High-Dose-Rate Brachytherapy in the Treatment of Carcinoma of the Prostate

A.M. Nisar Syed, MD, Ajmel Puthawala, MD, Anil Sharma, PhD, Sherief Gamie, MD, Adina Londrc, MD, Joel M. Cherlow, MD, PhD, Steven J. Damore, MD, Nashwa Nazmy, MD, Khalid M. Sheikh, PhD, and Stephen J. Ko, MD


Cancer Control. 2001;8(6) 

In This Article

Abstract and Introduction

Background: Although radical prostatectomy for localized disease is considered as a standard of care, external-beam radiotherapy and brachytherapy are equally effective. We report on the technique and preliminary results of high-dose-rate (HDR) brachytherapy using a temporary iridium-192 implant technique.
Methods: The authors reviewed the literature on the techniques, treatment protocols, and results of HDR brachytherapy in the treatment of carcinoma of the prostate, and they report their own protocols, technique, and results.
Results: The combination of HDR brachytherapy and external irradiation has been well tolerated by all 200 patients in our series, with less than 3% grade 3 late complications and with 95% PSA relapse-free survival with a median follow-up of 24 months.
Conclusions: HDR brachytherapy may be the most conformal type of irradiation in the treatment of carcinoma of the prostate regardless of tumor size, anatomical distortion, and organ mobility.

Carcinoma of the prostate is a common cancer in men in the United States. Treatment options include radical prostatectomy and radiation therapy (external-beam and brachytherapy), among others. Most reported series of treatment with radical prostatectomy with or without nerve-sparing treatment include patients who are younger than 70 years of age in good medical condition and exclude those with metastatic pelvic lymph nodes or gross extracapsular tumor extension. [1,2,3,4,5,6]

In contrast, patients treated with irradiation are older, they are in less than ideal medical condition, and they frequently have more extensive local tumors.

The effect of surgical staging on outcome of irradiation was documented by Asbell et al [7] in patients with clinical stages A2 and B carcinoma of the prostate. The 5-year disease-free survival rate was 76% in patients with surgically evaluated negative pelvic lymph nodes vs 63% for those with radiographically evaluated negative lymph nodes. The disease-free, metastasis-free, and overall survival rates were similar in patients with positive or negative radiographically assessed lymph nodes, indicating the limitations of this procedure in correctly evaluating lymph node status in these patients. The authors concluded that radiographic determination of lymph node status had no prognostic value and should not be used for stratification of patients in clinical trials. Thus, for a true comparison of results of radical prostatectomy or radiation therapy, all patients treated with either modality should be surgically staged or all patients should be randomized before treatment and receive therapy based on the findings of various staging procedures.

External irradiation is used as a definitive therapy in a large number of patients with clinical stage A, B, and C or locally extensive tumors. Tumor doses have ranged from 60-64 Gy for stage A1 (T1a) tumors, 65-70 Gy for stage A2 (T1b) and B (T2) tumors, and 70-72 Gy for stage C (T3) tumors. [8,9,10] Several retrospective studies indicate that dose affects local tumor control. Hanks and colleagues [11] reported the following actuarial 5-year local recurrence rates: 37% for patients treated with doses less than 60 Gy, 36% for 60-64.9 Gy, 29% for 65-69.9 Gy, and 19% for 70 Gy or more.

In most instances, the failure of radiotherapy to control organ-confined prostate cancer results from the persistence of prostatic tumor clonogens with inherent resistance to the radiation doses used. To avoid under-dosage relative to the prescribed schedule or even a complete miss of part of the tumor-containing prostate, conventional radiotherapy techniques should uniform-ly encompass significant portions of the bladder and rectum. Consequently, attempts to increase the tumor dose are frequently restricted by the high sensitivity of the rectum and bladder to the effects of radiation. The recently introduced high-precision radiation techniques, ie, three-dimensional (3D) conformal photon therapy, intensity-modulated radiation therapy, and proton-beam radiation therapy, provide a way to over-come these limitations on dose escalation, and preliminary reports are encouraging. [12,13,14,15,16] Neoadjuvant hormonal deprivation with external-beam radiotherapy (EBRT) in patients with locally advanced carcinoma of the prostate, metastatic pelvic lymph nodes, or Gleason score of 8-10 has significantly improved local control and survival in prospective, randomized trials by the European Organization for Research and Treatment of Cancer (EORTC) [17] and the Radiation Therapy Oncology Group (RTOG). [18]

The incidence of fatal complications in localized carcinoma of the prostate treated with conventional external irradiation is approximately 0.2%. The overall incidence of severe urinary and rectosigmoid sequelae is approximately 3%; moderate complications occur in 7%-10% of patients. The incidence of impotence from different series ranges from 31%-60%. [19,20,21]

Brachytherapy in the treatment of carcinoma of the prostate was reported as early as 1972 by Whitmore et al [22] using a retropubic approach with bilateral pelvic lymphadenopathy. In general, brachytherapy alone is used for tumors clinically staged as T1 and T2a, whereas stage T2b and T2c lesions with high risk of extracapsular extension and pelvic node metastases are usually treated by a combination of external irradiation and brachytherapy. Zelefsky et al [23] reported 56% and 34% local control rates in patients with T2a lesions at 10 and 15 years, respectively, following permanent iodine-125 implantation using a retropubic approach. Several authors have reported 5-year prostate-specific antigen (PSA) relapse-free survival rates of 85%-94% in low-risk patients, 33%-82% in intermediate-risk patients, and 5%-65% in high-risk patients using the transrectal ultra-sound (TRUS)-guided implant technique. [24,25,26,27] A majority of patients develop early grade 1 and 2 urinary symptoms (frequency, dysuria, and urgency of micturition) following brachytherapy. Late grade 3 and 4 genitouri-nary complications such as urethral stricture and incontinence occur in 3%-11% of patients, which increases to 18% in patients who had prior transurethral resection of the prostate. Grade 3-4 rectal complications were reported in 1%-2% of patients.[28,29]

Although the TRUS-guided technique significantly improved source distribution compared with the retropubic approach, several disadvantages of the permanent implant technique remain unresolved, such as the inability to implant seminal vesicles, extracapsular extension, apical lesions, and patients who had transurethral resection of the prostate. The most significant disadvantages are the inability to alter position of the seeds once implanted and migration of seeds in 5%-10% of patients.

We previously reported our technique and the results of a low-dose-rate (LDR) temporary iridium-192 implant technique using transperineal approach under ultrasound guidance, which resulted in positive biopsies following irradiation in 15% and an 85% actuarial survival rate. [30,31,32,33,34] Mate et al [35] and others [36,37,38,39,40] employed a similar technique but used high-dose-rate (HDR) rather than LDR with excellent PSA relapse-free survival and minimal complications. Encouraged by the long-term results of our LDR brachytherapy using a temporary iridium-192 implant technique and preliminary data of HDR brachytherapy, we developed an HDR brachytherapy protocol and began treating patients 6 years ago.[41,42]


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