Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

cExternal beam radiation results in minimal changes in post void residual urine volumes during... Background: To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer. Methods: 125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes. Results: The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment. Conclusion: Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes. Page 1 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 maintain a full or empty bladder during treatment may Introduction Increasingly sophisticated conformal radiotherapy deliv- influence the bladder and prostate interaction [9,11,18]. ery technologies and organ localization protocols have resulted in significant changes in treatment paradigms This body of research specifically addresses the influence offered to patients with clinically localized prostate can- of daily whole pelvic or prostate only daily radiation treat- cer. These technologies allow physicians to offer dose ments on weekly ultrasound determined post-void resid- escalations to the targets while respecting normal tissue ual (PVR) urine volumes in patients with clinically tolerances of surrounding organs [1-4]. Simultaneously, localized prostate cancer treated prone with an empty smaller treatment margins are employed to minimize side bladder. This analysis helps to provide insight into PVR effects and potential complications. As a result, the precise urine volume variations as patient's progress through evaluation of internal organ movement has become radiation treatments to determine if such changes are clin- extremely important to ensure optimal dose to the target ically significant. area. Three-dimensional conformal radiotherapy (3D- CRT) led to significant sparing of normal tissue by con- Methods One hundred and twenty five patients were treated for forming the dose to the prostate gland. As a result, 3D- CRT was the first modality to generate widespread con- clinical stage T1b-T3a (2002 AJCC) prostate cancer with cern about prostate gland motion during treatment. either definitive external beam radiation therapy to the Intensity modulated radiation therapy (IMRT) produces prostate only (n = 68) or to the whole pelvis followed by much steeper dose gradients than 3D-CRT and may result a prostate boost (n = 59) [19]. For patients with < 10% in tighter margins between the clinical target volume risk of pelvic lymph node involvement, the target volume (CTV) and the planning target volume (PTV). Internal consisted of the prostate gland and seminal vesicles with organ displacement of even a few millimeters may result margin [20]. For patients with > 10% risk of pelvic lymph in geographic miss of the target volume. Methods to mon- node involvement, the pelvic lymph nodes were included itor prostate motion have become increasingly important in the initial target volume. Intensity Modulated Radia- in the era of dose escalation. The use of computerized tion Therapy (IMRT) was utilized in all treatments. Patient tomography (CT) has been the gold standard for in vivo treated with prostate only radiation received 81 Gy. imaging as well as structure identification, and has been Patients who were treated with pelvic radiation received emphasized in numerous internal organ motion studies 45 Gy to the prostate and regional nodes followed by a 36 [5-9]. Although cone beam CT has been integrated into Gy boost to the prostate. linear accelerator systems, most CT studies are performed in a manner simulating treatment. For this reason, many All patients were irradiated in the prone position and institutions implant intraprostatic gold fiducial markers immobilized in a custom aquaplast hip-fix immobiliza- for identification on electronic portal imaging. This pro- tion device with an empty bladder and rectum at the time vides three dimensional information regarding prostate of simulation and treatment. Patients were instructed to position in relation to the treatment isocenter [10,11]. urinate immediately prior to initial CT simulation and Other technologies, such as the BAT ultrasound system daily during external beam radiation therapy. Patients and intraprostatic electromagnetic transponders are also were instructed to defecate prior to simulation and daily solutions to account for daily variations in prostate posi- radiation if the urge was felt. tioning [12,13]. At the time of CT simulation, PVR volumes were meas- Variables with the potential to influence prostate motion ured within 10 minutes of voiding by transabdominal are an important aspect of clinical research in the delivery ultrasonography (Bladder Scan BVI 3000, Diagnostic and treatment of prostate cancer. The two organs receiving Ultrasound, Brothel, Washington). PVR determinations the greatest scrutiny are the bladder and rectum secondary were obtained weekly throughout treatment. These values to the close proximity to the prostate gland. The literature were compared to the baseline PVR volume from the time demonstrates a robust relationship between the influence of simulation. PVR urine volumes determined by ultra- of rectal filling on prostate displacement, where as the sound were not compared to CT scan as previous investi- influence of the bladder is a little more controversial gators have determined there is a high degree of [6,7,9,14,15]. Researchers who have reported displace- correlation between bladder scanner volumes and Com- ment of the prostate by the bladder have typically demon- puted Tomography volumes and more importantly strated movement to be in the posterior and inferior weekly changes from baseline were measured by ultra- direction [6-8,10,16]. Conversely other researchers have sound and not computed tomography [18,21-23]. Previ- reported no or a minimal influence of bladder filling on ously published correlations for the BVI model 3000 prostate motion [5,9,15,17,18]. Techniques in patient range from 0.86–0.95 [21,23]. The bladder scanner is immobilization, treatment position and instructions to reported to operate within a margin of accuracy of ± 20 cc Page 2 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 in the range of 0 to 699 ml of urine volume. Accuracy of of PVR over time, various empirical regression functions the bladder scanner is reported by the manufacturer were tested for an optimum fit to the data, and either a or a logistic within the operator's manual and as based on scanning quadratic function, y = a + b * time + c * time -c * Time diagnostic ultrasound tissue equivalent phantoms [24]. regression function, y = a/1+ b * exp where y is either the PVR urine volume or the difference between the The BVI 3000 bladder scanner is a portable Ultrasound PVR urine volume and the baseline PVR urine volume, originally developed to measure residual urine volumes consistently outperformed linear regression by resulting after micturition. The scanning head is positioned on the in a larger correlation coefficient and therefore were used patient's body 2 cm above the pubic symphysis in a mid- uniformly throughout. line position. The bladder volume is calculated from a 2 MHz transducer which automatically rotates in 15 degree Results increments to provide a 3-dimensional model of the blad- Table 1 summarizes the clinical and treatment parameters der to estimate the urine volume. Two highly experienced of the study population, stratified by treatment cohort. nurses, specifically trained and competent in the use of The mean patient age was 73.9 ± 8.0 years with a mean the BVI 3000, performed all scans analyzed in this study. pre-treatment prostate volume of 53.3 ± 33.5 cubic cen- timeters, a mean PVR urine volume of 57.6 ± 77.3 cubic An alpha-blocker was initiated in 56 patients at a mean of centimeters. Patients treated with prostate only external 4.7 weeks ± 2.2 weeks into treatment. Alpha blockers were beam radiation therapy compared with patients treated initiated for urinary irritative or obstructive symptoms. with whole pelvic radiation therapy had statistically lower Alpha-blockers consisted of either tamsulosin hydrochlo- pre-treatment PSA (p = 0.011); lower Gleason Score (p < ride (0.4 – 0.8 mg daily) or terazosin hydrochloride (5–10 0.001); lower percent positive biopsies (p < 0.001; earlier mg daily). staged disease (p < 0.001); a lower incidence of perineural invasion (p = 0.001) and were less likely to have received One-way ANOVA, t-tests, and Fisher's exact chi-squared androgen deprivation therapy (ADT) (p < 0.001). No sta- were applied to the clinical and treatment parameters of tistical differences were demonstrated between the groups the two treatment cohorts (prostate only and pelvic radia- concerning patient age at treatment, prostate volume, tion patients). All data was analyzed using SPSS version post-void residual urine (PVR) volumes and the use of 14.0 software (SPSS, Inc., Chicago, IL). Statistical signifi- alpha-blockers during treatment. cance was set at a p < 0.05 for all analyses. In scatter plots Table 1: Clinical and treatment parameters of the study population stratified by treatment cohort. Continuous Variables Prostate only (n = 66) Pelvis (n = 59) All Patients (n = 125) Mean ± SD Median Mean ± SD Median p* Mean ± SD Median Age at treatment (years) 73.9 ± 7.8 75.5 73.9 ± 8.3 76.3 0.971 73.9 ± 8.0 75.8 Pre-treatment IPSS 10.9 ± 7.0 10.0 11.8 ± 8.3 11.5 0.526 11.3 ± 7.6 10.0 Pre-treatment PSA (ng/mL) 7.7 ± 5.3 6.5 29.6 ± 68.4 10.3 0.011 18.0 ± 48.0 7.3 Gleason Score 6.5 ± 0.7 6. 7.8 ± 1.2 8.0 < 0.001 7.1 ± 1.2 7.0 % positive biopsies 29.0 ± 23.7 18.5 62.3 ± 32.8 62.5 < 0.001 44.2 ± 32.6 33.3 Prostate volume (cm ) 54.8 ± 33.8 47.3 51.6 ± 33.2 42.0 0.597 53.3 ± 33.5 46.5 Post void residual (cc) 57.3 ± 67.0 30.0 58.0 ± 88.0 27.0 0.961 57.6 ± 77.3 28.0 BMI 27.8 ± 3.9 27.4 29.2 ± 5.0 28.5 0.950 28.4 ± 4.4 28.2 Categorical Variables Count (%) Count (%) p Count (%) Stage (median) T1b-T2b 65 (98.5) 46 (78.0) < 0.001 111 (88.8) ≥ T2c 1 (1.5) 13 (22.0) 14 (11.2) ADT none 55 (83.3) 19 (32.2) < 0.001 74 (59.2) ≤ 6 months 7 (10.6) 2 (3.4) 9 (7.2) > 6 months 4 (6.1) 38 (64.4) 42 (33.6) Diabetes 11 (16.9) 14 (23.7) 0.236 25 (20.0) Hypertension 43 (65.2) 39 (66.1) 0.531 82 (65.6) Alpha blocker 53 (80.3) 43 (72.9) 0.221 96 (76.8) Perineural invasion 13 (19.7) 28 (47.5) 0.001 41 (32.8) * p values calculated by one-way ANOVA ∀ p values determined by 2-sided Fisher's Exact Test Page 3 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 Of the 125 patients, 96 were exposed to alpha blockers a decrease from baseline measurements with the greatest during their treatment [Table 2, 3]. A total of 56 patients trend seen over the first three weeks of treatment. No sig- were placed on alpha blockers during treatment. Forty nificant differences were demonstrated concerning the patients were actively treated with alpha-blockers prior to magnitude of change from baseline PVR urine volumes radiation. Thirty patients were started on alpha blockers at when comparing pelvic radiation to prostate only radia- a mean of 4.70 ± 2.2 weeks in the prostate only group and tion. twenty-six patients initiated alpha-blockers at a mean of 4.7 ± 2.4 weeks in the pelvic radiation group (p = 0.941) Larger baseline PVR allows for a greater absolute volume [Table 2]. changes as radiation induced bladder irritability increases, therefore patients were stratified into two groups based on Table 3 summarizes the variation in PVR urine volume initial PVR. A cut-off of 40 cc was chosen as previous stud- readings over the course of the study, stratified by therapy ies have demonstrated that bladder volumes greater than cohort, alpha-blocker use, baseline PVR volume group 40 cc in addition to rectal filling had the potential to influ- and radiation cohort. Of the 125 patients included for ence daily prostate position while treated in the prone analysis, 66 patients were treated with prostate only radi- position [9]. Figure 2 shows the distribution of PVR ation and 59 patients were treated with whole pelvic radi- cohort by week and is stratified by pre-treatment PVR ≤ 40 ation therapy followed by a prostate boost. Seventy-six or > 40 cc. Patients were defined as having a worse PVR if patients had a PVR urine volume at the time of simulation they moved from a lower PVR category (≤ 40 cc) to the measured to be less than or equal to 40 cc. Forty-nine higher category (> 40 cc), while patients in the higher cat- patients had PVR urine volumes greater than 40 cc. For the egory who moved to a lower category were defined as bet- overall population, the mean PVR urine volume over the ter. During subsequent points in time, only a small entire course of radiation treatment was 48.2 cc. The mean fraction of patients with an initial PVR ≤ 40 cc exceeded 40 individual PVR urine volume over all weeks of the study cc, while patients with an initial PVR > 40 cc had a high for patients with a baseline PVR > 40 cc was 86.9 cc verses probability of a subsequent PVR < 40 cc. in comparison to 23.2 cc in the patient group with base- line PVR ≤ 40 cc (p < 0.001). No significant difference was Figure 3 graphically demonstrates the mean PVR urine found between the mean individual PVR urine volume volumes by week of radiation treatment for both prostate over all weeks of treatment in patients treated with pros- only and pelvic radiation patients to two standard devia- tate only versus pelvic radiation with values of 46.3 cc and tions. Over two standard deviations the mean PVR 50.2 cc, respectively (p = 0.725). reported are similar between the two groups albeit varia- ble due to the intrinsic accuracy of ± 20 cc of the bladder Figure 1a demonstrates that the mean PVR urine volume scanner. The radiation field utilized did not appear to between the two treatment cohorts were not significantly greatly influence the mean PVR compared to one another. different from each other (p = 0.664) over the duration of therapy. The mean PVR urine volumes demonstrated the Figure 4a graphically represents the mean PVR urine vol- greatest decreased over the first three weeks in both pros- umes versus weeks of radiation treatment, stratified by tate only and pelvic radiation groups, although became treatment group and baseline PVR urine volumes ≤40 or variable with time and demonstrated an increase towards >40 cc. The greatest changes over time in mean PVR were the end of therapy back to baseline measurements. The demonstrated in both treatment cohorts with base line magnitude of difference is less than 20 cc in both cohorts, volumes greater than 40 cc. As demonstrated in previous which are at the limit of accuracy of the bladder scanner. graphs the greatest and most consistent change is over the Figure 1b graphs the mean difference in baseline PVR first three weeks of treatment. Very little change in the urine volumes as a function of weeks of external beam mean PVR is demonstrated in the group of patients treated radiation therapy. Both cohorts of patients demonstrated with prostate only radiation with baseline PVR urine vol- Table 2: Week of alpha-blocker initiation relative to start of external beam therapy, stratified by radiation cohort. XRT Therapy Cohort Number. of patients* Alpha-blocker Initiated (weeks) p Mean ± SD Median Prostate Only 30 4.7 ± 2.2 4.5 0.941 Pelvis 26 4.7 ± 2.4 4.5 Overall 56 4.7 ± 2.3 4.5 * – Does not include patients who started alpha-blockers prior to treatment. p-value determined by one-way ANOVA Page 4 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 Table 3: Variation in individual post-void residual (PVR) volume readings over the course of the study, stratified by therapy cohort, alpha-blocker use, baseline PVR volume group, and radiation cohort. Parameter Group Number of patients Mean of N weeks of PVR p-value Mean Std. Dev. of N PVR p-value readings readings Mean ± SD Mean ± SD Alpha-blocker use No 29 26.5 ± 29.3 0.027 22.3 ± 18.8 0.011 Yes 96 54.7 ± 65.6 35.7 ± 36.9 Baseline PVR volume ≤ 40 cc 76 23.2 ± 31.7 < 0.001 23.4 ± 32.7 <0.001 > 40 cc 49 86.9 ± 72.7 46.7 ± 31.4 Radiation cohort Prostate only 66 46.3 ± 55.4 0.725 29.7 ± 21.6 0.317 Pelvis 59 50.2 ± 65.6 35.8 ± 43.9 Overall population 125 48.2 ± 60.2 32.5 ± 34.0 * The median number N of PVR readings was 10. p-values were calculated by independent samples t-test. umes less than or equal to 40 cc. The same is demon- should influence the prostate's position to a lesser degree strated in the pelvic radiation group with slightly greater as previously reported by Zelefsky et al [9]. Although PVR variability, although within the limits of the bladder scan- urine volumes were recently explored in cervical cancer ner. Figure 4b graphically represents the mean difference treatments, little data is available concerning PVR urine from baseline PVR urine volumes versus weeks of radia- volumes as patients progress through external beam radi- tion treatment, stratified by treatment group and baseline ation therapy for prostate cancer treated with an empty PVR urine volumes <40 or >40 cc. The data continues to bladder and in a prone position [22]. Posterior and infe- demonstrate very little change in PVR volumes over time rior movement of the prostate gland due to bladder filling for both treatment cohorts when baseline PVR urine vol- was first described by Ten Haken and colleagues, and umes are less than or equal to 40 cc. Both cohorts of reproduced by several investigators in subsequent studies patients continue to demonstrate greater differences in [6-8,10]. Melian et al. have reported that bladder filling mean PVR urine volumes from baseline over time in influenced the position of the prostate in patients treated patients with baseline urine volumes greater than 40 cc. in the prone position[8]. Zelefsky et al. also demonstrated The mean differences from baseline are greater in the less that bladder volumes greater than 40 cm could predict than or equal to 40 cc group in both treatment cohorts for greater than 3 mm deviations of the prostate and sem- and the converse is found in the greater than 40 cc group. inal vesicles while in the prone treatment position when the rectal volume is greater than 60 cc [9]. Zellars et al. Discussion reported that patients who were treated in the supine posi- In an era which is rapidly becoming defined by increas- tion and instructed to have a full bladder prior to treat- ingly sophisticated treatment planning and radiation ment demonstrated an associated posterior displacement delivery techniques, the basic tenant of irradiating what is of the prostate when evaluated 4 to 5 weeks after initiation intended to be treated while respecting normal tissue tol- of therapy [7]. Conversely, other researchers have not seen erance has never been more important. To achieve these a relationship between bladder filling and prostate posi- goals it is necessary to treat a dynamic and moving target, tion, although these patients were treated in the supine which is exemplified in prostate radiotherapy [14,25]. treatment position [5,15,17]. With dose escalation, strategies must be refined to decrease prostate treatment margins to minimize toxicity Bladder filling is more easily controlled on a daily basis to normal structures. Therefore, an investigation of all fac- than rectal filling, assuming that the patient voids imme- tors with the potential to influence prostate motion is crit- diately prior to treatment. This strategy is simple and ical. The bladder and rectum are regarded as the two most should help to remove the potential influence of the blad- important structures in terms of daily prostate motion. der on prostate motion. This paper specifically reports the This study details the post void residual urine volume influence of external beam radiation therapy on serial prior to daily radiation treatments and the influence of PVR urine volumes as patients proceed through treatment. external beam radiation therapy on PVR urine volumes Several strategies currently exist for daily image guidance throughout treatment. for prostate treatment, therefore the purpose of this paper is not to correlate specific PVR urine volumes with pros- If a patient is asked to empty his bladder prior to simula- tate motion, but rather determine the influence of exter- tion and then prior to radiation treatment, bladder filling nal beam radiation therapy on PVR urine volumes as Page 5 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 Distribu treatment post-void residual volume Figure 2 tion of PVR cohort by week and stratified by pre- Distribution of PVR cohort by week and stratified by pre-treatment post-void residual volume. Patients moving from the lower PVR category (≤ 50 cc) to the higher category (> 50 cc) were labeled as worse, while patients in the higher category who moved to the lower were labeled as better. The number of patients in each baseline category var- ies over time based upon treatment length. to prostate motion from the original planning CT simula- tion. Our study population consisted of patients treated with external beam radiation for prostate cancer. Two common types of radiation treatments were studied, pelvic radia- tion followed by a cone down to the prostate and prostate only radiation. As such the effects of PVR urine volumes could be compared in patients receiving whole pelvic radiation therapy for a portion of their treatment com- pared to prostate only radiation therapy. These two (A). Me externa b Figure 1 y radiation gr an l beam post-voi radiation thera oup d residual vol py (XRT) treatment, stratified ume as a function of week of cohorts provide insight in the potential for PVR urine vol- (A). Mean post-void residual volume as a function of ume changes in the most common clinical scenarios for week of external beam radiation therapy (XRT) definitive external radiation therapy for prostate. Patients treatment, stratified by radiation group. The bladder scanner operates within a margin of accuracy of ± 20 cc. (B) in the whole pelvic cohort had larger portions of their Mean difference from baseline in post-void residual (PVR) bladder irradiated and presumably had the potential for a volume as a function of week of external beam radiation greater degree of radiation induced bladder irritation. therapy (XRT) treatment, stratified by radiation group. The best-fit lines were determined by quadratic regression analy- There were significant differences in the clinical presenta- sis. The bladder scanner operates within a margin of accuracy tion between the two cohorts of patients within the two of ± 20 cc. radiation groups. These differences are attributable to our selection criteria. Importantly, these two groups of patients allowed us to study different treatment strategies, patients proceed through treatment [25]. If PVR urine vol- depending on risk of lymph node involvement, on PVR umes remain relatively stable throughout external beam urine volumes as patients progressed through external radiation treatment than there would be little correlation beam radiation treatment for prostate cancer. Patients Page 6 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 Pl versus week (base Figure 3 ot o line f mea ) pos n po of XRT treatment, t-vst- oid v oi re d re sidual sidu vol al volume ± u stratified by pre-treatment me 2 standard error Plot of mean post-void residual volume ± 2 standard error versus week of XRT treatment, stratified by pre-treatment (baseline) post-void residual volume. The number of patients in each baseline category varies over time based upon treatment length. treated with prostate only radiation were determined to have lower pre-treatment PSA, lower percent positive biopsies, lower Gleason Scores and clinical stage than patients treated with pelvic radiation. This finding is expected as higher PSA, Gleason Score and clinical stage predicts for a greater probability of lymph node involve- ment [20]. Our policy was to treat lymph nodes if the risk of involvement was greater than 10%. ( XRT treatment, stratified by ment (basel Figure 4 A) Plot of mean ine) post-voi post-voi d residual vo d resi treatmen dual vol lume t group and ume versus week pre-treat- of The mean individual PVR urine volume over all weeks of (A) Plot of mean post-void residual volume versus treatment in the pelvic and prostate radiation groups was week of XRT treatment, stratified by treatment not statistically different with values of 46.3 cc and 50.2 cc group and pre-treatment (baseline) post-void resid- respectively. However, mean PVR urine volumes stratified ual volume. The number of patients in each baseline cate- by week in both groups demonstrated the patients treated gory varies over time based upon treatment length. (B) Plot with whole pelvic radiation had larger baseline PVR urine of mean difference from baseline in post-void residual vol- ume versus week of XRT treatment, stratified by treatment volumes at the beginning of treatment. Larger baseline group and pre-treatment (baseline) post-void residual vol- PVR theoretically would allows for greater absolute vol- ume. The number of patients in each baseline category varies ume changes as radiation induced bladder irritability over time based upon treatment length. increased. Although higher baseline mean PVR urine vol- umes predicted for greater mean PVR urine volumes dur- ing treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of the greatest change during the first three weeks of treat- accuracy of the bladder scanner. Such small differences are ment and then became well within the limits of accuracy unlikely to result in any clinical significance in prostate of the bladder scanner. It is likely that patient attention to motion. Also of interest is that the difference from base- detail (i.e. bladder emptying) accounted for the changes line PVR urine volumes in both cohorts appeared to have during the first three weeks of treatment. As such, it is Page 7 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 probable that PVR volume determinations early in the References 1. Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Venkat- course of treatment may be sufficient with subsequent ramen ES, Reuter VE, Fair WR, Ling CC, Fuks Z: Dose escalation weekly determinations omitted. with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 1998, 41:491-500. Previous research by Zelefsky's group has demonstrated 2. Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, that bladder volumes greater than 40 cc had the potential Lee AK, Pollack A: Long-term results of the M.D. Anderson randomized dose-escalation trial for prostate cancer. Int J to influence daily prostate position while treated in the Radiat Oncol Biol Phys 2008, 70:67-74. prone position when rectal filling was greater than 60 cc 3. Pollack A, Zagars GK, Smith LG, Lee JJ, von Eschenbach AC, Antolak [9]. As such patients were stratified by radiation treatment JA, Starkschall G, Rosen I: Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 group and a baseline PVR cutoff of 40 cc. Patients with a Gy for prostate cancer. J Clin Oncol 2000, 18:3904-3911. baseline PVR = 40 cc did not experience any appreciable 4. Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams change in PVR during treatment while patients with a JA, Shipley WU: Comparison of conventional-dose vs high- dose conformal radiation therapy in clinically localized ade- baseline PVR > 40 cc were most likely to experience nocarcinoma of the prostate: A randomized controlled trial. changes (i.e. decrease) from the baseline PVR. This JAMA 2005, 294:1233-1239. 5. Pinkawa M, Asadpour B, Gagel B, Piroth MD, Holy R, Eble MJ: Pros- marked decline could result in a smaller degree of prostate tate position variability and dose-volume histograms in radi- motion but also in the setup being different from what otherapy for prostate cancer with full and empty bladders. was initially simulated. Although, patients who are iden- Int J Radiat Oncol Biol Phys 2006, 64:856-861. 6. Schild SE, Casale HE, Bellefontaine LP: Movement of the prostate tified with a higher PVR urine volume at the time of sim- due to rectal and bladder distention: implications for radio- ulation may require attention to bladder filling depending therapy. Med Dosim 1993, 18:13-15. on the technologies of daily prostate localization 7. Zellars RC, Roberson PL, Strawderman M, Zhang D, Sandler HM, Ten Haken RK, Osher D, McLaughlin PW: Prostate position late in employed. A shortcoming of our study is that patients the course of external beam therapy: patterns and predic- with substantial decreases in serial PVR's were not re- tors. Int J Radiat Oncol Biol Phys 2000, 47:655-660. 8. Melian E, Mageras GS, Fuks Z: Variation in prostate position planned via CT simulation (all patients however were quantitation and implications for three-dimensional confor- treated with daily cone beam CT guidance). mal treatment planning. Int J Radiat Oncol Biol Phys 1997, 38:73-81. 9. Zelefsky MJ, Crean D, Mageras GS, Lyass O, Happersett L, Ling CC, On average, alpha-blockers were prescribed 4.7 weeks Leíble SA, Fuks Z, Bull S, Koov HM, van Herk M, Kutcher GJ: Quan- into treatment. Alpha-blockers were not demonstrated to tification and predictors of prostate position variability in 50 influence PVR in either treatment cohort. This, however, is patients evaluated with multiple CT scans during conformal radiotherapy. Radiother Oncol 1999, 50:225-234. not surprising since the vast majority of changes in PVR 10. Crook JM, Raymond Y, Salhani D, Yan H, Esche B: Prostate motion occurred in the first three weeks or therapy. Alpha-block- during standard radiotherapy as assessed by fiducial mark- ers. Radiother Oncol 1995, 37:35-42. ers were initiated primarily for irritative symptoms. 11. Bayley AJ, Catton CN, Haycocks T, Kelly V, Alasti H, Bristow R, Cat- ton P, Crook J, Gospodarowicz MK, McLean M, Milosevic M, Warde P: A randomized trial of supine vsprone positioning in Conclusion patients undergoing escalated dose conformal radiotherapy External beam radiation therapy results in a clinically for prostate cancer. Radiother Oncol 2004, 70:37-44. insignificant change in weekly post-void residual urine 12. Lattanzi J, McNeeley S, Pinover W, Horwitz E, Das I, Schultheiss TE, Hanks GE: A comparison of daily CT localization to a daily volumes (especially when PVR urine volumes are less than ultrasound-based system in prostate cancer. Int J Radiat Oncol 40 cc), suggesting that radiation induced bladder irritabil- Biol Phys 1999, 43:719-725. ity does not substantially influence bladder residual urine 13. Balter JM, Wright JN, Newell LJ, Friemel B, Dimmer S, Cheng Y, Wong J, Vertatschitsch E, Mate TP: Accuracy of a wireless locali- volumes. zation system for radiotherapy. Int J Radiat Oncol Biol Phys 2005, 61:933-937. 14. Ghilezan MJ, Jaffray DA, Siewerdsen JH, Van Herk M, Shetty A, Sharpe Competing interests MB, Zafar Jafri S, Vicini FA, Matter RC, Brabbins DS, Martinez AA: The authors declare that they have no competing interests. Prostate gland motion assessed with cine-magnetic reso- nance imaging (cine-MRI). Int J Radiat Oncol Biol Phys 2005, 62:406-417. Authors' contributions 15. Antolak JA, Rosen II, Childress CH, Zagars GK, Pollack A: Prostate PFO has done statistical analysis as well as drafted the target volume variation during a course of radiotherapy. Int manuscript. GSM has made the selection of patients, J Radiat Oncol Biol Phys 1998, 42:661-672. 16. Ten Haken RK, Forman JD, Heimburger DK, Gerhardsson A, McShan involved with the study design, has been involved with DL, Perez-Tamayo C, Schoeppel SL, Lichter AS: Treatment plan- writing and revising the manuscript, statistical analysis ning issues related to prostate movement in response to dif- ferential filling of the rectum and bladder. Int J Radiat Oncol Biol and final approval of the version to be published. ZAA has Phys 1991, 20:1314-1324. been involved with the statistical analysis and design of 17. Beard CJ, Kijewski P, Bussiere M, Gelman R, Gladstone D, Shaffer K, the tables/figures. WMB has been involved with the statis- Plunkett M, Castello P, Coleman CN: Analysis of prostate and seminal vesicle motion: Implications for treatment planning. tical analysis. KEW has been involved in manuscript revi- Int J Radiat Oncol Biol Phys 1996, 34:451-458. sion and review of the intellectual content. BSK has been 18. Stam MR, Th. Van Lin EN, Vight LP Van Der, Kaanders JH, Visser AG: involved with statistical analysis. RWG has been involved Bladder filling variations during radiation treatment of pros- tate cancer: Can the use of a bladder ultrasound scanner and with statistical analysis and design of the tables/figures. biofeedback optimize bladder filling? Int J Radiat Oncol Biol Phys All authors read and approved the final manuscript. 2006, 65:371-377. Page 8 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 19. Greene FL, Balch CM, Fleming I, Fritz A, Haller DG, Morrow M, Page DL: AJCC Cancer Staging Manual 6th edition. Springer-Verlag New York, LLC; 2002. 20. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD: Contemporary update of prostate cancer staging nomo- grams (Partin Tables) for the new millennium. Urology 2001, 58:843-848. 21. O'Doherty UM, McNair HA, Norman AR, Miles E, Hooper S, Davies M, Lincoln N, Balyckvi J, Childs P, Dearnaley DP, Huddart RA: Vari- ability of bladder filling in patients receiving radical radio- therapy to the prostate. Radiotherapy and Oncology 2006, 79:335-340. 22. Ahmad R, Hoogeman MS, Quint S, Mens JW, de Pree I, Heijmen BJ: Inter-fraction bladder filling variations and time trends for cervical cancer patients assessed with a portable 3-dimen- sional ultrasound bladder scanner. Radiotherapy and Oncology 2008, 89:172-179. 23. Byun SS, Kim HH, Lee E, Paick JS, Kamg W, Oh SJ: Accuracy of bladder volume determinations by ultrasonography: Are they accurate over the entire bladder volume range? Urology 2003, 62:656-660. 24. BladderScan BVI 3000 Noninvasive Bladder Volume Instru- ment Operator's Manual. C 2004 by Diagnostic Ultrasound Corpo- ration . 25. Kupelian PA, Langen KM, Willoughby TR, Zeidan OA, Meeks SL: Image-guided radiotherapy for localized prostate cancer: Treating a moving target. Semin Radiat Oncol 2008, 18:58-66. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 9 of 9 (page number not for citation purposes) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Oncology Springer Journals

cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

Download PDF
9 pages

Loading next page...
 
/lp/springer-journals/cexternal-beam-radiation-results-in-minimal-changes-in-post-void-FtPi3to2AC

References (26)

Publisher
Springer Journals
Copyright
Copyright © 2009 by Orio et al; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Oncology; Radiotherapy
eISSN
1748-717X
DOI
10.1186/1748-717X-4-26
pmid
19624852
Publisher site
See Article on Publisher Site

Abstract

Background: To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer. Methods: 125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes. Results: The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment. Conclusion: Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes. Page 1 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 maintain a full or empty bladder during treatment may Introduction Increasingly sophisticated conformal radiotherapy deliv- influence the bladder and prostate interaction [9,11,18]. ery technologies and organ localization protocols have resulted in significant changes in treatment paradigms This body of research specifically addresses the influence offered to patients with clinically localized prostate can- of daily whole pelvic or prostate only daily radiation treat- cer. These technologies allow physicians to offer dose ments on weekly ultrasound determined post-void resid- escalations to the targets while respecting normal tissue ual (PVR) urine volumes in patients with clinically tolerances of surrounding organs [1-4]. Simultaneously, localized prostate cancer treated prone with an empty smaller treatment margins are employed to minimize side bladder. This analysis helps to provide insight into PVR effects and potential complications. As a result, the precise urine volume variations as patient's progress through evaluation of internal organ movement has become radiation treatments to determine if such changes are clin- extremely important to ensure optimal dose to the target ically significant. area. Three-dimensional conformal radiotherapy (3D- CRT) led to significant sparing of normal tissue by con- Methods One hundred and twenty five patients were treated for forming the dose to the prostate gland. As a result, 3D- CRT was the first modality to generate widespread con- clinical stage T1b-T3a (2002 AJCC) prostate cancer with cern about prostate gland motion during treatment. either definitive external beam radiation therapy to the Intensity modulated radiation therapy (IMRT) produces prostate only (n = 68) or to the whole pelvis followed by much steeper dose gradients than 3D-CRT and may result a prostate boost (n = 59) [19]. For patients with < 10% in tighter margins between the clinical target volume risk of pelvic lymph node involvement, the target volume (CTV) and the planning target volume (PTV). Internal consisted of the prostate gland and seminal vesicles with organ displacement of even a few millimeters may result margin [20]. For patients with > 10% risk of pelvic lymph in geographic miss of the target volume. Methods to mon- node involvement, the pelvic lymph nodes were included itor prostate motion have become increasingly important in the initial target volume. Intensity Modulated Radia- in the era of dose escalation. The use of computerized tion Therapy (IMRT) was utilized in all treatments. Patient tomography (CT) has been the gold standard for in vivo treated with prostate only radiation received 81 Gy. imaging as well as structure identification, and has been Patients who were treated with pelvic radiation received emphasized in numerous internal organ motion studies 45 Gy to the prostate and regional nodes followed by a 36 [5-9]. Although cone beam CT has been integrated into Gy boost to the prostate. linear accelerator systems, most CT studies are performed in a manner simulating treatment. For this reason, many All patients were irradiated in the prone position and institutions implant intraprostatic gold fiducial markers immobilized in a custom aquaplast hip-fix immobiliza- for identification on electronic portal imaging. This pro- tion device with an empty bladder and rectum at the time vides three dimensional information regarding prostate of simulation and treatment. Patients were instructed to position in relation to the treatment isocenter [10,11]. urinate immediately prior to initial CT simulation and Other technologies, such as the BAT ultrasound system daily during external beam radiation therapy. Patients and intraprostatic electromagnetic transponders are also were instructed to defecate prior to simulation and daily solutions to account for daily variations in prostate posi- radiation if the urge was felt. tioning [12,13]. At the time of CT simulation, PVR volumes were meas- Variables with the potential to influence prostate motion ured within 10 minutes of voiding by transabdominal are an important aspect of clinical research in the delivery ultrasonography (Bladder Scan BVI 3000, Diagnostic and treatment of prostate cancer. The two organs receiving Ultrasound, Brothel, Washington). PVR determinations the greatest scrutiny are the bladder and rectum secondary were obtained weekly throughout treatment. These values to the close proximity to the prostate gland. The literature were compared to the baseline PVR volume from the time demonstrates a robust relationship between the influence of simulation. PVR urine volumes determined by ultra- of rectal filling on prostate displacement, where as the sound were not compared to CT scan as previous investi- influence of the bladder is a little more controversial gators have determined there is a high degree of [6,7,9,14,15]. Researchers who have reported displace- correlation between bladder scanner volumes and Com- ment of the prostate by the bladder have typically demon- puted Tomography volumes and more importantly strated movement to be in the posterior and inferior weekly changes from baseline were measured by ultra- direction [6-8,10,16]. Conversely other researchers have sound and not computed tomography [18,21-23]. Previ- reported no or a minimal influence of bladder filling on ously published correlations for the BVI model 3000 prostate motion [5,9,15,17,18]. Techniques in patient range from 0.86–0.95 [21,23]. The bladder scanner is immobilization, treatment position and instructions to reported to operate within a margin of accuracy of ± 20 cc Page 2 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 in the range of 0 to 699 ml of urine volume. Accuracy of of PVR over time, various empirical regression functions the bladder scanner is reported by the manufacturer were tested for an optimum fit to the data, and either a or a logistic within the operator's manual and as based on scanning quadratic function, y = a + b * time + c * time -c * Time diagnostic ultrasound tissue equivalent phantoms [24]. regression function, y = a/1+ b * exp where y is either the PVR urine volume or the difference between the The BVI 3000 bladder scanner is a portable Ultrasound PVR urine volume and the baseline PVR urine volume, originally developed to measure residual urine volumes consistently outperformed linear regression by resulting after micturition. The scanning head is positioned on the in a larger correlation coefficient and therefore were used patient's body 2 cm above the pubic symphysis in a mid- uniformly throughout. line position. The bladder volume is calculated from a 2 MHz transducer which automatically rotates in 15 degree Results increments to provide a 3-dimensional model of the blad- Table 1 summarizes the clinical and treatment parameters der to estimate the urine volume. Two highly experienced of the study population, stratified by treatment cohort. nurses, specifically trained and competent in the use of The mean patient age was 73.9 ± 8.0 years with a mean the BVI 3000, performed all scans analyzed in this study. pre-treatment prostate volume of 53.3 ± 33.5 cubic cen- timeters, a mean PVR urine volume of 57.6 ± 77.3 cubic An alpha-blocker was initiated in 56 patients at a mean of centimeters. Patients treated with prostate only external 4.7 weeks ± 2.2 weeks into treatment. Alpha blockers were beam radiation therapy compared with patients treated initiated for urinary irritative or obstructive symptoms. with whole pelvic radiation therapy had statistically lower Alpha-blockers consisted of either tamsulosin hydrochlo- pre-treatment PSA (p = 0.011); lower Gleason Score (p < ride (0.4 – 0.8 mg daily) or terazosin hydrochloride (5–10 0.001); lower percent positive biopsies (p < 0.001; earlier mg daily). staged disease (p < 0.001); a lower incidence of perineural invasion (p = 0.001) and were less likely to have received One-way ANOVA, t-tests, and Fisher's exact chi-squared androgen deprivation therapy (ADT) (p < 0.001). No sta- were applied to the clinical and treatment parameters of tistical differences were demonstrated between the groups the two treatment cohorts (prostate only and pelvic radia- concerning patient age at treatment, prostate volume, tion patients). All data was analyzed using SPSS version post-void residual urine (PVR) volumes and the use of 14.0 software (SPSS, Inc., Chicago, IL). Statistical signifi- alpha-blockers during treatment. cance was set at a p < 0.05 for all analyses. In scatter plots Table 1: Clinical and treatment parameters of the study population stratified by treatment cohort. Continuous Variables Prostate only (n = 66) Pelvis (n = 59) All Patients (n = 125) Mean ± SD Median Mean ± SD Median p* Mean ± SD Median Age at treatment (years) 73.9 ± 7.8 75.5 73.9 ± 8.3 76.3 0.971 73.9 ± 8.0 75.8 Pre-treatment IPSS 10.9 ± 7.0 10.0 11.8 ± 8.3 11.5 0.526 11.3 ± 7.6 10.0 Pre-treatment PSA (ng/mL) 7.7 ± 5.3 6.5 29.6 ± 68.4 10.3 0.011 18.0 ± 48.0 7.3 Gleason Score 6.5 ± 0.7 6. 7.8 ± 1.2 8.0 < 0.001 7.1 ± 1.2 7.0 % positive biopsies 29.0 ± 23.7 18.5 62.3 ± 32.8 62.5 < 0.001 44.2 ± 32.6 33.3 Prostate volume (cm ) 54.8 ± 33.8 47.3 51.6 ± 33.2 42.0 0.597 53.3 ± 33.5 46.5 Post void residual (cc) 57.3 ± 67.0 30.0 58.0 ± 88.0 27.0 0.961 57.6 ± 77.3 28.0 BMI 27.8 ± 3.9 27.4 29.2 ± 5.0 28.5 0.950 28.4 ± 4.4 28.2 Categorical Variables Count (%) Count (%) p Count (%) Stage (median) T1b-T2b 65 (98.5) 46 (78.0) < 0.001 111 (88.8) ≥ T2c 1 (1.5) 13 (22.0) 14 (11.2) ADT none 55 (83.3) 19 (32.2) < 0.001 74 (59.2) ≤ 6 months 7 (10.6) 2 (3.4) 9 (7.2) > 6 months 4 (6.1) 38 (64.4) 42 (33.6) Diabetes 11 (16.9) 14 (23.7) 0.236 25 (20.0) Hypertension 43 (65.2) 39 (66.1) 0.531 82 (65.6) Alpha blocker 53 (80.3) 43 (72.9) 0.221 96 (76.8) Perineural invasion 13 (19.7) 28 (47.5) 0.001 41 (32.8) * p values calculated by one-way ANOVA ∀ p values determined by 2-sided Fisher's Exact Test Page 3 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 Of the 125 patients, 96 were exposed to alpha blockers a decrease from baseline measurements with the greatest during their treatment [Table 2, 3]. A total of 56 patients trend seen over the first three weeks of treatment. No sig- were placed on alpha blockers during treatment. Forty nificant differences were demonstrated concerning the patients were actively treated with alpha-blockers prior to magnitude of change from baseline PVR urine volumes radiation. Thirty patients were started on alpha blockers at when comparing pelvic radiation to prostate only radia- a mean of 4.70 ± 2.2 weeks in the prostate only group and tion. twenty-six patients initiated alpha-blockers at a mean of 4.7 ± 2.4 weeks in the pelvic radiation group (p = 0.941) Larger baseline PVR allows for a greater absolute volume [Table 2]. changes as radiation induced bladder irritability increases, therefore patients were stratified into two groups based on Table 3 summarizes the variation in PVR urine volume initial PVR. A cut-off of 40 cc was chosen as previous stud- readings over the course of the study, stratified by therapy ies have demonstrated that bladder volumes greater than cohort, alpha-blocker use, baseline PVR volume group 40 cc in addition to rectal filling had the potential to influ- and radiation cohort. Of the 125 patients included for ence daily prostate position while treated in the prone analysis, 66 patients were treated with prostate only radi- position [9]. Figure 2 shows the distribution of PVR ation and 59 patients were treated with whole pelvic radi- cohort by week and is stratified by pre-treatment PVR ≤ 40 ation therapy followed by a prostate boost. Seventy-six or > 40 cc. Patients were defined as having a worse PVR if patients had a PVR urine volume at the time of simulation they moved from a lower PVR category (≤ 40 cc) to the measured to be less than or equal to 40 cc. Forty-nine higher category (> 40 cc), while patients in the higher cat- patients had PVR urine volumes greater than 40 cc. For the egory who moved to a lower category were defined as bet- overall population, the mean PVR urine volume over the ter. During subsequent points in time, only a small entire course of radiation treatment was 48.2 cc. The mean fraction of patients with an initial PVR ≤ 40 cc exceeded 40 individual PVR urine volume over all weeks of the study cc, while patients with an initial PVR > 40 cc had a high for patients with a baseline PVR > 40 cc was 86.9 cc verses probability of a subsequent PVR < 40 cc. in comparison to 23.2 cc in the patient group with base- line PVR ≤ 40 cc (p < 0.001). No significant difference was Figure 3 graphically demonstrates the mean PVR urine found between the mean individual PVR urine volume volumes by week of radiation treatment for both prostate over all weeks of treatment in patients treated with pros- only and pelvic radiation patients to two standard devia- tate only versus pelvic radiation with values of 46.3 cc and tions. Over two standard deviations the mean PVR 50.2 cc, respectively (p = 0.725). reported are similar between the two groups albeit varia- ble due to the intrinsic accuracy of ± 20 cc of the bladder Figure 1a demonstrates that the mean PVR urine volume scanner. The radiation field utilized did not appear to between the two treatment cohorts were not significantly greatly influence the mean PVR compared to one another. different from each other (p = 0.664) over the duration of therapy. The mean PVR urine volumes demonstrated the Figure 4a graphically represents the mean PVR urine vol- greatest decreased over the first three weeks in both pros- umes versus weeks of radiation treatment, stratified by tate only and pelvic radiation groups, although became treatment group and baseline PVR urine volumes ≤40 or variable with time and demonstrated an increase towards >40 cc. The greatest changes over time in mean PVR were the end of therapy back to baseline measurements. The demonstrated in both treatment cohorts with base line magnitude of difference is less than 20 cc in both cohorts, volumes greater than 40 cc. As demonstrated in previous which are at the limit of accuracy of the bladder scanner. graphs the greatest and most consistent change is over the Figure 1b graphs the mean difference in baseline PVR first three weeks of treatment. Very little change in the urine volumes as a function of weeks of external beam mean PVR is demonstrated in the group of patients treated radiation therapy. Both cohorts of patients demonstrated with prostate only radiation with baseline PVR urine vol- Table 2: Week of alpha-blocker initiation relative to start of external beam therapy, stratified by radiation cohort. XRT Therapy Cohort Number. of patients* Alpha-blocker Initiated (weeks) p Mean ± SD Median Prostate Only 30 4.7 ± 2.2 4.5 0.941 Pelvis 26 4.7 ± 2.4 4.5 Overall 56 4.7 ± 2.3 4.5 * – Does not include patients who started alpha-blockers prior to treatment. p-value determined by one-way ANOVA Page 4 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 Table 3: Variation in individual post-void residual (PVR) volume readings over the course of the study, stratified by therapy cohort, alpha-blocker use, baseline PVR volume group, and radiation cohort. Parameter Group Number of patients Mean of N weeks of PVR p-value Mean Std. Dev. of N PVR p-value readings readings Mean ± SD Mean ± SD Alpha-blocker use No 29 26.5 ± 29.3 0.027 22.3 ± 18.8 0.011 Yes 96 54.7 ± 65.6 35.7 ± 36.9 Baseline PVR volume ≤ 40 cc 76 23.2 ± 31.7 < 0.001 23.4 ± 32.7 <0.001 > 40 cc 49 86.9 ± 72.7 46.7 ± 31.4 Radiation cohort Prostate only 66 46.3 ± 55.4 0.725 29.7 ± 21.6 0.317 Pelvis 59 50.2 ± 65.6 35.8 ± 43.9 Overall population 125 48.2 ± 60.2 32.5 ± 34.0 * The median number N of PVR readings was 10. p-values were calculated by independent samples t-test. umes less than or equal to 40 cc. The same is demon- should influence the prostate's position to a lesser degree strated in the pelvic radiation group with slightly greater as previously reported by Zelefsky et al [9]. Although PVR variability, although within the limits of the bladder scan- urine volumes were recently explored in cervical cancer ner. Figure 4b graphically represents the mean difference treatments, little data is available concerning PVR urine from baseline PVR urine volumes versus weeks of radia- volumes as patients progress through external beam radi- tion treatment, stratified by treatment group and baseline ation therapy for prostate cancer treated with an empty PVR urine volumes <40 or >40 cc. The data continues to bladder and in a prone position [22]. Posterior and infe- demonstrate very little change in PVR volumes over time rior movement of the prostate gland due to bladder filling for both treatment cohorts when baseline PVR urine vol- was first described by Ten Haken and colleagues, and umes are less than or equal to 40 cc. Both cohorts of reproduced by several investigators in subsequent studies patients continue to demonstrate greater differences in [6-8,10]. Melian et al. have reported that bladder filling mean PVR urine volumes from baseline over time in influenced the position of the prostate in patients treated patients with baseline urine volumes greater than 40 cc. in the prone position[8]. Zelefsky et al. also demonstrated The mean differences from baseline are greater in the less that bladder volumes greater than 40 cm could predict than or equal to 40 cc group in both treatment cohorts for greater than 3 mm deviations of the prostate and sem- and the converse is found in the greater than 40 cc group. inal vesicles while in the prone treatment position when the rectal volume is greater than 60 cc [9]. Zellars et al. Discussion reported that patients who were treated in the supine posi- In an era which is rapidly becoming defined by increas- tion and instructed to have a full bladder prior to treat- ingly sophisticated treatment planning and radiation ment demonstrated an associated posterior displacement delivery techniques, the basic tenant of irradiating what is of the prostate when evaluated 4 to 5 weeks after initiation intended to be treated while respecting normal tissue tol- of therapy [7]. Conversely, other researchers have not seen erance has never been more important. To achieve these a relationship between bladder filling and prostate posi- goals it is necessary to treat a dynamic and moving target, tion, although these patients were treated in the supine which is exemplified in prostate radiotherapy [14,25]. treatment position [5,15,17]. With dose escalation, strategies must be refined to decrease prostate treatment margins to minimize toxicity Bladder filling is more easily controlled on a daily basis to normal structures. Therefore, an investigation of all fac- than rectal filling, assuming that the patient voids imme- tors with the potential to influence prostate motion is crit- diately prior to treatment. This strategy is simple and ical. The bladder and rectum are regarded as the two most should help to remove the potential influence of the blad- important structures in terms of daily prostate motion. der on prostate motion. This paper specifically reports the This study details the post void residual urine volume influence of external beam radiation therapy on serial prior to daily radiation treatments and the influence of PVR urine volumes as patients proceed through treatment. external beam radiation therapy on PVR urine volumes Several strategies currently exist for daily image guidance throughout treatment. for prostate treatment, therefore the purpose of this paper is not to correlate specific PVR urine volumes with pros- If a patient is asked to empty his bladder prior to simula- tate motion, but rather determine the influence of exter- tion and then prior to radiation treatment, bladder filling nal beam radiation therapy on PVR urine volumes as Page 5 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 Distribu treatment post-void residual volume Figure 2 tion of PVR cohort by week and stratified by pre- Distribution of PVR cohort by week and stratified by pre-treatment post-void residual volume. Patients moving from the lower PVR category (≤ 50 cc) to the higher category (> 50 cc) were labeled as worse, while patients in the higher category who moved to the lower were labeled as better. The number of patients in each baseline category var- ies over time based upon treatment length. to prostate motion from the original planning CT simula- tion. Our study population consisted of patients treated with external beam radiation for prostate cancer. Two common types of radiation treatments were studied, pelvic radia- tion followed by a cone down to the prostate and prostate only radiation. As such the effects of PVR urine volumes could be compared in patients receiving whole pelvic radiation therapy for a portion of their treatment com- pared to prostate only radiation therapy. These two (A). Me externa b Figure 1 y radiation gr an l beam post-voi radiation thera oup d residual vol py (XRT) treatment, stratified ume as a function of week of cohorts provide insight in the potential for PVR urine vol- (A). Mean post-void residual volume as a function of ume changes in the most common clinical scenarios for week of external beam radiation therapy (XRT) definitive external radiation therapy for prostate. Patients treatment, stratified by radiation group. The bladder scanner operates within a margin of accuracy of ± 20 cc. (B) in the whole pelvic cohort had larger portions of their Mean difference from baseline in post-void residual (PVR) bladder irradiated and presumably had the potential for a volume as a function of week of external beam radiation greater degree of radiation induced bladder irritation. therapy (XRT) treatment, stratified by radiation group. The best-fit lines were determined by quadratic regression analy- There were significant differences in the clinical presenta- sis. The bladder scanner operates within a margin of accuracy tion between the two cohorts of patients within the two of ± 20 cc. radiation groups. These differences are attributable to our selection criteria. Importantly, these two groups of patients allowed us to study different treatment strategies, patients proceed through treatment [25]. If PVR urine vol- depending on risk of lymph node involvement, on PVR umes remain relatively stable throughout external beam urine volumes as patients progressed through external radiation treatment than there would be little correlation beam radiation treatment for prostate cancer. Patients Page 6 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 Pl versus week (base Figure 3 ot o line f mea ) pos n po of XRT treatment, t-vst- oid v oi re d re sidual sidu vol al volume ± u stratified by pre-treatment me 2 standard error Plot of mean post-void residual volume ± 2 standard error versus week of XRT treatment, stratified by pre-treatment (baseline) post-void residual volume. The number of patients in each baseline category varies over time based upon treatment length. treated with prostate only radiation were determined to have lower pre-treatment PSA, lower percent positive biopsies, lower Gleason Scores and clinical stage than patients treated with pelvic radiation. This finding is expected as higher PSA, Gleason Score and clinical stage predicts for a greater probability of lymph node involve- ment [20]. Our policy was to treat lymph nodes if the risk of involvement was greater than 10%. ( XRT treatment, stratified by ment (basel Figure 4 A) Plot of mean ine) post-voi post-voi d residual vo d resi treatmen dual vol lume t group and ume versus week pre-treat- of The mean individual PVR urine volume over all weeks of (A) Plot of mean post-void residual volume versus treatment in the pelvic and prostate radiation groups was week of XRT treatment, stratified by treatment not statistically different with values of 46.3 cc and 50.2 cc group and pre-treatment (baseline) post-void resid- respectively. However, mean PVR urine volumes stratified ual volume. The number of patients in each baseline cate- by week in both groups demonstrated the patients treated gory varies over time based upon treatment length. (B) Plot with whole pelvic radiation had larger baseline PVR urine of mean difference from baseline in post-void residual vol- ume versus week of XRT treatment, stratified by treatment volumes at the beginning of treatment. Larger baseline group and pre-treatment (baseline) post-void residual vol- PVR theoretically would allows for greater absolute vol- ume. The number of patients in each baseline category varies ume changes as radiation induced bladder irritability over time based upon treatment length. increased. Although higher baseline mean PVR urine vol- umes predicted for greater mean PVR urine volumes dur- ing treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of the greatest change during the first three weeks of treat- accuracy of the bladder scanner. Such small differences are ment and then became well within the limits of accuracy unlikely to result in any clinical significance in prostate of the bladder scanner. It is likely that patient attention to motion. Also of interest is that the difference from base- detail (i.e. bladder emptying) accounted for the changes line PVR urine volumes in both cohorts appeared to have during the first three weeks of treatment. As such, it is Page 7 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 probable that PVR volume determinations early in the References 1. Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Venkat- course of treatment may be sufficient with subsequent ramen ES, Reuter VE, Fair WR, Ling CC, Fuks Z: Dose escalation weekly determinations omitted. with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 1998, 41:491-500. Previous research by Zelefsky's group has demonstrated 2. Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, that bladder volumes greater than 40 cc had the potential Lee AK, Pollack A: Long-term results of the M.D. Anderson randomized dose-escalation trial for prostate cancer. Int J to influence daily prostate position while treated in the Radiat Oncol Biol Phys 2008, 70:67-74. prone position when rectal filling was greater than 60 cc 3. Pollack A, Zagars GK, Smith LG, Lee JJ, von Eschenbach AC, Antolak [9]. As such patients were stratified by radiation treatment JA, Starkschall G, Rosen I: Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 group and a baseline PVR cutoff of 40 cc. Patients with a Gy for prostate cancer. J Clin Oncol 2000, 18:3904-3911. baseline PVR = 40 cc did not experience any appreciable 4. Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams change in PVR during treatment while patients with a JA, Shipley WU: Comparison of conventional-dose vs high- dose conformal radiation therapy in clinically localized ade- baseline PVR > 40 cc were most likely to experience nocarcinoma of the prostate: A randomized controlled trial. changes (i.e. decrease) from the baseline PVR. This JAMA 2005, 294:1233-1239. 5. Pinkawa M, Asadpour B, Gagel B, Piroth MD, Holy R, Eble MJ: Pros- marked decline could result in a smaller degree of prostate tate position variability and dose-volume histograms in radi- motion but also in the setup being different from what otherapy for prostate cancer with full and empty bladders. was initially simulated. Although, patients who are iden- Int J Radiat Oncol Biol Phys 2006, 64:856-861. 6. Schild SE, Casale HE, Bellefontaine LP: Movement of the prostate tified with a higher PVR urine volume at the time of sim- due to rectal and bladder distention: implications for radio- ulation may require attention to bladder filling depending therapy. Med Dosim 1993, 18:13-15. on the technologies of daily prostate localization 7. Zellars RC, Roberson PL, Strawderman M, Zhang D, Sandler HM, Ten Haken RK, Osher D, McLaughlin PW: Prostate position late in employed. A shortcoming of our study is that patients the course of external beam therapy: patterns and predic- with substantial decreases in serial PVR's were not re- tors. Int J Radiat Oncol Biol Phys 2000, 47:655-660. 8. Melian E, Mageras GS, Fuks Z: Variation in prostate position planned via CT simulation (all patients however were quantitation and implications for three-dimensional confor- treated with daily cone beam CT guidance). mal treatment planning. Int J Radiat Oncol Biol Phys 1997, 38:73-81. 9. Zelefsky MJ, Crean D, Mageras GS, Lyass O, Happersett L, Ling CC, On average, alpha-blockers were prescribed 4.7 weeks Leíble SA, Fuks Z, Bull S, Koov HM, van Herk M, Kutcher GJ: Quan- into treatment. Alpha-blockers were not demonstrated to tification and predictors of prostate position variability in 50 influence PVR in either treatment cohort. This, however, is patients evaluated with multiple CT scans during conformal radiotherapy. Radiother Oncol 1999, 50:225-234. not surprising since the vast majority of changes in PVR 10. Crook JM, Raymond Y, Salhani D, Yan H, Esche B: Prostate motion occurred in the first three weeks or therapy. Alpha-block- during standard radiotherapy as assessed by fiducial mark- ers. Radiother Oncol 1995, 37:35-42. ers were initiated primarily for irritative symptoms. 11. Bayley AJ, Catton CN, Haycocks T, Kelly V, Alasti H, Bristow R, Cat- ton P, Crook J, Gospodarowicz MK, McLean M, Milosevic M, Warde P: A randomized trial of supine vsprone positioning in Conclusion patients undergoing escalated dose conformal radiotherapy External beam radiation therapy results in a clinically for prostate cancer. Radiother Oncol 2004, 70:37-44. insignificant change in weekly post-void residual urine 12. Lattanzi J, McNeeley S, Pinover W, Horwitz E, Das I, Schultheiss TE, Hanks GE: A comparison of daily CT localization to a daily volumes (especially when PVR urine volumes are less than ultrasound-based system in prostate cancer. Int J Radiat Oncol 40 cc), suggesting that radiation induced bladder irritabil- Biol Phys 1999, 43:719-725. ity does not substantially influence bladder residual urine 13. Balter JM, Wright JN, Newell LJ, Friemel B, Dimmer S, Cheng Y, Wong J, Vertatschitsch E, Mate TP: Accuracy of a wireless locali- volumes. zation system for radiotherapy. Int J Radiat Oncol Biol Phys 2005, 61:933-937. 14. Ghilezan MJ, Jaffray DA, Siewerdsen JH, Van Herk M, Shetty A, Sharpe Competing interests MB, Zafar Jafri S, Vicini FA, Matter RC, Brabbins DS, Martinez AA: The authors declare that they have no competing interests. Prostate gland motion assessed with cine-magnetic reso- nance imaging (cine-MRI). Int J Radiat Oncol Biol Phys 2005, 62:406-417. Authors' contributions 15. Antolak JA, Rosen II, Childress CH, Zagars GK, Pollack A: Prostate PFO has done statistical analysis as well as drafted the target volume variation during a course of radiotherapy. Int manuscript. GSM has made the selection of patients, J Radiat Oncol Biol Phys 1998, 42:661-672. 16. Ten Haken RK, Forman JD, Heimburger DK, Gerhardsson A, McShan involved with the study design, has been involved with DL, Perez-Tamayo C, Schoeppel SL, Lichter AS: Treatment plan- writing and revising the manuscript, statistical analysis ning issues related to prostate movement in response to dif- ferential filling of the rectum and bladder. Int J Radiat Oncol Biol and final approval of the version to be published. ZAA has Phys 1991, 20:1314-1324. been involved with the statistical analysis and design of 17. Beard CJ, Kijewski P, Bussiere M, Gelman R, Gladstone D, Shaffer K, the tables/figures. WMB has been involved with the statis- Plunkett M, Castello P, Coleman CN: Analysis of prostate and seminal vesicle motion: Implications for treatment planning. tical analysis. KEW has been involved in manuscript revi- Int J Radiat Oncol Biol Phys 1996, 34:451-458. sion and review of the intellectual content. BSK has been 18. Stam MR, Th. Van Lin EN, Vight LP Van Der, Kaanders JH, Visser AG: involved with statistical analysis. RWG has been involved Bladder filling variations during radiation treatment of pros- tate cancer: Can the use of a bladder ultrasound scanner and with statistical analysis and design of the tables/figures. biofeedback optimize bladder filling? Int J Radiat Oncol Biol Phys All authors read and approved the final manuscript. 2006, 65:371-377. Page 8 of 9 (page number not for citation purposes) Radiation Oncology 2009, 4:26 http://www.ro-journal.com/content/4/1/26 19. Greene FL, Balch CM, Fleming I, Fritz A, Haller DG, Morrow M, Page DL: AJCC Cancer Staging Manual 6th edition. Springer-Verlag New York, LLC; 2002. 20. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD: Contemporary update of prostate cancer staging nomo- grams (Partin Tables) for the new millennium. Urology 2001, 58:843-848. 21. O'Doherty UM, McNair HA, Norman AR, Miles E, Hooper S, Davies M, Lincoln N, Balyckvi J, Childs P, Dearnaley DP, Huddart RA: Vari- ability of bladder filling in patients receiving radical radio- therapy to the prostate. Radiotherapy and Oncology 2006, 79:335-340. 22. Ahmad R, Hoogeman MS, Quint S, Mens JW, de Pree I, Heijmen BJ: Inter-fraction bladder filling variations and time trends for cervical cancer patients assessed with a portable 3-dimen- sional ultrasound bladder scanner. Radiotherapy and Oncology 2008, 89:172-179. 23. Byun SS, Kim HH, Lee E, Paick JS, Kamg W, Oh SJ: Accuracy of bladder volume determinations by ultrasonography: Are they accurate over the entire bladder volume range? Urology 2003, 62:656-660. 24. BladderScan BVI 3000 Noninvasive Bladder Volume Instru- ment Operator's Manual. C 2004 by Diagnostic Ultrasound Corpo- ration . 25. Kupelian PA, Langen KM, Willoughby TR, Zeidan OA, Meeks SL: Image-guided radiotherapy for localized prostate cancer: Treating a moving target. Semin Radiat Oncol 2008, 18:58-66. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 9 of 9 (page number not for citation purposes)

Journal

Radiation Oncology – Springer Journals

Published: Jul 22, 2009

There are no references for this article.