Japanese Journal of Clinical Oncology Advance Access originally published online on June 23, 2008
Japanese Journal of Clinical Oncology 2008 38(7):469-473; doi:10.1093/jjco/hyn053
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author (2008). Published by Oxford University Press. All rights reserved
Four-year Experience of Interstitial Permanent Brachytherapy for Japanese Men with Localized Prostate Cancer
1 Department of Radiology
2 Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
3 Division of Radiation Oncology, Kitasato University Hospital, Sagamihara, Kanagawa, Japan
For reprints and all correspondence: Hiromichi Ishiyama, Department of Radiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Japan. E-mail: hishiyam{at}kitasato-u.ac.jp
Received April 17, 2008; accepted May 28, 2008
 |
Abstract |
|---|
 TOP Abstract INTRODUCTIONMETHODSRESULTSDISCUSSIONFundingReferences |
|---|
Objective: To report 4 year results obtained with our initial 100 patients with localized prostate cancer treated by interstitial permanent brachytherapy.
Methods: One-hundred Japanese men with clinically localized prostate cancer underwent interstitial permanent prostate brachytherapy using 125I seeds. Median follow-up was 36 months (range, 30–42 months). Median initial prostate-specific antigen (PSA) level was 6.7 ng/ml (range, 1.5–25.2 ng/ml). Of these 100 patients, 31 received neoadjuvant hormone therapy for several months. Treatment morbidities were assessed using Radiation Therapy Oncology Group (RTOG) scale and National Cancer Institute Common Toxicity Criteria.
Results: A mean of 95 seeds (range, 48–123 seeds) were successfully implanted in patients with prostate cancer. Mean prostate volume receiving at least 100% dose (V100) and dose to 90% of prostate volume (D90) for the 100 patients were 96.6% and 166.1 Gy, respectively. Urinary morbidity was common, but was usually not severe. Only four patients needed catheterization for urinary retention (Grade 3) during follow-up. Most patients displayed no rectal morbidity after implantation, with only 3% of patients showing RTOG Grade 2 rectal morbidity and no patients showing morbidity of Grade 3 or more. Three patients experienced biochemical failure according to Phoenix consensus definition during follow-up. One patient displayed clinical failure with lymph node recurrence.
Conclusions: These results indicate that interstitial permanent brachytherapy is safe and effective for Japanese patients with localized prostate cancer. The import of matured techniques developed in Western countries might allow bypass of the trial-and-error process in Japanese institutions.
Key Words: prostate cancer • brachytherapy • 125I • urinary morbidity • rectal morbidity
|
INTRODUCTION |
|---|
|
TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONFundingReferences |
|---|
Brachytherapy with a permanent 125I implant is now a popular treatment for early prostate cancer. However, few reports are available regarding Japanese patients treated with brachytherapy, since 125I seed implantation started in Japan only from 2003, approximately 15 years behind the USA. One of the most appealing reasons for selecting this treatment is the low degree of toxicity, which may reduce the impact on the quality of life (QOL) of patients. Evidence of low toxicity rate and sufficient tumor control rate after permanent interstitial brachytherapy is thus necessary to promote this treatment in Japanese men.
Permanent prostate brachytherapy was started at Kitasato University Hospital in 2004. We started this treatment under the guidance of highly experienced physicians from the USA. The 4-year results obtained with our initial 100 patients are reported herein.
|
METHODS |
|---|
|
TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONFundingReferences |
|---|
Patients
Between May 2004 and August 2005, a total of 102 Japanese men with clinically localized prostate cancer underwent transperineal interstitial permanent prostate brachytherapy using 125I seeds at Kitasato University Hospital. Of the 102 patients, one patient died of cerebral apoplexy a few weeks after implantation, and one patient was lost to follow-up. These two patients were excluded from this analysis. The median age of the 100 patients was 68 years (range, 52–84 years) and median follow-up was 36 months (range, 30–42 months).
In our treatment protocol criteria, patients in clinical stage T1c or T2a, with a prostate-specific antigen (PSA) of 10 ng/ml or less, and a Gleason score of seven or less are basically treated with permanent prostate brachytherapy as monotherapy. Clinical staging was decided from the results of digital rectal examinations and bone scintigraphy. Computed tomography (CT) and/or magnetic resonance imaging (MRI) were also used to determine the T stage. Clinical stages ranged from T1c to T2bN0M0 according to the definitions of the 2002 American Joint Committee on Cancer. Median initial PSA level was 6.7 ng/ml (range, 1.5–25.2 ng/ml) at the time of diagnosis. Final pathological diagnosis (including Gleason’s score) was made by a single pathologist in our institution. Thirty-one of the 100 patients received neoadjuvant hormone therapy for several months. We performed hormone therapy only in patients with a large prostate gland (>40 cm3). However, some patients had already received hormone therapy before visiting our hospital. Subject details are given in Table 1.
|
Treatment
Treatment was planned using Interplant 3.2 (CMS, St Louis, MO, USA). The prescribed dose to the prostate with 3–5 mm margin was 145 Gy. The procedure was performed in the extended lithotomy position under observation using a transrectal ultrasound (US) probe. Seeds were placed one by one transperineally through needles attached to a Mick applicator. In the first 28 patients, dosimetry was planned based on US images taken 4 weeks before implantation. In other patients, dosimetry was planned intraoperatively based on US images taken just before implantation in the anesthetized patient. An interactive plan technique was not used in this study population. All patients were hospitalized the day before seed implantation, and discharged 2 days after implantation.
Follow-up
Patients were monitored by measuring serum PSA level at each follow-up visit, every 3 months for the first 1 year and every 3–6 months thereafter. Urinary and rectal morbidity were assessed using the Radiation Therapy Oncology Group (RTOG) scale (1) and National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3. All patients received 
-blockers just after seed implantation to relieve urinary symptoms.
Dosimetric Analysis
Post-implantation dosimetric analysis was performed using a CT scan obtained 1 day and 4 weeks after implantation using Interplant 3.2 according to the recommendations of the American Brachytherapy Society. Dose volume histograms (DVHs) were calculated for every patient. As the shape of urethra could not be clearly contoured without balloon catheter, we used a next-day CT analysis with balloon catheter only for urethral DVH calculations. All of the other DVH parameters were calculated using CT images at 1 month after implantation.
The urethra was contoured on the same slices as the prostate contouring with a balloon catheter. The rectal wall was contoured, including sphincter muscle, on the same slices as the prostate contouring. Dose to 90% of prostate volume (pD90), prostate volume receiving at least 100% dose (pV100), prostate volume receiving at least 150% dose (pV150), dose to 90% of urethral volume (uD90), dose to 10% of urethral volume (uD10), urethral volume receiving at least 200% dose (uV200), dose to 90% of rectal volume (rD90), dose to 10% of rectal volume (rD10), rectal volume receiving at least 100% dose (rV100) and rectal volume receiving at least 150% dose (rV150) were calculated in each patient.
Statistical Analysis
The dosimetric and treatment-related factors (Table 2) affecting the risk of morbidities were analyzed by univariate analyses. Differences were regarded as statistically significant at P < 0.05.
|
|
RESULTS |
|---|
|
TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONFundingReferences |
|---|
Dosimetry
A mean of 95 seeds (range, 48–123 seeds) were successfully implanted in the patients. Mean value of pV100 and pD90 for the 100 patients were 96.6% and 166.1 Gy, respectively. Details of the DVH parameters are shown in Table 2.
Morbidity
Urinary and rectal morbidity as assessed using RTOG and NCI-CTC scales are shown in Tables 3 and 4. Acute morbidity was defined as morbidity occurring <12 months after implant and late morbidity as that occurring 
12 months. Genitourinary symptoms such as frequency, miction pain and retention were common, but usually not severe. Only four patients required catheterization for urinary retention (Grade 3) during follow-up. Grade 3 urinary retention developed at 1–3 months and disappeared at 3–24 months after implant, except in one patient who had not recovered as of final follow-up at 30 months. The mean duration of required catheterization was 15.3 months (range, 2–27 months).
|
|
Most patients displayed no rectal morbidity after implantation. Only 3% of patients showed RTOG Grade 2 morbidity, and no patients showed morbidity of Grade 3 or more. Diarrhea grade was counted by the number of bowel movements and did not necessarily mean that the patient had loose stools, with few patients experiencing loose or watery stools. Proctitis and hemorrhage might include not only the effects of radiation, but also hemorrhoids, due to the difficulties of differential diagnosis.
No significant relationship was identified between urethral or rectal morbidity and treatment-related parameters such as DVH.
Outcomes
One patient experienced clinical progression with lymph node recurrence at 18 months after implantation and received hormone therapy after diagnosis of clinical progression. Three patients displayed biochemical failure according to the Phoenix consensus definition (2) during follow-up. These patients had no risk factors for recurrence and had sufficiently high dose to the prostate without hormone therapy (Table 5).
|
In addition, one case of sudden death occurred <1 month after seed implantation, and has already been reported (3).
|
DISCUSSION |
|---|
|
TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONFundingReferences |
|---|
As post-implantation, CT analysis showed sufficient DVH parameters (Table 2). We believe that treatment was performed properly with administration of sufficient radiation dose. Because Stock et al. (4,5) reported a strong dose–response relationship between biologically effective dose and freedom from PSA failure, we intended to prescribe a high dose to the prostate.
As the use of 125I was legally approved only a few years ago in Japan, a small number of reports have examined morbidity associated with permanent prostate brachytherapy for Japanese patients. However, evidence from Japanese institutions is gradually increasing.
Regarding urinary morbidity, Ohashi et al. (6) reported that 111 of 130 patients (85.4%) experienced mild urinary morbidity, and only six of 130 patients (4.6%) required catheterization during a median follow-up period of 10.4 months. In another study (7), Ohashi et al. reported that 12 of 227 patients (5.3%) required catheterization for urinary retention during a median follow-up period of 16 months, and the number of needle and hormone manipulations might offer predictors for catheterization. Okaneya et al. (8) reported that only one of 100 patients (1%) required catheterization for urinary retention and 39% complained of mild poor stream or mild urinary frequency during a median follow-up period of 12.7 months. Ebara et al. (9) reported that two of 300 patients (0.6%) required catheterization during a median follow-up period of 18 months.
Similar to the above reports from Japanese institutions, our data demonstrated that urinary morbidity was common but not severe for Japanese patients using a longer follow-up period (median, 36 months) than other studies.
In terms of rectal morbidity, Ohashi et al. (10) reported that 10 of 227 patients (4.4%) developed Grade 2 rectal bleeding and one of 227 patients (0.4%) developed Grade 2 diarrhea according to RTOG toxicity criteria during a median follow-up period of 22 months. Okaneya et al. (8) reported no considerable rectal morbidity. As with these reports, rectal morbidity was mild and self-limiting in our patients. Snyder et al. (11) showed that the volume of rectum treated by the prescription dose correlates highly with development of grade 2 proctitis. The likelihood of developing proctitis in their study was 5% if <1.3 cc of anterior rectal wall received 160 Gy, and no patients developed proctitis if <0.8 cc of the rectal wall received 160 Gy. We followed these data for planning. In addition, we took into account the fact that some dosimetric differences are seen between the pre-plan US and post-implant CT analyses (12). As the tolerable rectum volume might be overestimated on CT, the volume of rectum wall receiving 145 Gy was restricted to <1.0 cc on US planning in most of our patients. Although several reports (7,11,13–17) have suggested predictive factors for degree of urinary and rectal morbidity, our data found no relationship between degree of morbidity and treatment-related factors such as DVH parameters. We consider that predictive factors could not be revealed due to the small number of morbid patients in this study.
Biochemical outcomes could not be fully evaluated in this report, since biochemical failure could not be distinguished from PSA bounce in the short follow-up (18–21). On the assumption that no PSA bounce had occurred as of the final follow-up, three patients displayed biochemical failures after implantation in our study. However, these patients had no risk factors for recurrence and had sufficiently high dose to the prostate without hormone therapy. These biochemical failures might thus have represented false-positive results due to PSA bounce. We could not identify any predictive factors for clinical or biochemical failures.
Morbidity rates in our study and from other Japanese institutions are equivalent to recently published results from Western countries (22–24). In addition, although these are still preliminary results, we achieved a sufficient tumor control rate. The importation of matured techniques developed in Western countries might allow bypass of the standard trial-and-error process in Japanese institutions. Our results indicate that interstitial permanent brachytherapy is safe and effective for Japanese patients with localized prostate cancer.
|
Funding |
|---|
|
TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONFundingReferences |
|---|
This study was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan.
Conflicts of interest statement
None declared.
|
References |
|---|
|
TOPAbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONFundingReferences |
|---|
1 Cox JD, Stetz J, Pajak TF. Toxicity criteria of the RTOG and EORTC. Int J Radiat Oncol Biol Phys (1995) 31:1341–6.[CrossRef][Web of Science][Medline]
2 Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO phoenix consensus conference. Int J Radiat Oncol Biol Phys (2006) 65:965–74.[CrossRef][Web of Science][Medline]
3 Kimura M, Satoh T, Fujita T, Okusa H, Matsumoto K, Iwamura M, et al. Sudden death after 125I brachytherapy in prostate cancer patient: a case report. Nippon Hinyokika Gakkai Zasshi (2005) 96:560–3.[Medline]
4 Stock RG, Stone NN, Cesaretti JA, Rosenstein BS. Biologically effective dose values for prostate brachytherapy: effects on PSA failure and posttreatment biopsy results. Int J Radiat Oncol Biol Phys (2006) 64:527–33.[Web of Science][Medline]
5 Stock RG, Stone NN, Tabert A, Iannuzzi C, DeWyngaert JK. A dose-response study for I-125 prostate implants. Int J Radiat Oncol Biol Phys (1998) 41:101–8.[CrossRef][Web of Science][Medline]
6 Ohashi T, Yorozu A, Toya K, Saito S, Momma T. Acute urinary morbidity following I-125 prostate brachytherapy. Int J Clin Oncol (2005) 10:262–8.[CrossRef][Medline]
7 Ohashi T, Yorozu A, Toya K, Saito S, Momma T. Predictive factors of acute urinary retention requiring catheterization following 125I prostate brachytherapy. Jpn J Clin Oncol (2006) 36:285–9.
8 Okaneya T, Nishizawa S, Nakayama T, Kamigaito T, Hashida I, Hosaka N. Permanent prostate brachytherapy for Japanese men: results from initial 100 patients with prostate cancer. Int J Urol (2007) 14:602–6.[CrossRef][Web of Science][Medline]
9 Ebara S, Katayama Y, Tanimoto R, Edamura K, Nose H, Manabe D, et al. Iodine-125 seed implantation (permanent brachytherapy) for clinically localized prostate cancer. Acta Med Okayama (2008) 62:9–13.[Medline]
10 Ohashi T, Yorozu A, Toya K, Saito S, Momma T, Nagata H, et al. Rectal morbidity following I-125 prostate brachytherapy in relation to dosimetry. Jpn J Clin Oncol (2007) 37:121–6.
11 Snyder KM, Stock RG, Hong SM, Lo YC, Stone NN. Defining the risk of developing Grade 2 proctitis following I-125 prostate brachytherapy using a rectal dose-volume histogram analysis. Int J Radiat Oncol Biol Phys (2001) 50:335–41.[CrossRef][Web of Science][Medline]
12 Ishiyama H, Kitano M, Satoh T, Niibe Y, Uemae M, Fujita T, et al. Difference in rectal dosimetry between pre-plan and post-implant analysis in transperineal interstitial brachytherapy for prostate cancer. Radiother Oncol (2006) 78:194–8.[CrossRef][Web of Science][Medline]
13 Gelblum DY, Potters L. Rectal complications associated with transperineal interstitial brachytherapy for prostate cancer. Int J Radiat Oncol Biol Phys (2000) 48:119–24.[Web of Science][Medline]
14 Han BH, Wallner KE. Dosimetric and radiographic correlates to prostate brachytherapy-related rectal complications. Int J Cancer (2001) 96:372–8.[CrossRef][Web of Science][Medline]
15 Merrick GS, Butler WM, Dorsey AT, Lief JH, Walbert HL, Blatt HJ. Rectal dosimetric analysis following prostate brachytherapy. Int J Radiat Oncol Biol Phys (1999) 43:1021–7.[CrossRef][Web of Science][Medline]
16 Mueller A, Wallner K, Merrick G, Ford E, Sutlief S, Cavanagh W, et al. Perirectal seeds as a risk factor for prostate brachytherapy-related rectal bleeding. Int J Radiat Oncol Biol Phys (2004) 59:1047–52.[CrossRef][Web of Science][Medline]
17 Merrick GS, Butler WM, Wallner KE, Allen ZA, Galbreath RW, Lief JH, et al. The impact of radiation dose to the urethra on brachytherapy-related dysuria. Brachytherapy (2005) 4:45–50.[CrossRef][Medline]
18 Crook J, Fleshner N, Roberts C, Pond G. Long-term urinary sequelae following 125 Iodine prostate brachytherapy. J Urol (2008) 179:141–6.[Medline]
19 Critz FA, Williams WH, Benton JB, Levinson AK, Holladay CT, Holladay DA. Prostate specific antigen bounce after radioactive seed implantation followed by external beam radiation for prostate cancer. J Urol (2000) 163:1085–9.[CrossRef][Web of Science][Medline]
20 Critz FA, Williams WH, Levinson AK, Benton JB, Schnell FJ, Holladay CT, et al. Prostate specific antigen bounce after simultaneous irradiation for prostate cancer; The relationship to patient age. J Urol (2003) 170:1864–7.[CrossRef][Web of Science][Medline]
21 Cavanagh W, Blasko JC, Grimm PD, Sylvester JE. Transient elevation of serum prostate-specific antigen following 125I/103Pd brachytherapy for localized prostate cancer. Semin Urol Oncol (2000) 18:160–5.[Medline]
22 Zelefsky MJ, Yamada Y, Cohen GN, Shippy A, Chan H, Fridman D, et al. Five-year outcome of intraoperative conformal permanent I-125 interstitial implantation for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys (2007) 67:65–70.[Web of Science][Medline]
23 Stone NN, Stock RG. Long-term urinary, sexual, and rectal morbidity in patients treated with Iodine-125 prostate brachytherapy followed up for a minimum 5 years. Urology (2007) 69:338–42.[CrossRef][Web of Science][Medline]
24 Lawton CA, DeSilvio M, Lee WR, Gomella L, Grignon D, Gillin M, et al. Results of a phase II trial of transrectal ultrasound-guided permanent radioactive implantation of the prostate for definitive management of localized adenocarcinoma of the prostate (radiation therapy oncology group 98-05). Int J Radiat Oncol Biol Phys (2007) 67:39–47.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Hashine, Y. Kusuhara, N. Miura, A. Shirato, Y. Sumiyoshi, and M. Kataoka Health-related Quality of Life using SF-8 and EPIC Questionnaires after Treatment with Radical Retropubic Prostatectomy and Permanent Prostate Brachytherapy Jpn. J. Clin. Oncol., August 1, 2009; 39(8): 502 - 508. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||