A total of 98 patients with T1–T2 prostate cancer (according to the International Union Against Cancer TNM Classification of Malignant Tumours 6th edition [10
]) underwent 125
I permanent radioactive seed implantation between April 2005 and September 2009 at Isesaki Municipal Hospital. Among them, 90 patients who did not receive adjuvant EBRT were followed up for more than 36 months. One was excluded from this study, because the computed tomography (CT) data for post-implant dosimetry could not be used. Hence, 89 patients were evaluated, and their clinical and treatment characteristics are shown in Table . According to the National Comprehensive Cancer Network Guidelines [11
], 48 and 39 patients had low-risk and intermediate-risk prostate cancer, respectively. The median age was 70 years (range 51–80 years), and the median initial prostate specific antigen (PSA) level before biopsy was 5.5 ng/ml (range 3.0–34.0 ng/ml). A total of 17 patients (19%) received anticoagulant therapy for various reasons. Neoadjuvant androgen deprivation therapy (ADT) was given to 43 patients (48.3%) for a median of 9 months (range 1–39 months). ADT consisted of a luteinizing hormone releasing hormone agonist alone in 40 patients or in conjunction with an anti-androgen in 2 patients or an anti-androgen alone in 1 patient. Written informed consent was obtained from each patient before treatment.
Clinical characteristics of patients
About one month before the actual implant procedure, a volumetric study of the prostate was performed for all patients with transrectal ultrasound (TRUS) with patients in the dorsal lithotomy position. The prostate was scanned at 5-mm intervals from the proximal seminal vesicles to the apex. The captured images were digitized with a planning computer. Treatment planning was performed with the brachytherapy planning system VariSeed 7.1 (Varian Medical Systems, Palo Alto, CA, USA) to calculate the well-designed dose volume histogram (DVH). 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 bilateral and anterior directions but no margin posteriorly. We set the treated volume to include the PTV within the prescribed isodose (145 Gy), using a modified peripheral loading technique. Implantation was performed under general anesthesia, via TRUS guidance of the preplanned seeds, with the patient in the extended lithotomy position, similar to the volumetric study. A Mick applicator (Mick Radionuclear Instruments, Bronx, NY, USA) was used to deposit the seeds.
One month after implantation, both computerized tomography (CT) and magnetic resonance imaging (MRI) were carried out for dosimetric analysis. A urinary catheter was placed during these examinations. Axial CT images 2.5 mm in thickness were obtained at 1.25-mm intervals, and T2-weighted images 2 mm in thickness were acquired within 1 h after CT examination. The CT and MR images were electronically fused using the manual-fusion procedure of the Variseed fusion system by fitting the urethra, and then the prostate, rectum and urethra were contoured. To provide consistency in defining rectal volumes, all rectal outlining was redone by one person (K.H.). Volumes were contoured as a solid structure defined by the outer wall from one slice above and below the prostate.
The calculated dosimetric parameters included the % volume of the post-implant prostate receiving 100 and 150% of the prescribed dose (V100 and V150, respectively) and values of the minimal dose received by 90% of the prostate volume (D90). The urethral dose was expressed as values of the minimal dose received by 5% of the urethral volume (UD5). The rectal volumes in cubic centimeters that received >50, 75, 100, 125, 150, 175 and 200% of the prescribed dose (RV50, RV75, RV100, RV125, RV150, RV175 and RV200, respectively) and the minimal doses received by 1, 2, 5, 10 and 30% of the rectum volume (RD1, RD2, RD5, RD10 and RD30, respectively) were determined.
After brachytherapy, patients were followed-up at 3-month intervals to record information concerning disease status, rectal bleeding and cause of death. If patients were unable to visit our hospital due to various reasons, the information was obtained through letters or telephone contact directly with patients or relatives or through communication with the referring physicians. Rectal bleeding was confirmed by rectal digital examination and endoscopy and was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [12
] (Table ). All time intervals were measured from the day of brachytherapy to occurrence of the rectal bleeding. The median follow-up time for this study was 42 months (range 18–73 months).
CTCAE version 4.0 rectal hemorrhage criteria
The student's t test and a chi-square test were used to compare the distribution of clinical and dosimetric parameters between the two groups. The cumulative incidence of rectal bleeding was calculated with the Kaplan-Meier method, and differences in cumulative incidence were compared with the log-rank test. Statistical significance was set at P < 0.05.