many urologists routinely use transrectal ultrasound ( trus ) for the diagnosis and staging of localized prostate cancer .
however , with the widespread use of prostate - specific antigen ( psa ) screening , there has been a shift to earlier stages and smaller volumes at the time of diagnosis .
furthermore , trus is limited in the detection of hypoechoic lesions and therefore shows a low predictive value . the probability that a hypoechoic lesion contains prostate cancer varies from 3% to 52% . most research to date
has focused on the diagnostic value of hypoechoic lesions on trus , and little is known about the biological significance of hypoechoic lesions in prostate cancer .
there are reports that the presence of hypoechoic lesions is associated with a higher stage on presentation , such as extracapsular invasion .
however , no study currently exists on the use of hypoechoic lesion status as an independent prognostic factor . in this study , therefore , we investigated the prognostic value of the presence of hypoechoic findings on trus in patients with localized prostate cancer and evaluated biochemical progression - free survival ( bpfs ) rates according to the presence of hypoechoic lesions .
a total of 71 patients diagnosed with pt2n0m0 disease following radical prostatectomy ( rp ) between january 2002 and december 2008 were enrolled in the study . of the 71 patients ,
the enrollment was confined to patients with pt2 disease to eliminate the impact of pathologic stage on different outcomes .
patients who had undergone other treatments such as radiation therapy or hormonal therapy before or after surgery were also excluded from the subject population . patients with positive surgical margins
were excluded to eliminate the confounding effects of a positive surgical margin and to identify the prognostic effects of other factors being considered .
patients were divided into two groups according to the presence of hypoechoic lesions on preoperative trus as interpreted by a single experienced radiologist .
the group with hypoechoic lesions was labeled group 1 , whereas the group without hypoechoic lesions was labeled group 2 .
preoperative and postoperative characteristics including pathologic t2 substage , preoperative serum psa levels , gleason scores on biopsy , and prostatectomy specimens were compared between the two groups .
microscopic extension of malignant cells , tumor involvement percentage , and perineural invasion were also examined .
the pathological stage was recorded on the basis of american joint committee on cancer prostate cancer staging , 7th edition .
patients were followed up and the psa level was assessed at regular intervals of about 3 months after rp during the first 2 years .
biochemical failure was defined as the first occurrence of two consecutive rises in the psa level of more than 0.2 ng / ml . each variable was compared by using student 's t - test for continuous data and the chi - square test for categorical data .
univariate and multivariate cox proportional hazard analyses were used to determine relevant prognostic indicators of biochemical progression . in these analyses , patients were stratified according to the psa level ( 9 or < 9 ml ) .
cutoff points for the variable psa level were chosen to separate the patient populations by a median value .
the bpfs rate was estimated by using the kaplan - meier curve , which compared each potential prognostic factor by using the log - rank test .
among the 71 enrolled patients , 35 had hypoechoic lesions and 36 had nonhypoechoic lesions on trus .
nonhypoechoic lesions consisted of either isoechoic regions or unidentifiable lesions , and hyperechoic lesions were excluded .
preoperative baseline characteristics were identical between the two groups ( table 1 ) . when group 2 was divided according to clinical stage , 14 of the 36 patients had clinical t2 disease ( 38.88% ) , and the others had clinical t1 disease .
as for postoperative parameters such as the gleason score of the prostatectomy specimen , the percentage of tumor involvement , and the presence of perineural invasion , there were no significant differences between the two groups ( table 2 ) .
the median follow - up period was 44.49 months in group 1 and 38.81 months in group 2 .
the bpfs rate over the first 24 months was 97.0% in group 1 and 97.1% in group 2
. however , divergence after 48 months significantly widened , to 75.3% vs. 91.7% , respectively .
group 1 had an overall shorter progression - free survival period than did group 2 ( fig .
1 ) . during the follow - up period , clinical failure was observed in 4 cases . in group 1 ,
l - spine metastasis was observed in two cases at 45 and 54 months after the operation and urethrovesical anastomosis site recurrence was observed in one case at 35 months after rp .
one case of l - spine metastasis was observed at 38 months after the operation in group 2 . to assess the prognostic value of each variable , univariate and multivariate analyses were carried out with the cox proportional hazard model . in the univariate analysis , preoperative psa level and the presence of hypoechoic lesions had prognostic significance ( table 3 ) .
age , body mass index , prostate volume , pathologic gleason score , and pt2 substage did not have prognostic significance .
as shown in table 3 , however , preoperative psa level and presence of hypoechoic lesions , which were shown to be significant in the univariate analysis , were not of statistical significance in the multivariate analysis .
few studies have examined the potential utility of hypoechogenicity , a trus - related indicator of potentially cancerous lesions in the prostate , as a prognostic factor .
we chose to focus on the prognostic value of hypoechoic lesions because , considering that only 3% to 52% of prostate cancers show hypoechoic lesions , its value as a diagnostic marker is limited , and we thought it appropriate to focus instead on its value for evaluation of disease progression .
furthermore , ohori et al .   noted that hypoechoic cancers were more likely to show extraprostatic extension , to have a poorly differentiated component , and to be nondiploid compared with isoechoic cancers .
however , these studies showed only that hypoechoic lesions were related to more advanced stage disease and did not focus on its value as a prognostic factor .
we restricted the subject population to patients with stage pt2n0m0 disease ; furthermore , to control the effects of bpfs , patients with positive postsurgical margins were excluded .
.   showed no significant difference in bpfc for t1c tumors that were visible on sonography .
however , they included all hypoechoic , isoechoic , and hyperechoic lesions that were visible on sonography as cases and thus did not exclusively examine hypoechoic lesions , as was done in the present study .
preoperative psa , gleason score , and tumor - node - metastasis stage are well - known prognostic parameters [ 7 - 9 ] .
caso et al . , in their study on postprostatectomy biochemical recurrence in each of the substages in pathologically confirmed t2 lesions , stated that the substages of t2 were of significance only on univariate analysis and that the most important factors were psa and the status of the surgical margins .
however , in our study , the univariate analysis differed in that only preoperative psa and the presence of hypoechoic lesions were correlated with the prognosis of prostate cancer . as shown in fig . 1 ,
no significant difference in bpfs was observed 30 months after the operation , but a subsequent divergence in bpfs became evident later .
considering that gleason 's score and other parameters such as perineural invasion and the percentage of tumor involvement did not differ significantly between the two groups during this period , it is possible that there are other factors yet to be isolated .
we assume the reason prostate cancer with hypoechoic lesions has a worse prognosis than other prostate cancers may be because hypoechoic prostate cancers have molecular markers related to prognosis and nondiploid dna .
a recent study showed that cases positive for the antibodies s0456 , ep1972 - 1 , s0725 m , and s5073 , which are directed against the protein products of the genes hey2 , stmn1 , cyp4z1 , and cdh1 , had poorer prognosis than did those that were negative for these antibodies .
although the study did not deal with hypoechoic lesions on trus , the authors speculated that such molecular markers may be detected in prostate cancer with hypoechoic lesions .
in addition , the absolute volume of the tumor can influence the detection rate of hypoechoic lesions , and the volume itself may be a prognostic factor on trus . also , because it has already been shown that digital rectal examination ( dre ) palpation is a prognostic factor , we think it will be relevant to study its relationship with hypoechoic lesions on trus . regrettably , this study did not examine the tumor volume or dre palpation findings . in the current study , univariate analysis and kaplan - meier curves showed that hypoechoic lesions were of prognostic significance for prostate cancer .
nevertheless , the statistical significance observed in the univariate analysis and kaplan - meier curves suggest that the presence of hypoechoic lesions on trus images may hold at least some importance as a prognostic factor for prostate cancer .
second , we did not review the dna findings through dna analysis and molecular marker analysis to support our hypothesis on the biochemical significance of hypoechoic lesions .
further studies involving larger subject populations appear to be necessary to fully evaluate the significance of the presence of hypoechoic lesions as a prognostic factor .
localized prostate cancers that present preoperatively with hypoechoic lesions on trus were associated with worse prognostic characteristics than were prostate cancers with no hypoechoic lesions . however
, such sonographic findings were shown to have no value as a prognostic factor . to further certify the results of this study and to investigate the associated underlying biological mechanisms , a larger - scale study on this subject is needed .
 purposethe purpose of this study was to investigate the value of hypoechoic lesions on transrectal ultrasound ( trus ) as a prognostic factor for patients with localized prostate cancer.materials and methodsthe patients consisted of 71 patients with pt2n0m0 disease following radical prostatectomy between 2002 and 2008 . 
 the group with hypoechoic lesions was labeled group 1 , whereas the group without hypoechoic lesions was labeled group 2 . 
 the presence of hypoechoic lesions on preoperative trus was analyzed as a prognostic factor along with several parameters , including preoperative factors and pathologic factors . 
 the biochemical progression - free survival ( bpfs ) rate was compared between the two groups according to the presence of hypoechoic lesions on trus.resultsa total of 35 patients had hypoechoic lesions on trus , whereas 36 had no hypoechoic lesions . 
 preoperative baseline characteristics were not significantly different between the two groups . in the univariate analysis , 
 bpfs showed significant differences according to the presence of hypoechoic lesions on trus and the preoperative prostate - specific antigen level . 
 the bpfs rates over the first 24 months were 97.0% in group 1 and 97.1% in group 2 ; however , the difference in the bpfs rate over 48 months significantly widened to 75.3% compared with 91.7% , respectively . despite this finding , no significant independent prognostic factor for bpfs 
 was found on multivariate analysis in this patient cohort.conclusionsthe presence of hypoechoic lesions on trus may suggest worse prognostic characteristics in pt2 prostate cancer . 
 further studies involving larger subject populations are needed to corroborate the significance of the presence of hypoechoic lesions as a prognostic factor . 
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSIONS