during the last decade , of the definition of the optimal treatment in high risk prostate cancer ( pca ) is among the topics that are of most interest to the urological community , but consensus in this field is still not reached .
up until a decade ago , most t3 pca patients underwent radiotherapy ( rt ) or androgen deprivation therapy ( adt ) or a combination of both , while only about 36% were initially treated by surgery .
recent publications have revealed that in selected cases of locally advanced and high - grade tumors , surgery as monotheraphy or as part of a multimodality treatment may be used instead of rt .
the high risk pca population , usually described as having prostate specific antigen ( psa ) > 20 ng / ml , biopsy gleason score 8 or an advanced clinical stage ( t3a - b ) is however not homogeneous .
recent studies have shown that treatment outcomes can vary widely , depending on whether patients present with only one , or rather a combination of those high - risk factors , with the latter patients having the worst outcomes [ 47 ] .
it is still unclear which patients , according to the accepted predictors of aggressive disease behavior , are the best candidates for surgery , mostly due to the lack of data on long - term oncologic outcomes and randomized clinical trials . according to the european association of urology guidelines ,
surgery is optional in patients presenting with ct3a , gleason score 8 - 10 or psa > 20 ng / ml , and life expectancy of more than 10 years . even in highly selected patients with ct3b or cn1 pca ,
we believe that radical prostatectomy is indeed an appropriate treatment for more aggressive pca , but data for confirming that are still insufficient . the purpose of this study is to present the oncologic outcomes of patients having pt3a pca after surgery , including overall survival ( os ) , disease progression free survival ( dpfs ) , cancer specific survival ( css ) and biochemical progression free survival ( bpfs ) .
during the period 2002 - 2007 , 840 radical retropubic prostatectomies ( rrp ) were performed in our institution .
final analysis was carried out using the data of 126 patients with complete follow - up .
biopsy gleason score 7 or psa > 10 ng / ml or clinical stage t3 were indications for lymph nodes removal .
71 of 126 ( 56.3% ) patients of our study population had such criteria . for other
the pathological examination of radical prostatectomy specimens and bilateral pelvic lymph nodes were performed by one dedicated uropathologist .
serum psa and physical examination were performed every 3 months in the first year after surgery , every 6 months in the second and third years , and annually thereafter .
data about patients death and cause of death were received from the national cancer registry .
css was defined as the time from surgery to death caused by pca or complications of this disease .
biochemical progression was defined as the time from surgery to psa level 0.2 ng / ml confirmed by repeated test .
disease progression was defined as the development of either local disease recurrence or distant metastasis .
adjuvant treatment was defined as either adt or rt given within 3 months after surgery .
salvage treatment was defined as any kind of therapy ( rt or adt ) given later than 3 months after surgery .
the kaplan - meier survival analysis was used to calculate the os , css , dpfs and bpfs .
5-year rates for os , css and dpfs in our study cohort were 96% , 98.7% and 97.3% , respectively ( fig .
cox regression analysis revealed that from all parameters ( age , biopsy and surgery gleason score , surgical margin and lymph nodes status , preoperative psa level ) only preoperative psa ( p = 0.037 , hr 1.054 , 95% ci 1.003 - 1.108 ) and postoperative gleason score ( p = 0.008 , hr 2.05 , 95% ci 1.202- 3.506 ) had an impact on biochemical relapse ( table 2 ) . according cox regression analysis
, there were no parameters influencing overall and cancer specific mortality or disease progression . 
 
kaplan - meier analysis for overall survival ( a ) , disease progression free survival ( b ) and biochemical progression free survival ( c ) in all study patients .
r  positive surgical margins , psa  prostate specific antigen cox multivariate regression analysis of preoperative and histopathologic parameters for biochemical progression free survival . 

a mean of 6.3 ( range 1 - 15 ) lymph nodes were removed , and the overall positive node detection rate was 2.8% . because of this small number of positive nodes we could not perform analysis in survival . 

the mean surgery gleason score was significantly worse when after biopsy ( 6.4 vs. 6.9 , p = 0.001 ) .
gleason score upgrading was detected in 51.2% of cases , downgrading in 4.9% of cases .
the kaplan - meier analysis demonstrates significant differences between gleason 7 and 8 for os ( fig .
the estimated 5-year os , css , dpfs and bpfs rates in patients with gleason score 8 were 80.8% , 88.9% , 80.8% and 27.3% , respectively , while in gleason score 7 , 5-year os , css , dpfs and bpfs were 97.8% , 100% , 99% and 62.6%% , respectively .
kaplan - meier analysis with log - rank test for overall survival ( a ) , biochemical progression free survival ( b ) and disease progression free survival ( c ) stratified for prostate gleason score . 

preoperative psa < 10 ng / ml had 67.2% , psa 10 - 20 ng / ml  25.6% and > 20 ng / ml  7.2% of study patients .
there were no differences in 5-year dpfs comparing groups according psa level but at psa < 10ng / ml 5-year os , css and bpfs rates was significantly higher when in patients group with psa > 20 ng / ml ( fig . 3a 
there were no difference between groups with psa < 10 and 10 - 20 ng / ml ( table 3 ) . 
 
kaplan - meier analysis with log - rank test for biochemical progression free survival ( a ) and overall survival ( b ) stratified for prostate specific antigen level .
kaplan - meier analysis results in overall ( os ) , cancer specific ( css ) , disease progression free ( dpfs ) and biochemical progression free survival ( bpfs ) according prostate specific antigen ( psa ) and gleason score subgroups .
p < 0.05 between different parameters p < 0.05 between different parameters p < 0.05 between different parameters 
 post - operative treatment .
therefore , adjuvant or salvage treatment ( rt or adt ) are often applied . in our study population ,
adt received 14.3% , rt  5.5% and rt with adt was applied to 1.6% of patients . at final visit the psa > 0.2 ng / ml was detected in 23.2% of cases 
 surgical margins status .
this parameter did not have significant impact in survival , disease progression or biochemical relapse .
during the last decade , the discussion about the role of surgery in locally advanced pca became increasingly active . before that time , treatment of locally advanced pca was mostly in hands of radiation oncologists .
such discussion became possible for several reasons : successful treatment of high risk pca with rt monotherapy requires high radiation doses ( 74 - 80gy ) , leading to higher rates of adverse events . on the other hand ,
our single center study shows that surgical treatment may indeed be a reasonable treatment option in locally advanced pt3a pca with 96% os , 98.7% css , 97.3% dpfs and 60% bpfs at the 5-year follow - up mark .
the survival rates of the pt3a patients in our study are similar to those reported by hsu et al . in a study of 200 patients with unilateral ct3a treated by surgery .
they also showed that progression - free survival rates of patients with pt3a pca did not differ significantly from those with pt2 disease .
some other authors have also reported their outcomes of surgical treatment for t3 pca . summarizing those results , 5-year css and os rates varied from 85 to 100% and from 75 to 98% , respectively [ 912 ] .
direct comparison of the outcomes of surgery and radiation are inadequate because of inherent selection biases , gleason score upgrading or stage migration after surgery .
nevertheless , this issue partially could be solved using data from the rtog trials , which compared rt vs. a combined approach using rt and adt . in a review of those rtog trials ,
different pca risk groups were identified with group 2 ( gleason 6 , t3nx - n1 ; or gleason 7 , t1 - 2nx ) and group 3 ( gleason 7 , t3nx - n1 ; or gleason 8 , t1 - 2nx ) most closely corresponding with our study population .
after radiation , the 5-year os and css rates were 82% and 94% for group 2 , and 68% and 83% for group 3 respectively .
outcomes from another long - term study comparing rt vs. rt with concomitant adt were reported by bolla et al . .
in the eortc - trial , 412 patients with locally advanced pca were treated with rt alone or in combination with adt .
five - year os and css rates were respectively 62 and 79% in the radiation alone group .
our study data showed a comparable 98.7% 5-year css , similar to rt and adt combination therapy .
psa and specimen gleason score have a significant impact on the survival analysis . according to our study ,
patients with a psa < 10 ng / ml had significantly better os , css and bpfs when compared to those with a psa level > 20 ng / ml ( log rank p = 0.048 , p = 0.001 and p = 0.001 , respectively ) .
patients with a psa level of 10 to 20 ng / ml did not have significantly different os , css or bpfs when compared to psa < 10 ng / ml but they have different css and bpfs when compared to psa > 20 ng / ml ( log rank p = 0.04 , p = 0.008 , respectively ) . in the study cohort ,
some recent studies studied the role of psa in survival and biochemical or disease progression [ 5 , 15 , 16 ] .
all authors agreed that psa > 20 ng / ml indeed could be considered as a high risk factor .
gleason score has long been recognized as an important risk indicator for worse outcome . in locally advanced pca
, biopsy gleason sum has a tendency to be upgraded , and in our series upgrading was indeed frequent ( up to 50% ) .
in fact , in our study , specimen gleason score was identified as one of the most important outcome predictor .
our data showed a significant difference between survival curves ( os , css , dpfs and bpfs ) comparing gleason score 6 - 7 vs. 8 - 9 .
patients with postoperative gleason 8 are associated with a 2-fold increased risk for biochemical relapse .
most of the published studies confirm that gleason score 8 - 10 indeed determines worse biochemical or disease free survival both in locally advanced and organ confined disease [ 1720 ] .
our study shows that 5-year os , css , dpfs or bpfs rates in gleason score 8 - 9 pca were 80.8% , 80% , 80.8% and 27.3% compared to 97.8%,100% , 99% and 62.6% if gleason score was 6 - 7 .
however , significant survival differences between high and moderate grade pca does not mean that a more advanced tumor grade is a contraindication for surgery .
tewari et al . pointed out that long term results in high grade pca after surgery are better when comparing surgically treated patients with those who underwent rt or conservative treatment . in 453 patients with biopsy
gleason 8 - 10 , median os after surgery was 9.7 years , while for radiation this was 6.7 years and for conservative treatment 5.2 years .
the risk of cancer - related death after surgery was 68% lower than after conservative treatment and 48% lower than after rt . generally , it is accepted that patients with locally advanced pca at final histology are ideal candidates for additional treatment after surgery .
rt , adt or a combination  is the best choice to decrease the risk of disease progression following surgery . in the present study , only 21.4% of cases received adjuvant or salvage treatment and it demonstrate that rrp alone in pt3a pca could yield very good cancer control especially in cases with psa < 10 ng/ ml and gleason score 7 . with 5-year os and css of 96% and 98.7% ,
our study supports the notion that radical prostatectomy with adjuvant or salvage therapy when needed may provide comparable outcomes as rt plus adt in locally advanced pca , especially in pt3a .
in locally advanced pt3 pca , surgery can yield very good cancer control and survival rates especially in cases with psa < 10 ng / ml and gleason score 7 .
psa and gleason score after surgery are the most significant predictors of outcomes after radical prostatectomy .
 introductionthe aim of this study is to present the oncologic outcomes and to determine prognostic parameters of overall ( os ) , cancer specific survival ( css ) , disease progression free survival ( dpfs ) and biochemical progression free survival ( bpfs ) after surgery for pt3a prostate cancer ( pca).material and methodsbetween 2002 and 2007 , a pt3a stage after radical prostatectomy was detected in 126 patients at our institution . 
 kaplan - meier analysis was used to calculate os , css , dpfs and bpfs . 
 cox regression was used to identify predictive factors of survival.resultsfive-year os , css , dpfs and bpfs rates were 96% , 98.7% , 97.3% and 60% , respectively . among patients with prostate specific antigen ( psa ) < 10 ng / ml and psa > 20 ng / ml the 5-year os was 98.8% and 80% , respectively , whereas 5-year bpfs was 66% and 16.6% , respectively . 
 survival was different when comparing surgery gleason score 7 and 8 . 
 5-year os and bpfs were 98% vs. 80% , and 62.6% vs. 27.3% , respectively . 
 specimen gleason score and preoperative psa were significant predictors of bpfs . 
 the risk of biochemical progression increased up to 2-fold when a gleason score 8 was present at final pathology.conclusionsin locally advanced pt3 pca , surgery can yield very good cancer control and survival rates especially in cases with psa < 10 ng / ml and gleason score 7 . 
 psa and gleason score after surgery are the most significant predictors of outcomes after radical prostatectomy . 
INTRODUCTION
MATERIAL AND METHODS
RESULTS
DISCUSSION
CONCLUSIONS