Complications

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Urinary toxicity

One of the major perceived benefits of prostate brachytherapy is lower long-term complications, because of the presumably lower radiation doses to adjacent normal tissue. Whether this perception is confirmed by published series is unclear, however, with at least one study showing no benefit to urinary, bowel or sexual domains of quality of life (QOL) surveys with brachytherapy compared with RRP or XRT.87 Nearly all patients will develop some urinary symptoms acutely after implantation, including urinary urgency and frequency. In the MSKCC series, 55% of patients developed acute Grade 2 urinary toxicity, defined as irritative voiding symptoms requiring medication, and 3% developed acute Grade 3 urinary toxicity, defined as urinary retention requiring catheterization.81 The long-term urinary toxicity and complications require more attention. At MSKCC, late urinary toxicity, defined as symptoms persisting or developing de novo longer then 1 year after treatment, occurred in nearly half of patients. Forty per cent of patients developed late Grade 2 urinary toxicity with a 5-year actuarial rate of 41%.81 Late Grade 3 urinary toxicity, defined as urethral obstruction or stricture requiring trans-

urethral resection, occurred in 9% of patients, with a 5-year actuarial incidence of 10%; the median time to development of stricture was 18 months. One patient (0.4%) developed a late Grade 4 urinary toxicity requiring urinary diversion and colos-tomy in the MSKCC series. Beyer et al. reported slightly better late urinary toxicity results, with 4% of patients developing Grade 2 or 3 urinary toxicity.86 Seven patients (1%) in this series were incontinent, with over half (four patients) incontinent after TURP.

TURP has been implicated as a risk factor for incontinence after brachytherapy. In an earlier study from Ragde and Blasko of implant monotherapy and implant plus adjuvant XRT, 551 patients were evaluated.88 Severe late urinary complications requiring urinary diversion occurred in nine patients, and 28 patients developed mild stress incontinence. In this group of 37 patients, 36 had undergone prior TURP. Conversely, in a small study from MSKCC totalling 19 patients who had a history of prior TURP, only one patient developed incontinence after brachytherapy treatment, giving a 3-year actuarial freedom from incontinence of 94%.89 With the awareness that the central, peri-urethral region of the prostate does not require as high a radiation dose, the incontinence rate decreased in the

Seattle series, and the prognostic effect of prior TURP on incontinence after prostate brachytherapy appears less significant.88

Impotence

In a large prospective study examining 482 men receiving prostate brachytherapy who were potent prior to treatment, the 5-year actuarial impotency rate was 47%.90 When stratified for implant monotherapy, implant plus adjuvant XRT, implant plus NHT or implant plus adjuvant XRT and NHT, the 5-year actuarial impotency rates were 76%, 56%, 52% and 29%, respectively. Multivariate analysis identified pretreatment NHT use and patient age as independent predictors of post-treatment impotence in this study. In a subset analysis of 84 men who tried sildenafil for erectile dysfunction after treatment, patients who did not receive NHT had a significantly better response then those treated with NHT. These results are similar to a comparative study examining 3D conformal XRT and 125I prostate brachytherapy in the favorable risk patient by Zelesky.91 This study noted a 5-year likelihood of erectile dysfunction of 53% after implantation in men who were potent before treatment, and was slightly higher but not significantly different then the XRT group (43%). A multivari-ate analysis to identify predictors of post-treatment erectile dysfunction recognized only radiation dose delivered (>75.6 Gy for XRT or ^160 Gy for brachytherapy) as an independent predictor of impotence; age younger or older then 60 years, prior TURP, use of NHT and mode of treatment (XRT or brachytherapy) were not significant predictors of post-treatment impotence.91 The potency rate for brachytherapy, unlike after RRP, appears to worsen over time, with Stock etal. noting a decrease in potency from 3 years to 6 years of 79% to 59% after brachytherapy.92

Bowel toxicity

Bowel toxicity after prostate brachytherapy includes similar symptoms to those after XRT, namely proctitis, tenesmus, urgency, rectal bleeding, rectal stenosis, necrosis, and recto-vesical or rectourethral fistula formation. In Zelefsky's series at MSKCC, severe bowel complications were rare, with a 5-year actuarial rate of Grade 2 rectal bleeding of 9%, and one patient (0.4%) developing a Grade 4 rectourethral fistula requiring urinary diversion and colostomy.81 A slightly higher Grade 4 rectal complication rate of 1% was noted in the series of Grado etal.84 Although these complications involved only five of 490 patients, less serious bowel toxicities were not mentioned.84 Overall, severe bowel toxicity resulting from implant monotherapy is rare and appears less common than in XRT.

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