EFFECT OF SUBCLINICAL INFLAMMATION IN PROSTATE BIOPSY SPECIMENS ON TPSA AND FPSA VALUES IN

PATIENTS WITHOUT CLINICALLY DETECTABLE PROSTATE CANCER

Goran Stimac, Davor Trnski, Jordan Dimanovski, Boris Ruzic, Ante Reljic, Borislav Spajic, Monika Ulamec & Ognjen Kraus

Department of Urology

“Sestre milosrdnice” University Hospital,

Zagreb, Croatia, 2006.

STUDIES ANALYZING EFFECT OF HISTOLOGICAL INFLAMMATION ON TPSA & FPSA

AUTHORS SAMPLES ANALYZED

INFLAMMATION GRADING (GROUPS) TPSA FPSA

Ornstein PROSTATE BIOPSY

Acute Chronic

0 0

0 0

Morote PROSTATE BIOPSY

Acute Chronic

0 0

+ 0

Scatonni OP Acute Chronic

0 0

+ 0

Meyer BIOPSY, TURP,OP

Asymptomatic prostatitis, BPH, PC + -

Stancik PROSTATE BIOPSY

Asymptomatic prostatitis, BPH, PC + -

Minardi BIOPSY, TURP,OP

Asymptomatic prostatitis, BPH, PC + -

Jung PROSTATE BIOPSY

Asymptomatic prostatitis, BPH, PC + -

MATERIAL AND METHODS December 2002 - june 2005: 106 patients Inclusion criteria: - TPSA<=10 ng/ml,

- eight core TRUS guided prostate biopsy negative for PC - no clinical signs of prostatitis

- prostate volume <= 40 g

Inflamm

ation Type

Inflamm

ation A

ggressiveness

0 no inflammation 1  MN infiltrate (chronic)

2  MN and PMN infiltrate (chronic active)

3 PMN infiltrate (acute)

0 no inflammation 1  stromal infiltrate

2 stromal infiltrate and limited epithelial degeneration 3  stromal infiltrate and extensive epithelial degeneration

Regression factor

reduction analysis

MORE ACUTE

MORE AGGRESSIVE

MORE CHRONIC

LESS AGGRESSIVE

Patient grouping

TPSA (ng/ml) FPSA (ng/ml) F/TPSA (%)

Inlammation type (groups)

More acute More acute More acute More chronic More chronic More chronic

Median 7,3 0,79 12 6,4 1,09 15

p (Mann-Whitney) 0,2 0,003* <0,001*

RESULTS – INFLAMMATION TYPE

4561N =

AkutnijeKronicnije

F/T

PS

A (

ng/m

l)

40

30

20

10

0

4561N =

AkutnijeKronicnije

FP

SA

(ng

/ml)

2,5

2,0

1,5

1,0

,5

0,04561N =

AkutnijaKronicnija

TP

SA

(ng

/ml)

12

10

8

6

4

2

TPSA

(ng/

ml)

FPSA

(ng/

ml)

F/TP

SA (%

) MORE CHRONIC MORE ACUTE MORE CHRONIC MORE ACUTE MORE CHRONIC MORE ACUTE

TPSA (ng/ml)

11109876543

FPSA

(ng/

ml)

3,5

3,0

2,5

2,0

1,5

1,0

,5

0,0

Upala

Akutnija

Kronicnija

MORE CHRONIC

MORE ACUTE

TPSA (ng/ml)

FPSA (ng/ml)

RESULTS – INFLAMMATION TYPE

<0,001* <0,001* 0,16 p (Mann-Whitney)

16 1,1 6,39 10,7 0,79 7,3

Median

Less aggressive Less aggressive Less aggressive More aggressive More aggressive More aggressive Inlammation

aggressiveness (groups)

F/TPSA (%) FPSA (ng/ml) TPSA (ng/ml)

RESULTS – INFLAMMATION AGGRESSIVENESS

4759N =

Jace agresivnaManje agresivna

TP

SA

(ng

/ml)

12

10

8

6

4

24759N =

Jace agresivnaManje agresivna

F/T

PS

A (

ng/m

l)

40

30

20

10

04759N =

Jace agresivnaManje agresivna

FP

SA

(ng

/ml)

2,5

2,0

1,5

1,0

,5

0,0TPSA

(ng/

ml)

FPSA

(ng/

ml)

F/TP

SA (%

)

LESS AGGRESSIVE MORE AGGRESSIVE LESS AGGRESSIVE MORE AGGRESSIVE LESS AGGRESSIVE MORE AGGRESSIVE

TPSA (ng/ml)

11109876543

FPSA

(ng/m

l)

3,5

3,0

2,5

2,0

1,5

1,0

,5

0,0

Upala

Jace agresivna

Manje agresivna

RESULTS – INFLAMMATION AGGRESSIVENESS

LESS AGGRESSIVE

MORE AGGRESSIVE

TPSA (ng/ml)

FPSA (ng/ml)

SPEARMAN NONPARAMETRIC CORRELATION MATRIX

<0,001 <0,001 <0,001 0,23 1

0,96 -0,45 -0,34 0,12 INFLAMMATION AGGRESSIVENESS

FACTOR SCORE

<0,001 <0,001 0,001 0,21

0,96 1

-0,43 -0.31 0,12 INFLAMMATION TYPE

FACTOR SCORE

<0,001 <0,001 <0,001 0,17

-0,45 -0,43 1

0,82 -0,13 F/TPSA

<0,001 0,001 <0,001 <0,001

-0,34 -0,31 0,82 1

0,4 FPSA

0,23 0,21 0,17 <0,001

0,12 0,12 -0,13 0,4 1 TPSA

P<0,01 sign.

INFLAMMATION AGGRESSIVENESS

FACTOR SCORE

INFLAMMATION TYPE

FACTOR SCORE F/TPSA FPSA TPSA

r

CONCLUSIONS

1) Almost each of the studied biopsies showed inflammatory cells. 2) Subclinical, histological inflammation of the prostate seems to have significant influence on free and percent-free PSA values in patients with total PSA levels up to 10 ng/ml, without detectable prostate cancer and clinical signs of prostatitis. 3) It is not characterized by moderately elevated total PSA concentrations alone but also by a decreased percentage of free PSA, a tendency similar to that in prostate cancer, especially in patients with small prostates. 4) In the assessment of needle biopsy results negative for prostate cancer, it might be helpful to evaluate the degree and extension of histological inflammation, especially in terms of the necessity of subsequent repeated biopsies.