Japanese Journal of Clinical Oncology Advance Access originally published online on May 12, 2006
Japanese Journal of Clinical Oncology 2006 36(5):285-289; doi:10.1093/jjco/hyl008
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© 2006 Foundation for Promotion of Cancer Research
Predictive Factors of Acute Urinary Retention Requiring Catheterization Following 125I Prostate Brachytherapy
1 Department of Radiology and 2 Department of Urology, Tokyo Medical Center, National Hospital Organization, Tokyo, Japan
For reprints and all correspondence: Toshio Ohashi, Department of Radiology, Tokyo Medical Center, National Hospital Organization, 5-1, Higashigaoka 2 chome, Meguro-ku, Tokyo 152-8902, Japan. E-mail: tohashi{at}ntmc.hosp.go.jp
Received November 28, 2005; accepted February 3, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Objective: To analyze predictive factors of acute urinary retention requiring catheterization after 125I prostate brachytherapy.
Methods: A group of 227 consecutive patients with localized prostate cancer were treated with 125I prostate brachytherapy between September 2003 and December 2004. The clinical, treatment-related and dosimetric factors were evaluated for the need for catheterization owing to urinary retention.
Results: Twelve patients (5.3%) required catheterization. The median time to onset was 2 days after implantation (range 1–7 days). Univariate analysis demonstrated that pre-implant ultrasound prostate volume, number of seeds, number of needles and neoadjuvant hormonal manipulation were predictive for catheterization. In multivariate analysis, the number of needles and neoadjuvant hormonal manipulation were significant independent predictive factors for catheterization (P = 0.002 and 0.025, respectively). The risk of catheterization in the cluster in which the number of needles was >24 was 4.07 times as high as that in the cluster in which the number of needles was 
24 [11.3% versus 3.0%, P = 0.020; 95% confidence interval (CI) 1.24–13.36], and the risk in the hormonally manipulated patients was 7.05 times as high as that in the hormone-naïve patients (7.7% versus 1.2%, P = 0.034; 95% CI 0.89–55.64).
Conclusion: Our data suggest that the number of needles and hormonal manipulation might be the strongest predictors for catheterization.
Key Words: prostate cancer • brachytherapy • iodine-125 • urinary morbidity • catheterization
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Over the past decade, transperineal permanent prostate brachytherapy has been a popular treatment option for localized prostate cancer. Recent evidence has confirmed equivalent biochemical control rates with permanent seed implantation to those with radical prostatectomy or external beam radiotherapy (EBRT) (1,2). This has prompted us to undertake a more careful evaluation. When compared with radical prostatectomy, the side effects of prostate brachytherapy are generally thought to be more tolerable. Han et al. (3) reported that the vast majority of patients develop some degree of acute urinary irritative/obstructive symptoms after prostate brachytherapy. Recent brachytherapy studies have detailed multiple aspects of urinary function after implantation (4,5). Urinary retention requiring the use of a catheter is a well-recognized side effect of the procedure (6–8); several reports have assessed the predictive factors for this complication (9–12).
In Japan, the use of 125I was legally approved in July 2003, and the first 125I prostate brachytherapy was performed at the Tokyo Medical Center, National Hospital Organization, in September 2003. To date, 300 patients with localized prostate cancer have been treated in our hospital and this method is becoming more popular in Japan. Here, we report for the first time on acute urinary retention requiring catheterization among 227 consecutive patients in Japan and present an analysis to identify independent predictive factors that are associated with the urinary retention.
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PATIENTS AND METHODS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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PATIENT SELECTION
During the period September 2003 through December 2004, we treated 227 consecutive patients with localized prostate cancer using 125I permanent seed implantation at the Tokyo Medical Center, National Hospital Organization. The clinical characteristics of these patients are shown in Table 1.
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The patients were classified into three groups according to risk factors [T-category (according to the 1997 American Joint Commission on Cancer), prostate specific antigen (PSA) and Gleason score]: (i) the low-risk group (T1-2a, PSA <10 ng/ml and Gleason score
6); (ii) the intermediate-risk group (one adverse factor: T2b or greater, PSA 
10 ng/ml, or Gleason score 7); and (iii) the high-risk group (two or three adverse factors) (13). For the low-risk group, seed implantation alone (monotherapy) was recommended, whereas for the high-risk group a combination of 125I seed implantation at a reduced prescribed radiation dose and EBRT was preferred (combined therapy). In the intermediate-risk group, individual treatment decisions were made, although combined therapy was recommended in general. A neoadjuvant hormonal treatment was prescribed to 142 patients (62.6%) for a median of 8 months, ranging from 1 to 48 months. Hormone therapy consisted of a luteinizing hormone releasing hormone (LHRH) agonist alone for 90 patients and in conjunction with an anti-androgen therapy for 52 patients.
In our hospital, many patients had to wait for a long time to receive brachytherapy, in some cases more than 1 year; hence, most received neoadjuvant hormonal therapy irrespective of prostate volume. Written informed consent was obtained from each patient before 125I permanent seed implantation.
SEED IMPLANTATION
The pre-implant treatment planning was carried out for 
1 month before the implant procedure. Our pre-planning technique has been described previously (14,15). For the procedure, the patient should be in the extended lithotomy position. Implants are planned from transrectal ultrasound (TRUS) images of the prostate taken at 5 mm intervals from the base through the apex. An aerated jelly in the urethral catheter allowed for the identification of the urethra. The captured images were digitized using a planning computer. The treatment planning was performed using the planning system VariSeed 7.1 (Varian Medical Systems, Palo Alto, CA, USA).
The gross target volume (GTV) was defined as the prostate itself visualized on the TRUS images. The planning target volume (PTV) was determined from the GTV plus a treatment margin of 3 mm in the lateral direction. There were no margins in the craniocaudal and anterior–posterior directions. We set the treated volume to include the PTV within the prescribed isodose, using a modified peripheral loading technique (16). The prescribed dose was 145 Gy in the monotherapy group and 100 Gy in the combined therapy group.
The implantation was performed under spinal anesthesia, via TRUS guidance of the pre-planned seeds, with the patient in the extended lithotomy position, similar to the pre-implant treatment planning. A Mick applicator (Mick Radionuclear Instruments, New York, USA) was used to deposit the seeds; 125I was the only source used, with a mean activity of 0.33 mCi/seed (range 0.32–0.39). In order to minimize micturition problems, an alpha-blocker (tamsulosin hydrochloride 20 mg/day, orally) was routinely prescribed for all patients from the day after implantation.
For post-implant dosimetric analysis, a computed tomography (CT) scan was obtained 1 day after implantation (day 1), with a urinary catheter in place for accurate assessment of the urethral dose. Axial CT scan images of the pelvic area were taken at 5 mm intervals. The image information was transferred to the planning system using a DICOM interface. The same person contoured the prostate and urethra carefully for each patient. The ratio of the post-implant CT prostate volume to the pre-implant ultrasound (US) prostate volume (CT/US ratio) was used as a surrogate for the extent of post-implantation prostatic edema. The catheter was removed after the post-implant CT scans.
The calculated dosimetry parameters used were the percentage volume of the prostate receiving 100, 150 and 200% of the prescribed dose (V100, V150 and V200, respectively) and the values of the minimal dose received by 90% of the prostate volume (D90). In addition, the maximum urethral dose and values of the minimal dose received by 10% of the urethra volume (D10 of urethra) were determined. The urethral dose was defined by doses at the urinary catheter (17). In the combined therapy group, supplemental EBRT was started 1 month after the brachytherapy. The prescribed doses of EBRT were 45 Gy in 25 fractions of 1.8 Gy per fraction using 6 MV photons delivered using a 3D-conformal technique with the patient in a supine position, including the prostate and seminal vesicles plus a 0.8–1.0 cm margin on the rectal side and a 1.5 cm margin on the other sides.
FOLLOW-UP
Clinical follow-up was started from the day of implantation (day 0). All patients were reviewed clinically at 2 and 4 weeks, 2 and 3 months, and every 3 months thereafter. Any patient requiring catheterization after catheter removal on the day following implantation was considered obstructed. Alpha-blockers were continued until they were no longer required symptomatically. Steroids were not administered to patients requiring catheterization.
STATISTICAL ANALYSIS
The clinical, treatment-related and dosimetric factors were assessed for univariate and multivariate correlations with the risk of urinary retention requiring catheterization. The clinical and treatment-related factors include patient age, initial PSA, pre-implant International Prostate Symptom Score (IPSS), pre-implant US prostate volume, CT/US ratio, number of seeds inserted, number of needles used and the utilization of neoadjuvant hormonal manipulation; the dosimetric factors include V100, V150, V200, D90, the maximal urethral doses and D10 of the urethra.
A univariate analysis was performed using an independent samples t-test. The variables that showed univariate significance (P 0.10) were then included in a multivariate analysis using a logistic regression test. Analyses were carried out using SPSS 12.0 (SPSS Inc., Chicago, IL, USA). Differences were regarded as statistically significant at P-value < 0.05.
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RESULTS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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The implantation data and the post-implant dosimetric factors are shown in Table 2. The median follow-up was 16.0 months (range 8.0–24.2 months). Alpha-blockers were administered for a median of 3 weeks (range 1.0–15.0 weeks).
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During the follow-up, 12 patients (5.3%) developed urinary retention requiring catheterization; the median time to onset was 2 days after implantation (range 1–7 days). The median duration of catheterization for urinary retention was 14 days (range 2–25 days). Of the 12 patients who required catheterization, 8 were in the monotherapy group and 4 were in the combined therapy group. All four patients in the combined therapy group developed urinary retention before the start of EBRT. None of the patients requiring catheterization experienced the recurrence of urinary retention after the removal of the urinary catheter.
On the basis of univariate analysis (Table 3), urinary retention requiring catheterization had significant correlations with the utilization of neoadjuvant hormonal manipulation (P = 0.033), pre-implant US prostate volume (P = 0.008), the number of seeds inserted (P = 0.020) and the number of needles (P = 0.009). On subsequent multivariate logistic regression analysis (Table 3), the significant factors were the utilization of neoadjuvant hormonal manipulation (P = 0.025) and the number of needles (P = 0.002). Of the 12 patients who required catheterization, 11 had neoadjuvant hormonal therapy. The median duration of hormonal therapy was 6 months (range 4–24 months). The hormonal therapy comprised LHRH agonist in conjunction with an anti-androgen in all 11 patients. The median number of needles was 22 (range 14–30) in the hormone-naïve patients and 20 (range 12–36) in the hormonally manipulated patients.
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The number of needles was analyzed in two clusters: one in which the number of needles was
24 and the other in which the number was >24. The risk of catheterization was significantly higher in the >24 needles cluster than in the 24 cluster (11.3% versus 3.0%; P = 0.020). The risk of catheterization in the >24 cluster was 4.07 times as high as in the 24 cluster [95% confidence interval (CI) 1.24–13.36] (Table 4). The risk of catheterization in the hormonally manipulated patients was 7.05 times as high as in the hormone-naïve patients (7.7% versus 1.2%, P = 0.034; 95% CI 0.89–55.64).
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Over the past decade, prostate brachytherapy has been increasingly utilized as definitive management for early-stage carcinoma of the prostate gland. The results of prostate brachytherapy have been reported to be as favorable as the most positive radical prostatectomy series, with a decreased incidence of urinary incontinence and sexual dysfunction (2,9,18–20).
Various studies have reported the risk of catheterization, giving rates between 5 and 22% (4,7–12,21–25). Crook et al. (21) found a rate of 13% for acute urinary retention requiring temporary insertion of a catheter after permanent prostate seed implantation. Multivariate analysis showed the US prostate volume and the prior androgen ablation to be independent predictors of urinary retention. Bucci et al. (11) reported that urinary retention requiring catheterization developed in 15% of patients and also showed that the pre-implant IPSS was the most important predictive factor for catheterization on both univariate and multivariate analyses. Terk et al. (22) were able to perform a multivariate analysis in 251 patients treated with 125I or 103Pd monotherapy, which revealed that the pretreatment IPSS was the most important predictor of post-implant urinary retention, which occurred in 5.6% of the patients. The risk of urinary retention for pre-implant IPSS values of <10, 10–19 and >20 was 2, 11 and 29%, respectively.
Our data show that urinary retention requiring catheterization occurred in 12 patients (5.3%), which was a relatively favorable result compared with previous reports. The number of needles and neoadjuvant hormonal manipulation were predictors for catheterization on multivariate analysis in the current study, although many previous reports had described the pretreatment IPSS or the prostate volume as predictive factors. Few reports have identified the number of needles to be a significant predictor of catheterization. Lee et al. (10) demonstrated the number of needles, the pretreatment US prostate volume and the post-treatment CT prostate volume to be significant predictors, but no multivariate analysis was performed because of the small number of patients. Eapen et al. (23) reported that the number of peri-urethral needle manipulations contributed to acute urinary toxicity in 28 patients. To our knowledge, there are no reports concerning the relationship between acute urinary retention and the number of needles on multivariate analysis of larger populations. Our current study, with a greater number of patients, demonstrated the number of needles to be predictive of catheterization on multivariate analysis. Most of the urinary obstructions requiring catheterization occurred shortly after the procedure, when the dose deposited in the tissue was low, suggesting a traumatic effect on the prostate gland rather than a dose-related factor, which agreed with the result of our study.
Regarding a possible correlation between hormonal therapy and urinary dysfunction following brachytherapy, conflicting data have been reported recently. Although some studies have implicated hormonal therapy in an increased risk of urinary retention following brachytherapy, others have not. In recent studies, Crook et al. (21,24) reported that the prostate volume and hormonal therapy were independent predictors of urinary retention, and the Mount Sinai group (22) reported that neoadjuvant therapy in conjunction with 103Pd monotherapy increased the risk of urinary retention in selected patients. In contrast, Merrick et al. (25) reported that hormonal manipulation did not statistically impact urinary catheter dependence in their study of 760 men. Similarily, Keole et al. (26) failed to confirm a relationship between hormonal therapy and retention in a study of 420 men.
In our study, most patients (62.6%) had neoadjuvant hormonal therapy, and this proportion was relatively higher than that in other reports. In our institution, many patients had been waiting for a long time to receive brachytherapy, sometimes for more than 1 year; therefore, most received neoadjuvant hormonal therapy irrespective of prostate volume. In our study, prostate volume reduced by a median of 36.7% after hormonal therapy (not shown among the results because the prostate volume before hormonal therapy was measured in only 40% of the hormonally manipulated patients). Despite the reduction of prostate volume and possibly the number of needles, the hormonally manipulated group remained at an increased risk of post-implant catheterization (7.7% compared with 1.2% for the hormone-naïve group).
Acute urinary obstruction requiring catheterization is a well-known adverse event after 125I prostate brachytherapy. Prior knowledge of an individual's relative risk would be useful in counseling patients before the procedure. In this study of 227 consecutive patients, the number of needles and neoadjuvant hormonal therapy were independent predictors of acute urinary obstruction requiring catheterization.
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References |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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