[Show abstract][Hide abstract] ABSTRACT: To evaluate the relationship between pre-treatment erectile function and all-cause mortality in patients with prostate cancer treated with brachytherapy.
In all, 1279 consecutive patients with clinically localized prostate cancer and pre-implant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) underwent brachytherapy. Potency was defined as an IIEF-6 score of ≥13 without pharmacological or mechanical support. Patients were stratified into IIEF-6-score cohorts (≤12, 13-23 and 24-30). The median follow-up was 5.0 years.
The 8-year overall survival (OS) of the study population was 85.1%. The 8-year OS for IIEF-6scores ≤12, 13-23 and 24-30 were 78.0%, 92.8% and 91.4%, respectively (P < 0.001). Cardiovascular events accounted for a significant portion of deaths in each IIEF-6 group. When combined with other risk factors for cardiovascular disease, an IIEF-6 score of ≤12 had an additive effect on all-cause mortality (IIEF-6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%).
A pre-implant IIEF-6score of ≤12 was associated with a higher incidence of all-cause mortality. Pre-treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients. Aggressive treatment of medical co-morbidity is warranted to impactOS.
Full-text · Article · Jul 2011 · BJU International
[Show abstract][Hide abstract] ABSTRACT: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment.
Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike.
There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase ≥ 25%, 23% of men experienced a decrease ≥ 25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21).
Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response does not seem related to temporal testosterone changes.
Full-text · Article · Apr 2011 · International journal of radiation oncology, biology, physics
[Show abstract][Hide abstract] ABSTRACT: To report the incidence of transition zone (TZ) cancer in patients undergoing transperineal template-guided mapping biopsy (TTMB) of the prostate gland.
Five hundred thirty-nine consecutive patients underwent TTMB by means of an anatomic technique with sampling of 24 defined prostate regions. The position of each biopsy core was recorded in 3 dimensions. For every patient, the location of each positive biopsy core, the number of positive cores, the Gleason score, the percentage involvement of each core, and the presence/absence of perineural invasion was documented.
The median volumetric prostate volume was 56.0 cm(3) with an ellipsoid TZ volume of 20.1 cm(3). The median number of TTMB cores was 58 with a median of 11 TZ cores. Two hundred eighty-seven (53.2%) were diagnosed with prostate cancer. TZ cancer was detected in 130 (45.3%) of patients with prostate cancer but only 6 (4.6%) were confined to the TZ. Overall, 38.9% of TZ cores were positive for malignancy. Of the TZ cancers, 37 (28.5%), 64 (49.2%), and 29 (22.3%) were assigned Gleason scores 6, 7, and 8-10. Compared with a standard 12-core biopsy approach, the results of the TZ biopsy upgraded the Gleason score in 24.6% of patients. Only 4 cancers (3.1%) involving the TZ were classified as clinically insignificant.
Although only 4.6% of cancers were confined to the TZ, 45.3% of all prostate cancer patients had TZ involvement.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of prostate brachytherapy case volume on postimplant dosimetric quality in Pro-Qura proctored programs.
From August 1999 to December 2008, the computed tomography datasets for 6,600 prostate implants performed by 129 brachytherapists were submitted to Pro-Qura for dosimetric analysis. Brachytherapists were divided into three roughly equal-sized terciles based on total case volume. Postimplant computed tomography scans were obtained at a median of 30 days. Excellent target coverage was defined by a V100≥90% and D90≥100% minimum prescribed peripheral dose. To determine if the number of excellent implants improved with increasing case numbers, each brachytherapist's series of implants was bisected into early and late experience by a moveable critical point.
For the entire cohort, the mean V100 and D90 were 89.2% and 102.8%, respectively, with 47.7% of the implants scored as excellent. Brachytherapists in the highest-case tercile had a significantly greater fraction of excellent target coverage (57.9%) than did those in the two lower terciles (39.5% and 45.7%, p=0.015). Twenty-one (25.6%) of the 82 brachytherapists with sufficient case volume for dosimetric improvement analyses demonstrated quality improvement over time. Although there was no significant difference between prostate volume and seed strength, the number of seeds used was significantly greater in adequate implants.
The highest-volume brachytherapists were most likely to obtain excellent target coverage. We are encouraged that in general practice, nearly 48% of all implants were scored excellent. It is conceivable that with greater expert third-party involvement, an even greater percentage of cases with excellent target coverage will become reality.
Full-text · Article · Feb 2011 · International journal of radiation oncology, biology, physics
[Show abstract][Hide abstract] ABSTRACT: To determine whether periprostatic treatment margins correlate with biochemical control in prostate brachytherapy patients with optimized intraprostatic dosimetry.
Nineteen biochemically failed brachytherapy patients were matched to 74 dosimetric and clinically equivalent nonfailures. The median followup time for the entire study population was 9.4 years. Eligibility requirements included a Day 0 intraprostatic D(90) of 100% or greater and V(100) of 90% or greater, absence of androgen deprivation therapy, and no evidence of distant metastasis in biochemically failed patients. A 5-mm annulus was constructed around the perimeter of each prostate. D(90) and V(100) at the anterior, posterior, superior, inferior, right lateral, and left lateral aspects of the annulus were evaluated for patients with biochemically controlled and failed disease. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen level of 0.40ng/mL or less after nadir. D(90) and V(100) parameters were compared between the controlled and failed groups using logistic regression. Predictors of biochemical failure were identified using Cox regression.
No statistically significant differences in prostate-specific antigen level, Gleason score, percent positive biopsies, or intraprostatic dosimetry were observed between the controlled and failed patients. The D(90) and V(100) at the anterior, posterior, superior, inferior, right lateral, and left lateral aspects of the annulus were not statistically different between biochemically controlled and failed groups.
In this study, there was no relationship observed between annular dosimetry and biochemical control. It is unlikely that further radial dose intensification would have altered treatment outcome in this population of patients with optimized intraprostatic dosimetry.
[Show abstract][Hide abstract] ABSTRACT: Purpose: To determine brachytherapy implant dosimetry differences between biochemical failures and matched non‐failures based on prostate, annular margins, and various sectors.
Materials and Methods: Nineteen hormone‐naïve men with a planning target volume (PTV) day 0 D90 > 100% of Rx and V100 > 90% were biochemical failures after brachytherapy. They were matched to dosimetrically equivalent non‐failures on a 1:4 basis. Patients were also matched in terms of type of therapy, Gleason score, PSA, clinical stage, % positive biopsy, and year of implant. Implants were between 1995 and 2006 and had at least 3 years of follow‐up. The prostate and PTV were drawn prior to initial post‐implant dosimetry. For this study, the PTV was divided into sectors, and the prostate and annulus between the prostate and PTV were analyzed separately.
Results: Using conditional logistic regression, there was no significant difference in D90 or V100 between failures and controls in terms of either 12 prostate or annular sectors. The lowest dose was in the anterior superior annulus, with mean D90 = 90.7% ± 15.6% and mean V100 = 75.6% ± 19.2%. All other annular sectors had D90 >108% and V100 > 90%. Four‐fold radial combinations of sectors into superior, medial and inferior regions showed no dosimetric difference between failures and controls. Three‐fold longitudinal combinations of sectors into anterior, posterior, and left and right lateral regions also found no dosimetric differences. The anterior region was the coolest and the lateral regions the hottest. Overall annular dosimetry had mean D90 = 116.8% ± 14.8% and mean V100 = 95.1% ± 3.9%.
Conclusion: There were no significant dosimetric differences between biochemical failures and controls in terms of prostate, annular margins or any of 12 sectors and various sector combinations analyzed. I n a population with good dosimetry, dosimetry was inadequate to explain biochemical failure.
[Show abstract][Hide abstract] ABSTRACT: To investigate the dosimetry, treatment-related morbidity, and biochemical outcomes for brachytherapy in patients with prostate glands <20 cm(3).
From November 1996 to October 2006, 104 patients with prostate glands <20 cm(3) underwent brachytherapy. Multiple prostate, urethral, and rectal dosimetric parameters were evaluated. Treatment-related urinary and rectal morbidity were assessed from patient questionnaires. Cause-specific survival, biochemical progression-free survival, and overall survival were recorded.
The median patient age, follow up, and pre-treatment ultrasound volume was 64 years, 5.0 years and 17.6cm(3), respectively. Median day 0 dosimetry was significant for the following: V100 98.5%, D90 126.1% and R100 <0.5% of prescription dose. The mean urethral and maximum urethral doses were 119.6% and 133.8% of prescription. The median time to International Prostate Symptom Score resolution was 4 months. There were no RTOG grade III or IV rectal complications. The cause-specific survival, biochemical progression-free survival, and overall survival rates were 100%, 92.5%, and 77.8% at 9 years. For biochemically disease-free patients, the median most recent postbrachytherapy PSA value was 0.02 ng/mL.
Our results demonstrate that brachytherapy for small prostate glands is highly effective, with an acceptable morbidity profile, excellent postimplant dosimetry, acceptable treatment-related morbidity, and favorable biochemical outcomes.
Full-text · Article · Apr 2010 · International journal of radiation oncology, biology, physics
[Show abstract][Hide abstract] ABSTRACT: Purpose: PSA spikes occur in a significant minority of brachytherapy patients following permanent interstitial brachytherapy for clinically localized prostate cancer. The etiology of PSA spikes remains unclear. In this study we evaluated the relationship between PSA spikes and changes in serum testosterone.
Materials and Methods: From January 2008 - March 2009, 202 consecutive patients underwent 103Pd brachytherapy without androgen deprivation therapy for clinically localized prostate cancer. Of these patients, 129 (63.9%) received supplemental external beam radiation therapy. No patient received androgen deprivation therapy either neoadjuvantly or following brachytherapy. The median day 0 D90 was 119.3% of prescription dose. A pre-brachytherapy PSA and serum testosterone (normal range 241-827 ng/dL) were obtained for each patient. A baseline PSA and serum testosterone were obtained 3 months following brachytherapy and repeated at least every 6 months thereafter. A PSA spike was defined as an increase > 0.20 ng/mL. Multiple clinical, treatment and dosimetric parameters were evaluated to determine an association between PSA spikes and temporal changes in serum testosterone.
Results: Of the 202 patients, 21 (10.4%) experienced a PSA spike on average 9 months following brachytherapy. The mean pre-spike PSA was 0.40 ng/mL and the mean spike PSA was 0.75 ng/mL. By 21 months following brachytherapy all spikes had resolved. In patients with a PSA spike, the serum testosterone nadired at the time of PSA spike (mean 9 months) followed by a recovery in serum testosterone levels. In spike patients, the serum testosterone decreased from a mean of 440 ng/dL at 3 months to 370 ng/dL (a decrease of 15.9%) at 9 months. By month 15 the decrease in serum testosterone had resolved. In contrast, no mean differences in serum testosterone for the first 15 months were noted in non spike patients. In multivariate analysis, the serum testosterone 3 months following brachytherapy was the strongest predictor of PSA spike. Age, pre-treatment PSA and Gleason score did not predict for spike.
Conclusions: The results of this study demonstrate an association between a PSA spike and a concomitant decrease in serum testosterone. The PSA spike phenomenon and other changes in short-term changes in PSA may be related to serum testosterone kinetics.
[Show abstract][Hide abstract] ABSTRACT: In this study, the effect of prostate brachytherapy seed activity on postimplant rectal dosimetry was evaluated in Pro-Qura (Prostate Brachytherapy Quality Assurance; Seattle, WA) proctored, community-based programs.
Twenty-three hundred patients (1563 iodine-125 [(125)I] and 737 palladium-103 [(103)Pd]) from 78 brachytherapists with postimplant rectal dosimetry were identified. Seed activity was stratified into three tertiles for each isotope (≤0.300, 0.301-0.326, and >0.326 mCi/seed for (125)I and ≤1.330, 1.331-1.547, and >1.547 mCi/seed for (103)Pd). Postimplant dosimetry was performed in a standardized fashion. The rectum was contoured by outlining the outer rectal wall. The volume of the rectum receiving 100% of the prescription dose (R(100)) was calculated in cubic centimeters. The prostate V(100) and D(90) volumes were also calculated.
The mean prostate volume was 35.8 and 32.3 cm(3) for (125)I and (103)Pd. The median time to postimplant CT was 30 days. For (125)I, the V(100) increased from 91.0% to 93.7% (p=0.012) and the D(90) increased from 105.9% to 108.7% (p<0.001) for the lowest to the highest (125)I seed activities. In contrast, no significant changes in V(100) (p=0.751) or D(90) (p=0.200) were discerned when stratified by seed activity. For both isotopes, there was no correlation between seed activity and R(100), and R(100) was highest for the intermediate seed activities. Overall, the R(100) was lower for (103)Pd vs. (125)I (0.63 vs. 0.82 cm(3), p<0.001).
Within the confines of seed activities used in this study, higher activity seeds did not result in a deleterious effect on rectal dose. Higher activity seeds were associated with improved prostate dosimetry for (125)I, whereas (103)Pd dosimetry was not dependent on seed activity.
[Show abstract][Hide abstract] ABSTRACT: PSA Kinetics following High Dose Intensity Modulated External Beam Radiation Therapy with and without Image Guidance
J. L. Reed, G. S. Merrick, W. M. Butler, Z. A. Allen, B. S. Kurko, B. C. Murray, and R. W. Galbreath
Schiffler Cancer Center, Wheeling, WV
Purpose/Objective(s): It has previously been reported that PSA kinetics in the first year following definitive external beam radiation therapy are predictive of biochemical progression-free and overall survival in patients treated with radiation therapy alone. In this study, we evaluated PSA kinetics in the first two years following high-dose intensity modulated external beam radiation therapy (IMRT) with and without image guidance.
Materials/Methods: One hundred consecutive patients (the last 50 IMRT patients treated without image-guidance and the first 50 patients treated with image-guidance) were evaluated. All patients received 81 Gy in 1.8 Gy fractions calculated to the 90% isodose line. No patient received androgen deprivation therapy. All patients were irradiated in the prone position in a custom Aquaplast hip-fix immobilization device with an empty bladder and rectum. For image-guided patients, a daily cone-beam CT scan was obtained prior to treatment with positioning readjustments due to internal organ motion corrected for prior to the daily treatment. For non-imaged guidance patients, laser parameters were used on a daily basis to ensure appropriate setup. Weekly portal films were obtained for all 100 patients. Multiple clinical and treatment parameters were evaluated for impact on PSA kinetics.
Results: The mean patient age was 72 years with a mean pre-treatment PSA of 7.0 ng/ml, a mean Gleason score of 6.6 and a mean prostate volume of 40.5 cm3. No statistical differences in clinical parameters were identifiable between the two cohorts. At 6, 9, 12, 15, 18 and 24 months no statistically significance differences in post-treatment PSA were discerned between patients with and without image-guidance. At 12 and 24 months post-treatment, the mean PSA was 0.70 and 0.40 without image-guidance and 0.60 and 0.38 with image-guidance, respectively. Possibly because of the homogeneity of the evaluated population, none of the evaluated parameters predicted for short-term PSA kinetics.
Conclusions: Within the confines of this study, our results suggest that patients immobilized in the prone position in a custom hip-fix immobilization device have comparable PSA kinetics to patients treated in an identical manner but with the addition of daily cone-beam image guidance. Excellent PSA responses were noted in both cohorts.
No preview · Article · Nov 2009 · Fuel and Energy Abstracts
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: In this study, the effect of prostate brachytherapy seed activity on post-implant rectal dosimetry was evaluated in Pro-Qura proctored, community-based programs.
MATERIALS AND METHODS: 2,300 patients (1,563 125I and 737 103Pd) from 78 brachytherapists with post-implant rectal dosimetry were identified. Seed activity was stratified into 3 tertiles for each isotope (≤ 0.300, 0.301-0.326 and > 0.326 mCi/seed for 125I and ≤ 1.330, 1.331–1.547 and > 1.547 mCi/seed for 103Pd). Post-implant dosimetry was performed in a standardized fashion. The rectum was contoured by outlining the outer rectal wall. The volume of the rectum receiving 100% of the prescription dose (R100) was calculated in cm3. The prostate V100 and D90 were also calculated.
RESULTS: The mean prostate volume was 35.8 cm³ and 32.3 cm3 for 125I and 103Pd. The median time to post-implant CT was 30 days. For 125I, the V100 increased from 91.0% – 93.7% (p = 0.012) and the D90 increased from 105.9 % – 108.7 % (p < 0.001) for the lowest to the highest 125I seed activities. In contrast, no significant changes in V100 (p = 0.751) or D90 (p = 0.200) were discerned when stratified by seed activity. For both isotopes, there was no correlation between seed activity and R100, and R100 was highest for the intermediate seed activities. Overall, the R100 was lower for 103Pd versus 125I (0.63 versus 0.82 cm3, p < 0.001).
CONCLUSIONS: Within the confines of seed activities used in this study, higher activity seeds did not result in a deleterious effect on rectal dose. Higher activity seeds were associated with improved prostate dosimetry for 125I, whereas 103Pd dosimetry was not dependent on seed activity.
No preview · Article · Nov 2009 · International Journal of Radiation OncologyBiologyPhysics