Funding: Supported in par1 by a grant from HybritechlBeckman,Inc., Fullerton, CA.
sub-population of men showed that the AUC of cPSA was statistically greater thantotal PSA of 0.631 and 0.546, respectively (p<0.003). The AUC for %free PSAwas 0.635 and no statistical improvement over the use of cPSA was observed(p=0.923). The table below shows the significant findings with respect tosensitivity and specificity in the sub-population of men evaluated.
CONCLUSIONS: cPSA reduces unnecessary biopsies in the 2.6 to 4.0 ng/mLPSA range. The use of cPSA as a single test provided improved specificity overtotal PSA. The use of %free provided no additional benefit in the differentiation ofbenign and malignant disease over cPSA within this clinically relevant IPSA range.
Source of Funding: Bayer Corp.
453PROGNOSTIC VALUE OF HIGH GRADE PROSTATICINTRAEPITHELIAL NEOPLASIA AND ATYPIA IN THEEXTENDED PROSTATE BIOPSY ERA Courtenay K Moore*,Shridevi Karikehalli, Tipu Nazeer, Hugh A Fisher, Ronald P Kaufman, BadarM Mian, Albany, NY
INTRODUCTION AND OBJECTIVE: High-grade prostatic intraepithelialneoplasia (HGPIN) and atypical small acinar proliferation (Atypia) found inprostate biopsy specimens are often followed by a repeat biopsy. Previous studiesof repeat prostate biopsy for HGPIN and Atypia, that report cancer detection ratesof 40-70%, are based on the sextant biopsy scheme. Currently, extended prostatebiopsy schemes that incorporate lateral/anterior peripheral zone are routinelyutilized at most centers because of the associated increased cancer detection ratewhen compared to sextant biopsy. Our objective was to determine the prognosticvalue of HGPIN and Atypia in men who underwent prostate biopsy utilizing theextended biopsy scheme.
METHODS: Between 1998 and 2002, 805 prostate biopsies were performedusing a scheme incorporating sextant plus lateral/anterior peripheral zone biopsieswith or without transitional zone biopsies (10 to 14 cores). Of these, 38 men withHGPIN and 33 men with Atypia underwent repeat extended prostate biopsy. Also,
9 men with HGPIN and I man with Atypia underwent a second repeat biopsy. Themean age and PSA were 62 and 7.1, respectively. Patients in both groups weresimilar in age, race, clinical stage and pre-op PSA. Median interval betweenbiopsies was 3 months (range 1-16). Fisher's exact test (2-sided) was used forstatistical analysis.
RESULTS: Of the 38 repeat biopsies performed for HGPIN, only 2 (5%) werediagnostic of cancer, while 16 of 33 (49%) biopsies for Atypia detected prostatecancer (p < 0.005). None of the 9 men who underwent a second repeat biopsy forHGPIN had cancer, while the only man with Atypia undergoing a third biopsy hadcancer. Thus, 17 of 18 cancers were detected on first repeat biopsy. In the Atypiagroup, prostate cancer was found at the same site in only 9 (56%) cases, and in theipsilateral side in 13 (81%) men. Mean number of cores positive for cancer was 1.4(range; 1-3). The median Gleason score was 6 (range 5-8).
CONCLUSIONS: In the contemporary era of extended peripheral zonesampling, the prognostic value of HGPIN has diminished significantly. Thus. menwith HGPIN should not undergo a repeat biopsy, while those with Atypia shouldstill be offered a repeat biopsy. The extended biopsy scheme should be utilized forrepeat biopsy, since directing the biopsy to the site of previous lesion will lead toa significant number of undetected cancers.
Source of Funding: None.
455PROSTATE INTRAEPITHELIAL NEOPLASIA PREDICTSPROSTATE CANCER IN REPEAT SYSTEMATIC 12-COREBIOPSIES Herb Singh*, Eduardo I Canto, Houston, TX.; Shahrokh FShariat, Dallas, TX.; Dov Kadmon, Brian J Miles, Thomas M Wheeler, KevinM Slawin, Houston, TX.
INTRODUCTION AND OBJECTIVE: Urologists are increasingly adopting10- or 12-core systematic biopsy as the initial biopsy method. Since these biopsyregimens detect a higher percentage of the cancers present than sextant biopsy, therole of repeat biopsies in this population remains to be defined. Our objective inthis study is to examine the predictors of prostate cancer on a second systematic12-core biopsy (SI2C) in patients with an initial SI2C without evidence of prostatecancer.
METHODS: This study evaluated 1,047 consecutive patients who underwentan initial SI2C biopsy. 144 of these patients had a SI2C without evidence ofprostate cancer and underwent a repeat SI2C biopsy. Of these patients, 95 had a
454CAN THE NUMBER OF CORES WITH HIGH-GRADEPROSTATE INTRAEPITHELIAL NEOPLASIA PREDICTCANCER IN MEN WHO UNDERGO REPEAT BIOPSY? YoshioNaya*, Alberto G Ayala, Pheroze Tamboli, Richard J Babaian, Houston, TX.
INTRODUCTION AND OBJECTIVE: Previous study indicated that thenumber of cores with high-grade prostate intraepithelial neoplasia (PIN) was apredictor of cancer in the men following diagnosis of high-grade PIN on the initialbiopsy. We previously reported that the presence of atypical glands was the mostsignificant independent predictor of cancer and that high-grade PIN was notpredictive on repeat biopsy in the men who underwent extended multi-site biopsy.In this study, we evaluated whether the number of cores with high-grade PIN in themen who underwent extended multi-site biopsy could predict which men wouldhave prostate cancer.
METHODS: Between June 1997 and April 2002, 976 men underwent initialprostate biopsy for early detection of prostate cancer using an extended multi-sitescheme (10 or II cores, incorporating the anterior hom of the peripheral zoneand/or the transition zone). Of these, 147 had at least one repeat biopsy (range 1-3)of any type (extended, sextant or directed). Of these 147 men, 44 had high-gradePIN on initial biopsy and 19 had atypical glands. Of the 44 men, 4 had 4 cores withhigh-grade PIN, 5 had 3 cores, 10 had 2 cores, and remaining 25 had I core withhigh-grade PIN.
RESULTS: Overall repeat biopsy identified cancer in 19.7% of the men. If onlyone repeat biopsy had been performed on the 147 men, 18.4% of the men wouldhave been found to have cancer. Of the 44 men with high-grade PIN, 7 were foundto have cancer (15.9%), None the 4 men with 4 cores of high-grade PIN had cancer.Cancer was found in 1 of the 5 men with 3 cores of high-grade PIN and in I of 10men with 2 cores of high-grade PIN, and in 5 of the 25 men with a single core ofhigh-grade PIN. Ten (52.6 %) of the 19 men with atypical glands had cancer(52.6%). Upon multivariate stepwise logistic regression analysis, only the presenceof atypical glands was a significant independent predictor of cancer on repeatbiopsy in the men who underwent an initial extended multi-site biopsy (p<O.OOI).High serum prostate-specific antigen (PSA) at initial biopsy, free-to-total PSAratio, digital rectal examination, and rate of change of serum PSA did not predictcancer.
CONCLUSIONS: CONCLUSIONS: The numbers of cores with high-gradePIN did not predict cancer in the men who underwent extended multi-site biopsy.
Source of Funding: None.
%freePSA--Cutoff ng/ml Spec %
24,2 120203 27.317.4 38.7
cPSACutoff ng/ml Spec %
2.2 14.72.3 24.02.4 34.7
tPSACutoff ng/ml Spec %
2.73 11.32.75 11.32.82 17.3
Sensitivity%959085
452RELATION BETWEEN PREOPERATIVE PSA RANGE AND 10YEAR PROGRESSION-FREE SURVIVAL FOLLOWINGRADICAL PROSTATECTOMY FOR STAGE TIC DISEASE JoAnn V Antenor*, Kimberly A Roehl, William J Catalona, St. Louis, MO
INTRODUCTION AND OBJECTIVE: There is controversy about whetherdetecting prostate cancer in the 2.6 to 4.0 ng/mL PSA range would provide aprogression-free survival advantage as compared with detecting cancer in higherPSA ranges. Previous studies evaluating this issue have been limited by insufficientstatistical power and/or patient follow-up. The objective of this study is todetermine biochemical progression-free survival estimates as a function ofpreoperative PSA level in a large cohort of patients with stage Tic prostate cancertreated with radical prostatectomy (RRP) and monitored in prospective follow-upstudies.
METHODS: 2718 men with clinical stage Tlc prostate cancer were treatedwith RRP and monitored prospectively in follow-up studies. Study parametersincluded preoperative PSA, age, pathologic tumor stage, and Gleason sum. Patientswere monitored every six months. A postoperative PSA >0.2 ng/mL wasconsidered biochemical evidence of cancer progression. The main outcomeparameter was lO-year biochemical progression-free survival estimates. Theactuarial probability was generated using the Kaplan-Meier method and comparedusing the log-rank test.
RESULTS: The pathologic stage, Gleason sum, and 10-year biochemicalprogression-free survival rates as a function of preoperative PSA level are shownin the table.
CONCLUSIONS: Detection of prostate cancer in the 2.6-4.0 ng/mL PSA rangeprovides a significantly greater percentage of organ-confined tumors andsignificantly better lO-year biochemical progression-free survival rates comparedwith detection of cancer in higher PSA ranges.
Outcomes of prostate cancer detection andtreatment asa function of preoperetive PSAlevel
118 THE JOURNAL OF UROLOGY® Vol. 169, No.4, Supplement, Sunday, April 27, 2003
METHODS: From June 1999 to October 2002 an additional 200 menunderwent systematic ultrasound guided biopsy using the transperinealtemplate technique. All patients had undergone at least one and 160 (80%) hadundergone two or more previous sets of biopsies. Additionally, study inclusionrequired high risk parameters, including prostate specific antigen (PSA)acceleration greater than 0.75 ngiml per year, PSA greater than 10 ngiml, orprevious prostatic intraepithelial neoplasia and/or atypical small cell acinarproliferation on biopsy. Patients with a prostate volume less than 45 cc.underwent at least 16 biopsies while those with a prostate volume greater than45cc. underwent 20 or more biopsies.
RESULTS: Cancer was identified in 74 of the 200 men (37%) in this highrisk subgroup undergoing repeat biopsy. The most common biopsy grade was6 (range 3 to 9). Adenocarcinoma was identified in the transition zone area in58 of 74 cases (78.4%), including 34 (45.9%) in which disease was detected inthe transition zone only. Twenty-two of the 24 men (91.7%) who underwentradical prostatectomy at our institution had stage pT2A or pT2B disease despiteelevated PSA. Overall results from the entire cohort March 1997 to October2002 (N=288) reveal detection of cancer in 112 patients (38.9%). Identificationof adenocarcinoma in the transition zone occurred in 87 of 112 cases (77.7%),including 49 (43.8%) in which disease was detected in the transition zone only.Thirty of the 39 men (76.9%) who underwent radical prostatectomy hadorgan-confined disease.
CONCLUSIONS: Systematic transperineal template biopsy of the prostate is auseful repeat saturation biopsy technique for the detection of adenocarcinoma iuhigh risk patients. These tumors appear to be localized anteriorly, and we suggestthat this technique allows improved sampling of anterior and lateral regions.
458PROSTATE INTRAEPITHELIAL NEOPLASIA PREDICTSPROSTATE CANCER IN REPEAT SYSTEMATIC 12-COREBIOPSIES Herb Singh", Eduardo Canto, Houston, TX; Shahrokh Shariat,Dallas, TX; Dov Kadmon, Brian J Miles, Thomas M Wheeler, Kevin MSlawin, Houston, TX
INTRODUCTION AND OBJECTIVE: Urologists are increasingly adopting10- or 12-core systematic biopsy as the initial biopsy method. Since these biopsyregimens detect a higher percentage of the cancers present than sextant biopsy, herole of repeat biopsies in this population remains to be defined. Our objective inthis study is to examine the predictors of prostate cancer on a second systematic12-core biopsy (SI2C) in patients with an initial SI2C without evidence of prostatecancer.
METHODS: This study evaluated 1,047 consecutive patients who underwentan initial SI2C biopsy. 144 of these patients had a SI2C without evidence ofprostate cancer and underwent a repeat S12C biopsy. Of these patients, 95 had aprostate serum antigen (PSA) at initial biopsy between 2.5 and 10 (ng/ml) andultimately comprised the study population. Parameters that were evaluatedincluded initial and repeat biopsy PSA, initial and repeat percent free PSA(%fPSA), initial and repeat biopsy digital rectal exam (ORE) status (normal versusabnormal), presence of high grade prostatic intraepithelial neoplasia (PIN) oninitial biopsy, presence of atypical small acinar proliferation (ASAP) on initialbiopsy, poor DRE change (initial normal -> repeat abnormal), PSA doubling-time(PSAdt= log(2) * (number of days between PSA measurement)! (log(repeatPSA)-Iog(initial PSA)), and yearly inter-biopsy PSA changes ( yibPSA= «repeatPSA)- (initial PSA»i(number of days between PSA measurement) * 365).Statistical methods included the Mann-Whitney U test, Pearson Chi-Square test,and multivariable logistic regression analysis.
RESULTS: In univariable analyses PSAdt, yibPSA, initial and repeat PSA,initial and repeat %fPSA, poor ORE change, repeat ORE status, nor presence ofASAP were significant predictors of prostate cancer at repeat biopsy. However,both initial ORE status (p=.034) and the presence of PIN (p=.01O) weresignificant predictors of prostate cancer at repeat biopsy. In multivariable logisticregression analysis, only the presence of PIN remained a significant predictor ofprostate cancer (p=.OI2).
CONCLUSIONS: Our results suggest that for patients with a PSA between 2.5and 10 nglmL, whose initial S12C biopsy contains PIN but not cancer, the presenceof PIN alone is an indication to re-biopsy. Further studies are needed to confirmthis finding in patients undergoing an initial systematic 12- or 10- core biopsy.
Source of Funding: None.
Source of Funding: None.
prostate serum antigen (PSA) at initial biopsy between 2.5 and 10 nglml andultimately comprised the study population. Parameters that were evaluatedincluded initial and repeat biopsy PSA, initial and repeat percent free PSA(%fPSA), initial and repeat biopsy digital rectal exam (ORE) status [normal versusabnormal}, presence of high grade prostatic intraepithelial neoplasia (PIN) oninitial biopsy, presence of atypical small acinar proliferation (ASAP) on initialbiopsy, poor ORE change {initial normal-erepeat abnormal}, PSA doubling-time(PSAdt= log(2) * (number of days between PSA measurement)1 {log(repeatPSA)-Iog(initial PSA) }), and yearly inter-biopsy PSA changes ( yibPSA = {(repeatPSA)- (initial PSA) }/(number of days between PSA measurement) * 365).Statistical methods included the Mann-Whitney U test, Pearson Chi-Square test,and multivariable logistic regression analysis.
RESULTS: In univariable analyses PSAdt, yibPSA, initial and repeat PSA,initial and repeat %fPSA, poor ORE change, repeat ORE status, nor presence ofASAP were significant predictors of prostate cancer at repeat biopsy. However,both initial ORE status (p=.034) and the presence of PIN (p=.01O) weresignificant predictors of prostate cancer at repeat biopsy. In multivariable logisticregression analysis, only the presence of PIN remained a significant predictor ofprostate cancer (p= .012).
CONCLUSIONS: Our results suggest that for patients with a PSA between 2.5and 10 nglml, whose initial S12C biopsy contains PIN but not cancer, the presenceof PIN alone is an indication to re-biopsy. Further studies are needed to confirmthis finding in patients undergoing an initial systematic 12- or 10- core biopsy.
Source of Funding: None.
456THE IMPACT OF EXTENDED BIOPSY STRATEGIES ON THENEED FOR REPEAT BIOPSIES IN PATIENTS WITHPROSTATE INTRAEPITHELIAL NEOPLASIA Jon Pohland,Steven Schwartz, Neil F Wasserman, Joel W Slaton*, Minneapolis, MN
INTRODUCTION AND OBJECTIVE: The diagnosis of prostaticintraepithelial neoplasia (PIN) using the traditional sextant biopsy necessitated upto two repeat biopsies due to the high risk for coexistent prostate cancer. With theadvent of the extended core biopsy strategies, the early diagnosis of prostate cancerhad been enhanced. We investigated the effect of extended core biopsy strategieson the identification of PIN during the initial biopsy as well as ability to identifycancer on subsequent biopsies.
METHODS: We reviewed records of 2028 patients who underwent 2603biopsies between 1998 and 2002. Seventy-two percent of the patients underwent asextant biopsy with occasional lesion-directed biopsies while 28% underwenteither a 1O-core of 12 core biopsy with additional directed biopsies. Patients werestratified according the type of biopsy and the diagnosis on the initial biopsy(negative, PIN alone, cancer alone, and PIN plus cancer). The pathology of repeatbiopsies in patients with a diagnosis of PIN were assessed for the presence ofcancer.
RESULTS: The presence of no pathology, PIN, PIN plus cancer, or cancer wasidentified in 54%, 10%, 14%, and 21% of patients undergoing a sextant biopsy and50%, 9%, 17%, and 25%. Yield of cancer increased by 13% by the use of anextended core strategy. Among the 151 patients who underwent sextant biopsy andfound to have PIN, 120 (79%) did and 31 (79%) did not undergo repeat biopsy.Among those undergoing repeat biopsy, 41 (34%) patients had no cancer, 45 (38%)patients had persistent PIN, and 34 (28%) had cancer. Among the 56 patients whounderwent an extended core biopsy and found to have PIN, 43 (77%) did and 13(23%) patients did not undergo repeat biopsy; on repeat biopsy, 18 (41%) patientshad no cancer, 19 (44%) had persistent PIN, 6 (14%) had cancer. When wecompared risk of cancer on repeat biopsy after a diagnosis of PIN, we found astrong statistical trend toward reduction risk for cancer among patients undergoingrepeat biopsy after an extended core biopsy when compared to sextant biopsy((6143, 14% versus 34/120, 28%, p=0.06).
CONCLUSIONS: Our results suggest that an extended core biopsy strategy,which utilizes increased number of biopsy cores to increase the diagnosis prostatecancer, will identify patients with PIN who will have a reduced risk for cancer onrepeat biopsies. Physicians can utilize this information when counseling patientsregardng the need for repeat biopsies after a diagnosis of PIN.
Source of Funding: None.
457SYSTEMATIC TRANSPERINEAL ULTRASOUND GUIDEDTEMPLATE BIOPSY OF THE PROSTATE IN PATIENTS ATHIGH RISK FOR PROSTATE CANCER: AN UPDATE Todd CIgel, David M Pinkstaff*, Gregory A Broderick, Steven P Petrou, Michael JWehle, Paul R Young, Jacksonville, FL
INTRODUCTION AND OBJECTIVE: An alternative systematic biopsytechnique for evaluating men at high risk for prostate cancer with previouslynegative biopsies has been described. We provide an update on our experience withthis technique.
*Presenting author.
Mean Age (years)Mean PSAMean Previous NegativeCoresMean Prostate Volume(ee)
Overall
66.313.5
173
62.6
Positive TemplaleBiopsy
68.016.1
15.7
56.6
Negative TemplateBiopsy
65.311.9
18.3
65.9
Vol. 169, No.4, Supplement, Sunday, April 27, 2003 THEJOURNALOFUROLOGY@ 119
459LOW AMERICAN UROLOGICAL ASSOCIATION SYMPTOMSCORE INDEPENDENTLY PREDICTS POSITIVE PROSTATENEEDLE BIOPSY: RESULTS FROM A RACIALLY DIVERSEPROSPECTIVE SERIES OF 411 PATIENTS Christopher R Porter s,Seattle, WA; Jason Kim, Stony Brook, NY; Ashutosh Tewari, Detroit, Ml
INTRODUCTION AND OBJE CTI VE: Transrectal Ultrasound (TRUS )biopsies are associa ted with high false negative rates. We evaluated pre-biopsyparameters,including American Urological Associa tion Symptom Score (AUASS)that may be predictive of positive biopsy.
METHOD S: 41 I co nsecutive men unde rgo ing TR US biop sy we reprospectively evaluated. Indicat ions for biopsy were abnormal digital rectal exa m(DRE) and/or elevated Prostate Specific Antigen (PSA) . AUASS was equivilant tothe AUA symptom index for BPH (copyright (992). All men were examined by asingle surgeon: DRE and TRUS were each given a level of suspicion (LOS),between I =low suspicion (smooth DRE, homgenious TRUS) and 5 = highsuspicion(hard DRE,hypoechoic lesion). LOS > = 3 was graded abnormal. Prebiopsy parameters were PSA, age, race, biopsy history, prostate volume (PV) ,TRUS lesion and AUASS.
RESULTS: Of 411 men, 62% were African American and 38% Caucasian. MeanPSA was 11.6 ng/ml. Mean patient age was 65.3 years and 32% of patients had priorbiopsies . Overall 39% men had abnormal DRE and 32% abnormal TRUS. MeanAUASS was 9.3. The positive biopsy (adenocarcinoma) rate was 40.8%. Univariateanalysis (Chi Square & T test) demonstrated that age, PSA, PV, abnormal DRE, TRUSlesion and AUASS « 7, low) were all predictive of positive biopsy (p<0.05). Racewas nor significant (p= 0.38). Detailed analysis of AUASS in 411 men indicated 4 1%had low symptom scores « 7), 32% had moderate scores (8-19) and 27% had severescores (20-35). In the group of men with low symptoms (N=169), univariate analysis(UVA) demonstrated that age «65), PSA (> 10 ng/ml), PV « 45cc) and abnormalTRUS were all significant predictors positive biopsy (p< 0.05). In men with moderateand severe AUASS UVA of pre-biopsy parameters did not demonstrate significance.Multivariate analysis (Logistic regression) of the 411 men, demonstrated that age« 65), PSA (> IOng/mI), PV « 45cc), abnormal DRE and low AUASS « 7.0), wereall independent predictors of positive biopsy (p<0.05). AUASS indexed to PV was notfound to be significant
CONCLUSIONS: In this prospective study independent predictors of positiveTRUS biopsy include age, PSA, prostate volume, abnormal DRE and low AUASS.Low AUASS « 7) appears to be an important predictor of biopsy outcomeindependent of PSA, prostate volume, age and race. Low AUASS may be animportant variable to consider when counseling patients prior to biopsy and whendesigning patient algorithms for prostate biopsy.
Source of Funding: None.
460PREDICTING CANCER ON REPEAT BIOPSY: RESULTS OF AMULTICENTER PROSPECTIVE EVALUATION OF COMPLEXED PSA Georg Bartsch, Innsbruck, Austria; Michael Brower", Seattle,WA; Carol D Cheli, Tarrytown, NY; Wolfgang Hom inger, Innsbruck, Austria;Richard Babaian, Herbert A Fritsche, Houston, TX.; Samir Taneja, HerbertLepor, New York, NY; Stacy J Childs, Cheyenne, WY; Thomas A Stamey,Stanford, CA; Lori Sokoll, David Chan, Alan W Partin, Baltimore, MD
INTRODUCTION AND OBJECTIVE: Approximately 20% of men undergoing aprostate biopsy will be shown on repeat biopsy to have prostate cancer (CaP). Thus,alternate strategies are needed to enhance cancer detection and minimize false positivebiopsies. We conducted a multicenter prospective evaluation of Complexed PSA(cPSA). As part of this evaluation, we enrolled men indicated for a repeat biopsy andsought to compare the diagnostic performance of cPSA in comparison to tPSA, thefree/total PSA ratio (f/tPSA) and complexedltotal PSA ratio (dtPSA).
METHOD S: Men undergoing repeat biopsy consisting of > 10 prostate tissuecores after an initial negative biopsy were prospectively enrolled at each of 7evaluation sites. Serum was collected and tested with the Bayer Immuno 1 tPSAand cPSA methods and Beckman Access fPSA and tPSA methods. ReceiverOperating Characteristic (ROC) curve analysis was performed and the area underthe curve (AUe) was calculated for tPSA, cPSA and PSA ratios .
RESULTS: 264 men were evaluated and 91 (34%) had carcinoma detected onrepeat biopsy. Median PSA values for men with CaP was 7.85 ng/mL and for thosewith benign disease was 7.15 ng/mL. ROC analysis indicated that the AUC fortPSA, cPSA, f/tPSA and c/tPSA were .567, .583, .648, and .666, respectively. TheAUC for cPSA was statistically greater than tPSA (p= .0 17) and c/tPSA provideda statistically significant improvement in the AUC over cPSA (p=.03). The AUCfor f/tPSA was not statistically greater than cPSA (p= . IO). The table shows thesignificant findings with respect to sensit ivity and specificity.
CONCLUSIONS: These data indicate that the use of cPSA may be useful as a firstline test for CaP detection over traditional tPSA testing. dtPSA further improvedspecificity at clinically relevant sensitivity for CaP detection and outperformed f/tPSA.Use of c/tPSA can aid in selecting men indicated for repeat biopsy procedure.
461RESULTS OF PROSTATE BIOPSY IN MEN WITH LOW SERUMTESTOSTERONE Emani L Rhoden, Abraham Morgentaler", Brookline, MA
INTRODUCTION AND OBJECTIVE: To evaluate the prevalence of occultprostate cancer in a group of symptomatic hypogonadal men.
METHODS: Two hundred and sixty four consecutive men with normal PSA levelsand subnormal levels of total (TT) or free testosterone (FT) underwent prostate biopsyprior to initiating a program of testosterone replacement therapy (TRT). Low levels ofTT and FT levels were defined as values under 300 and 1.5ng/dL, respectively. Normallevels of PSA were considered values between 0 and 4ng/dL. Prostate biospy resultswere correlated with PSA, TT,FT and digital rectal exam.
RESULTS: Prostate cancer was found in 39(14.8%) cases. DRE was normal in173(65.5%) men, and in this group 10.9% had prostate cancer. The DRE was abnormalin 34.5% and in this group prostate cancer was diagnosed in 21.9%. Comparison ofmen with and without cancer did not reveal differences in mean age, TT or FT. ThePSA levels and the prevalence of prostatic intraepithelial neoplasia were higher amongmen with prostate cancer (P< 0.05). Prostate cancer was identified in 16.7% of menwith low levels of both TT and FT, in 12.9% of men with normal TT and low FT, andin 8.3 % of the men with low TT and normal FT.
CONCLUSIONS: Clinically occult prostate cancer can be identified by routineprostate biopsy in a significant number of hypogonadal men with normal PSA. Therisk of cancer is doubled if there is any abnormality on DRE. Men who present withlow levels of both FT and TT are at greatest risk of prostate cancer. The results ofthis study underscore the importance of careful prostatic eva luation in men who arecandidates for TRT.
Source of Funding: None.
462THE VIENNA NOMOGRAMS: A NOVEL BIOPSY STRATEGYDEFINING THE OPTIMAL NUMBER OF CORES BASED ONPSA, AGE AND PROSTATE VOLUME Bob Djavan*, Mesut Remzi,Christ ian Seitz, Vienna, Austria; Theodore Anagnostou, Athens, Greece;Michael Dobrovits, Mike Harik, Michael Marberger, Vienna, Austria
INTRODUCTION AND OBJECTIVE: We conducted a multicenter trialin patients with PSA levels from 2 to 10 ng/ml to validate a newly developednom ogram defining the optimal number of biopsy cores required forprostate cancer detection based on PSA, patient age and prostate volume (VIENNANomogram). Thus optimiz ing not only cancer detection but also eliminating theneed for repeat biopsies. The nomogram was employed and compared to a matchedgroup of patients undergoing a standard octant biopsy protocol.
METHODS: A total of 935 patients underwent the standard octant biopsyprotocoll. All underwent transrectal ultrasound guided needle sextant and 2transition zone biopsies of the prostate. All patients with benign disease on initialbiopsy underwent repeat biopsies within I to 2 months. A total of 394 patientsunderwent prostate biopsy using the Vienna Nomogram .Uni and multivariatestatistical analysis using the SAS system (CARY, North Carolina) and ROC curveswere used to compare both techniques. In addition morbidity was evaluated asdefined by early and delayed morbidity based on a patient based questionnaire andregistered morbidi ty at follow up.
RESULTS: Of the 935 patients in the standard group, 263 (28.1%) had PCa,213 (22.8%) on first and 50 (7,1%) on repeat biopsy. In compari son, cancerdetection using the VIENNA nomogram was 38.7% after the first set of biopsies,which was significantly superior (p= 0.(02) to the octant biopsy technique andeven superior to a combination of first and repeat biopsy. Using the cumulativelogistic plot analysis the probability of a positive first/repeat biopsy was analyzed .Morbidity was significantly lower in the VIENNA nomogram group as comparedto the first + repeat biopsy protocol.
CONCLUSIONS: The VIENN A Nomogram offers an easy tool to select theoptimal number of prostate biopsy cores based on patient age, PSA and volume.Cancer detection is significantly improved and repeat biopsies become thereforunnecessary. Early and delayed morbidity is also significantly reduced suggestingan advantage not only in terms of improved cancer detection and economic s butalso in patient acceptance and morbidity.
Source of Funding: None.
120 THE JOURNAL OF UROLOGY® VoL 169, No.4, Supplement, Sunday, April 27, 2003
a new set of patients from VAMC with consistent performance. The model wouldlikely be improved by retraining with additional patient data from a more diversepopulation and including additional variables such as number of previous biopsiesand percent free-PSA. Such a model may be useful to practitioners and patientswhen considering biopsy for suspicion of prostate cancer.
Source of Funding: Institute for Clinical Research at the Veterans AffairsMedical Center, Washington, DC.
465MORBIDITY OF TRANSRECTAL ULTRASOUND (TRUS)GUIDED PROSTATE BIOPSIES IN PATIENTS FOLLOWINGTHE CONTINUED USE OF LOW DOSE ASPIRIN Zafar Maan*,Uday Patel, Colin Cutting, Sally Kerry, Peter Pietrzak, Matthew Perry, RogerS Kirby, Epsom, UK
INTRODUCTION AND OBJECTIVE: To study whether low dose aspirinincreases the morbidity after TRUS guided sextant prostate biopsy.
METHODS: Single centre, prospective cohort study of 177 patients whounderwent sextant prostate biopsies. Patients who routinely take low doseaspirin were encouraged to continue to do so before and after biopsy. Morbidityin each case was determined by use of a standardized questionnaire that patientscompleted in the seven day period following biopsy. The presence ofhaematuria, per-rectal bleeding and haematospermia were recorded. Thequestionnaire also directed the patient to record fevers, use of analgesia and anyfurther treatment received.
RESULTS: Thirty-six patients took aspirin, whilst the other 141 patients didnot. There were no major complications in either group. Of the aspirin group, 20patients (56%) experienced haernaturia, compared with 83 patients (59%) in thosenot taking aspirin, (a risk difference of 3%, 95% CI minus 15 to 21). Overallbleeding (haernaturia, rectal bleeding and heamatospermia) occurred in 22 patientsor 61% of the aspirin group, and 105 (74%)in the no aspirin group, a difference of13%,95% CI minus 4 to 31.
CONCLUSIONS: Statistically there was no significant difference in theincidence of haematuria or overall bleeding post biopsy between the two groups.There is no evidence to show that aspirin needs to be discontinued prior to sextantprostate biopsy.
Source of Funding: None.
466PROSTATE CANCER (CAP) DETECTION IN THE MEDICALTHERAPY OF PROSTATIC SYMPTOMS (MTOPS) TRIALGerald L Andriole*, St. Louis, MO; Oliver M Bautista, Rockville, MD; EDavid Crawford, Denver, CO; John W Kusek, Bethesda, MD; John DMcConnell, Dallas, TX; Scott Lucia, Denver, CO; Leroy M Nyberg, Bethesda,MD; Kevin M Slawin, Houston, TX; Joseph A Smith, Nashville, TN; StephenC Jacobs, Baltimore, MD; for the MTOPS Research Group, St. Louis, MO
INTRODUCTION AND OBJECTIVE: The incidence of CaP among men withLUTS due to BPH and the effect of therapy with alpha blockers or 5-alphareductase inhibitors is not well established.
METHODS: 3047 men with moderate LUTS secondary to BPH wererandomized at 17 centers to placebo (P), doxazosin (0), finasteride (F) orcombination (D&F) therapy and followed for a mean 404 years to observe theireffects on clinical progression of BPH. 1067 (35.0%) men participated in a biopsy(Bx) substudy. A scheduled biopsy (SB) was performed at baseline, I year and 3-5years after randomization. An additional 260 men (8.5%) underwent clinicallyindicated biopsy (CIB) for either PSA rise and! or suspicious ORE. A doublingalgorithm was used to report PSA of F-treated men. Prior to randomization, menwith PSA>4 were required to have a negative Bx.
RESULTS: For any biopsy performed there is a lower rate of CaP in the F alonegroup; however, among the 1554 pts who received F (+1-0),103 (6.6%) developedCaP. This is not significantly different from P treated pts. Approximately one half ofall CaP were detected among men with no clinical indication for biopsy (140/220); thepositive bx rate for clinically indicated biopsy among men receiving F alone or incombo was comparable to that of P or D treated men.
CONCLUSIONS: The rates of prostate cancer detected among the three activetreatment groups were similar in the MTOPS Study. The usefulness of ORE andPSA (if doubled) as means to detect CaP in men with LUTS secondary to BPHdoes not appear to be compromised among 5-alpha reductase treated men.
463UTILITY OF BASAL CELL COCKTAIL (P63+34BE12) IN THEDIAGNOSIS OF ATYPICAL PROSTATIC GLANDULARPROLIFERATIONS Rajal B Shah*, Lakshmi P Kunju, Ronglai Shen,Michelle Leblanc, Michelle Leblanc, Ming Zhou, Mark A Rubin, AnnArbor, MI
INTRODUCTION AND OBJECTIVE: Basal cell cytokeratin antibody (34f3EI2)is widely used in workup of prostate cancer (Pea). Recent studies have showed p63, anuclear protein, also to be a very useful basal cell marker. The diagnosis of Pea issubstantiated by lack of basal cell staining in atypical foci. However, false lack of stainor patchy staining may occur which may be difficult to interpret. The goal of this studyis to determine if inclusion of both p63 and 34f3E12 antibodies (cocktail) isadvantageous over either marker used alone in work up of an atypical focus in needlebiopsies (NBXs) and transurethral resections (TURF).
METHODS: 37 NBXs and 3 TURP, with atypical foci were stained withmonoclonal p63, 34f3E12 and the basal cell cocktail antibodies. Stainingintensity, percentage of positive basal cells in benign and atypical foci andnumber of negative benign glands were evaluated for p63, 34f3E12 andcocktail. Standard statistical tests were utilized to evaluate overall basal cellstaining differences and assess staining variance between three markers inbenign and atypical glands.
RESULTS: 7 NBXs were diagnosed with Pea, II with post atrophic hyperplasia,9 with HGPIN, including 3 with adjacent small atypical glands, 6 with adenosis, 2benign atypical, I basal cell hyperplasia and 4 were excluded due to loss of tissue. AllPea NBXs were completely negative with all three basal markers (l00% specific). p63showed overall higher basal cell staining in benign (mean difference=0.22, p=O.03)and atypical foci (mean difference=OA, p=0.02), compared to 34f3EI2. Basal cellcocktail, however significantly improved basal cell staining in both benign and atypicalfoci compared to p63 and 34f3E12used alone (p<. 0001). p63 showed lower stainingvariance in benign (p=0.OO3) and atypical (p=O.04) foci compared to 34f3EI2. Thestaining variance for cocktail however is smallest compared to 34f3E12«0.000I) andp63 «0.000I) in both benign and atypical foci.
CONCLUSIONS: p63 is more sensitive and less variable than 34f3E12 instaining basal cells, when used alone. However, basal cell cocktail complementsreaction of both markers and not only improves the sensitivity of basal celldetection, but also reduces staining variability. As diagnosis of Pea is substantiatedby lack of basal cell staining, basal cell marker with highest possible sensitivity andlowest possible variability is critical, We recommend routine use of basal cellcocktail in work up of an atypical focus.
Source of Funding: National Cancer Institute, Specialized Program ofResearch Excellence in Prostate Cancer (NCI Grant P50CA69568).
464A PREDICTIVE MODEL FOR PROSTATE BIOPSY OUTCOMEUTILIZING READILY AVAILABLE CLINICAL VARIABLES EDavid Crawford", Denver, CO; Christopher R Porter, Seattle, WA; GeorgBartsch, Wolfgang J Horninger, lnnsbruck, Austria; Ashutosh Tewari,Detroit, MI; Helmut Klocker, Innsbruck, Austria; Eduard J Gamito, ColinO'Donnell, Denver, CO
INTRODUCTION AND OBJECTIVE: We have developed a predictive modelusing artificial neural networks (ANN) to assess the risk of positive prostate biopsyvalidated on data from two institutions.
METHODS: The model was developed using data from 3,814 menparticipating in the Tyrol Screening Project (Europe) from January 1993 to April2001. Variables used in the model were age, prostate specific antigen (PSA) level,PSA density, prostate volume, digital rectal exam (DRE) findings, and transrectalultrasound (TRUS) findings. A feed-forward, back-error-propagation ANN wastrained and validated using three unique cross-validation sets (splits) of the Tyroldata. Additional validation was done with data from 320 consecutive patientsundergoing biopsy at the Veterans Administration Medical Center (VAMC) inWashington, DC between October 1999 and January 2001. A stepwise logisticregression (LR) model was developed concurrently with the same data.
RESULTS: The mean age was 63, mean PSA = 9.6 ng/rnl., and mean prostatevolume = 37.5 cc. DRE was suspicious in 581 (15.2%) and TRUS was suspiciousin 531 (13.9%) of the men. Men with both suspicious DRE and TRUS numbered198 (5.2%). Carcinoma was confirmed by biopsy in 1,022 (26.8%) men.Performance measures for the ANN and LR models were very similar withdifferences not reaching statistical significance. The mean area under the receiveroperating characteristic curve (AUROC) for the cross-validation sets was 0.75 +0.007. The AUROC for the VAMC validation set was 0.74. For the crossvalidation model with the median AUROC (0.75), an output cutoff of 0.17 had asensitivity of 0.90, specificity = 0.36, negative predictive value (NPV) = 0.91, andpositive predictive value (PPV) = 0.33. A cutoff of 004 yielded a sensitivity =0041, specificity = 0.90, NPV = 0.58 and PPV of 0.81.
CONCLUSIONS: The predictive model was stable as indicated by the lowvariance between AUROCs for the cross validations and was able to generalize to
*Presenting author.
Vol, 169, No.4, Supplement, Sunday, April 27, 2003 THE JOURNAL OF UROLOGY® 121
Incontinence: Evaluation and TherapyPodium
The test is performed using the isothermic nucleic acid based amplification(NASBA) method and the two targets are simultaneously detected in real timeusing specific beacons as probes in an Easy Q instrument. The test was performedon the first voided urine obtained after careful digital rectal examination of theprostate in men undergoing TRUS guided prostate biopsy.
RESULTS: A total of 402 evaluable samples were obtained from patientsundergoing biopsy in 5 centers. Of these 402 patients, 13% had a total PSA below4 ng/ml, 61% between 4 and 10 ng/ml and 26% above 10 ng/m!. The percentageof biopsies positive for cancer in these three groups were respectively 19%, 35%and 45%. The overall uPM3 sensitivity and specificity were 50% and 93%, a sens.of 52% and spec. of 95% in patients with tPSA between 4 and 10 ng/ml and sens.of 40% and spec. of 93% in patients with tPSA below 4 ng/m!. The positivepredictive value of uPM3 was 81% compared to 38% for tPSA.
CONCLUSIONS: These results suggest that the uPM3 urine molecular testprovides an innovative method for a more accurate identification of patients athigher risk of prostate cancer.
Source of Funding: None.
471OUTCOMES FOLLOWING REVISION AND SECONDARYIMPLANTATION OF THE ARTIFICIAL URINARY SPHINCTERIN CASES OF DEVICE MALFUNCTION, URETHRALATROPHY AND EROSION Ganesh V Raj*, Andrew C Peterson, KhaiLee Toh, George D Webster, Durham, NC
INTRODUCTION AND OBJECTIVE: Durable success with the artificialurinary sphincter (AUS) is common but device revision and replacement is oftenneeded for a variety of reasons. We examine our indications and outcomesfollowing these secondary procedures.
METHODS: Medical records of all patients undergoing primary and secondarybulbar urethral AUS implantations and revisions from January 1990 to September2002 were reviewed for a variety of demographic and surgical variables.
RESULTS: Of 554 men undergoing AUS implantation or revision, 119patients underwent 159 secondary procedures. Average age of this cohort was 67.9(26-86) years. Durability of the original AUS prior to second procedure was 45.8(1-184) months, and mean follow-up after secondary implant was 27.8 (1-168)months. Reasons for revision include mechanical (n= 45, 28.3%) and non-
470CHARACTERIZATION OF SIGNIFICANTLY OVEREXPRESSED GENES IDENTIFIED BY HIGH THROUGHPUTCDNA MICROARRAYS AS NEW BIOMARKERS IN PROSTATECANCER Chunde Li*, Stockholm, Sweden; Jacques Lapointe, Stanford,CA; Lars Egevad, Xiaolei Fang, Alexander Valdman, Stockholm, Sweden;James Brooks, David Botstein, Stanford, CA; Peter E Ekman, Stockholm,Sweden; Janathan R Pollack, Patrick 0 Brown, Stanford, CA
INTRODUCTION AND OBJECTIVE: Prostate cancer is the most commoncancer in men and presently can only be cured by radical surgery at early stage.Measurement of increased serum PSA levels can lead to the early detection of asignificant number of cases. However, the preoperative prognostic value of PSA isnot satisfactory. In this study, we aimed at searching for new tumor markers toimprove the present status of preoperative prognosis of patients with tumorsdetected at the early stage.
METHODS: We employed cDNA arrays to scan expression levels of over20,000 genes in tissue samples of prostate cancer, lymph node metastasis andnormal prostate from 14 patients. To further verify the results, tumor samples froma panel of 205 prostate cancer patients consecutively treated only by radical surgerywere analyzed by immunohistochemistry.
RESULTS: Thirty-nine genes showed significant over expression in prostatecancer and lymph node metastases. One third of these genes encode cellmembrane-bound or secreted proteins, suggesting their high potentials as newtumor markers. So far, the expressions of a secreted protein and a membranereceptor have been characterized in correlation to clinical and histopathologicalparameters. The over expression of these two proteins showed significantcorrelation to increased Gleason score and pathological stage.
CONCLUSIONS: The final output of our study is expected to provide a set ofnew biomarkers for prostate cancer diagnosis and prognosis.
Source of Funding: NCI.
3:30-5:30 PMSunday, April 27, 2003
467PROSTATE CANCER DETECTION IN PATIENTS WITH ANABNORMAL DIGITAL RECTAL EXAM AND LOW SERUMPROSTATE SPECIFIC ANTIGEN Caleb B Bozeman*, Brett S Carver,Dennis D Venable, Shreveport, LA; James A Eastham, New York, NY
INTRODUCTiON AND OBJECTIVE: An abnormal digital rectal exam(DRE) is an indication for prostate biopsy in patients with low serum prostatespecific antigen (PSA) levels. We evaluated the patients at our institution whounderwent prostate biopsy and were documented to have an abnormal digital rectalexam and a PSA < 4.0 ng/m!.
METHODS: From 1994 to 2000, a total of 916 patients were documented tohave an abnormal DRE and a PSA < 4.0 ng/ml. We examined the positivepredictive value of abnormal DRE correlated with PSA levels, age, and race.Statistical analyses were performed to determine which patient characteristics weresignificant predictors for detecting cancer on prostate biopsy.
RESULTS: There were 326 African-American and 590 Caucasian patients inour study. Overall, the positive predictive value of an abnormal DRE was 8.8%.Prostate cancer detection rates were similar between blacks and whites (8.6% vs9.0%). Inpatients with PSA levels between 0-0.9,1-1.9,2-2.9, and 3-3.9 ng/ml, thepositive predictive value was 1.8,5.8, 12.7, and 21.0% respectively. Inpatients lessthan 50, between 50-59, 60-69, and greater than 70 years of age the positivepredictive value was 5.36, 6.25, 9.20, and 11.26% respectively. Age (p < 0.03) andPSA (p < 0.000l) were both statistically significant predictors of prostate cancer.
CONCLUSIONS: PSA and age were statistically significant predictors ofprostate cancer in patients with an abnormal DRE and PSA levels less than 4.0ng/m!. While the digital rectal exam remains an important adjunct to PSA inprostate cancer screening, its positive predictive value decreases significantly withdeclining PSA levels.
Source of Funding: None.
469MULTICENTER STUDY OF THE UPM3 TEST, A NEWMOLECULAR URINE ASSAY TO DETECT PROSTATECANCER Fred Saad*, Armen G Aprikian, Montreal, QC, Canada; JeanDessureault, Quebec, QC, Canada; Mostafa M Elhilali, Montreal, QC,Canada; Claude Trudel, Laval, QC, Canada; Lyson Piche, Camille Chypre,Ste-Foy, QC, Canada; Yves Fradet, Quebec, QC, Canada
INTRODUCTiON AND OBJECTIVE: There is a need for better methods toidentify patients at risk of prostate cancer. The aim of this multicenter study wasto evaluate the diagnostic performances of a new molecular test uPM3 detectingprostate cancer cells in the urine.
METHODS: The uPM3 test is a nucleic acid amplification assay detecting inthe urine the relative expression of PSA mRNA as a marker of prostate cells andPCA3 mRNA which is selectively expressed in the majority of prostate cancers.
468UPM3 TEST: A NEW MOLECULAR ASSAY DETECTINGPROSTATE CANCER IN URINE SAMPLES; A NEW FUTUREPERSPECTIVE Martina Tinzl", Babak Djavan, Michael Marberger,Vienna, Austria
INTRODUCTiON AND OBJECTIVE: Serum markers currently available forprostate cancer detection lack sensitivity and specially sufficient specificity. TheuPM3 test is a new molecular assay which can detect prostate cancer cells in urinesamples and can identify patients at high risk for prostate cancer. The purpose ofthis prospective study was to evaluate the uPM3 test in men referred for earlyprostate cancer detection with total PSA levels from 2.5 to 10 ng/m!.
METHODS: The uPM3 test is a nucleic acid based amplification assay(NASBA technique). It detects the relative expression of PSAmRNA as a markerof prostate cells in the urine sample and PCA 3mRNA which selectively isexpressed in the majority of prostate cancer patients. A total of 82 patients havebeen included in our study. After a careful digital rectal examination the patientsfirst voided urine ( 20 to 30 ml) was collected prior to biopsy to perform the uPM3assay. The urine sample was immediately fixed with a buffer solution andrefrigerated. After centrifugation a lysis buffer solution was added to the cell pelletbefore extracting and amplifying the PCA3 mRNA and PSAmRNA. The twotargets then are detected in real time using specific beacons as probes in an EasyQinstrument. Final pathological results were compared and statistical analysisperformed (decisional tree S+ analysis, Seattle USA).
RESULTS: A total of 82 urine samples were obtained. Cancer detection ratewas 31 % in our study population. The overall uPM3 sensitivity were 60 % andspecificity 81 % respectively.
CONCLUSIONS: The uPM3 test offers the advantage of an a office based noninvasive test combining high sensitivity and high specificity values. UPM3 test canimprove cancer detection especially in low PSA ranges.
