Biomedical subjects

Jonathan H Lief

Publications and source records attributed to Jonathan H Lief.

At least 19 recordsLinked to original sources

PubMed2005

Erectile function after prostate brachytherapy.

PURPOSE: To evaluate erectile function after permanent prostate brachytherapy using a validated patient-administered questionnaire and to determine the effect of multiple clinical, treatment, and dosimetric parameters on penile erectile function. METHODS AND MATERIALS: A total of 226 patients with preimplant erectile function determined by the International Index of Erectile Function (IIEF) questionnaire underwent permanent prostate brachytherapy in two prospective randomized trials between February 2001 and January 2003 for clinical Stage T1c-T2c (2002 American Joint Committee on Cancer) prostate cancer. Of the 226 patients, 132 were potent before treatment and, of those, 128 (97%) completed and returned the IIEF questionnaire after brachytherapy. The median follow-up was 29.1 months. Potency was defined as an IIEF score of > or =13. The clinical, treatment, and dosimetric parameters evaluated included patient age; preimplant IIEF score; clinical T stage; pretreatment prostate-specific antigen level; Gleason score; elapsed time after implantation; preimplant nocturnal erections; body mass index; presence of hypertension or diabetes mellitus; tobacco consumption; the volume of the prostate gland receiving 100%, 150%, and 200% of the prescribed dose (V(100/150/200)); the dose delivered to 90% of the prostate gland (D(90)); androgen deprivation therapy; supplemental external beam radiotherapy (EBRT); isotope; prostate volume; planning volume; and radiation dose to the proximal penis. RESULTS: The 3-year actuarial rate of potency preservation was 50.5%. For patients who maintained adequate posttreatment erectile function, the preimplant IIEF score was 29, and in patients with brachytherapy-related ED, the preimplant IIEF score was 25. The median time to the onset of ED was 5.4 months. After brachytherapy, the median IIEF score was 20 in potent patients and 3 in impotent patients. On univariate analysis, the preimplant IIEF score, patient age, presence of nocturnal erections, and dose to the proximal penis predicted for postimplant erectile function. However, in multivariate analysis, only the preimplant IIEF score and the D(50) to the proximal crura were statistically significant predictors of brachytherapy-related erectile function. CONCLUSIONS: Using a patient-administered validated quality-of-life instrument, brachytherapy-induced ED occurred in 50% of patients at 3 years. On multivariate analysis, preimplant erectile function and the D(50) to the proximal crura were the best predictors of brachytherapy-related erectile function. Because the proximal penis is the most significant treatment-related predictor of brachytherapy-related ED, techniques to minimize the radiation dose to the proximal penis may result in improved rates of potency preservation.

Age Factors↗

PubMed2005

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.

Aged↗

PubMed2005

The impact of radiation dose to the urethra on brachytherapy-related dysuria.

PURPOSE: To determine the effect of urethral dose on dysuria after permanent prostate brachytherapy. METHODS AND MATERIALS: One hundred eight patients without a preimplant history of a transurethral resection underwent brachytherapy on one of two prospective randomized trials for clinical T1c-T2c (2002 AJCC) prostate cancer. Urethral dose was stratified into cohorts of <150% and 150% minimum peripheral dose (mPD) respectively. No patient received prophylactic alpha blockers. The median follow-up was 27.4 months. Dysuria was defined as pain and/or burning on urination and was evaluated on a 0-10 scale. Normalization of dysuria was defined as a return to within 1 point of baseline. Dysuria surveys were obtained before brachytherapy and at 1, 3, 6, and 12 months after implantation. Clinical, treatment, and dosimetric parameters evaluated included urethral dose, age, preimplant International Prostate Symptom Score (I-PSS), ultrasound volume, hormonal status, supplemental XRT, isotope, V(100/200), D(90), the maximum post-implant I-PSS, and the time to I-PSS resolution. RESULTS: The incidence of dysuria peaked at 85% one month after brachytherapy with subsequent resolution over time. Radiation dose to the urethra (stratified into cohorts of <150%, and 150% mPD) was not a significant predictor of prevalence, severity, or resolution of dysuria. In a multivariate analysis, isotope predicted for dysuria normalization while preimplant I-PSS and D(90) predicted for maximum dysuria; however, the area under the ROC curve and the Pearson correlation coefficient revealed weak correlations. CONCLUSIONS: Dysuria is common after brachytherapy, but typically minimal in severity. Urethral doses did not predict for either dysuria severity or normalization. Although preimplant I-PSS was the strongest predictor of maximum dysuria and isotope the best predictor for dysuria normalization, robust predictors for brachytherapy-related dysuria were not identified.

Aged↗

PubMed2005

Variability of prostate brachytherapy pre-implant dosimetry: a multi-institutional analysis.

PURPOSE: To conduct a multi-institutional comparison of prostate brachytherapy pre-implant dosimetry of Pd-103 and I-125. METHODS AND MATERIALS: Eight experienced brachytherapists submitted Pd-103 and I-125 monotherapeutic and boost pre-implant dosimetry plans for central review. All 32 plans were calculated using the same transrectal ultrasound volumetric study. Seeds of any strength were acceptable, but were restricted to Theraseed Model 200 (Theragenics Inc., Buford, GA) and Oncura Oncoseed Model 6711 (Oncura, Plymouth Meeting, PA). The dosimetric analysis included evaluation of target volume, target to prostate ratio, target length, number of needles, seed activity, number of seeds, total activity, total activity divided by treatment planning volume, the use of extracapsular seeds, and average treatment margins (defined as the perpendicular distance between the prostate capsule and the 100% isodose line). Prostate coverage was defined in terms of V(100)/V(150)/V(200)/V(300) and D(100)/D(90)/D(50), whereas urethral dosimetry consisted of UV(100)/UV(150)/UV(200) and UD(90)/UD(50). RESULTS: The mean planning target volume to prostate volume ratio varied dramatically (mean 1.29, range 0.99-1.76) with the target length ranging from 3.5 to 4.5 cm. Although the prostate V(100) was >95% in all cases, the V(150) ranged from 29.9% to 92.1% and the V(200) from 6.72% to 52.5%. The urethral V(100) was 100% in all cases with six of the eight brachytherapists limiting the UV(150) to <3%. However, the median urethral dose varied by up to 50%. Treatment margins also varied significantly (average 3.98 mm, range 0.32-7.68 mm). All brachytherapists used extracapsular seeds with five implanting >25% of the seeds in extracapsular locations (range 6.4-58.2%). In addition, significant variability existed in the number of needles, number of seeds, and seed strength. CONCLUSIONS: This study highlights the substantial variability that exists regarding target volume, seed strength, dose homogeneity, treatment margins, and extracapsular seed placement, although prostate brachytherapy prescription doses are uniform. The standardization of pre-implant dosimetry is essential for meaningful multi-institutional comparisons of biochemical outcomes and morbidity.

Brachytherapy↗

PubMed2005

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.

Adenocarcinoma↗

PubMed2005

Brachytherapy-related dysuria.

OBJECTIVE: To evaluate the incidence and temporal resolution of dysuria after permanent prostate brachytherapy, and to identify predictors of brachytherapy-related dysuria. PATIENTS AND METHODS: The study included 130 patients with no history of transurethral resection of the prostate before treatment, who had brachytherapy on one of two prospective randomized trials, with explicitly planned and executed urethral-sparing techniques (100-150% minimum peripheral dose) using either 103Pd or 125I for clinical T1c-T2c prostate cancer. The median follow-up was 22.6 months. An alpha-blocker was initiated either prophylactically 2 weeks before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to normal, or withheld until the onset of significant brachytherapy-related urinary morbidity. Dysuria was evaluated on a 0-10 scale, before brachytherapy and then at 1, 3, 6 and 12 months afterward, with a median of four dysuria questionnaires per patient. Clinical, treatment and dosimetric variables evaluated included alpha-blocker, age, IPSS before and the maximum after treatment, prostate volume on ultrasonography, hormonal status, supplemental radiotherapy, isotope, urethral dose, V(100/200), D90, and time to obtaining a normal IPSS. RESULTS: The maximum incidence of dysuria was 85% at 1 month after brachytherapy, with subsequent resolution over time. The use of prophylactic tamsulosin resulted in a statistically lower dysuria severity score (difference of 2.7 vs 4.2, P < 0.005) at 1 month, with no discernible differences at 3, 6, 12 and 18 months. Patients with dysuria had a statistically higher IPSS. The dysuria resolved faster in patients implanted with 103Pd but was unaffected by the use of supplemental radiotherapy and/or androgen deprivation therapy. In multivariate analysis, prophylactic alpha-blockers resulted in statistically lower maximum dysuria scores, while the maximum IPSS after implantation and isotope type (but only at 6 months) were the best predictors of the resolution of dysuria. CONCLUSIONS: Dysuria is common after brachytherapy but is typically mild. Prophylactic alpha-blockers gave significantly lower maximum dysuria scores but did not affect the time to the resolution of dysuria. The maximum IPSS after the implant was the best predictor of the resolution of dysuria.

Adrenergic alpha-Antagonists↗

PubMed2004

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.

Aged↗

PubMed2004

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.

Aged↗

PubMed2003

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.

Aged↗

PubMed2003

Dysuria after permanent prostate brachytherapy.

PURPOSE: Although numerous prostate cancer quality-of-life studies have been reported, a paucity of data exists regarding brachytherapy-related dysuria. In this study, we evaluated the incidence and temporal resolution of dysuria, along with the influence of multiple treatment, clinical, and dosimetric parameters. MATERIALS AND METHODS: Five hundred eighty-one consecutive patients without a preimplant history of transurethral resection of the prostate underwent brachytherapy between January 1998 and December 2001 for clinical T1c-T3a (1997 AJCC) adenocarcinoma of the prostate gland. The evaluated population consisted of the 546 patients who had completed at least two postimplant dysuria evaluations. The median patient follow-up was 26.4 months. In all patients, alpha-blocker therapy was initiated before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to baseline. The frequency of dysuria was assessed on a 1-5 scale using the IPSS scoring criteria. The dysuria severity was scored on a 1-10 scale. The clinical parameters evaluated included age, T stage, preimplant IPSS, ultrasound volume, and elapsed time since implantation. The treatment parameters included the use of neoadjuvant hormonal manipulation, use of supplemental external beam radiotherapy, isotope, and total implanted seed strength. The dosimetric parameters included values of the minimal dose received by 90% of the prostate, the percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose, and the median and maximal urethral doses. RESULTS: The incidence of dysuria peaked at 52% 1 month after implantation. The median dysuria frequency score was 0 of 5 for all patients and 2 of 5 for those reporting dysuria. The median severity score was 0 of 10 for the entire cohort and 3 of 10 for those reporting dysuria. For the entire group, both the frequency and the severity of dysuria steadily improved with time, with near complete resolution of dysuria at 45 months. For those patients reporting dysuria, neither the frequency nor the severity revealed any durable improvement for approximately 36 months. Patients with dysuria displayed higher postimplant IPSSs. Of the 7 IPSS questions, nocturia and incomplete voiding were the best surrogates for dysuria. The isotope, supplemental external beam radiotherapy, hormonal status, minimal dose received by 90% of the prostate, and urethral dose did not predict for dysuria. CONCLUSIONS: After permanent prostate brachytherapy, dysuria is a relatively common event, but only rarely severe in frequency or intensity. At approximately 45 months after brachytherapy, dysuria appears to resolve in almost all patients.

Aged↗

PubMed2003

Prostate-specific antigen (PSA) velocity and benign prostate hypertrophy predict for PSA spikes following prostate brachytherapy.

PURPOSE: To evaluate if variants of serum PSA or benign prostatic hypertrophy correlate with the development of a PSA spike following permanent prostate brachytherapy. METHODS AND MATERIALS: Two-hundred-eighteen hormone-naïve patients with clinical T1b-T3a (1997 AJCC) prostate cancer who were treated with brachytherapy between August 1995 and November 1999, with or without supplemental external beam radiation therapy, and who remained free of biochemical failure were analyzed. The median follow-up was 46 months. A PSA spike was defined as a rise > or =0.2 ng/mL followed by a durable decline. Biochemical disease-free survival was defined by the ASTRO Consensus Definition with the additional constraint that the most recent PSA be < or =1.0 ng/mL. In addition, none of the patients possessed equivocal biochemical results (1 or 2 consecutive PSA rises or a declining PSA >1.0 ng/mL). In addition to previously reported clinical, treatment, and dosimetric parameters evaluated for spike, PSA density, transition zone (TZ) PSA density, percent free PSA, PSA velocity, PSA doubling time, TZ volume, and transition zone index (TZI) were included. The PSA kinetics of 18 hormone naïve patients who were implanted during the same time period and subsequently failed were also evaluated. RESULTS: Fifty-two (23.9%) developed a PSA spike. Of the demographic and preimplant clinical parameters, patient age, TZ volume, TZI, TZ PSA density, and 125I were statistically significant predictors for a PSA spike. Of the postimplant parameters, V200, follow-up, first postimplant PSA, and most recent PSA predicted for a PSA spike. In multivariate Cox regression analysis, PSA nadir, TZI, follow-up, age, months to PSA nadir and preimplant PSA velocity were significant predictors for spike. However, when variables only determinable after a PSA spike were included in the multivariate analysis, TZI, age, PSA velocity, and first postimplant PSA were predictors for a spike. Using categorical cutpoints of TZI >0.25, age at implant <62 years, and first postimplant PSA >1.0 ng/mL in the regression analysis, a positive likelihood ratio for a PSA spike of >1.8 was noted for each variable. Patients with PSA progression displayed significantly different PSA kinetics than those with a spike. CONCLUSIONS: In multivariate analysis, PSA nadir, TZI, patient age, months to PSA nadir, follow-up, and preimplant PSA velocity were predictive of a PSA spike. However, when only variables identifiable prior to a spike were evaluated, TZI, patient age, preimplant PSA velocity, and first postimplant PSA were the strongest predictors for a PSA spike.

Aged↗

PubMed2002

The importance of radiation doses to the penile bulb vs. crura in the development of postbrachytherapy erectile dysfunction.

PURPOSE: Recent studies have implicated the proximal penis as a potential site-specific structure for radiation-related erectile dysfunction (ED). In this study, we evaluated by means of a validated patient-administered questionnaire whether radiation doses to the bulb of the penis and/or the proximal corporeal bodies were predictive for the development of brachytherapy-induced ED. METHODS AND MATERIALS: Thirty patients who underwent permanent prostate brachytherapy between April 1995 and October 1999 and developed brachytherapy-induced ED were paired with 30 similar men who maintained potency after implantation. None of the 60 patients received supplemental external beam radiation therapy, either before or after implantation. Potency was assessed by patient self-administration of the specific erectile questions of the International Index of Erectile Function. The questionnaire consisted of 5 questions with a maximum score of 25. Postimplant potency was defined as an International Index of Erectile Function score > or =11. Mean and median follow-up was 48.3 +/- 14.4 months and 48.0 months, respectively (range: 26.6-79.3 months). The bulb of the penis and the proximal crura were outlined at 0.5-cm intervals on the Day 0 postimplant CT scan. The radiation dose distribution to the bulb of the penis and adjacent crura was defined in terms of the minimum dose delivered to 25%, 50%, 70%, 75%, 90%, and 95% of the bulb (D(25), D(50), D(70), D(75), D(90), and D(95)). RESULTS: The radiation dose delivered to the bulb of the penis and the proximal crura in men with brachytherapy-induced ED was statistically greater for all evaluated dosimetric parameters (D(25), D(50), D(70), D(75), D(90), and D(95)). Stepwise linear regression analysis indicated that penile bulb dose parameter D(50), the postimplant prostate CT volume, and patient age at implant were predictive of postimplant ED, whereas the crura dose D(25) approached statistical significance. Seventy-five percent of the impotent men had a bulb D(25) >60% of prescribed minimum peripheral dose (mPD), whereas 80% of potent men had a bulb D(25) < or =60% mPD. Using the D(50) bulb parameter, 70% of ED men had a dose >40% mPD, whereas 90% of potent men had a dose < or =40% mPD. Similar cut points for D(25) and D(50) crura doses were 40% and 28% mPD. The crura D(25) cut point was exceeded by 50% of the ED patients and only 7% of the potent patients. CONCLUSION: This is the first study to evaluate potency preservation and radiation doses to the proximal penis by means of a validated patient-administered quality-of-life instrument. Our data confirm prior reports that radiation doses to the proximal penis are predictive of brachytherapy-induced ED. In a stepwise linear regression analysis, the strongest predictors of potency preservation were bulb D(50), postimplant prostate CT volume, and patient age. With Day 0 dosimetric evaluation, the penile bulb D(50) and D(25) should be maintained below 40% and 60% mPD, respectively, whereas the crura D(50) and D(25) should be maintained below 40% and 28% mPD, respectively, to maximize posttreatment potency.

Age Factors↗

PubMed2002

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.

Adenocarcinoma↗

PubMed2002

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.

Aged↗

PubMed2002

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.

Aged↗

PubMed2002

Permanent prostate brachytherapy-induced morbidity in patients with grade II and III obesity.

OBJECTIVES: To determine the influence of obesity on the development of urinary, bowel, and sexual dysfunction after brachytherapy by means of patient-administered questionnaires. The effect of obesity on dosimetric quality and biochemical outcome was also evaluated. METHODS: Thirty-two patients with grade II and III obesity underwent brachytherapy from June 1997 through April 2001. Grade II and III obesity was defined as a body mass index of 35.0 to 39.9 and 40.0 kg/m2 or greater, respectively. Serial International Prostate Symptom Score (IPSS) evaluations were obtained at predetermined intervals. Bowel and sexual function were assessed by a rectal function assessment score (R-FAS) and the specific erectile questions of the International Index of Erectile Function (IIEF). The median follow-up was 26.4 months. An alpha-blocker was initiated before implantation and continued at least until the IPSS normalized. Catheter dependency, alpha-blocker dependency, and the incidence of urethral strictures were also evaluated. The efficacy of sildenafil in brachytherapy-induced erectile dysfunction was also evaluated. Dosimetric parameters evaluated included the percentage of the prostate receiving 100%, 150%, and 200% of the prescribed dose (V100, V150, and V200), the minimal dose received by 90% of the prostate (D90), urethral doses, and rectal doses. Biochemical outcome was determined by the ASTRO consensus conference definition. RESULTS: Of the 32 patients, 31 (97%) had the urinary catheter permanently removed on day 0, and no patient required a urinary catheter for longer than 1 day. One patient developed a urethral stricture. No patient required a transurethral resection or developed urinary incontinence. On average, the IPSS peaked 2 weeks after implantation and returned to baseline at a median of 8 weeks (mean 16). The post-treatment R-FAS was 3.6. No patient developed a rectal ulcer or fistula. Of the 22 patients who were potent before implantation, 7 (31.8%) maintained potency. With pharmacologic support, 59.1% maintained erections sufficient for vaginal penetration. Day 0 dosimetry demonstrated a median V100 and D90 of 96.5% and 113.5%. At last follow-up, all patients remained free of biochemical failure, with a median prostate-specific antigen level of 0.1 ng/mL. CONCLUSIONS: No difference in quality-of-life parameters was discerned in patients with grade II and III obesity. In addition, the dosimetric quality of the implants was outstanding, and the short-term biochemical outcome was encouraging.

Adenocarcinoma↗

PubMed2002

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.

Adenocarcinoma↗

PubMed2002

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.

Adenocarcinoma↗