1. Factors Predicting for Urinary Incontience Following Prostate Brachytherapy Tracy L. McElveen, M.D., Frank M. Waterman, Ph. D., Hayeon Kim, M.S., and Adam P. Dicker M.D., Ph.D. Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSION & RECOMMENDATIONS REFERENCES Quality of life has become increasingly important to patients faced with choosing a treatment modality for favorable risk prostate cancer. Quality of life issues often include rectal bleeding or diarrhea, sexual dysfunction, irritative urinary symptoms, and urinary incontinence. Urinary incontinence has been most commonly associated with radical prostatectomy and, according to the National Medicare Experience, over 47% of patients have reported some degree of incontinence after this procedure [3]. Rates over a broad range of 0%–40% after brachytherapy have been reported [1, 2, 4, 5, 6, 7, and 8]. Many reports, however, contain physician-acquired information that has been shown to correlate poorly with data collected from patient self- assessment questionnaires [3, 9, 10, 11, 12 and 13]. Much of the published literature on this topic lacks dosimetric information and does not specifically include urinary incontinence in the grading scale. This study sought to evaluate the incidence of urinary incontinence and to determine predictive factors for this complication. Hypothesis This study sought to evaluate the incidence of urinary incontinence and to determine predictive factors for this complication. Patient Population 153 patients implanted from October 1996 to December 2001 All patients were evaluated with an H&P, baseline I-PSS, and most had internal pathologic review Patient characteristics included: PSA < 10 Gleason score (GS) < 6 Stage < T2b Excluded from our study Patients who received external beam radiation Patients implanted with 103Pd Implant Technique Preimplant CT scans were obtained and used to assess prostate volume, to evaluate for pubic arch interference, and to plan treatment. The implants were planned (Variseed, Varian, Palo Alto, CA) to deliver a minimum dose of 145 Gy to the gland plus a symmetric 3–5-mm margin. 125I seeds (0.4–0.6 mCi, NIST-99) were loaded peripherally, with the seeds kept within the prostate, except at the apex. Implants were performed under general anesthesia using a Mick applicator (Mick Radio-Nuclear Instruments, Inc., Mount Vernon, NY) with a Foley catheter in place to visualize the urethra. Postoperative dosimetry was calculated in accordance with ABS guidelines from a CT scan performed approximately 30 days after the procedure to allow for resolution of prostatic edema. Survey Tool Urinary incontinence after 125I prostate brachytherapy was evaluated using a patient self-assessment questionnaire based on the NCI Common Toxicity Criteria (version 2).). NCI CTC ver 2 was used because it allowed for the evaluation of several possible treatment-related side effects not covered by the I-PSS or the commonly used RTOG grading scale currently, all NCI cooperative groups have implemented this toxicity scale for use in clinical trials Evaluating Incontinence NCI-CTC ver 2 Do you experience any involuntary loss of urine? YesNo If yes, please describe your level of incontinence Grade 0 No leakage of urine Grade 1 Some leakage of urine on sneezing, coughing or laughing Grade 2 Leakage requiring a pad, some control Grade 3 No control Survey Results 153 patients surveyed 112 (72%) responded Median follow-up was 47 months (range 14–74 months) 37 patients (33%) reported developing some degree of incontinence following prostate brachytherapy Grade 1: 30 patient (81%) Grade 2: 7 patients (19%) Grade 3- no patients Clinical Parameters EvaluatedDosimetric Parameters Evaluated AgeUrethral D5, D10, D25, D50, D75, D90, and D100 StageProstate D90, V300, V200, V150, V100 Gleason scoreProstate volume Pretreatment PSANumbers of needles Preimplant I-PSS Number of seeds Length of follow-up Seed activity and total activity of the implant Telephone Interview Confirm the presents of incontinence Determine baseline incontinence Determine the onset of symptoms Number of pads used per day Incidence of Incontinence Twenty-eight patients reported Grade 1 incontinence (26%), and 5 patients reported Grade 2 (5%). Patients with Grade 1 and 2 incontinence were analyzed together, because of the small number of patients who experienced Grade 2. No patients reported Grade 3 incontinence. Urethral dose The urethral DVHs of the patients who did (Grades 1, 2) and did not (Grade 0) experience incontinence were separately averaged and are plotted in Fig. 1. This figure shows that the patients experiencing incontinence received a significantly higher dose at all levels of coverage. The most significant difference was noted at the D10 level: The mean urethral D10 dose for patients with Grade 0 was 314 ± 78 Gy, compared with 394 ± 147 Gy for patients who experienced incontinence (p = 0.002). The incidence of incontinence is plotted in Fig. 2 as a function of the urethral D10 dose. This figure illustrates that the incidence of incontinence increased with the urethral D10 dose. Although there is no clear dose threshold, the incidence of incontinence increased noticeably when the D10 dose exceeded 350 Gy, increasing to nearly 60% when the dose exceeded 450 Gy. The first 3 bars in Fig. 2 represent dose increments of 100 Gy. The last bar includes all of the patients who had a D10 dose ≥450 Gy and extends to 810 Gy, the highest D10 dose observed. These patients were grouped together, because there were only 17 patients with a D10 dose ≥450 Gy. Preimplant I-PSS The incidence of incontinence is plotted in Fig. 3 as a function of the preimplant I- PPS. This figure indicates that the incidence of incontinence was relatively insensitive to the preimplant I-PPS in the range 0–14. When the I-PPS is 15 or greater, however, the incidence of incontinence increased sharply to about 70%. These results show that patients with an I-PSS ≥15 are at a much higher risk of incontinence. The first 3 bars in Fig. 3 represent an I-PPS score increment of 5. The last bar was extended from 15 to 24, because there were only 14 patients with an I- PPS ≥15. Multivariate analysis indicated that the urethral D10 dose and the preimplant I-PSS are both predictive of postimplant incontinence. Fig. 3 includes patients who may be incontinent as a result of the urethral D10 dose and does not reflect solely the incontinence attributable to the I-PSS score. Similarly, the incidence of incontinence plotted in Fig.2 does not reflect solely the incontinence attributable to the D10 dose. Although we cannot completely separate the influence of these two variables, we can reduce the influence of the D10 dose by deleting patients with a D10 dose ≥350 Gy from Fig.3. As shown in Fig. 4, this reduced the incidence of incontinence from about 25% to 12% for patients with an I-PPS <10 but did not alter the incidence of incontinence for patients with an I-PPS ≥15. This finding strongly suggests that patients with a preimplant I-PPS ≥15 are at a high risk for incontinence regardless of the urethral dose, whereas patients with an I-PPS <10 are at minimal risk unless they receive a high urethral dose. Nonsignificant Variables No relationship was noted between incontinence and prostate volume, total activity implanted, or the number of needles used (p = 0.83, p = 0.89, p = 0.36, respectively). Preimplant I-PSS and urethral D10 dose predicted for urinary incontinence on univariante and multivariante analysis (p=0.003 and p=0.002 respectively) There is a clear dose response for the urethra and urinary incontinence. The risk of incontinence doubles as the urethral D10 dose increased above 450 Gy A significant increase in the incidence is noted when pre-implant I-PSS scores are above fifteen Patients with a preimplant I-PPS ≥15 are at a high risk for incontinence regardless of the urethral dose, whereas patients with an I-PPS <10 are at minimal risk unless they receive a high urethral dose The incontinence encountered in our patients was generally mild stress incontinence. To prevent this complication, we recommend limiting the urethral dose to as close to the prescription dose as possible and selecting patients with an I-PSS less than fifteen. 1. H. Ragde, J.C. Blasko, P.D. Grimm et al., Brachytherapy for clinically localized prostate cancer: Results at 7- and 8-year follow- up. Semin Surg Oncol 13 (1997), pp. 438–443. 2. Ragde H, Elgamal AA, Snow PB, et al. 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