25 THE SCREENING TEST NEGATIVE INTERVAL CANCERS CAUSE MORE MORTALITY THAN THE SCREENING TEST POSITIVES

administered, study-specific questionnaire was completed including questions on voiding symptoms. If the respondent had any degree of LUTS they were regarded as having LUTS. The association between LUTS and PC was investigated in a logistic regression model also including age, T-PSA, and prostate volume. Results: In the cohort, median age was 63.3 years (IQR: 60.0 - 66.1), median T-PSA was 3.8 (IQR: 3.3 - 4.9) and median prostate volume was 37.8 cc (IQR: 30.0 – 48.6). According to the biopsy results 643 men (27 %) had PC and 1731 (73 %) men had a benign PAD outcome. Men who reported LUTS had a lower frequency of PC (23 % versus 31 %, p < 0.001). Subject characteristic are shown in table 1. Table 1

No LUTS

LUTS

P-value

Md age

63.3 yrs

63.5 yrs

n.s

Md prostate volume

35.3 cc

41.3 cc

<0.001

Number of PC cases

382(31%)

261(23%)

<0.001

Number of advanced PC

30 (49%)

31(51%)

n.s

Total number of men

1240

1134

Standard error

P-value

Odds Ratio

95% Confidence Interval

Age

0.013

< 0.001

1.087

1.061 - 1.113

Prostate volume

0.004

< 0.001

0.958

0.951 - 0.966

PSA value

0.015

< 0.001

1.093

1.064 - 1.124

LUTS (pos)

0.078

0.014

0.782

0.643 - 0.952

Conclusions: LUTS in men with elevated PSA is inversely related to the risk of PC. The presence of urinary symptoms could therefore be a factor worth considering when evaluating the indication for prostate biopsies.

24

Lower urinary tract symptoms and the risk of biopsy detectable prostate cancer in a screening setting (ERSPC Rotterdam)

Roobol M.J., Bul M., Zhu X., Van Leeuwen P.J., Schröder F.H. Erasmus Medical Centre, Dept. of Urology, Rotterdam, The Netherlands Introduction & Objectives: Lower urinary tract symptoms (LUTS) are reported in up to 30-50% of men over 50 years old. Often, both patient and physician request reassurance that these symptoms are not due to prostate cancer (PCa) resulting in frequent PSA testing in men with LUTS. Here we assess whether LUTS is associated with PCa and whether PSA testing on the basis of LUTS is justified. Materials & Methods: At the initial screening round of the Dutch part of the European Randomised study of Screening for Prostate Cancer (ERSPC, Rotterdam) a total of 3,647 men with complete data on IPSS score, were biopsied (sextant) on the basis of PSA >= 4.0 ng/ml and/or abnormal DRE (1993-1997) or PSA >= 3.0 ng/ml (1997-2000). Men were subdivided according to their IPSS score into mild (score 0-7), moderate (score 8-19) and severe (20-35) LUTS. We assessed the number of PCa cases at 1st screening and at 1st screening including 12 years of follow-up. Results: The results of PCa detection at initial screening and after 12 years of follow-up are displayed in the table. At initial screening the PCa detection rate (PPV) was highest in men with mild LUTS. This could however be caused by the fact that men with more severe LUTS in general have larger prostates and with the sextant biopsy technique applied PCa might have been missed. Additional data including 12 year follow-up show however a similar picture. Hazard ratios of moderate and severe LUTS, after correcting for age and PSA at initial screening were 0.77 (0.69-0.88) and 0.68 (0.52-0.89) respectively. Conclusions: Men with moderate to severe LUTS are at lower risk of having PCa over a period of 12 year. PSA testing simply on the basis of the presence of moderate or severe LUTS is not justified and can lead to unnecessary biopsies and missing the detection of PCa in men with no or mild LUTS symptoms. AUA symptom score at 1st screening round 1st screening

No PCa

Mild 0-7 (N,%) 1750 (73.7)

Moderate 8-19 (N,%) 811 (78.5)

Eur Urol Suppl 2011;10(2):36

Severe 20-35 (N,%)

188 (79.0)

626 (26.3)

222 (21.5)

50 (21.0)

898 (24.6)

Total

2376 (100)

1033 (100)

238 (100)

3647 (100)

1st screening + 12 yr follow-up

Mild 0-7 (N,%)

Moderate 8-19 (N,%)

Severe 20-35 (N,%)

Total (N,%)

No PCa

1518 (63.9)

732 (70.9)

173 (72.7)

2423 (66.4)

PCa

858 (36.1)

301 (29.1)

65 (27.3)

1224 (33.6)

Total

2376 (100)

1033 (100)

238 (100)

3647 (100)

25

In a logistic regression model all four variables were significantly associated with biopsy outcome. Age (p < 0.001) and T- PSA (p < 0.001) were positively correlated to PC while prostate volume (p < 0.001) and presence of LUTS (p = 0.014) were negatively correlated to PC in biopsies. Variable

PCa

Total (N,%)

2749 (75.4)

The screening test negative interval cancers cause more mortality than the screening test positives

Santti H.H.1, Joutsi T.2, Määttänen L.3, Kujala P.4, Tammela T.L.5, Ruutu M.1, Auvinen A.6 1 Helsinki University Central Hospital, Dept. of Urology, Helsinki, Finland, 2Satakunta Central Hospital, Dept. of Surgery, Pori, Finland, 3Finnish Cancer Registry, Helsinki, Finland, 4Tampere University Hospital, Dept. of Pathology, Tampere, Finland, 5 Tampere University Hospital, Dept. of Urology, Tampere, Finland, 6University of Tampere, School of Public Health, Tampere, Finland Introduction & Objectives: The European Randomized Study of Screening for Prostate Cancer (ERSPC) recently showed a 20% reduction in prostate cancer mortality. Interval cancers detected outside the screening protocol both in the screening test negative and positive men may cause deaths and reduce the impact of screening on mortality. Materials & Methods: The Finnish prostate screening trial comprised of 80,379 men aged 55-67 years at entry. The screening arm consisted of 31,970 men of whom 23,608 (74%) participated in a PSA test at 4-year intervals. Biopsy was indicated when PSA was >4 ng/ml, or 3–4 ng/ml with suspect digital rectal examination or proportion of free PSA <0.16. A repeat biopsy was allowed, if PSA was >10 or histology was suspicious of cancer or showed prostatic intraepithelial neoplasia. Cancers detected among screened men outside the screening protocol were considered interval cancers and were identified through linkage with the Finnish Cancer Registry. Clinical data were abstracted from medical records and causes of death were assessed by a committee using ERSPC definitions. Results: We identified 367 cancers outside the screening protocol and excluded 16 cancers that were found either as an incidental finding in autopsy or after refusal from biopsy. We found 123 screening test negative and 244 screening test positive interval cancers. Screening-negative interval cases had more frequently PSA<4, but Gleason and stage distributions were comparable (Table 1). Prostate cancer caused 18 deaths during the median follow-up time of 6.0 years. Prognosis was worse in the screening-negative cases in terms of overall, prostate cancer specific as well as metastasis free survival (HR 1.95 (95% CI 1.19-3.18), HR 3.50 (1.369.05), and HR 2.46 (1.29-4.71), respectively). The fatal group showed a higher PSA velocity (8.9 vs. 1.0 ng/ml/y, P < 0.001) and a shorter PSA doubling time (0.8 vs. 3.1 y, P = 0.001) compared to the non-fatal group. Table 1. Basic characteristics of the interval cancers Screening negative

Screening positive

Non-fatal (n=112)

Fatal (n=11)

Non-fatal (n=237)

Fatal (n=7)

<3

18%

0%

1%

0%

3-4

15%

0%

3%

0%

4-10

48%

18%

51%

43%

10-20

7%

9%

31%

0%

20-100

3%

27%

11%

57%

>100

0%

36%

0%

0%

Missing

9%

9%

2%

0%

2-6

68%

0%

73%

28%

7

19%

36%

18%

29%

8-10

8%

64%

6%

43%

PSA

Gleason

Missing

5%

0%

3%

0%

Local

86%

9%

92%

57%

Locally advanced

9%

0%

5%

14%

Metastatic

2%

91%

3%

29%

Missing

4%

0%

1%

0%

Localization

Conclusions: The screening test negative interval cancers had poorer survival compared to the screening test positives. As expected, screen-negative cases include rapidly growing cancers appearing de novo during the screening interval and at the time of diagnosis many of them had metastasized. The number of missed cases might be reduced by shortening the screening interval, but it remains unclear to what extent.

26

Results from the gothenburg randomised prostate cancer screening trial

Hugosson J. , Aus G. , Bergdahl S. , Carlsson S. , Khatami A. , Lodding P. , Stranne J.1, Holmberg E.2, Lilja H.3 1 Institution of Clinical Sciences, Dept. of Urology, Gothenburg, Sweden, 2 Onkologiskt Centrum, Dept. of Oncology, Gothenburg, Sweden, 3Memorial SloanKettering Cancer Center, Dept. of Clin Lab, New York, United States of America 1

1

1

1

1

1

Introduction & Objectives: Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. Published studies (ERSPC and PLCO) have so far had relatively short follow-up. Materials & Methods: In December, 1994, 20 000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10 000) or to a control group not invited (n=10 000). Men in the screening group were invited up to the upper age limit (median 69, range 67–71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing. This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31, 2008. This study is registered as an International Standard Randomised Controlled Trial ISRCTN54449243. Results: : In each group, 48 men were excluded from the analysis because of death or emigration before the randomisation date, or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12·7% in the screening group and 8·2% in the control group (hazard ratio 1·64; 95% CI 1·50–1·80; p<0·0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0·40% (95% CI 0·17–0·64), from 0·90% in the control group to 0·50% in the screening group. The rate ratio for death from prostate cancer was 0·56 (95% CI 0·39–0·82; p=0·002) in the screening compared with the control group. The rate ratio of death from prostate cancer for attendees compared with the control group was 0·44 (95% CI 0·28–0·68; p=0·0002). Overall, 293 (95% CI 177–799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. Conclusions: This study shows that prostate cancer mortality was reduced almost by half over 14 years. The benefit of prostate-cancer screening compares favourably to other cancer screening programs. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes.

Poster Session 3 ESWL Saturday, 19 March, 08.30-10.00, Hall E2

27

Evaluation of risk factors for prognosis of temporary renal impairment after secondary extracorporeal shock wave lithotripsy (ESWL) in renal stone treatment

Weissflog C., Oehlschlaeger S., Wirth M. University of Technology, Dept. of Urology, Dresden, Germany Introduction & Objectives: ESWL as primary treatment of renal stone disease leads traceable to temporary renal impairment. The correlation between age, comorbidic factors (arterial hypertension, diabetes mellitus and chronic ischaemic

heart disease) and elevated levels of retention parameters is well known. With respect to different treatment possibilities (ESWL, ureterorenoscopic stone extraction, PNL) a predictable model to calculate renal impairment prior to ESWL would be of great interest. This might lead to a supportive therapy without or with less renal impairment. Materials & Methods: 111 patients were examined with primary and recurrent nephrolithiasis. 63 underwent immediate secondary ESWL. The presence of nephrolithiasis was assessed by ultrasound and/or radiological examination of the kidneys and upper urinary tract. We analysed for age, sex, body mass index, body surface, stone location (side; upper, medium and lower calyx, ureteral stones excluded), creatinine and GFR prior (0) and after first (1) and second EWSL (2), prior stone treatment, arterial hypertension, diabetes mellitus, chronic ischaemic heart disease, fluoroscopy time for stone localisation, amount and intensity of shock waves, stone size, sonografic skin-stone-distance, renal stasis and in situ DJ-catheter. Results: There was a non-significant decrease between GFR 1 vs. GFR 0. The significantly decrease of GFR 2 vs. GFR 0 (p<0.01) was correlated with sex, age and arterial hypertension. GFR

Mean ± SD (ml/min/1,73m2 )

Prior to ESWL (0)

98,7 ± 22,5

After 1. ESWL (1)

97,5 ± 20,6 (p<0,08)

After 2. ESWL (2)

93,4 ± 21,1 (p<0,01)

Patients with decrease > 6 points in GFR, after secondary ESWL, can be predicted with the logit sum model. Variable

Regression­-coefficient

Intercept

-4.5125

p-value

Creatinine prior to ESWL

0.0317

0.0309

GFR prior to ESWL

0.0446

0.0023

BMI

-0.1538

0.0472

Arterial hypertension

1.2910

0.0076

The probability of decreased GFR has been calculated by summing up the regression-coefficients and including it into the following formula of the logit transformation: p = exp (logit sum)/ (1+exp (logit sum)), result in percent. Conclusions: There was a non-significant decrease between GFR 1 vs. GFR 0. The significantly decrease of GFR 2 vs. GFR 0 (p<0.01) was correlated with sex, age and arterial hypertension. The study showed a significant decrease of GFR after secondary ESWL. Patients at risk can be predicted by using our evaluated statistic model. Those patients might profit of a conditioning of renal function or an optimized treatment of comorbidic factors prior to ESWL.

28

Endothelin plasma concentrations and Resistive index as parameter of changes in renal perfusion after extracorporeal shockwave lithotripsy

Hiroš M.1, Huskić J.2, Selimović M.1, Spahović H.1, Sadović S.1, Dilić M.3 1 Clinical Center University Sarajevo, Urology Clinic, Sarajevo, Bosnia and Herzegovina, 2Medical School University of Sarajevo, Institute for Physiology and Biochemistry, Sarajevo, Bosnia and Herzegovina, 3Clinical Center University Sarajevo, Institute of Vascular Diseases, Sarajevo, Bosnia and Herzegovina Introduction & Objectives: ESWL is effective and minimal invasive treatment for the most urinary stones, but also with significant acute renal injuries and longterm complications. It is known that ESWL increased plasma levels of vasoactive substances, such as endothelin-1,potent vasoconstricting peptid. Effects on renal vasculature can be evaluated by color Doppler ultrasonography measuring renal resistive index(RI). This prospective study aimed to determine the influence of number of delivered SW-s and used kV on the endothelin plasma concentration and changes in renal resistive index. Materials & Methods: Total of 40 patients, both male and female, age ranged from 22-58 years( average 42,7 years) undergoing ESWL for renal stones, size 6-18mm, were included in this study. Patients were divided in two groups: Group l (N=20) received 2000SW-s;0-2 units (0,5IU on each 500SW-s) Group ll (N=20) received 4000SW-s;kV 0-4units (0,5IU on each 500SW-s) Peripheral blood samples were analyzed for endothelin before, 1, 3 and 5 days after ESWL. RI was measured at interlobar artery before, 1, 3 and 5 days after treatment on treated kidney and contralateral nontreated kidney. Results: Plasma endothelin-1 concentration were elevated after ESWL in both group of patients but significantly in patients group ll. In treated kidneys RI significantly increased first and third day after treatment from 0,62±0,05 at baseline to 0,67±0,05,p<0,001 at first and 0,66±0,1,p<0,007 on the third day after treatment. Increase of RI fifth days after treatment is not significant (0,63±0,05). The contralateral, nontreated kidney showed significant changes in RI only first day after treatment (0,64±0,05),p<0,01. Conclusions: This data support the idea that the number of delivered SW-s

Eur Urol Suppl 2011;10(2):37