prostate cancer is the most common non - cutaneous cancer in men . according to the most recent seer data , 217 730 men are estimated to have been diagnosed with prostate cancer in 2010 resulting in 32 050 prostate cancer related deaths . transperineal interstitial prostate implant , either by itself or in combination with external beam radiotherapy ( ebrt ) , is a well accepted treatment modality for men with low and intermediate risk of disease . data have shown that appropriate patient populations treated with prostate brachytherapy have improved biochemical relapse - free survival ( brfs ) as compared to patients treated with radical prostatectomy ( rp ) and ebrt [ 25 ] . computed tomography ( ct ) of the pelvis and transrectal prostate ultrasound ( trus ) are central to the evaluation and management of patients with prostate cancer . pelvic ct is often recommended for staging patients with a risk of pelvic lymph node involvement greater than 20% . in addition to being a part of the staging work - up , ct is used in determining post - implantation seed placement and in calculating the dose delivered to the prostate and to the structures at risk . trus is generally used to assess pre - implant prostate volumes as well as intra - operative placement of radioactive sources . trauma from brachytherapy seed implantation is associated with a significant increase in prostate size which may affect post - procedure dose volume calculations . if the post - implant ct used for dosimetry calculations is performed shortly after the procedure , the calculated delivery dose may appear suboptimal . waterman et al . performed pre- and post - procedure serial ct scans on 10 patients who underwent either palladium-103 or iodine-125 prostate seed brachytherapy . the study showed a mean 1.52-fold increase in prostate volumes , ranging from 1.33 to 1.96 . edema was most notable on the first day after the procedure and resolved exponentially with time . mean edema half - life was 9.3 days ( range 4 to 25 days ) . other authors have examined post- implantation edema 's dosimetric effects using ct , ultrasound , and magnetic resonance imaging ( mri ) ; many have proposed methods for the correction of dosimetric discrepancy due to prostate swelling [ 921 ] . current guidelines from the american association of physicists in medicine ( aapm ) advocate that in i-125 seed implantation , dosimetry should be calculated 1 month (  1 week ) after implantation to allow for resolution of edema . despite its limitations , ct continues to be the most commonly used imaging modality for obtaining post - implant dosimetric calculations within the community setting . in addition to the debate over imaging modality , the factors which influence edema are not well agreed upon by the research community . thus , further research is warranted to elucidate relevant factors for post - implant prostate edema and resultant effects on dosimetry . this study was designed to track the pattern of edema resolution over time , evaluate the extent of prostate swelling following i-125 seed implantation , and examine the effects of several treatment - related variables on magnitude of edema . we analyzed the effect of prostate volume changes on post - implant dosimetry and proposed an uncomplicated correction factor to estimate the change in dosimetry between day 1 and day 30 . this study was approved by the institutional review board . between february 2006 and december 2006 we enrolled 37 patients . eight patients did not have sufficient follow - up , so 29 were included in the preliminary analysis . patients received either brachytherapy alone or a combined modality approach with pb and ebrt in a non - randomized fashion based on the clinical stage , gleason score , and prostate - specific antigen ( psa ) level . patients with a gleason score of  6 and psa of  10 with no other significant risk factors were placed in brachytherapy alone . for patients receiving ebrt , sequencing of brachytherapy and ebrt fourteen patients were treated with brachytherapy alone ( group 0 ) and fifteen patients received a combination treatment . in the combined modality group , seven patients underwent prostate implant immediately following completion of ebrt to 50 gy ( group 1 ) . the remaining eight received ebrt four to five weeks after the procedure ( group 2 ) . in addition to radiation , five patients from the three groups received hormonal therapy three months prior to receiving brachytherapy . patients in groups 1 and 2 were statistically similar in their averaged gleason and psa . patient characteristics are listed in table 1 and the general management schema is illustrated in fig . 1 . overview of treatment summary of patient and treatment characteristics psa  prostate - specific antigen ; ebrt  external beam radiation therapy ; group 0  pb alone ; group 1  pb after ebrt ; group 2  pb followed by ebrt ; n / a  not available pelvic ct with urethrogram was used for all prostate volume ( pv ) measurements . the urethrogram was performed by inserting the tip of a syringe containing a radio - opaque contrast material into the urethral meatus and injecting 10 cc of contrast into the urethra . the prostate was outlined on each 3 mm ct slice by a single observer and prostate volume was computed automatically . all patients had a pre - implant prostate ct with urethrogram prior to the procedure . post - brachytherapy serial pv measurements were done on post - op day 1 ( pv1 ) , day 9 ( pv9 ) , day 30 ( pv30 ) , and day 60 ( pv60 ) . the influence of several variables on post - implantation pv was examined using univariate analysis . the variables included in the analysis were the following : 1 ) pre - implant prostate volume ; 2 ) number of needles used ; 3 ) number of needle insertion attempts ; 4 ) number of seeds ; 5 ) seed activity ; 6 ) gleason score ; 7 ) hormonal ablation therapy ( hat ) ; 8) ebrt . the quality of an implant was assessed by determining the dose received by 90% of the prostate ( d90 ) . d90day1 and d90day30 were computed using prostate contours delineated from scans taken on post - op day 1 and day 30 , respectively . a volume correction factor ( cf ) was calculated for each patient as a ratio of their prostate volume measured on day 30 ( pv30 ) to that on day 1 ( pv1).1cf = pv30/pv1 
  the estimated d90day30 ( ed90day30 ) and the average estimated d90day30 ( ed90day30 ) were calculated by dividing d90day1 by the individual 's cf as well as the study 's mean cf as illustrated in equations 2 and 3 , respectively . estimated d90 on day 30 ( per individual):2ed90day30=d90day1/individual cf 
  average estimated d90 on day 30 ( per individual):3ed90day30=d90day1/average cf 
  d90day1 and ed90day30 ( from equation 3 ) were compared with ed90day30 ( from equation 2 ) using the sign test . this is an exploratory , hypothesis - generating study to find a model which simulates the dose received by 90% of the prostate ( d90 ) on day 30 . data were summarized and non - parametric statistical tests , sign and wilcoxon rank - sum tests , were conducted to compare the relevant variables . univariate regression analysis was performed to test the relation between different variables and the change in prostate volume one day post - implantation . all reported p values are two - sided and values of 0.05 or lower are considered to indicate statistical significance . this study was approved by the institutional review board . between february 2006 and december 2006 we enrolled 37 patients . eight patients did not have sufficient follow - up , so 29 were included in the preliminary analysis . patients received either brachytherapy alone or a combined modality approach with pb and ebrt in a non - randomized fashion based on the clinical stage , gleason score , and prostate - specific antigen ( psa ) level . patients with a gleason score of  6 and psa of  10 with no other significant risk factors were placed in brachytherapy alone . for patients receiving ebrt , sequencing of brachytherapy and ebrt fourteen patients were treated with brachytherapy alone ( group 0 ) and fifteen patients received a combination treatment . in the combined modality group , seven patients underwent prostate implant immediately following completion of ebrt to 50 gy ( group 1 ) . the remaining eight received ebrt four to five weeks after the procedure ( group 2 ) . in addition to radiation , five patients from the three groups received hormonal therapy three months prior to receiving brachytherapy . patients in groups 1 and 2 were statistically similar in their averaged gleason and psa . patient characteristics are listed in table 1 and the general management schema is illustrated in fig . 1 . overview of treatment summary of patient and treatment characteristics psa  prostate - specific antigen ; ebrt  external beam radiation therapy ; group 0  pb alone ; group 1  pb after ebrt ; group 2  pb followed by ebrt ; n / a  not available the urethrogram was performed by inserting the tip of a syringe containing a radio - opaque contrast material into the urethral meatus and injecting 10 cc of contrast into the urethra . the prostate was outlined on each 3 mm ct slice by a single observer and prostate volume was computed automatically . all patients had a pre - implant prostate ct with urethrogram prior to the procedure . post - brachytherapy serial pv measurements were done on post - op day 1 ( pv1 ) , day 9 ( pv9 ) , day 30 ( pv30 ) , and day 60 ( pv60 ) . the influence of several variables on post - implantation pv was examined using univariate analysis . the variables included in the analysis were the following : 1 ) pre - implant prostate volume ; 2 ) number of needles used ; 3 ) number of needle insertion attempts ; 4 ) number of seeds ; 5 ) seed activity ; 6 ) gleason score ; 7 ) hormonal ablation therapy ( hat ) ; 8) ebrt . the quality of an implant was assessed by determining the dose received by 90% of the prostate ( d90 ) . d90day1 and d90day30 were computed using prostate contours delineated from scans taken on post - op day 1 and day 30 , respectively . a volume correction factor ( cf ) was calculated for each patient as a ratio of their prostate volume measured on day 30 ( pv30 ) to that on day 1 ( pv1).1cf = pv30/pv1 
  the estimated d90day30 ( ed90day30 ) and the average estimated d90day30 ( ed90day30 ) were calculated by dividing d90day1 by the individual 's cf as well as the study 's mean cf as illustrated in equations 2 and 3 , respectively . estimated d90 on day 30 ( per individual):2ed90day30=d90day1/individual cf 
  average estimated d90 on day 30 ( per individual):3ed90day30=d90day1/average cf 
  d90day1 and ed90day30 ( from equation 3 ) were compared with ed90day30 ( from equation 2 ) using the sign test . this is an exploratory , hypothesis - generating study to find a model which simulates the dose received by 90% of the prostate ( d90 ) on day 30 . data were summarized and non - parametric statistical tests , sign and wilcoxon rank - sum tests , were conducted to compare the relevant variables . univariate regression analysis was performed to test the relation between different variables and the change in prostate volume one day post - implantation . all reported p values are two - sided and values of 0.05 or lower are considered to indicate statistical significance . a total of 139 pv measurements were obtained . prostate size increased by an average factor of 1.440.37 at the time of maximum swelling , which occurred in the immediate post - operative period . the mean prostate volume recorded on post - operative day 1 ( 67.7 cm ) was 18.8 cm greater than the average pre - op value of 48.9 cm ( sd 15.6 ) . the difference between pre- and post - operative prostate volumes was no longer significant ( fig . 2 , tables 2 and 3 ) . 
  pattern of prostate volume changes over time in individual patients mean change in pv and ipss over time pv  prostate volume , pvx pv on dayx 
  mean difference in prostate volume change from days 0 , 1 , 9 , and 30 to later measurement pv  prostate volume , pvx +  indicates increase and    decrease with respect to the pv on days 0 , 1 , 9 , or 30 , as indicated in each row 
 figure 3 is a regression fit graph representing the relationship between the pre and post - implant prostate volumes . one can estimate a pv on a given post - operative day by plotting the pre - implant value on the x - axis and tracing the value to the regression line , and reading off the expected value . correlation between pre- and post - implant prostate volume on post - operative ( a ) day 1 , ( b ) day 9 , ( c ) day 30 , and ( d ) day 60 we examined several factors and their influence on the degree of prostate swelling . using logistic regression analysis , we assessed which variables lead to a greater than one third increase of the initial prostate volume one day after the implantation . our results indicate that seed activity (  0.4 vs.>0.4 mci ) , treatment modality ( brachytherapy alone vs. combined modality ) , and gleason score (  6 vs.>6 ) were statistically significant variables with respect to prostate edema ( p values=0.02 , 0.02 , and 0.046 respectively ) . there was a tendency for higher seed activity ( > 0.4 mci ) , low gleason score (  6 ) , and treatment with brachytherapy alone to be associated with a greater change in prostate volume . within our study , patients with low - risk disease ( as determined by gleason and psa ) were implanted with higher activity seeds and were found to have an average prostate swelling of 24.8 cm , compared to only a 13.1 cm volume increase in patients implanted with lower activity seeds ( p value=0.02 ) . none of the remaining factors such as pre - implant prostate volume , number of needles and insertion attempts , number and activity of seeds , use of hormonal therapy , or the sequencing of ebrt were found to be significantly correlated with the degree of prostate edema one day after the procedure . the individual 's volume correction factor was calculated as a ratio of pv30 to pv1 as described by equation 1 ( cf = pv30/pv1 ) . the mean volume correction factor was determined to be 0.760.21 . for each patient , an estimated d90day30 value ( ed90day30 ) was calculated using the individual 's cf and the mean cf , as illustrated in equations 2 and 3 , respectively . the discrepancy between the day 1 and day 30 dosimetry was significant with the calculated ratio between day 1 and day 30 dosimetry ( actual d90day1/actual d90day 30 ) found to be 0.7117 ( p=0.0078 ) ( table 4 ) . using our proposed cf , we next compared the mean estimated d90 ( ed90day30 ) to the actual d90 for day 30 ( d90day30 ) . our cf was therefore successful in accounting for the effects of edema on day 1 dosimetry . mean ratio of actual day 1 and day 30 values to estimated day 30 dosimetry and estimated day 30 dosimetry to actual day 30 dosimetry across all patients p values were calculated for actual day 1 and estimated day 30 values as compared with the actual day 30 dosimetry a total of 139 pv measurements were obtained . prostate size increased by an average factor of 1.440.37 at the time of maximum swelling , which occurred in the immediate post - operative period . the mean prostate volume recorded on post - operative day 1 ( 67.7 cm ) was 18.8 cm greater than the average pre - op value of 48.9 cm ( sd 15.6 ) . the difference between pre- and post - operative prostate volumes was no longer significant ( fig . 2 , tables 2 and 3 ) . 
  pattern of prostate volume changes over time in individual patients mean change in pv and ipss over time pv  prostate volume , pvx pv on dayx 
  mean difference in prostate volume change from days 0 , 1 , 9 , and 30 to later measurement pv  prostate volume , pvx +  indicates increase and    decrease with respect to the pv on days 0 , 1 , 9 , or 30 , as indicated in each row 
 figure 3 is a regression fit graph representing the relationship between the pre and post - implant prostate volumes . one can estimate a pv on a given post - operative day by plotting the pre - implant value on the x - axis and tracing the value to the regression line , and reading off the expected value . correlation between pre- and post - implant prostate volume on post - operative ( a ) day 1 , ( b ) day 9 , ( c ) day 30 , and ( d ) day 60 we examined several factors and their influence on the degree of prostate swelling . using logistic regression analysis , we assessed which variables lead to a greater than one third increase of the initial prostate volume one day after the implantation . our results indicate that seed activity (  0.4 vs.>0.4 mci ) , treatment modality ( brachytherapy alone vs. combined modality ) , and gleason score (  6 vs.>6 ) were statistically significant variables with respect to prostate edema ( p values=0.02 , 0.02 , and 0.046 respectively ) . there was a tendency for higher seed activity ( > 0.4 mci ) , low gleason score (  6 ) , and treatment with brachytherapy alone to be associated with a greater change in prostate volume . within our study , patients with low - risk disease ( as determined by gleason and psa ) were implanted with higher activity seeds and were found to have an average prostate swelling of 24.8 cm , compared to only a 13.1 cm volume increase in patients implanted with lower activity seeds ( p value=0.02 ) . none of the remaining factors such as pre - implant prostate volume , number of needles and insertion attempts , number and activity of seeds , use of hormonal therapy , or the sequencing of ebrt were found to be significantly correlated with the degree of prostate edema one day after the procedure . the individual 's volume correction factor was calculated as a ratio of pv30 to pv1 as described by equation 1 ( cf = pv30/pv1 ) . the mean volume correction factor was determined to be 0.760.21 . for each patient , an estimated d90day30 value ( ed90day30 ) was calculated using the individual 's cf and the mean cf , as illustrated in equations 2 and 3 , respectively . the discrepancy between the day 1 and day 30 dosimetry was significant with the calculated ratio between day 1 and day 30 dosimetry ( actual d90day1/actual d90day 30 ) found to be 0.7117 ( p=0.0078 ) ( table 4 ) . using our proposed cf , we next compared the mean estimated d90 ( ed90day30 ) to the actual d90 for day 30 ( d90day30 ) . our cf was therefore successful in accounting for the effects of edema on day 1 dosimetry . mean ratio of actual day 1 and day 30 values to estimated day 30 dosimetry and estimated day 30 dosimetry to actual day 30 dosimetry across all patients p values were calculated for actual day 1 and estimated day 30 values as compared with the actual day 30 dosimetry the pattern of edema resolution shown in our study is consistent with previously published reports . the timing of pv measurement was chosen based on published data regarding edema resolution pattern . the preponderance of data suggests that edema half - life is 810 days on average , returning to pre - implant size by day 30 [ 821 ] . our results pertaining to the prostate edema resolution pattern are similar to previously published data . the results are also consistent with current aapm recommendations which suggest the use of post - implantation ct at day 30 to allow for resolution of edema . waterman et al . also determined the edema half - life to be 9.3 days ( range : 4 to 25 days ) . the post - implant dosimetry was based on ct - based contours , as in our study . in our study , we found the edema half - life to be 17.3 days . waterman found a positive correlation between seed spacing and pv , but did not appreciate any correlation between intra - operative variables such as number of needles , radioisotope , number of seeds implanted , and the total source strength . similarly , our study found no appreciable correlation between number of needles and number of seeds . in another study , pre - implant prostate volumes were measured by trans - rectal ultrasound , and post - procedure prostate size was calculated by serial ct scans on days 1 , 8 , 30 , 90 , and 180 . their data showed that the majority of the edema resolved in the first week with very little volume decrease observed past day 30 . despite the differences in techniques used between this study and ours , the findings strongly support that the post - implant edema resolves within one month . sophisticated bio - mathematical models have been developed based on both edema resolution pattern and the half - life of the isotope used for treatment [ 1012 , 17 ] . these studies are based on dynamic changes in prostate volume and seed location during dose delivery . based on these models , the optimum timing of ct dosimetry ( to maintain the mean error below 5% ) for iodine-125 is 5 to 9 weeks post - implantation . did not recommend specific timing for ct dosimetry , but confirmed substantial improvement in prostate prescription dose coverage from 77% on day 1 to 85% on day 28 . tanaka et al . prospectively studied 74 patients undergoing i-125 prostate implant using ct / mri fusion ; dosimetry was performed on day 1 and day 30 . low quality implants from day 1 ( with v100 of<80% ) were associated with substantial edema which improved by day 30 . ohashi et al . compared intra - operative trus based dosimetry with actual day 1 and day 30 coverage and found no difference between intra - operative and day 30 target coverage . while this may eliminate the need for post - operative ct - based dosimetry in the future , a large proportion of centers have not yet adopted an intra - operative planning approach and , therefore , must continue to depend on post - implant ct - based dosimetry to evaluate the quality of their implants . in addition to the resolution pattern of prostate edema , we analyzed the effect of several variables on the extent of the swelling . in contrast to previous reports , we found that those patients who had monotherapy , low gleason score , and higher activity seeds experienced greater edema in the prostate gland ( p values=0.02 , 0.046 , 0.02 respectively ) . when brachytherapy is used as a boost to ebrt , lower activity seeds ( 0.3 mci ) patients who received lower activity seeds experienced on average 33% less swelling than patients in whom 0.5 mci seeds were used . these findings suggest that edema may not be simply a result of physical trauma to the gland , but may be affected by the radiation dose as well . further examination of seed strength as an independent variable may pose a challenge given its relationship to other factors . patients with a low gleason score and low risk overall receive monotherapy with high strength seeds ; as such , it is difficult to assess seed strength , gleason score , and monotherapy as individual factors . of note , we did not appreciate a generalized trend suggesting that the gleason score has an inverse relationship to the degree of edema . our data showed that only the group with gleason  6 who received high dose seeds had statistically greater edema ( p=0.046 ) . our study 's sample size does not provide the statistical power to fully validate these conclusions and may be strengthened on further patient accrual . also , the choice of ct imaging to monitor change in prostate volume as opposed to mri increases the likelihood of volume discrepancies . given the prevalence of ct in treatment planning and dosimetry calculations , it is important to explore areas of improvement in our current techniques . although we were able to eliminate inter - observer variability by having a single radiation oncologist contour all prostate volumes , we were unable to adequately address intra - observer variability , which could result in inaccurate prostate volumes . prostate dosimetry calculations can easily be underestimated when post - implant ct scans are performed prior to the resolution of prostate swelling . similar to previous studies , we found that edema frequently has an adverse effect on implant dosimetry . in the study by waterman et al . , edema affected post - implant dosimetry in seven of ten cases . in prestidge 's study , the prostate volume covered by the 80% isodose line increased from 85.6% on postoperative day 1 to 92.2% on day 180 ( 9 ) . in our study , patients had an average d90 of 83% on day 1 as compared to day 30 . while the discrepancy between the day 1 and day 30 dosimetry was significant , our method of estimating the day 30 dosimetry using a cf yielded values that were an approximation of the actual d90 . comparing our estimates to actual dosimetry revealed a non - significant ratio , supporting this approximation ( table 4 ) . while there is consensus that edema in the immediate post - operative period negatively affects prostate coverage , it is often desirable to perform ct shortly after the procedure . this allows for faster feedback , but may result in underestimation of the prostate dose . when it is not possible for a patient to return for a day 30 scan , d90day1 could be divided by a correction factor to more accurately reflect the quality of the implant . we found that maximum prostate size is observed in the immediate post - operative period , returning to the pre- implant volume by day 30 . there were several factors which we were able to identify as associated with greater prostate edema , namely low gleason (  6 ) score , higher seed activity (  4 mci ) , and monotherapy use . we found a significant difference between day 1 and day 30 dosimetry ; it was 83% on day 1 as compared to day 30 . this suggests that post - implant dosimetry should be obtained at least one month after implantation in order to obtain an accurate sense of implant quality . this could allow for resolution of swelling and avoids the consequential underestimation of gland coverage . in the event that such scheduling is not feasible , we found that day 30 dosimetry can be estimated by dividing d90day1 by a volume correction factor of 0.76 . further analysis of a larger cohort could validate a corrected d90 value that more accurately reflects dose to the prostate than using day 1 or day 9 ct - based dosimetry .
purposewe evaluated the post - operative pattern of prostate volume ( pv ) changes following prostate brachytherapy ( pb ) and analyzed variables which affect swelling.material and methodstwenty - nine patients treated with brachytherapy ( 14 ) or combined brachytherapy and external beam radiotherapy modality ( 15 ) underwent pre- and post - implant computed tomography ( ct ) . 
 prostate volume measurements were done on post - operative days 1 , 9 , 30 , and 60 . 
 an observer performed 139 prostate volume ( pv ) measurements . 
 we analyzed the influence of pre - implant pv , number of needles and insertion attempts , number and activity of seeds , gleason score , use of hormonal therapy and external beam radiation therapy on the extent of edema . 
 we computed a volume correction factor ( cf ) to account for dosimetric changes between day 1 and day 30 . using the calculated cf , the dose received by 90% ( d90 ) of the prostate on day 30 ( d90day30 ) 
 was obtained by dividing day 1 ( d90day1 ) by the cf.resultsthe mean pv recorded on post - operative day 1 was 67.7 cm3 , 18.8 cm3 greater than average pre - op value ( sd 15.6 cm3 ) . 
 swelling returned to pre - implant volume by day 30 . 
 seed activity , treatment modality , and gleason score were significant variables . 
 the calculated cf was 0.76 . 
 after assessment using the cf , the mean difference between estimated and actual d90day30 was not significant.conclusionswe observed maximum prostate size on post - operative day 1 , returning to pre - implant volume by day 30 . 
 this suggests that post - implant dosimetry should be obtained on or after post - operative day 30 . 
 if necessary , day 30 dosimetry can be estimated by dividing d90day1 by a correction factor of 0.76 .