Prostate volume determination: Differential volume measurements comparing CT and TRUS

Radiotherapy and Oncology 81 (2006) 179–183 www.thegreenjournal.com

Prostate radiotherapy

Prostate volume determination: Differential volume measurements comparing CT and TRUS Karl Mikael Ka ¨lknera,*, Gregory Kubicekc, Josef Nilssonb, Marie Lundellb, Seymour Levitta,c, Sten Nilssona a

Department of Oncology, and bDepartment of Medical Physics, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden, c Department of Therapeutic Radiology, University of Minnesota, Minneapolis, MN, USA

Abstract Purpose: To compare the differences in prostate volume assessed by computerized tomography (CT), step-section transrectal ultrasound (TRUS-step), and TRUS with ellipsoid-formula volume calculation (TRUS-ellipsoid). Methods and materials: Thirty-one patients with localized prostate cancer treated with combined external conformal radiotherapy and high dose rate brachytherapy, who had prostate volumes evaluated using CT, TRUS-step and TRUSellipsoid according to our clinical routine for dose planning. The measurements were collected retrospectively based on actual dose-plans. Results: The prostate volume was on average 34 cc (range 18–60 cc) according to CT, 28 cc (range 12–57 cc) and 24 cc (range 13–44 cc) according to TRUS-step and TRUS-ellipsoid, respectively. The differences between the lengths measured were most pronounced with a mean length of 4.5 cm (range 3.0–6.0 cm) defined by CT as compared to 3.6 cm (range 3.0–5.0 cm) and 3.6 cm (range 2.8–5.0 cm) when defined by TRUS-step and TRUS-ellipsoid, respectively. Conclusion: CT defined volumes are 30% larger than volumes defined with TRUS-step. This is probably due to uncertainty in defining the apex of the prostate and thereby the length of the prostate using CT. When defining target in radiotherapy, it is important to be aware of the differences in volumes depending on the technique used. c 2006 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 81 (2006) 179–183.



Keywords: Prostate volume; Computerised tomography (CT); Transrectal ultrasound (TRUS); Brachytherapy

Accurate measurement of the prostate volume has a significant impact on the treatment regime for the patient. Volume calculations using transrectal ultrasound (TRUS) with elliptical volume formula (TRUS-ellipsoid) calculation are often the first step in evaluating the prostate size to determine available treatment options. Computerized tomography (CT) images and TRUS images are often used for dose planning and target definition in both external beam radiotherapy (EBR) and brachytherapy, both low dose rate (LDR) and high dose rate (HDR) [1–3]. Patients receive sub-optimal treatment when planning measurements do not correspond to the true volume. If external beam radiation planning with CT or TRUS does not reflect the true prostate volume than patients receive either inadequate radiation doses that predispose the patient to recurrence or unnecessary radiation that increases the risk for adverse side effects. Two previous studies have reported larger prostate volumes when using CT as compared to TRUS [4,5]. However, another study reported no significant differences in prostate volume comparing CT and TRUS [6]. Our study adds to the



growing data collection concerning the difference in volume measurement determined by the different imaging techniques. It is also to our knowledge, the first report to compare the two types of TRUS in relation to CT volumes and also to compare the effect of the different prostate dimensions (height, length, width) on the determination of volume differences.

Methods and materials Patient characteristics Thirty-one patients with localized prostate cancer receiving combined radiotherapy with external and HDR brachytherapy, all of whom had prostate volume determined with both TRUS and CT were evaluated. At the Radiumhemmet, Karolinska University Hospital, external radiotherapy and a boost with HDR brachytherapy have been used since 1998 with a method described by Lennernas et al. [7]. Briefly, 50 Gy EBR is delivered to the plan-

0167-8140/$ - see front matter c 2006 Published by Elsevier Ireland Ltd. doi:10.1016/j.radonc.2006.10.003

180

Prostate volume according to CT and TRUS

ning target volume (PTV) including the prostate and the vesicles with a 2 cm margin in all directions except posterior where the margin is 1.5 cm, and two fractions of 10 Gy HDR brachtherapy where PTV is defined as the prostate with a 3 mm margin. The dose planning for the external beam radiation utilizes CT, while the HDR dose distribution is based on TRUS with a step-section of 5 mm.

Measurement characteristics The CT scans were performed (GE Light Speed 16 slices, US) with the patient in a supine position and scans at every 5 mm. The images were sent on-line to the dose planning program (Eclipse, v 6.5, Varian, US). The prostate was delineated in each image and the volume was calculated. Seminal vesicles were not included in the volume determination. The CT scans were performed before the TRUS and were not used in determining the prostate volume via TRUS. For the TRUS an ultrasound machine (Falcon 2101, BK Medicals, Denmark) equipped with a transrectal probe (article number 8658, BK Medicals, Denmark) was used and the patient was placed in a gynecologic table with the patient in lithotomy position. A TRUS was performed to define the prostate size expressed in three dimensions; length (cranial–caudal direction), height (hip-to-hip dimension) and width (anterior –posterior). These measurements were used to calculate the prostate volume (TRUS-ellipsoid) by the ellipsoid formula (length (cm) * width (cm) * height (cm) * (p/6)). Defining the prostate volume with step-section (TRUS-step), TRUS images were taken with 5 mm steps, and sent on-line to the dose planning system (BrachyVision, v 6.5, Varian, US), where the prostate was delineated in each image and the volume was calculated. The same physician performed the TRUS for ellipsoid formula and the TRUS for step-section images. The cranial–caudal dimension defined with TRUS was used to calculate the number of 5 mm slices to be used in the step-section TRUS. Thus, every patient had three types of volume measurement: CT with 5 mm slices, TRUS-step sectioning with 5 mm slices, and TRUS-ellipsoid using the ellipsoid formula.

Statistics

were on average 16% larger (range 37 to 94%) than the volumes assessed by TRUS-ellipsoid. The mean of the differences in volume assessed by TRUS-step and CT was larger in patients with small prostate (<33 cc defined on TRUSstep) compared with patients with a prostate volume exceeding 33 cc. This was statistically significant (p = 0.05). When grouping the prostate volume in <20 cc, 20 to <30, 30 to <40 and more than 40 cc on TRUS-step the mean of differences was lower in large glands, demonstrated in Fig. 1. There was a statistically significant correlation between the TRUS-step volumes and the CT volumes (r = 0.83, p < 0.05). The correlation between CT and TRUS-ellipsoid volumes was r = 0.81 (p < 0.05). The correlation between TRUS-step and TRUS-ellipsoid methods was 0.95 (p < 0.05). The degree of correlation between the different prostate dimensions; the length (cranial–caudal dimension), height (anterior–posterior dimension) and width (hip-to-hip dimension) were investigated and summarized in Table 1. The highest grade of correlation was seen when comparing the two TRUS measurements. The dimension with the lowest grade of correlation between TRUS and CT was the cranial–caudal dimension (prostate length). Comparing the mean length revealed a statistically significant difference between the CT and TRUS-step. This was also true for the height of the prostate, however the width did not differ significantly, as demonstrated in Fig. 2. The TRUS is performed with patient in the lithotomy position, and the CT is performed in the supine position, which could explain the shorter length found when using TRUS due to the rotation, see Fig. 3. The length of the prostate assessed by CT (average 4.5 cm (4.3–4.7 cm, 95% confidence interval)) becomes the length of the hypotenuse (denoted a in Fig. 3) when the prostate is rotated while the patient is in lithotomy position. The length of the prostate assessed by TRUS-step (average 3.8 cm (3.5–4.0 cm, 95% confidence interval)) with patient in lithotomy position becomes the longer side of a triangle (denoted b in Fig. 3). Using trigonometry an angle of rotation a = 33° (21°–42°, 95% confidence interval) could explain the observed differences in CT defined length and length assessed by TRUS-step.

The T-test for dependent samples was made to compare the means between the groups. Correlation between the groups was made using Pearson’s correlations rank. A p-value 60.05 was determined to be statistically significant.

Results The median prostate volume according to CT was 31 cc (range 18–60 cc). The TRUS-step demonstrated a median prostate volume of 24 cc (range 12–57 cc). The median prostate volume using TRUS-ellipsoid was 21 cc (range 13–44 cc). The prostate volume assessed by CT was on average 30% larger than the volume assessed by TRUS-step (range 15% to 160%). Only 2 patients had a TRUS-step measured prostate volume larger than that based on CT. The CT assessed prostate volumes were on average 48% (range 22% to 171%) larger compared to the volumes calculated by TRUS-ellipsoid. The TRUS-step assessed prostate volumes

Fig. 1. The mean of differences between volume assessed by CT and volume assessed by TRUS-step according to category of the prostate volume assessed by TRUS-step. Bars denote ±1.96 SE.

¨lkner et al. / Radiotherapy and Oncology 81 (2006) 179–183 K.M. Ka

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Table 1 Correlations between different modalities to assess the prostate volume and the prostate dimensions; length, width and height (anterior– posterior) Dimension

Volume

Cranial–caudal length

Anterior–posterior height

Hip-to-hip width

Comparison CT vs TRUS-step CT vs TRUS-ellipsoid TRUS-step vs TRUS-ellipsoid

0.73 0.72 0.85

0.37 0.19* 0.58

0.61 0.72 0.88

0.61 0.67 0.83

*

Not statistically significant.

5.0 4.5

Distance (cm)

4.0 3.5 3.0 2.5 +1.96*SE +SE Mean -SE -1.96*SE

2.0 1.5 1.0 0.5 0 CT TRUS-step assessed assessed width width

CT TRUS-step CT TRUS-step assessed assessed assessed assessed height height length length

Fig. 2. The average value of length, height and width of the prostate gland using CT and TRUS-step.

Fig. 3. Schematic illustration of the rotation of the prostate due to patient’s position. A (above) – the prostate in supine position and CT assessed length (a). B (below) – the prostate in lithotomy position and TRUS-step assessed length (b). a – denotes the angle of rotation of the prostate due to the positioning of patient in gynecologic chair.

Discussion The first step towards optimizing treatment for prostate cancer is to know the limitations of the treatment tools. The purpose of this study was to examine the prostate volume assessed by TRUS-step, TRUS-ellipsoid and CT. TRUSstep calculates the volume from the sum of sequential areas in cross-sectional images of the prostate. Prostate volume can also be calculated using prostatic dimensions (length, height, and width) in various mathematical descriptions.

TRUS-step is generally considered the gold standard compared to TRUS-ellipsoid [8,9], due to superior accuracy (agreement with volume of surgically removed prostates) [10,11], precision (accounting for variations in the external contour of the prostate from the bladder base to the apex) [12] and reproducibility (less intra- and interobserver variation) [13]. However, the manual outlining of the consecutive cross sections is time consuming. Alternatively, TRUS-ellipsoid use a formula describing a spheroid volume using half the mean of width, height, and length as radius represents an adequate method for quick volume assessment with reasonable accuracy. In the present report the Pearson correlation coefficient between the TRUS section and the TRUS-ellipsoid is 0.84 and this in agreement with Bosch et al. who recently reported a correlation coefficient at 0.87 [14]. Previously reports on the topic of comparing CT and TRUS in defining the prostate volume have used a variety of TRUS systems, Hoffelt et al. [5] used the TRUSellipsoid formula while Narayana et al. [4] and Badiozamani et al. [6] both used the TRUS step-section method with 5 mm slices. These results are summarized in Table 2. In the two studies which reported larger prostate volumes defined by CT, Hoffelt et al. [5] reported a 50% difference between TRUS and CT while Narayana et al. [4] reported a 20%. Badiozamani et al. [6] reported no volume overestimation between CT and TRUS. In the present study, the prostate volume defined with CT was 35% larger than TRUSstep and 38% larger than TRUS-ellipsoid. It is unclear why all four studies looking at the topic of prostate volume have reported different findings for CT volume overestimation. One explanation could be selection bias, with differing proportions of patients with large volume prostate glands in the various studies. In the present study, patients treated with neoadjuvant hormonal therapy are included. The prostate volume is decreasing during testosterone depletion and therefore we have included a higher proportion of patients

Table 2 Literature review Study

Pts

CT/TRUS correlation

CT volume overestimation

Hoffelt Narayana Badiozamani

48 10 10

0.925

1.5 1.5 NSA

0.9

NSA: authors concluded that CT did not overestimate prostate volume compared to CT.

182

Prostate volume according to CT and TRUS

with small prostate volume. It has previously been reported that prostate volume exceeding 33 cc demonstrated lower discrepancy between the CT assessed and the TRUS assessed volumes [15]. This is in agreement with present results. We also found a trend of smaller mean differences when the prostate volume increased. In our study we have a median TRUS-step volume at 24 cc, which is smaller than median volume at 30 cc reported by Bosch et al. in a populationbased trial examining the natural history of benign prostatic hyperplasia [14]. A second explanation could be whether one or several observers, as in the present study, are involved in defining the prostate volume, since each observer has a different way of estimating the prostate [16,17]. A third explanation could be the position of the patient when the CT or TRUS is performed. We attempted to determine the difference in measurement between TRUS and CT. Comparing the different prostate dimensions will not be correct if there is a significant difference in the slice angle between the measuring modalities. Some reports have explained this as the ‘Salami effect’. Basically, the angle of the slice will affect the prostate dimensions; a more horizontal slice will decrease the cranial–caudal dimension but will increase the anterior–posterior dimension. In the present study an angle of 33° could explain the differences in length assessed by CT and TRUS-step. This is probably a realistic angle when the pelvis is rotated with the patient in the lithotomy position and the TRUS probe is always horizontally positioned during image grabbing and treatment. However, all the prostate dimension measurements are larger using CT compared with TRUS-step and thus slice angle alone cannot fully account for the volume differences. Together with the present study, three out of four studies have found a significant degree of CT volume overestimation. Based on these results it would appear that patients are either receiving inadequate brachytherapy doses based on under-estimating the volume on TRUS, which may lead to treatment failure. On the other hand, patients may be overtreated with external beam radiation, based on overestimation of the prostate volume with CT. While this study was not designed to determine which volume, TRUS or CT, gives the most accurate anatomical volume of the prostate, other research has examined the accuracy of TRUS and anatomical volume. Terris and Stamey compared prostate volumes in 150 patients using TRUS and prostatectomy specimens and reported a correlation of 0.93 between TRUS-step and prostatectomy specimens and a correlation of 0.90 with TRUS-ellipsoid [10]. Park et al. also found that TRUS volumes closely correlated with real prostate volume determined via prostatectomy in 16 patients, with a correlation of 0.833 with TRUS-ellipsoid [18]. Roach et al. compared MR and CT prostate volumes, reporting a 32% volume overestimation with CT and a 0.89 correlation between the images modalities [19]. Thus, it is likely that CT-based volumes represent a greater than true volume and that radiation treatment plans utilizing CT over-treat the patient. Even small volume differences can have significant dose effects. Roach et al. found that increasing the margins by 0.5 cm (from 1 to 1.5 cm) resulted in a 25% greater rectal dose (63–88%) [20]. To minimize treatment complications, target volumes should closely approximate physiological volumes. While

MR-based treatment plans could reduce the volume overestimation seen with CT, planning with MR is more time intensive and expensive than CT planning. Another solution would be better understanding of the anatomical areas of the prostate where the excessive volume estimation occurs. It is commonly believed that the dimensions of the base and apex regions of the prostate are over-estimated with CT. In the present study, the lowest correlation (r = 0.19, p = 0.23) was found between the length assessment by CT and TRUS-step. This suggests that prostate length is the critical dimension in volume overestimation; however, measurement differences secondary to rotation of the pelvis during TRUS set-up could partly explain this difference.

Conclusion Strong correlation exists between CT and TRUS (using both step-section and ellipsoid formula) volumes, but CT assessed prostate volumes are 30% and 48% larger than prostate volumes assessed by TRUS-step and TRUS-ellipsoid, respectively. Awareness of the fact CT volume overestimation is a risk, and that the most likely prostate regions for overestimation are the base and the apex, may help clinicians reduce the extent of volume difference. It may be helpful to use TRUS determined prostate length in CT contouring to obtain prostate volumes closer to anatomical values.

Acknowledgement This project was supported by grants from Cancerfo ¨reningen i Stockholm. * Corresponding author. Karl Mikael Ka ¨lkner, Department of Oncology, Radiumhemmet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. E-mail address: [email protected] Received 18 April 2006; received in revised form 5 October 2006; accepted 6 October 2006

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