Urinary Tolerance

In general, almost all patients after prostate brachytherapy develop acute urinary symptoms such as urinary frequency, urinary urgency, and occasional urge incontinence. Depending upon the isotope used, these symptoms often peak at one to three months after the procedure and subsequently gradually decline over the ensuing three to six months. Most patients significantly benefit from the use of an alpha-blocker, which ameliorates such symptoms in 60% to 70% of patients.

Grimm et al. [25] summarized the tolerance outcome in 310 patients who received I-125 or Pd-103 for localized disease. During the first 12 months after the procedure, approximately 90% of the patients had grade 1 or 2 acute urinary symptoms, which included urinary frequency, urinary urgency, and obstructive symptoms. Grade 3 acute toxicity was reported in 8% of patients, and 1.5% experienced a grade 4 toxicity. Late grade 3 and 4 toxicities were noted in 7% and 1%, respectively. These authors also documented urinary incontinence rates ranging from 6% to 48% among patients with a prior history of TURP. Among those patients without a history of TURP and with modest gland volumes, the incidence of chronic urethritis and incontinence was found to be less than 3%.

The five-year tolerance outcome of CT-preplanned implantation at Memorial Sloan-Kettering Cancer Center was reported by Zelefsky et al. [26]. One hundred thirty-five patients (55%) developed acute grade 2 urinary symptoms after permanent I-125 interstitial implantation. These symptoms included urinary frequency and urgency, which were generally treated with alpha-blocker medications. Patients were characterized as having late grade 2 urinary toxicity if acute symptoms persisted for more than one year after TPI or had become clinically manifest at that time. One hundred patients (40%) developed late grade 2 urinary toxicity, and the five-year actuarial likelihood of grade 2 urinary toxicity was 41%. These symptoms often persisted in these patients during the first year after seed implantation and were effectively managed with alpha-blocker therapy. The actuarial likelihood of grade 2 urinary symptom resolution at one, two, and three years after TPI was 19%, 50%, and 70%, respectively. Twenty-three patients (9%) developed urethral strictures after brachytherapy (grade 3 urinary toxicity). The five-year likelihood of stricture development was 10%, and the median time to development was 18 months.

Brown et al. [27] reported on 87 patients who underwent prostate brachyther-apy and whose urinary symptoms were carefully assessed after the procedure. Urinary effects such as frequency, nocturia, and dysuria generally developed two to three weeks postimplantation and peaked three to four months after the procedure. A gradual decline in the severity of symptoms was noted in approximately 75% of the patients during the first 12 months. In this series, 41% of the patients experienced acute grade 2 or 3 urinary morbidity, with 6% having acute grade 3 urinary morbidity. After 12 months, 22% of the patients experienced persistent urinary morbidity. Of this latter group, approximately 70% were characterized as having persistent grade 1 and 30% as having persistent grade 2 or 3 symptoms.

According to the aforementioned reports, there appears to be a higher incidence of acute grade 2 genitourinary symptoms with standard implantation techniques than with conformal radiotherapy. The increased likelihood of such symptoms is related to the higher doses inevitably delivered to the urethra, which generally average 1.5 to 2 times more than the prescription dose. The uniform source and needle placement initially used by the Seattle group were associated with central doses that were in excess of 200% of the prescription dose. These observations influenced these investigators to use a modified peripheral seed-loading approach to minimize the urethral dose to 150% or less of the prescription dose. Several reports have noted that acute urinary symptoms and late urinary morbidity after seed implantation correlate with the central target doses and the proximity of seed placement to the urethra. Others [28] demonstrated a reduction in grade 2 symptoms (from 42% to 19%) when the central dose was reduced by placement of half-strength radioactive seeds in the periurethral area. Wallner et al. [29] demonstrated a correlation of late urethral toxicity with the urethral dose from prostate brachytherapy. In that study, the average maximal urethral dose among patients with late grade 2 and 3 urinary toxicities was 592 Gy, compared with 447 Gy for those who had minimal (grade 1) or no late urinary toxicity (p = 0.03).

With the introduction of intraoperative conformal planning for ultrasound-based implantation at Memorial Sloan-Kettering Cancer Center in 1996, a significant reduction in the average and maximal urethral doses achieved with this approach translated into an improved urinary tolerance profile and quality of life for treated patients. Zelefsky et al. [30] reported a reduced incidence of grade 2 acute urinary symptoms and more rapid resolution of symptomatology with this technique compared with a preplanned technique previously used at the institution (Fig. 3). These data highlight the important relationship between the urethral dose and urinary symptoms after prostate brachytherapy. Careful

Prostate Bed Rectal Tolerance

0 8 16 24 32 40 48 56 64 72 80 Months

Fig. 3. Time to urinary symptom resolution

0 8 16 24 32 40 48 56 64 72 80 Months

Fig. 3. Time to urinary symptom resolution attention to this parameter during intraoperative planning is important for achieving an optimal outcome, and a modified peripherally loaded implant not in conjunction with computer-generated planning will not necessarily consistently achieve lower urethral doses.

Rectal Tolerance

The reported incidence of grade 2 rectal toxicity after prostate brachytherapy ranges from 2% to 12%. Grade 3 or 4 rectal toxicity is unusual (<2%). Grimm et al. [25] reported grade 2 late proctitis in 2% to 12% of patients treated at the Seattle Prostate Institute, but no grade 3 or 4 gastrointestinal complications were reported. The actuarial incidence of late grade 2 rectal bleeding was 9%. In general, such symptoms were treated with conservative measures and resolved in all cases. One patient (0.4%) developed a grade 4 rectal complication.

Waterman and Dicker [31] reported on the dosimetric predictors of late rectal toxicity in 98 patients who were treated with I-125 implantation. Based on dose-surface histograms performed in all cases, late rectal morbidity correlated strongly with the percentage of the rectal surface that received at least 100 Gy. The probability of late rectal morbidity was 0.4%, 1.2%, and 4.7% when the maximal rectal dose was 150, 200, and 300 Gy, respectively. According to that report, constraining the rectal dose to 100, 150, and 200Gy to 30%, 20%, and 10% of the rectal surface, respectively, should result in less than 5% rectal morbidity. Snyder et al. [32] also observed a correlation between the volume of the rectum irradiated to the prescription dose and late rectal toxicity after prostate brachytherapy. The five-year likelihood of rectal toxicity was 18% for patients in whom more than 1.3 cm3 of rectal tissue was exposed to 160 Gy or higher, compared with a 5% incidence among patients in whom less than 1.3 cm3 of the rectum was exposed to these dose levels. The incidence of rectal toxicity correlated with the volume irradiated: 0% for 0.8cm3, 7% to 8% for >0.8 to 1.8cm3, and 25% for >1.8cm3. Meticulous attention to needle and seed placement in the operating room as well as intraoperative dose-volume histograms of normal tissue should reduce the rectal doses and the risks of toxicity to minimal levels.

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