positron emission tomography ( pet ) is a procedure for evaluating biochemical and physiological processes by use of radiopharmaceuticals labeled with positron - emitting radionuclides .
f - fluoro-2-deoxyglucose ( f - fdg ) pet scanning has been widely utilized for the diagnosis of various tumors ; for the staging and restaging of various malignancies , including head and neck , esophageal , lung , breast , colorectal , and gynecological cancers , as well as melanoma and lymphoma ; and for assessing brain function and heart muscle metabolism . however , the positive predictive value of f - fdg pet is low for cancer , including for prostate cancer .
fdg uptake in the prostate is nonspecific for cancer and may result from an inflammatory condition such as prostatitis .
moreover , the maximum standardized uptake value ( suv ) of fdg is not essential for the differential diagnosis of prostatic lesions ; nevertheless , several studies have reported a high correlation between fdg uptake and prostate cancer .
for example , fdg uptake without coincidental calcification indicates the possibility of prostate cancer , suggesting the need for additional diagnostic methods , including digital rectal examinations ( dres ) and measurements of serum concentrations of prostate - specific antigen ( psa ) .
incidental fdg uptake in the prostate is often experienced in clinical practice , but suv alone can not determine whether increased uptake indicates a malignancy or a benign state .
detection of second primary cancers , particularly early cancers that require radical treatment , is important because these cancers can significantly influence patient management .
we therefore investigated the prevalence and clinical significance of incidental prostate fdg uptake and evaluated its impact on patient management .
the medical records of all patients who underwent fdg pet at our hospital between october 2004 and march 2014 were reviewed .
the study was performed with the approval and oversight of the institutional review board , which waived the requirement for informed consent because of the retrospective design of this study . during the study period ,
of the 47,109 males , 1,335 ( 2.83% ) demonstrated incidental fdg uptake in the prostate .
of the 144 patients who underwent prostate biopsy , the 45 who had undergone fdg pet for staging or restaging of prostate cancer were excluded .
finally , 99 patients who underwent prostate biopsy following fdg uptake in the prostate were included in this study ( fig .
patients underwent fdg pet on one of the three scanners operated in our hospital ( discovery st [ ge healthcare , wauwatosa , wi , usa ] and biograph 16 and biograph 40 [ siemens medical solutions , malvern , pa , usa ] ) .
after their venous blood glucose concentration was confirmed as being < 150 mg / dl , the patients were intravenously injected with f - fdg ( 5.2 mbq / kg body weight ) , with pet / computed tomography ( ct ) scanning started 50 minutes later .
images were reconstructed by using a three - dimensional ordered subset expectation maximization algorithm , and ct attenuation maps were used for attenuation correction .
pet , ct , and fused pet / ct images were available for review and were displayed in axial , coronal , and sagittal planes on a viewer system .
the suv was calculated according to the standard formula , with the use of lean body mass as the body weight .
fdg uptake in the prostate was visually defined as positive or negative , with physiological uptake in the prostate urethra on coronal , sagittal , and axial views considered negative .
patterns of fdg uptake ( focal or diffuse ) were evaluated on axial views ( fig .
baseline demographic and clinical characteristics , including patient age , serum total psa concentration , dre findings , and transrectal ultrasound ( trus)-derived information ( prostate volume ) were obtained by reviewing medical records .
psa concentrations were measured by using a psa - riact assay system ( cis bio international , gif - sur - yvette , france ) .
all patients underwent trus - guided laterally directed systematic 12-core biopsies of the prostate the primary study end point was the histological presence of adenocarcinoma of the prostate in the biopsy specimen .
all samples were graded by genitourinary pathologists at our institute , with grading based on the gleason scoring system .
the outcomes in patients with prostate cancer , including treatment methods , survival , and causes of death , were also assessed .
patients were divided into three groups according to their prostate biopsy results , as follows : those with normal prostate , prostate cancer , and prostate invasion , except for prostate cancer .
clinicopathological factors were compared in the benign lesion and prostate cancer groups by using pearson chisquare test for categorical variables and student t - test for continuous variables .
factors associated with a diagnosis of prostate cancer were evaluated by using logistic regression analysis , with variables of p<0.1 on univariate analysis included in the multivariable analysis .
correlations between clinical outcomes and the assessed variables are expressed as odds ratios ( ors ) and 95% confidence intervals ( cis ) .
the group of patients with prostate invasion , except for prostate cancer , was analyzed separately .
all statistical analyses were performed by using the pasw statistics ver . 18.0 ( spss inc . , chicago , il , usa ) .
during the study period , 92,203 patients ( 47,109 males and 45,094 females ) underwent fdg pet .
of the 47,109 males , 1,335 ( 2.83% ) demonstrated incidental fdg uptake in the prostate .
of the 144 patients who underwent prostate biopsy , the 45 who had undergone fdg pet for staging or restaging of prostate cancer were excluded .
finally , 99 patients who underwent prostate biopsy following fdg uptake in the prostate were included in this study ( fig .
patients underwent fdg pet on one of the three scanners operated in our hospital ( discovery st [ ge healthcare , wauwatosa , wi , usa ] and biograph 16 and biograph 40 [ siemens medical solutions , malvern , pa , usa ] ) . all patients fasted for at least 6 hours before the examination . after their venous blood glucose concentration was confirmed as being < 150 mg / dl , the patients were intravenously injected with f - fdg ( 5.2 mbq / kg body weight ) , with pet / computed tomography ( ct ) scanning started 50 minutes later .
images were reconstructed by using a three - dimensional ordered subset expectation maximization algorithm , and ct attenuation maps were used for attenuation correction .
pet , ct , and fused pet / ct images were available for review and were displayed in axial , coronal , and sagittal planes on a viewer system .
the suv was calculated according to the standard formula , with the use of lean body mass as the body weight .
fdg uptake in the prostate was visually defined as positive or negative , with physiological uptake in the prostate urethra on coronal , sagittal , and axial views considered negative .
patterns of fdg uptake ( focal or diffuse ) were evaluated on axial views ( fig .
baseline demographic and clinical characteristics , including patient age , serum total psa concentration , dre findings , and transrectal ultrasound ( trus)-derived information ( prostate volume ) were obtained by reviewing medical records .
psa concentrations were measured by using a psa - riact assay system ( cis bio international , gif - sur - yvette , france ) .
the primary study end point was the histological presence of adenocarcinoma of the prostate in the biopsy specimen .
all samples were graded by genitourinary pathologists at our institute , with grading based on the gleason scoring system .
the outcomes in patients with prostate cancer , including treatment methods , survival , and causes of death , were also assessed .
patients were divided into three groups according to their prostate biopsy results , as follows : those with normal prostate , prostate cancer , and prostate invasion , except for prostate cancer .
clinicopathological factors were compared in the benign lesion and prostate cancer groups by using pearson chisquare test for categorical variables and student t - test for continuous variables .
factors associated with a diagnosis of prostate cancer were evaluated by using logistic regression analysis , with variables of p<0.1 on univariate analysis included in the multivariable analysis .
correlations between clinical outcomes and the assessed variables are expressed as odds ratios ( ors ) and 95% confidence intervals ( cis ) .
the group of patients with prostate invasion , except for prostate cancer , was analyzed separately .
table 1 shows the clinical characteristics of the 52 patients with benign lesions and the 41 patients ( 44.1% ) with prostate cancer .
the mean age of all 93 patients was 65.8 years , with the mean ages of the benign lesion and prostate cancer groups being 62.8 and 69.6 years , respectively ( p=0.001 ) .
patients with prostate cancer were more likely to have higher serum psa concentrations ( p=0.001 ) and focal fdg uptake ( p=0.036 ) .
only 1 of the 26 patients ( 3.8% ) with serum psa<2.5 ng / ml had prostate cancer , compared with 40 of the 67 patients ( 59.7% ) with serum psa2.5 ng / ml . the trus - determined prostate volume in all 93 patients was 38.8 ml and was similar in the benign lesion and prostate cancer groups ( 39.7 ml vs. 37.7 ml , p=0.672 ) .
in addition , mean maximum suv was similar in the two groups ( p=0.116 ) .
univariate analysis showed that age ( or , 1.08 ; 95% ci , 1.02 - 1.13 ; p=0.003 ) , serum psa concentration ( or . 1.31 ; 95% ci , 1.14 - 1.50 ; p=0.001 ) , and the presence of focal lesions ( or , 3.80 ; 95% ci , 1.10 - 14.50 ; p=0.043 ) were significant predictors of a final diagnosis of prostate cancer .
multivariable analysis showed that the presence of focal lesions was an independent predictor of a diagnosis of prostate cancer ( or , 5.50 ; 95% ci , 1.09 - 27.64 ; p=0.038 ) , as were age ( or , 1.06 ; 95% ci , 1.01 - 1.11 ; p=0.031 ) and serum psa concentration ( or , 1.28 ; 95% ci , 1.10 - 1.47 ; p=0.001 ) ( table 2 ) .
table 3 shows the clinical characteristics of the six patients with prostate invasion , except for prostate cancer .
these six patients had a mean age of 59.0 years , a mean serum psa concentration of 3.2 ng / ml , and a mean prostate volume of 49.3 ml .
histologically , two of these patients ( 33.3% ) had bacillus calmette - guerin - granuloma , two ( 33.3% ) had lymphoma , one ( 16.7% ) had gastrointestinal stromal tumor , and one ( 16.7% ) had colon cancer .
table 4 shows the patterns of treatment in the 41 patients with prostate cancer , most of whom had organconfined tumors .
of these 41 patients , 12 ( 29.3% ) underwent radical prostatectomy and 25 ( 60.9% ) received hormone therapy .
of the 11 patients who died , 9 did so from primary cancer progression , with only 1 patient dying from prostate cancer .
because f - fdg pet is becoming more widely used in cancer diagnosis , staging , and restaging , as well as in monitoring response to treatment , more incidental lesions , including prostate lesions , are being detected .
the rise in incidental findings has created a problem for clinicians and often leads to unnecessary diagnosis and treatment , consequently increasing patient concern .
thus , determining the clinical significance of fdg uptake in the prostate is extremely important .
our results showed that prostate cancer was strongly associated with serum psa concentration , with tumors detected in 40 of 67 patients ( 59.7% ) with serum psa2.5 ng / ml but in only 1 of 26 patients ( 3.8% ) with serum psa<2.5 ng / ml . this difference is much greater than that observed in community - based populations . in general , prostate cancers are detected in approximately 2% of men with psa of 2 - 4 ng / ml and in 11% of those with psa of 4 - 10 ng / ml . our multivariate analysis also showed that the serum psa concentration was an independent predictor of a diagnosis of prostate cancer ( or , 1.28 ; 95% ci , 1.10 - 1.47 ; p=0.001 ) .
these findings suggest that patients with fdg uptake in the prostate should undergo secondary evaluation , including measurement of serum psa , and that those with high serum psa should be evaluated by prostate biopsy .
fdg pet is relatively insensitive in the detection of primary tumors , with sensitivities ranging from 19% to 64% .
fdg uptake in the prostate is not specific to cancer , but is also positive in patients with benign prostatic hypertrophy ( bph ) and inflammatory conditions such as prostatitis .
fdg uptake tends to be higher in poorly differentiated prostate tumors and in those with higher serum psa concentrations than in tumors with lower psa levels , a more localized clinical stage , and lower gleason scores , perhaps because the level of glucose transporter-1 expression rises with increasing malignancy grade .
therefore , fdg pet may not be useful in the diagnosis or staging of clinically organ - confined disease , because the levels of fdg accumulation in normal prostate tissue , bph , and prostate cancer may overlap .
however , focal fdg uptake is important because most of our patients with prostate cancer had focal fdg uptake , and other studies have reported that focal uptake in the peripheral zone correlates with prostate cancer .
bph is characterized by nodular hyperplasia of the fibromuscular tissue and epithelium within the transition zone and periurethral area . by contrast , most prostate cancers arise from the peripheral zone . in some solitary tumors ,
maximum suv closely correlates with pathologic grade , which suggests that this parameter could be used for diagnosis and for assessing prognosis . in our study and others , however , there was no correlation between the maximum suv of uptake in the prostate and prostate cancer .
although the degree of fdg uptake by primary prostate tumors was greater in patients with higher psa than in those with lower psa levels , psa levels can also increase in benign conditions such as bph .
an ideal candidate for radical prostatectomy is free of comorbidities that may make the operation unacceptably risky .
surgery is not indicated for patients with a large number of comorbidities or a short life expectancy , however , and these patients should receive hormone therapy or radiation therapy , which may effectively control tumor progression . of our 41 patients with prostate cancer , 37 ( 90.2% ) received treatment , with only 1 patient ( 2.4% ) dying of prostate cancer ; thus , a diagnosis of prostate cancer in patients with incidental prostate fdg uptake could have affected their prognosis .
this study had several limitations , including its retrospective design , the relatively small patient cohort , and the significant differences in several clinical variables between the groups of patients with normal prostate and prostate cancer . moreover ,
our study was limited by selection bias , because prostate cancer was not histologically confirmed in all patients .
although the most accurate tool for diagnosing prostate cancer is biopsy , some patients showing incidental focal fdg uptake on pet did not undergo prostate biopsy ; thus , the sensitivity of fdg pet could not be determined in this patient cohort .
nonetheless , the present study is the first to analyze the clinical significance of incidental prostate fdg uptake and to evaluate the prevalence of prostate cancer according to psa and clinical outcomes .
this study showed that patients with fdg uptake and elevated serum psa should be evaluated by prostate biopsy , especially if their scans show focal lesions .
the prevalence of incidental fdg uptake in the prostate was not high ; however , patients with elevated serum psa had a high incidence of prostate cancer .
therefore , patients showing fdg uptake in the prostate should undergo further evaluation , including measurements of serum psa concentration , with those having a high serum psa evaluated by prostate biopsy .
the results of this study may be helpful in planning the management of patients with incidental fdg uptake in the prostate .
because the study cohort was relatively small , however , further studies are needed to determine the clinical validity of this management strategy .
 purposeto investigate the prevalence and clinical significance of incidental prostate fluoro-2-deoxyglucose ( fdg ) uptake and to evaluate its impact on patient management.materials and methodsof 47,109 men who underwent fdg positron emission tomography between 2004 and 2014 , 1,335 ( 2.83% ) demonstrated incidental fdg uptake in the prostate , with 99 of the latter undergoing prostate biopsy . 
 the primary end point was the histological presence of prostate adenocarcinoma in the biopsy specimen . 
 outcomes , including treatment methods , survival , and causes of death , were also assessed . 
 factors associated with the diagnosis of prostate cancer were evaluated by using logistic regression analysis.resultspatients with prostate cancer were more likely to have higher serum prostate - specific antigen ( psa ) ( p=0.001 ) and focal fdg uptake ( p=0.036 ) than were those without . 
 prostate cancer occurred in 1 of 26 patients ( 3.8% ) with serum psa<2.5 ng / ml , compared with 40 of 67 patients ( 59.7% ) with serum psa2.5 ng / ml . 
 multivariable analysis showed that focal lesions ( odds ratio [ or ] , 5.50 ; p=0.038 ) , age ( or , 1.06 ; p=0.031 ) , and serum psa ( or , 1.28 ; p=0.001 ) were independent predictors of prostate cancer diagnosis . 
 most patients with prostate cancer had organ - confined tumors . 
 of these , 12 ( 29.3% ) underwent radical prostatectomy and 25 ( 60.9% ) received hormone therapy . 
 of the 11 patients who died , 9 died of primary cancer progression , with only 1 patient dying from prostate cancer.conclusionsthe prevalence of incidental fdg uptake in the prostate was not high , although patients with elevated serum psa had a higher incidence of prostate cancer . 
 patients with fdg uptake in the prostate should be secondarily evaluated by measuring serum psa , with those having high serum psa undergoing prostate biopsy . 
INTRODUCTION
MATERIALS AND METHODS
1. Patients
2. 
3. Patient demographic and clinical characteristics
4. Study outcomes
5. Statistical analysis
RESULTS
DISCUSSION
CONCLUSIONS