Preprocedural Planning
The amount of radiation to be delivered to the prostate and the configuration of the implants must be determined before the implants are placed. As experience with the technique has broadened, the planning and dosimetry stage has evolved from preplanning days to weeks in advance to intraoperative planning.
The American Brachytherapy Society (ABS) has devised the following terminology to clarify the differences in brachytherapy planning techniques:
Preplanning – Creation of a plan days or weeks before the implant procedure
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Intraoperative planning – Treatment planning in the operating room (OR), without moving the patient or the ultrasound probe
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Intraoperative preplanning – Creation of a plan in the OR just before the procedure, with immediate execution of the plan
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Interactive planning – Stepwise refinement of a plan using computerized dose calculations derived from images of needle placement
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Dynamic dose calculation – Constant updating of dose distribution calculations using continuous deposited seed position feedback
Intraoperative treatment planning does not eliminate the need for postimplant dosimetric analysis.
Preprocedural Evaluation
Laboratory studies
Laboratory studies that should be ordered before brachytherapy include the following:
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Complete blood count
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Prothrombin time
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Activated partial thromboplastin time
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Metabolic panel
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Urine culture
Imaging studies
In order to perform accurate dosimetry and real-time visualization of percutaneous source placement, the prostate and the margins of adjacent organs (eg, the rectum and bladder) must be well visualized. Transrectal ultrasonography (TRUS) and computed tomography (CT) are the 2 major modalities currently in use.
TRUS has the advantages of providing real-time imaging and sharply delineating the contours of the posterior prostate and rectal wall; its disadvantage is that its accuracy depends on the operator’s skill. The accuracy of CT scanning, on the other hand, does not depend on the operator’s skill, but prostate margins are less well defined with this imaging modality.
With either TRUS or CT, initial 5-mm slices are obtained from the base of the bladder to the pelvic floor. A target, which includes the prostate contour, with a generous allotment to the apex and a tighter margin at the base, is developed from these images. The apex tends to allow less seed migration because of the presence of the pelvic floor muscles at this site, as opposed to the looser periprostatic tissue at the base. Traditionally, a portion of the seminal vesicles is included in the target.
Information on the target volume and margins is then transmitted to a computer program, and the computer helps perform the dosimetry, plan the number of seeds, and define the location of the seeds on a 2-dimensional grid (see the image below).
The optimal strategy for seed placement is somewhat controversial. Some experts advocate uniform distribution of seeds, whereas others emphasizing placement on the periphery of the prostate, where most cancers arise.
Endorectal coil MRI is helpful in assessing the severity of prostate cancer. By placing a coil in the rectum to obtain high-quality images of the prostate, an accurate assessment can be made of seminal vesicle and capsular invasion. The Department of Radiation Oncology at Memorial Sloan-Kettering Cancer Center recently published a study that used endorectal coil MRI to assess recurrence of prostate cancer after treatment with combination brachytherapy and external-beam radiotherapy. The study concluded that extracapsular extension, tumor size, and T stage were all associated with biochemical relapse; however, extracapsular extension was the only imaging finding that was an independent predictor of recurrence. [23]
Equipment
Currently, the 2 most common permanent radioactive sources for brachytherapy seeds are I-125 and Pd-103. Of the 2, Pd-103 has a higher radiobiologic effect, and thus, its total dosing can be lower. Clinical evidence to guide selection of the radionuclide is lacking. However, because in vitro data have raised some concerns about the efficacy of I-125 in poorly differentiated and rapidly growing tumors, Pd-103 is used more commonly in higher-grade prostate cancers.
A prospective randomized multicenter trial examining the long-term morbidity associated with the use of I-125 or Pd-103 in the treatment of low-risk prostate cancer found that patients who received I-125 were more likely to develop proctitis, whereas those who received Pd-103 were more likely to develop prostatitis. [24]
Careful treatment planning should mitigate the adverse effects associated with I-125. A study by Niehaus et al evaluated International Prostate Symptom Scores (IPSSs) in 976 patients treated with brachytherapy and demonstrated that neither isotope was superior to the other in terms of IPSS resolution, catheter dependence, or need for postbrachytherapy surgical intervention. [25]
There is growing interest in the use of cesium (Cs)-131 for permanent prostate brachytherapy. Cs-131 is an attractive alternative to I-125 and Pd-103, in that its average energy is similar to that of I-125 and it has a half-life of only 9.7 days.
Patient Preparation
Epidural, spinal, or general anesthesia may be used for placement of implants. The patient is placed in a lithotomy position for brachytherapy (see the image below).
Brachytherapy for prostate cancer. Lithotomy positioning and graphic representation of how brachytherapy is performed.
In addition, the following measures are taken preoperatively:
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Bowel preparation, both mechanical and antibiotic
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Prophylactic intravenous antibiotics at the time of the procedure
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Subcutaneous heparin if the patient has a history of deep venous thrombosis
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Stoppage of all anticoagulants, including aspirin, nonsteroidal anti-inflammatory drugs, and warfarin
Monitoring and Follow-up
After brachytherapy, prostate-specific antigen (PSA) levels should be measured and a digital rectal examination (DRE) should be performed every 3-6 months for 5 years and yearly thereafter. If the PSA or DRE findings are abnormal at follow-up, an appropriately increased follow-up frequency (for PSA abnormalities only) or biopsy (for DRE abnormalities) should be considered.
Evaluation of disease-free survival
The proper use of the PSA level to define disease freedom after radiotherapy for prostate cancer is still disputed. Historically, 2 main approaches have been used to define biochemical failure. The first approach is to use absolute values to define failure, much as PSA levels are currently employed after prostatectomy. Various cutoff points have been used, ranging from 4 to 0.2 ng/mL. The second approach is to use increasing values of PSA over time as a definition of failure.
The American Society for Therapeutic Radiology and Oncology (ASTRO) has proposed that 3 consecutive elevations should define failure if each elevation satisfies certain requirements. A principal rationale behind the ASTRO definition is the well-documented occurrence of benign spikes in PSA levels that can occur after brachytherapy; allowing for these spikes prevents an incorrect diagnosis of a recurrence.
Studies have shown that the ASTRO Consensus Panel definition of biochemical failure after radiation therapy correlates well with clinical distant metastases–free survival, disease-free survival, and cause-specific survival. These findings suggest that this definition may be a surrogate for clinical progression and survival.
However, determining the date of recurrence has been controversial. In the ASTRO definition, the date of failure is the point halfway between the nadir and the first rise in the PSA level. This ambiguity, coupled with the poor performance of this definition in patients treated with hormone ablation, has led to the development of a new definition. This new definition, the Phoenix definition, is characterized by a rise in the PSA level of 2 ng/mL above the nadir. It is used to define biochemical failure after EBRT, with or without hormone ablation.
Both the ASTRO definition and the Phoenix definition are currently used in brachytherapy research protocols. Regardless of the definition used, the reported date of biochemical control should be cited as 2 years short of the median follow-up. In other words, prolonged follow-up is necessary in good studies.
The faster the PSA level nadir is reached, the better the outcomes. The following are the PSA level nadir levels and their corresponding 5-year disease-free survival rates:
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PSA level < 0.5 ng/mL - 79%
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PSA level 0.5-0.99 ng/mL - 66%
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PSA level 1-1.99 ng/mL - 49%
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PSA level >2 ng/mL- 25%
Assessment of quality of life
The ABS recommends using validated, patient-administered health-related quality-of-life methods to evaluate baseline and follow-up bowel, urinary, and sexual dysfunction. Studies have shown that over time, quality of life among patients who have undergone radical prostatectomy is comparable to that among patients who have undergone brachytherapy alone. Initial differences in the adverse-effect profile dissipate over time (2-4 y).
However, quality of life is significantly worse at all time points in patients treated with brachytherapy and intensity-modulated radiation therapy (IMRT) than in in those treated with radical prostatectomy and brachytherapy alone. The effect of androgen ablation on health-related quality of life is mixed, with some studies suggesting a worsening of health-related quality of life and others finding no discernible change.
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Brachytherapy for prostate cancer. Lithotomy positioning and graphic representation of how brachytherapy is performed.
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Brachytherapy for prostate cancer. Dosimetry plan.
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Brachytherapy for prostate cancer. Needle insertion of radioactive implants.
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Brachytherapy for prostate cancer. Abdominal radiograph following the procedure.
Tables
Studies |
No. of Patients |
Isotope (Dose) |
Disease-Free Survival |
Median Follow-Up (Range) |
Koutrouvelis et al, 2003 [11] |
31 |
Pd-103 in 26, I-125 in 5 |
87% (biochemical control) |
30 mo |
Beyer, 1999 [12] |
17 |
I-125 (120 Gy) in 15, Pd-103 (90 Gy) in 2 |
53% (5-y PSA progression by ASTRO* criteria) |
54 mo (23-147 mo) |
Grado et al, 1999 [13] |
49 |
I-125 or Pd-103 |
34% (5-y PSA progression by 2 successive rising PSA values above posttreatment PSA nadir) |
64 mo |
ASTRO = American Society for Therapeutic Radiology and Oncology; PSA = prostate-specific antigen. |
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