Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy.

PURPOSE: Recent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT. METHODS AND MATERIALS: Between April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. RESULTS: At 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p=0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p=0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p=0.14). CONCLUSIONS: Men with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason pattern 5.

The impact of diabetes mellitus on survival in men with clinically localized prostate cancer treated with permanent interstitial brachytherapy.

PURPOSE: Patients with cancer of any origin with preexisting diabetes mellitus (DM) are at increased risk for all-cause mortality compared with those without DM. However, the influence of DM on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) has not been clearly defined for men with clinically localized prostate cancer treated with brachytherapy. MATERIALS AND METHODS: From April 1995 to May 2006, 1624 consecutive patients underwent brachytherapy with or without supplemental therapies. A prebrachytherapy diagnosis of diabetes was present in 199 patients (12.3%). Median follow-up was 7.8 years. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate-resistant disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. RESULTS: In patients without (n=1425) and with (n=199) DM, CSS was 97.2% versus 100% (P=0.168), bPFS was 95.6% versus 95.7% (P=0.960), and OS was 77.3% versus 56.0% at 12 years (P=0.003). In Cox regression analysis, OS in nondiabetic patients was most closely related to patient age, coronary artery disease, tobacco consumption, and androgen deprivation. In patients with diabetes, OS was related to patient age and coronary artery disease. In patients without diabetes, CSS was associated with Gleason score and clinical stage. No patient with diabetes died of prostate cancer. Patients with DM were more likely to die of cardiovascular disease (17.8% vs. 12.4%, P=0.007). CONCLUSIONS: DM does not impact CSS or bPFS after brachytherapy. OS is significantly lower in patients with diabetes due to more deaths from cardiovascular disease.

Influence of body mass index on biochemical outcome after permanent prostate brachytherapy.

OBJECTIVES: To evaluate the impact of body mass index (BMI) on the 8-year biochemical outcome after permanent prostate brachytherapy with or without the addition of supplemental external beam radiotherapy and/or androgen deprivation therapy (ADT). METHODS: From April 1995 through February 2001, 686 consecutive patients underwent brachytherapy using either palladium-103 or iodine-125 for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) prostate cancer. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 59.5 months. The evaluated BMI subgroups were less than 25, 25.0 to 29.9, 30.0 to 34.9, and 35 or more kg/m2. Biochemical progression-free survival was defined by a prostate-specific antigen (PSA) level of 0.4 ng/mL or less after a nadir. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included BMI, patient age, clinical T stage, Gleason score, preimplant PSA level, risk group, percentage of positive biopsies, isotope, use of supplemental external beam radiotherapy, use of ADT, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose, minimal percentage of dose covering 90% of the target volume, tobacco use, and the presence of hypertension and diabetes. RESULTS: For the entire group, the actuarial 8-year biochemical progression-free survival rate was 95.8%, 95.6%, 94.1%, and 100% for patients in BMI categories less than 25, 25.0 to 29.9, 30.0 to 34.9, and 35 or more kg/m2, respectively. In hormone-naive and hormone-manipulated patients free of biochemical progression, the median post-treatment PSA level was less than 0.1 ng/mL. When integrated across risk groups and ADT use, BMI had no statistically significant impact on biochemical progression-free survival. At last follow-up, 5 patients (0.7%) had died of metastatic prostate cancer. In multivariate Cox regression analysis, pretreatment PSA level, Gleason score, clinical stage, percentage of positive biopsies, ADT use, and tobacco status, but not BMI, were statistically significant predictors of 8-year biochemical progression-free survival. CONCLUSIONS: Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low, intermediate, and high-risk patients. When integrated across risk groups and hormonal status, BMI had no statistically significant influence on biochemical progression-free survival.

Impact of supplemental external beam radiotherapy and/or androgen deprivation therapy on biochemical outcome after permanent prostate brachytherapy.

PURPOSE: To evaluate the impact of supplemental external beam radiotherapy (EBRT) and/or androgen deprivation therapy (ADT) on 8-year biochemical outcome after permanent prostate brachytherapy. METHODS AND MATERIALS: Between April 1995 and January 2001, 668 consecutive patients underwent brachytherapy using either (103)Pd or (125)I for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) adenocarcinoma of the prostate gland. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 58.6 months. Biochemical progression-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included supplemental EBRT, ADT, patient age, clinical stage, Gleason score, preimplant prostate specific antigen (PSA), risk group, percentage of positive biopsies, isotope used, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of prescribed dose, minimal percentage of dose covering 90% of target volume, tobacco status, hypertension, and diabetes. RESULTS: For the entire group, the actuarial 8-year biochemical progression-free survival rate was 98.2%, 98.4%, and 88.2% for low-, intermediate-, and high-risk patients, respectively, with a median PSA level of <0.1 ng/mL for all risk groups and ADT and EBRT subgroups. At last follow-up, only 5 patients (0.8%) had died of metastatic prostate cancer. In multivariate analysis, Gleason score, percentage of positive biopsies, and ADT predicted for biochemical outcome in high-risk patients. In low- and intermediate-risk patients, none of the evaluated variables predicted for biochemical outcome. For the entire population, pretreatment PSA level, Gleason score, ADT, and clinical stage predicted for 8-year biochemical progression-free survival, with the percentage of positive biopsies approaching statistical significance. CONCLUSION: Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low-, intermediate-, and high-risk patients. Although the role of supplemental EBRT could not be adequately evaluated in high-risk patients, it did not improve biochemical outcome in low- and intermediate-risk patients. However, ADT resulted in a statistically significant improvement in progression-free survival for high-risk patients.

The effect of hormonal manipulation on urinary function following permanent prostate brachytherapy.

PURPOSE: To evaluate the effect of hormonal manipulation on catheter dependency, the resolution of urinary symptomatology, and the need for postbrachytherapy transurethral/transincisional resection (TURP/TUIP). METHODS AND MATERIALS: Seven hundred sixteen consecutive patients (median follow-up, 29 months) underwent brachytherapy for clinical T1b-T3a (1997 AJCC) prostate cancer from January 1998 through August 2002. Of the evaluated cohort, 400 patients were hormone naïve, 227 received short-course cytoreductive (< or = 6 months) hormonal therapy, and 89 received extended (>6 months) hormonal therapy. An alpha-blocker was initiated prior to implantation and continued at least until the International Prostate Symptom Score (I-PSS) returned to baseline levels. Evaluated parameters included age, T-stage, preimplant I-PSS, ultrasound volume, treatment planning volume, hormonal status, supplemental external beam radiation therapy (XRT), isotope, urethral dose, total implant activity, D90, and V100/150/200. Catheter dependency and the incidence of TURP/TUIP were also evaluated. RESULTS: Six hundred fifty three patients (91.2%) had the urinary catheter permanently removed on day 0 with 15 patients (2.1%) requiring a catheter beyond 4 days. The I-PSS returned to within 1 point of the antecedent value at a median of 4 months. Sixteen patients (2.2%) underwent postimplant TURP/TUIP. A Cox regression indicated that preimplant I-PSS, supplemental XRT, planning target volume, hormonal therapy, and number of seeds were the strongest predictors for I-PSS resolution. Using all available data, the strongest predictors for I-PSS at 18 months following brachytherapy included variants of I-PSS, isotope, and days of catheter dependency. The maximum I-PSS, planning target volume, and XRT best predicted for prolonged (#10878;4 days) catheter dependency. The need for postimplant TURP/TUIP was most closely associated with days of catheter dependency and the maximum increase in I-PSS. However, when only data available prior to implantation was entered into the model, hormonal therapy predicted for postsurgical intervention. CONCLUSIONS: In this retrospective evaluation, hormonal manipulation did not statistically impact short-term or prolonged urinary catheter dependency or I-PSS at 18 months, but did influence time to I-PSS normalization and the need for postbrachytherapy surgical intervention.

Effect of cigarette smoking on biochemical outcome after permanent prostate brachytherapy.

PURPOSE: Recent studies have suggested that cigarette smoking may be associated with an increased risk of death from prostate cancer. In this study, we evaluated the effect of cigarette smoking on the presentation and biochemical outcome after permanent prostate brachytherapy for prostate cancer. METHODS AND MATERIALS: A total of 582 patients underwent brachytherapy with generous periprostatic margins using either (103)Pd or (125)I with or without supplemental external beam radiotherapy between April 1995 and September 2000. Of the 582 patients, 178 (30.6%) had never smoked, 306 (52.6%) were former smokers, and 98 (16.8%) were current smokers. The median patient age was 67.9 years, and the median follow-up was 54.5 months. No patient was lost to follow-up. No patient underwent routine seminal vesicle biopsy or pathologic lymph node staging. The clinical, treatment, and dosimetric parameters evaluated included tobacco status, age, clinical stage, Gleason score, pretreatment prostate-specific antigen level, risk group, percentage of positive biopsies, ultrasound volume, isotope used, planning volume, hormonal status, use of external beam radiotherapy, and postimplant dosimetry (percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose and percentage of prescribed dose covering 90% of the target volume). Biochemical outcome was determined using the American Society for Therapeutic Radiology and Oncology consensus definition. RESULTS: No differences in the clinical, treatment, or dosimetric parameters were identified, except that current smokers were statistically younger than those who had never smoked or former smokers (65.9 vs. 67.8 vs. 68.3 years, respectively, p = 0.016). Specifically, no relationship was discerned between tobacco history and risk group, supplemental external beam radiotherapy, choice of isotope, or use of hormonal therapy. The overall biochemical freedom from progression survival rate at 7 years was 96.2%, 95.6%, and 91.6% for patients who had never smoked, former smokers, and current smokers, respectively (p = 0.126). When stratified by risk group and hormonal status, tobacco consumption did not predict outcome, although a trend for poorer biochemical progression-free survival was noted in current smokers. The median prostate-specific antigen level for hormone-naive and hormonally manipulated disease-free patients was <0.1 ng/mL. In multivariate Cox regression analysis, Gleason score, pretreatment prostate-specific antigen level, risk group, and hormonal status were predictors of biochemical outcome. CONCLUSION: In this prostate brachytherapy cohort, tobacco consumption did not predict for risk group stratification or treatment approach. Although no statistically significant difference was found in biochemical progression-free survival, a trend for poorer biochemical outcome was demonstrated in current smokers.

Long-term urinary quality of life after permanent prostate brachytherapy.

PURPOSE: To evaluate late urinary function after permanent prostate brachytherapy using a validated, patient-administered quality-of-life instrument. METHODS AND MATERIALS: A total of 225 consecutive patients underwent prostate brachytherapy between April 1995 and March 1998. Of the 225 patients, 17 had died and 3 had been institutionalized secondary to Alzheimer's disease. Of the remaining 205 patients, each was mailed a self-administered questionnaire (the urinary function component of the Expanded Prostate Cancer Index [EPIC] and the International Prostate Symptom Score [IPSS]). Of the 205 surveys mailed, 195 (95.1%) were returned. The mean and median follow-up was 66.3 and 64.0 months, respectively. The clinical parameters evaluated included age, pretreatment prostate-specific antigen level, Gleason score, stage, risk group, prostate volume, presence of diabetes and hypertension, and tobacco consumption. The treatment parameters included the ultrasound planning volume, hormonal status, use of supplemental external beam radiotherapy, isotope, and follow-up. The dosimetric parameters included values of the minimal dose received by 90% of the prostate gland and the percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose. Because detailed baseline urinary function was not available, a cross-sectional survey was performed in which 51 newly diagnosed prostate cancer patients of comparable demographics served as controls. RESULTS: When the survey scores for the implant patients were compared with the control group, no significant differences in either the IPSS or function, bother, incontinence, or irritation/obstruction subscales of the urinary EPIC were discernible. In addition, no significant difference was observed between the implant and control groups when the EPIC and IPSS surveys were evaluated by each individual question. Of all the evaluated parameters, the use of tobacco was the best predictive variable for diminished quality of life. CONCLUSION: No significant difference was noted in the overall long-term urinary quality of life when brachytherapy patients were compared with a group of newly diagnosed prostate cancer patients of comparable demographics. Of all parameters evaluated, tobacco consumption was the single strongest predictor of late urinary function.

Prophylactic versus therapeutic alpha-blockers after permanent prostate brachytherapy.

OBJECTIVES: To evaluate the influence of prophylactic versus therapeutic alpha-blockers on urinary morbidity after permanent prostate brachytherapy. Multiple clinical and treatment parameters were evaluated to identify the factors associated with acute urinary morbidity. METHODS: A total of 234 consecutive patients underwent permanent prostate brachytherapy in one of two prospective randomized studies from October 1999 through February 2001 using either palladium-103 or iodine-125 for clinical Stage T1b-T2b (1997 American Joint Commission on Cancer staging system) prostate cancer at either the Schiffler Cancer Center or Puget Sound Health Care System. The mean and median follow-up was 8.8 +/- 4.6 months and 6 months, respectively. In 142 patients, an alpha-blocker was initiated before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to baseline levels; 92 patients either did not receive an alpha-blocker or received a therapeutic alpha-blocker after implantation because of urinary obstructive symptoms. The clinical and treatment parameters evaluated for urinary morbidity included prophylactic versus therapeutic alpha-blockers, age, preimplant IPSS, ultrasound volume, use of neoadjuvant hormones, use of supplemental external beam radiotherapy, isotope, urethral dose, and multiple dosimetric quality indicators (minimal dose received by 90% of the prostate gland and percentage of prostate volume receiving 100% or 200% of the prescribed minimal peripheral dose). Catheter dependency and the duration of alpha-blocker dependency were also evaluated. RESULTS: In both the prophylactic and the therapeutic cohorts, the IPSS peaked 1 month after implantation. Patients receiving a prophylactic alpha-blocker returned to baseline at a mean of 4 months and a median of 3 months postoperatively. For those patients not receiving prophylactic alpha-blockers, the IPSS returned to the antecedent value at a mean and median of 10 months and 6 months, respectively. Of the 125 patients receiving prophylactic alpha-blockers, 102 (81.2%) remained medication dependent at the conclusion of the study, and 140 (78.2%) of 179 patients receiving alpha-blockers other than for hypertensive purposes did so. The incidence of prolonged urinary catheter dependency (greater than 3 days) and the need for postimplant transuretheral incision of the prostate/transurethral resection of the prostate were not affected by alpha-blocker use. Cox regression analysis revealed that only the prophylactic use of alpha-blockers and the difference between the preimplant IPSS and the 1-month IPSS were predictive of the time to return to the referent zone. CONCLUSIONS: Prophylactic use of alpha-blockers results in significantly less urinary morbidity than either the absence or therapeutic use of alpha-blockers. In patients receiving prophylactic alpha-blockers, the IPSS normalized significantly faster but had no impact on urinary retention or the ultimate need for postimplant surgical intervention.

Biochemical outcome for hormone-naïve patients with high-risk prostate cancer managed with permanent interstitial brachytherapy and supplemental external-beam radiation.

PURPOSE: The purpose of this article is to report the 5-year biochemical disease-free outcome for hormone-naive patients with high-risk disease who underwent permanent prostate brachytherapy. Multiple clinical and treatment parameters were also evaluated to determine whether any of these influence biochemical outcome. MATERIALS AND METHODS: Sixty-six hormone-naïve patients underwent transperineal ultrasound-guided permanent prostate brachytherapy with generous periprostatic margins by use of either 103Pd or 125I for high-risk prostate cancer from April 1995 to October 1999. High-risk patients presented with two or three of the following risk factors: Gleason score > or = 7, prostate-specific antigen > or = 10 ng/mL, and clinical stage > or = T2b, 1997 AJCC. No patient underwent pathological lymph node staging. Only one patient was implanted with monotherapy, whereas 65 patients received supplemental external-beam radiation therapy before a prostate brachytherapy boost. The median patient age was 69 years (range, 50-81 years). No patient was lost to follow-up. The mean follow-up and median follow-up were 53.2 +/- 14.9 months and 53.7 months, respectively (range, 19.8-79.7 months). Follow-up was calculated from the day of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiology and Oncology consensus definition. Clinical parameters evaluated for biochemical disease-free survival included patient age, clinical stage, Gleason score, and pretreatment prostate-specific antigen. Treatment parameters included use of supplemental external-beam radiation therapy and choice of isotope. RESULTS: The 5-year actuarial biochemical disease-free survival rate was 79.9%. In multivariate analysis, preimplantation prostate-specific antigen (P = 0.008) was the only clinical or treatment parameter that predicted for biochemical failure. The mean and median posttreatment prostate-specific antigen levels were 0.13 +/- 0.22 ng/mL and < 0.1 ng/mL, respectively. DISCUSSION: At a median follow-up of 53.7 months, hormone-naive patients with high-risk disease who undergo permanent prostate brachytherapy have a high probability of 5-year biochemical disease-free survival and an apparent plateau on the biochemical disease-free survival curve.

Biochemical outcome for hormone-naive patients with Gleason score 3+4 versus 4+3 prostate cancer undergoing permanent prostate brachytherapy.

OBJECTIVES: To determine the effect of the dominant pattern in Gleason score 7 histologic findings on biochemical no evidence of disease survival for hormone-naive patients undergoing permanent prostate brachytherapy. METHODS: A total of 114 hormone-naive patients with Gleason score 7 histologic findings underwent transperineal ultrasound-guided permanent prostate brachytherapy for clinical T1c-T3a NxM0 adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. Sixty-four patients were diagnosed with Gleason score 3+4 and 50 with Gleason score 4+3 prostate cancer. Twenty-one patients were implanted with either palladium 103 or iodine 125 monotherapy, and 93 patients received supplemental external beam radiotherapy with a brachytherapy boost. The median patient age was 69 years (range 49 to 79). The median follow-up was 46.4 months (range 20 to 80). The American Society for Therapeutic Radiology and Oncology consensus definition was used to determine the biochemical disease-free survival. RESULTS: The actuarial 5-year biochemical disease-free survival rate was 90.3%. No statistically significant difference in outcome was found when stratified by the dominant pattern in Gleason score 7 histologic features (89.4% versus 91.5% for 3+4 and 4+3, respectively, P = 0.700). The biochemical no evidence of disease survival analysis in terms of the Gleason cohorts revealed no difference in terms of the choice of isotope, use of supplemental external beam radiotherapy, or preimplant prostate-specific antigen level. The median and mean postimplant prostate-specific antigen level was less than 0.1 ng/mL and 0.12 +/- 0.20 ng/mL, respectively, without a significant difference between Gleason score 3+4 and 4+3. CONCLUSIONS: Our results indicate that the 5-year biochemical outcome with a hormone-naive prostate brachytherapy approach that uses multiple periprostatic seeds is not dependent on Gleason score 3+4 versus 4+3 histologic features.

Erectile function after permanent prostate brachytherapy.

PURPOSE: To determine the incidence of potency preservation after permanent prostate brachytherapy using a validated patient-administered questionnaire and to evaluate the effect of multiple clinical and treatment parameters on penile erectile function. MATERIALS AND METHODS: Four hundred twenty-five patients underwent permanent prostate brachytherapy from April 1995 to October 1999. Two hundred nine patients who were potent before brachytherapy and who at the time of the survey were not receiving hormonal therapy were mailed the specific erectile questions of the International Index of Erectile Function (IIEF) questionnaire with a self-addressed stamped envelope. The questionnaire consisted of 5 questions, with a maximal score of 25. Of the 209 patients, 181 (87%) completed and returned the questionnaire. The mean and median follow-up was 40.4 +/- 14.9 and 40.6 months, respectively (range 19-75). Preimplant erectile function was assigned using a three-tiered scoring system (2 = erections always or nearly always sufficient for vaginal penetration; 1 = erections sufficient for vaginal penetration but considered suboptimal; 0 = the inability to obtain erections and/or erections inadequate for vaginal penetration). Postimplant potency was defined as an IIEF score >/=11. The clinical parameters evaluated for erectile function included patient age, preimplant potency, clinical T-stage, pretreatment prostate-specific antigen level, Gleason score, elapsed time after implantation, hypertension, diabetes mellitus, and tobacco consumption. Treatment parameters included radiation dose to the prostate gland, use of hormonal manipulation, use of supplemental external beam radiotherapy (EBRT), choice of isotope, prostate volume, and planning volume. The efficacy of sildenafil citrate in brachytherapy-induced erectile dysfunction (ED) was also evaluated. RESULTS: Pretreatment erectile function scores of 2 and 1 were assigned to 125 and 56 patients, respectively. With a 6-year follow-up, 39% of patients maintained potency after prostate brachytherapy, with a plateau on the potency preservation curve. Postimplant preservation of potency (IIEF >/=11) correlated with preimplant erectile function (50.4% vs. 13.2% for preimplant scores of 2 and 1, respectively, p <0.001), patient age (57.4%, 38.2%, and 21.9% for patients <60, 60-69, and >/=70 years old, respectively, p <0.004), use of supplemental EBRT (52.0% vs. 26.4% for patients without and with EBRT, p <0.001), and a history of diabetes mellitus (41.4% vs. 0% for patients without and with diabetes, respectively, p = 0.017). In multivariate analysis, clinical stage, radiation dose to the prostate gland, hormonal manipulation, choice of isotope, history of hypertension, and tobacco consumption had no effect on the ultimate preservation of potency. Only the preimplant potency score, use of supplemental EBRT, and diabetes maintained statistical significance. Sixty-two patients used sildenafil, with 53 (85%) reporting a favorable response. When potent patients were grouped with the ED patients who used sildenafil, the 6-year actuarial rate of potency preservation was 92%. Including the 70 impotent patients who never used sildenafil, the actuarial 6-year rate of potency preservation with and without pharmacologic support was 54% and 39%, respectively. CONCLUSION: Our results suggest that brachytherapy-induced ED is more common than previously reported and may be the result of obtaining patient information by means of a validated quality-of-life instrument by mail and not by personal interview. In multivariate analysis, only pretreatment potency, supplemental EBRT, and diabetes maintained statistical significance. Most patients with brachytherapy-induced ED responded favorably to sildenafil. Although the 6-year actuarial incidence of potency preservation was 39%, 52% of patients not receiving supplemental EBRT maintained potency. In addition, with pharmacologic support, 92% of patients maintained potency.

The dosimetry of prostate brachytherapy-induced urethral strictures.

PURPOSE: There is a paucity of data regarding the incidence of urethral strictures after prostate brachytherapy. In this study, we evaluate multiple clinical, treatment, and dosimetric parameters to identify factors associated with the development of brachytherapy-induced urethral strictures. METHODS AND MATERIALS: 425 patients underwent transperineal ultrasound-guided prostate brachytherapy using either (103)Pd or (125)I for clinical T1b/T3a NxM0 (1997, American Joint Committee on Cancer) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. 221 patients were implanted with (103)Pd and 204 patients with (125)I. The median patient age was 68 years (range 48-81 years). The median follow-up was 35.2 months (range 15-72 months). Follow-up was calculated from the day of implantation. Thirteen patients developed brachytherapy-induced strictures, and all strictures involved the membranous urethra. A control group of 35 patients was rigorously matched to the stricture patients in terms of treatment approach; i.e., choice of isotope, plus or minus radiation therapy, and plus or minus hormonal manipulation. Nine of the 13 stricture patients had detailed Day 0 urethral dosimetry available for review. The apex of the prostate gland and the membranous urethra were defined by CT evaluation. Urethral dosimetry was reported for the prostatic urethra, the apical slice of the prostate gland, and the membranous urethra which was defined as extending 20 mm in length. RESULTS: The 5-year actuarial risk of a urethral stricture was 5.3%, with a median time to development of 26.6 months (range 7.8-44.1 months). Of multiple clinical and treatment parameters evaluated, only the duration of hormonal manipulation (>4 months, p = 0.011) was predictive for the development of a urethral stricture. The radiation dose to the membranous urethra was significantly greater in patients with strictures than those without: 97.6% +/- 20.8% vs. 81.0% +/- 19.8% of prescribed minimum prostate dose, mPD (p = 0.031). The urethral dose 20 mm distal to the prostate apex was 57.6% +/- 23.8% vs. 31.5% +/- 13.9% of mPD for the stricture and control patients, respectively (p = 0.011). In addition, the extent of the 75% mPD and 50% mPD levels beyond the prostatic apex was also significantly greater for stricture patients, 16.6 +/- 5.3 mm vs. 11.9 +/- 4.5 mm (p = 0.010) and 19.0 +/- 3.2 mm vs. 16.0 +/- 3.4 mm (p = 0.021), respectively. Dose to the prostatic urethra was not predictive of stricture, but the magnitude and extent of high-dose regions within the prostate were predictive of stricture. Twelve of the 13 patients who developed urethral strictures were successfully managed by dilatation/transurethral incision. To date, 1 of the 12 patients has required a second dilatation. The remaining patient developed an iatrogenic induced injury and was catheter-dependent for 6 months. CONCLUSIONS: After prostate brachytherapy, the actuarial 5-year incidence of urethral strictures is 5.3% with a median time to development of 26.6 months. All strictures involved the membranous urethra and occurred within the first 44 months after brachytherapy. In most cases, membranous urethral strictures are easily managed with dilatation/incision. Factors predicting for the development of a urethral stricture included the magnitude and extent of high-dose regions within the prostate, the mean membranous urethra dose and the dose 20 mm distal to the prostatic apex, the maximum extent along the membranous urethra of certain dose levels, and the duration of hormonal manipulation.

Relationship between percent positive biopsies and biochemical outcome after permanent interstitial brachytherapy for clinically organ-confined carcinoma of the prostate gland.

PURPOSE: Recently, the percentage of positive prostate biopsies has been reported to be statistically significant in predicting the biochemical outcome after either radical prostatectomy or 3-dimensional conformal external beam radiotherapy. In this study, we evaluated the impact of the percentage of positive prostate biopsies in predicting the 5-year biochemical outcome for patients with clinically organ-confined prostate cancer undergoing permanent interstitial brachytherapy. METHODS AND MATERIALS: Two hundred sixty-two hormone naive patients underwent transperineal ultrasound-guided permanent prostate brachytherapy with generous periprostatic margins, using either 103Pd or 125I for clinical T1b/T2b NXM0 (1997 AJCC) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. The actual percentage of positive biopsies (number of positive biopsies/total number of biopsies) was determinable for 255 of the 262 patients. Of the evaluated cases, 133 patients were implanted with 103Pd and 122 patients with 125I. The median patient age was 68 years (range 48-81). The median follow-up was 38.6 months (range 6-73). Follow-up was calculated from the day of implantation. Patients were stratified by the percentage of positive biopsies into the following groups: <34%, 34-50%, and >50%. Additional clinical parameters evaluated included patient age, clinical T-stage, Gleason score, pretreatment prostate specific antigen (PSA), risk group, and prostate volume. Low-risk patients were staged as clinical T1c/T2a, Gleason score < or =6, and pretreatment PSA < or =10 ng/mL, intermediate-risk patients presented with one unfavorable prognostic parameter, and high-risk patients presented with two or more unfavorable prognostic parameters (clinical stage T2b, PSA >10 ng/mL, Gleason score > or =7). Treatment parameters included the use of supplemental external beam radiation and choice of isotope. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology consensus definition. RESULTS: For the 255 evaluated patients, the 5-year actuarial biochemical no evidence of disease survival rate was 92.5%. For patients with low, intermediate, and high-risk disease, 95.8%, 98.1%, and 79.4% of patients were free of biochemical failure, respectively. When each risk group was stratified into the percent positive biopsy categories of <34%, 34-50%, and >50%, no statistical difference was found in biochemical outcome for the biopsy subgroups. In multivariate analysis, none of the clinical or treatment parameters predicted for failure in the low-risk group; only Gleason score was predictive for intermediate-risk patients and only PSA for high-risk patients. In the overall population, PSA and Gleason score were both found to be predictors of biochemical failure, but not risk group, clinical stage, or percentage of positive biopsies. There was no significant dependence between the percent positive biopsy group and the Kaplan-Meier biochemical survival rates for any of the various subgroups of clinical and treatment parameters, except for clinical stage T1c-T2a (p = 0.006). The median postimplant PSA was 0.2 ng/mL for patients with either low-risk disease or <34% positive biopsies and 0.1 ng/mL for all other risk groups or percent positive biopsy subgroups. CONCLUSION: Although a significant trend was found for biochemical failure with increasing percent positive biopsies in the overall population, our results suggest that the percentage of positive biopsies is not statistically significant in predicting the 5-year biochemical disease-free outcome for patients with low, intermediate, and high-risk disease undergoing permanent prostate brachytherapy. Only the Gleason score in intermediate-risk patients and the pretreatment PSA level in high-risk patients was predictive of biochemical failure. We believe this relative lack of significance for the percentage of positive biopsies is a result of dose escalation far exceeding other radiotherapy modalities and the ability to aggressively treat the periprostatic region compared with radical prostatectomy by way of the accurate placement of periprostatic seeds.