the inclusion and exclusion criteria were established based on the standards of diagnostic research published by the cochrane methods group for screening and diagnostic testing ( http://www.cochrane.org/docs/sadtdocl.htm ) . this systematic review includes only prospective observational studies in which the results of the diagnostic test of interest were compared with that of a reference standard - histological biopsy , radical prostatectomy , or surgery . the objective of this study is to evaluate the value of mrs in diagnosing prostate cancer . all scans were read by radiology medicine doctors which were " blinded " to the patients ' history , clinical presentation , and physical examination . the studies which were " blindly read " were not mentioned to be in the exclusion criteria . moreover , the subjects had not previously undergone hormone or radiotherapy before they underwent an mri and mrs . the relevant publications were identified in the database by querying the medline ( http://www.ncbi.nlm.nih.gov/entrez/query.fcgi ? ) , elsevier , springer , ovid , cnki ( china national knowledge infrastructure ) , and embase databases by computer from 1994 to 2006 . next , a manual research of the reference lists cited in the original articles of the relevant journals had also been done . all medical subject headings with diagnosis were combined with words : ( carcinoma of prostate or prostate cancer or prostate carcinoma or prostate tumor ) and diagnosis and ( mrs or mr spectroscopic imaging or magnetic resonance spectroscopic imaging or mr spectroscopy or magnetic resonance spectroscopy ) and sensitivity and specificity . the publication languages were restricted to english and chinese and the research subjects were human . all articles were checked by two independent reviewers and any disagreement was resolved employing the arbitration of a third reviewer . according to a hierarchy of evidence in the diagnostic test studies from the cochrane methods group ( 7 , 8) , only studies in grade a ( an independent , blind comparison with reference standard among an appropriate population of consecutive patients ) and grade b ( an independent , blind comparison with reference standard among an appropriate population of non - consecutive patients or confined to a narrow population of study patients ) were included in this review . the common information including the articles ' grade , author , published time , number of subjects , mean age , lesions , and level of psa . were extracted . other data such as true positive value ( tp ) , true negative value ( tn ) , false positive value ( fp ) , false negative value ( fn ) , sensitivity ( sen ) , specificity ( spe ) , accuracy ( acc ) , positive likelihood ratio , negative likelihood ratio were also extracted . the meta - test software ( version 0.9 joseph lau , md - new england medical center , boston , ma ) was used for the data analysis and synthesis . group differences between two diagnosis criteria were considered significant at a p value of < 0.05 by fisher 's exact test . i ) homogeneity test : diagnostic meta - analysis achieved by pooling the results of individual studies . the results produce a common effect size . as a result , before the data were pooled and calculated , a test of the homogeneity of results between the different studies was necessary using the q statistic of the chi - square value test . 2 ) statistical model : the statistical model used in the meta - analysis included a fixed effects model which was chosen following the determination of the absence of heterogeneity . alternatively , if the heterogeneity test failed , a random effects model was selected to analyze the data ( 9 ) . 3 ) meta - analysis : the appropriate statistical model was selected to calculate pooled weighted values of sensitivity and specificity with the corresponding 95% ci ( 95% confidence interval ) . according to moses et al . ( 10 ) , we established a linear regression equation between d and s as follows : d = logit ( tpr ) - logit ( fpr ) ; s = logit ( tpr ) + logit ( fpr ) ( tpr - true positive rate , fpr - false positive rate ) . the model is d = a + bs ( a is the regression intercept and b is the regression coefficient ) . , the model can be transformed back to the conventional axes of tpr against fpr , which facilitates the determination of a sroc curve to calculate the area under the sroc . if the curve is closer to top - left corner , the area under curve ( auc ) is larger , which means that the diagnosis is more accurate . the inclusion and exclusion criteria were established based on the standards of diagnostic research published by the cochrane methods group for screening and diagnostic testing ( http://www.cochrane.org/docs/sadtdocl.htm ) . this systematic review includes only prospective observational studies in which the results of the diagnostic test of interest were compared with that of a reference standard - histological biopsy , radical prostatectomy , or surgery . the objective of this study is to evaluate the value of mrs in diagnosing prostate cancer . all scans were read by radiology medicine doctors which were " blinded " to the patients ' history , clinical presentation , and physical examination . the studies which were " blindly read " were not mentioned to be in the exclusion criteria . moreover , the subjects had not previously undergone hormone or radiotherapy before they underwent an mri and mrs . the relevant publications were identified in the database by querying the medline ( http://www.ncbi.nlm.nih.gov/entrez/query.fcgi ? ) , elsevier , springer , ovid , cnki ( china national knowledge infrastructure ) , and embase databases by computer from 1994 to 2006 . next , a manual research of the reference lists cited in the original articles of the relevant journals had also been done . all medical subject headings with diagnosis were combined with words : ( carcinoma of prostate or prostate cancer or prostate carcinoma or prostate tumor ) and diagnosis and ( mrs or mr spectroscopic imaging or magnetic resonance spectroscopic imaging or mr spectroscopy or magnetic resonance spectroscopy ) and sensitivity and specificity . the publication languages were restricted to english and chinese and the research subjects were human . all articles were checked by two independent reviewers and any disagreement was resolved employing the arbitration of a third reviewer . according to a hierarchy of evidence in the diagnostic test studies from the cochrane methods group ( 7 , 8) , only studies in grade a ( an independent , blind comparison with reference standard among an appropriate population of consecutive patients ) and grade b ( an independent , blind comparison with reference standard among an appropriate population of non - consecutive patients or confined to a narrow population of study patients ) were included in this review . the common information including the articles ' grade , author , published time , number of subjects , mean age , lesions , and level of psa . were extracted . other data such as true positive value ( tp ) , true negative value ( tn ) , false positive value ( fp ) , false negative value ( fn ) , sensitivity ( sen ) , specificity ( spe ) , accuracy ( acc ) , positive likelihood ratio , negative likelihood ratio were also extracted . the meta - test software ( version 0.9 joseph lau , md - new england medical center , boston , ma ) was used for the data analysis and synthesis . group differences between two diagnosis criteria were considered significant at a p value of < 0.05 by fisher 's exact test . i ) homogeneity test : diagnostic meta - analysis achieved by pooling the results of individual studies . the results produce a common effect size . as a result , before the data were pooled and calculated , a test of the homogeneity of results between the different studies was necessary using the q statistic of the chi - square value test . 2 ) statistical model : the statistical model used in the meta - analysis included a fixed effects model which was chosen following the determination of the absence of heterogeneity . alternatively , if the heterogeneity test failed , a random effects model was selected to analyze the data ( 9 ) . 3 ) meta - analysis : the appropriate statistical model was selected to calculate pooled weighted values of sensitivity and specificity with the corresponding 95% ci ( 95% confidence interval ) . according to moses et al . ( 10 ) , we established a linear regression equation between d and s as follows : d = logit ( tpr ) - logit ( fpr ) ; s = logit ( tpr ) + logit ( fpr ) ( tpr - true positive rate , fpr - false positive rate ) . the model is d = a + bs ( a is the regression intercept and b is the regression coefficient ) . , the model can be transformed back to the conventional axes of tpr against fpr , which facilitates the determination of a sroc curve to calculate the area under the sroc . if the curve is closer to top - left corner , the area under curve ( auc ) is larger , which means that the diagnosis is more accurate . according to criteria set in the index words , a total of 140 papers were screened from the above - mentioned databases . however , only 7 studies remained after taking into account the inclusion and exclusion criteria . among these articles , two were of grade a , whereas the other five were of grade b ( table 1 ) . in clinical practice , the classification system described by kurhanewicz et al . ( 6 ) was often used : normal - a voxel of signal intensity ratios of ( choline + creatine ) / citrate lower than 0.75 ; suspicious - between 0.75 and 0.86 ; definitive tumor - above this threshold . to calculate the sensitivity and specificity , descriptive statistical data ( tp , tn , fp , and fn ) were determined by using two dichotomized rating systems : one with a voxel ratio of less than 0.75 which was not determined to be cancer , as opposed to a voxel ratio greater than 0.75 which represented a finding of cancer . while another cut - off value was 0.86 . five studies used a diagnostic value of 0.75 as a cut - off criteria ( table 2 ) , as opposed to five studies , which used a diagnostic cut - off value of 0.86 ( table 3 ) . the homogeneity test showed : q1 = 37.20 , p1 < 0.01 , q2 = 23.17 , p2 < 0.01 . therefore , in these two groups , the random effects models was used for the meta - analysis . forest plots for two groups were constructed and the pooled weighted sensitivity , specificity , and corresponding 95% ci were calculated ( fig . 1 , table 4 ) . because sroc can inflect a non - linear relationship between the sensitivity and specificity simultaneously , it was better used ( 18 ) to assess the accuracy of the diagnostic tests . here we drew and analyzed sroc and calculated auc for these two groups ( figs . 2 , 3 ) . the pooled weighted sensitivity of the first criterion was higher 0.82 ( 0.73 , 0.89 ) than the second 0.64 ( 0.55 , 0.72 ) , in which the p - value was < 0.0001 , chi - square value = 57.13 however , its specificity is lower [ 0.68 ( 0.58 , 0.76 ) vs. 0.86 ( 0.79 , 0.91 ) ] than , a p - value < 0.0001 , chi - square value = 118.30 . however , the difference between the two aucs was not significant , 83.40 versus 82.70 ( if the difference between two aucs was greater than 5% , the diagnostic performance between two objects had statistics significance , which suggested that the accuracy would be same ) ( table 4 ) . according to criteria set in the index words , a total of 140 papers were screened from the above - mentioned databases . however , only 7 studies remained after taking into account the inclusion and exclusion criteria . among these articles , two were of grade a , whereas the other five were of grade b ( table 1 ) . in clinical practice , the classification system described by kurhanewicz et al . ( 6 ) was often used : normal - a voxel of signal intensity ratios of ( choline + creatine ) / citrate lower than 0.75 ; suspicious - between 0.75 and 0.86 ; definitive tumor - above this threshold . to calculate the sensitivity and specificity , descriptive statistical data ( tp , tn , fp , and fn ) were determined by using two dichotomized rating systems : one with a voxel ratio of less than 0.75 which was not determined to be cancer , as opposed to a voxel ratio greater than 0.75 which represented a finding of cancer . while another cut - off value was 0.86 . five studies used a diagnostic value of 0.75 as a cut - off criteria ( table 2 ) , as opposed to five studies , which used a diagnostic cut - off value of 0.86 ( table 3 ) . the homogeneity test showed : q1 = 37.20 , p1 < 0.01 , q2 = 23.17 , p2 < 0.01 . therefore , in these two groups , the random effects models was used for the meta - analysis . forest plots for two groups were constructed and the pooled weighted sensitivity , specificity , and corresponding 95% ci were calculated ( fig . 1 , table 4 ) . because sroc can inflect a non - linear relationship between the sensitivity and specificity simultaneously , it was better used ( 18 ) to assess the accuracy of the diagnostic tests . here we drew and analyzed sroc and calculated auc for these two groups ( figs . 2 , 3 ) . the pooled weighted sensitivity of the first criterion was higher 0.82 ( 0.73 , 0.89 ) than the second 0.64 ( 0.55 , 0.72 ) , in which the p - value was < 0.0001 , chi - square value = 57.13 however , its specificity is lower [ 0.68 ( 0.58 , 0.76 ) vs. 0.86 ( 0.79 , 0.91 ) ] than , a p - value < 0.0001 , chi - square value = 118.30 . however , the difference between the two aucs was not significant , 83.40 versus 82.70 ( if the difference between two aucs was greater than 5% , the diagnostic performance between two objects had statistics significance , which suggested that the accuracy would be same ) ( table 4 ) . further , cancers detected by dre are in an advanced stage in up to 50% of cases . using a psa cut - off value of 4 ng / ml as an indication of carcinoma of the prostate , up to 25% of men with cancer in addition , the positive predictive value of the test is only 30% in asymptomatic men ( 4 ) . an mri performed using an endorectal coil is unsuitable as a primary diagnostic tool for detecting prostate cancer due to its low specificity and low positive predictive value ( 19 ) ; although , the accuracy of mri staging for stages b and c is 77% and there is a high sensitivity of detection for extraprostatic tumor extension and seminal vesicle infiltration ( 20 , 21 ) . to date , the histopathologic examinations of biopsy tissue remain the gold standard for diagnosis of prostate cancer . however , this method only results in a sensitivity of 50% and specificity of 82% . in these cases , malignancies are easily overlooked because of their multi - focal and heterogeneous nature , which happens in as many as 85% of patients ( 22 , 23 ) . it has been reported that after a radical prostatectomy , the biopsy - determined result increased in as many as 54% of patients ( 24 ) . therefore , an accurate and noninvasive way of determining prostate cancer is needed to improve the ability to define subsets of patients in which a cure is possible and necessary . the mrs can detect a resonance spectrum from different chemical compounds in tissues , which in turn , reveals structural information about the chemical compound as well as the metabolic information of the tissues . in normal prostate tissue , however , in the case of prostate cancer , citrate levels diminish or are undetectable because of a conversion from citrate - producing to citrate - oxidating metabolism . moreover , the choline level is elevated due to a high phospholipids cell membrane turnover rate in the proliferating malignant tissue . hence , the method for depicting tumors is based on an increased ( choline + creatine ) / citrate ratio ( 22 ) . a meta - analysis is a statistical analysis that combines or integrates the results of several independent studies considered to be combinable . the reliability of the results depends on the quality of the included studies and whether the result of the analysis is reliable . according to cochrane 's methods of screening and diagnosis ( table 5 ) , the suggested quality in the five levels of diagnostic procedures were ( grade a and grade b ) for analysis by two reviewers ' independent evaluation , which may lead to a selection bias with more information . all the studies we used for this study are prospective observational ( independent ) , blind comparisons with a reference standard , in which radiologists scan and diagnose the patients after the scientific experiment design . according to our selection criteria this meta - analysis included only 7 studies out of the many reviewed articles . one reason for this low number is that mrs has been used in diagnosing prostate cancer for only a few years and related studies are scarce . another factor is that the quality of these studies on the basis of inclusion in meta - analyses are not high . case in point , only two studies qualified as grade a , whereas the other five studies included subjects that all had prostate cancer , which represented a selection bias of the subjects , though the mrs tests the peak of choline , citrate , and creatine in the different voxels of whole prostates . moreover , the two radiologists are unaware of which patient has prostate cancer . according to table 1 , our intentions were to analyze the homogeneity of the basic information of all studies including psas , gleason grades which may affect the assessment of the results ( 6 ) . however , it is impossible to achieve this because data is not integral . in some studies detected voxels , a biopsy is inaccurate because prostate cancer is multi - focal and heterogeneous in nature , and it is limited in examining all cancers , sites , and grades ( 24 ) . hence , their ( 15 , 16 ) positive results are much smaller than the negative results and the sensitivity is not so reliable . according to kristen et al . ( 25 ) who measured the mr spectroscopic imaging , and the ratio of prostate tumor for ( cho + cr ) / cit ratio . his data indicated that in the diagnosis , cancer with a gleason score of 3 + 3 , the mr spectroscopic imaging tumor detection sensitivity was 44.4% , and the sensitivity increased to 89.5% in cancers with a gleason score of more than 8 . thus , a large proportion of tumors with a gleason score of 6 and under 6 did not generate abnormal voxel metabolite ratios . one possible explanation for this finding is that these tumors tended to be smaller , thereby permitting a volume averaging with noncancerous tissue . another is that low - grade tumors ( below 6 ) may be missed , due to slight alterations in citrate and choline levels . in all studies except that of prando 17 ) we have not talked about tumor or volume , so we did n't further analyze it . the advantage of sroc curves is that the curves may be tested for symmetry and therefore can be determined if a subgroup analysis is appropriate . a disadvantage of sroc curves is that if a large variability is present between subgroups , the goodness of fit using sroc curves will be limited ( 26 ) . in this meta - analysis , we have only compared the value of two criteria . the two aucs are similar ; however , their sensitivity and specificity possess noticeable differences . hence , the combination of the two criteria may improve the accuracy in clinical use . in china , however , their study results were compared to biopsy and non - pathologic results , which yielded a different set of outcomes . at the present time , we still need large samples and multi - center studies to increase the confidence in the results . in conclusion , we could not analyze the literature with a more reasonable option than we have now , due to poor reporting in the primary studies and small quantity of studies . here , we supply just the primary assessment of the value for mrs in clinic .