Multisector prostate dosimetric quality: analysis of a large community database.

PURPOSE: To evaluate multi-institutional prostate brachytherapy dosimetric quality using multisector analysis. METHODS AND MATERIALS: In the database, 4547 patients underwent brachytherapy (3094 for (125)I, 1437 for (103)Pd, and 16 for (131)Cs). The original prostate postimplant dosimetry was reported using the maximum dose covering 90% of the prostate volume (D90) and the percentage of the prostate volume covered by the prescription dose (V100). Retrospectively, the dosimetry of all implants was recalculated after segmenting the prostate into 12 sectors (anterior, left and right lateral and posterior, about the center of gravity, and subdivided lengthwise into three-base, midgland, and apex). The dosimetric quality of each sector and combinations of sectors was compared across radionuclides. RESULTS: For each radionuclide, there was no significant difference between monotherapy and boost in terms of V100 or D90. When classified as excellent (V100 ≥ 90%), standard (V100 ≥ 80%), or minimal (V100 < 80%), 33.0%, 4.6%, and 10.5% of all base, midgland, and apical sectors, respectively, were of minimal quality. Specifically, 59.2% of the anterior base and 30.3% of the posterior base sectors were minimal. At the anterior midgland and apex, 22% and 19% of sectors were minimal. Excellent quality was observed in more than 90% of lateral and posterior midgland sectors and in >70% of lateral and posterior sectors. When stratified by (103)Pd vs. (125)I, sector analysis did not result in clinically significant dosimetric differences. CONCLUSIONS: Coverage of base sectors was inferior to midgland and apical sectors, and coverage of anterior sectors was notably inferior to lateral and posterior sectors. Further critique of brachytherapy planning and intraoperative technique is necessary for brachytherapists to minimize these dosimetric differences.

Permanent prostate brachytherapy extracapsular radiation dose distributions: analysis of a multi-institutional database.

PURPOSE: Periprostatic brachytherapy doses impact biochemical control. In this study, we evaluate extracapsular volumetric dosimetry following permanent prostate brachytherapy in patients entered in a multi-institutional community database. MATERIAL AND METHODS: In the database, 4547 patients underwent brachytherapy (3094 - (125)I, 1437 - (103)Pd and 16 - (131)Cs). Using the originally determined prostate volume, a 5 mm, 3-dimensional peri-prostatic anulus was constructed around the prostate (except for a 2 mm posterior margin), and evaluated in its entirety and in 90° segments. Prostate dosimetric parameters consisted of a V100 and D90 while the annular dosimetry was reported as a V100. RESULTS: The intraprostatic V100 and D90 for (103)Pd, and (125)I were statistically comparable when stratified by isotope and/or monotherapy vs. boost. The overall mean V100 for the periprostatic annulus was 62.8%. The mean V100 at the base (51.6%) was substantially less than the apex (73.5%) and midgland (65.9%). In addition, for all patients, the anterior V100 (45.7%) was less than the lateral (68.8%) and the posterior (75.0%). The geometric V100 annular differences were consistent when evaluated by isotope. Overall, the V100 was higher in the (125)I cohort. CONCLUSIONS: The optimal extracapsular brachytherapy dose and radial extent remains unknown, but will prove increasingly important with reductions and/or elimination of supplemental external beam radiation therapy. The large multi-institutional community database demonstrates periprostatic annular doses that are not as robust as those in selected high volume brachytherapy centers, and may be inadequate for optimal biochemical control following monotherapeutic brachytherapy, especially in higher risk patients.

Impact of small prostate size on postimplant prostate dosimetry: analysis of a large community database.

PURPOSE: Achieving high-quality permanent interstitial brachytherapy in smaller prostates is thought to be more difficult than in larger glands. This study evaluates 4547 implants in a large community database to test this hypothesis. METHODS AND MATERIALS: From January 2003 to October 2010, 4547 prostate brachytherapy implants from a large community database were analyzed. The cohort was divided into three groups based on size, namely smaller (<30cm(3), n=1301), medium (30-40cm(3), n=1861), and large (>40cm(3), n=1385). Postimplant dosimetry, including D90, V100, and V100 by prostate sector, was performed for each implant. Comparison of mean V100 among small, medium, and larger prostate volume cohorts was performed using a one-way analysis of variance test. RESULTS: For the overall cohort, the D90 was 105% and 104% for monotherapy and boost, respectively. Mean D90 for small prostates was 106% and 104% for monotherapy and boost, respectively. Mean V100 for small prostates was 91.1% and 90.0%, respectively. Coverage for small prostates was as good or slightly better than larger glands. V100 by prostate sector revealed that there were no sectors for which smaller glands had significantly inferior coverage compared with larger glands. CONCLUSION: Although smaller prostates may in some respects be more technically difficult to implant than larger glands, a review of community-based brachytherapists reveals that with current implant techniques, good quality implants are readily achievable in men with smaller glands.

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.

Patient-reported long-term rectal function after permanent interstitial brachytherapy for clinically localized prostate cancer.

PURPOSE: To evaluate the effect of permanent interstitial brachytherapy with or without supplemental therapies on long-term rectal function using a patient-administered quality-of-life instrument. METHODS AND MATERIALS: One hundred thirty four of the initial 219 prostate brachytherapy patients who remain alive and have participated in a prospective evaluation of rectal function were mailed the rectal function assessment score (R-FAS). Of the 134 patients, 3 have a colostomy because of colorectal cancer, 2 failed to respond, and 129 (99.2% of eligible patients) returned a completed R-FAS. R-FAS ranges from 0 to 27 with lower scores indicative of better bowel function. Median followup was 14 years. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on bowel function. RESULTS: For the current cohort, R-FAS was 3.35, which was comparable to the 1999 (4.29), 2002 (3.92), and 2006 (4.00) surveys. In the 2011 survey, 10 (7.8%), 17 (13.1%), and 102 (78.3%) patients reported bowel function to be worse, improved, or unchanged after brachytherapy. No patient has developed a rectal ulcer or fistula. The number of preimplant bowel movements, tobacco, and diabetes mellitus correlated with R-FAS. Consistent with the previous thee surveys, patient's perception of overall rectal quality of life was inversely related to the use of supplemental external beam radiation. CONCLUSIONS: Long-term rectal function after prostate brachytherapy is favorable with a small number of patients reporting deterioration in bowel function. The judicious use of supplemental external beam radiation with particular attention to rectal doses may further improve long-term function.

Prognostic importance of tobacco use in men receiving definitive prostate brachytherapy.

PURPOSE: Several prominent publications have identified an overall association between tobacco use and an increased risk of disease recurrence and disease-specific mortality in prostate cancer patients. The authors explored whether tobacco use adversely impacts treatment outcomes in men treated with permanent interstitial brachytherapy. METHODS AND MATERIALS: From April 1995 to August 2008, 2057 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.5 years. The role of tobacco use as a prognostic factor for biochemical progression-free survival, cause-specific survival, and overall survival was investigated. Differences in survival between smokers and nonsmokers were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Current smokers presented with a lower body mass index (p<0.001), smaller prostate size (p=0.003), younger age (p<0.001), higher prostate-specific antigen level (p=0.002), a trend toward higher percentage biopsy core involvement (p=0.08), higher incidence of perineural invasion (p=0.015), and higher risk disease (p<0.001) than former or nonsmokers. There was no difference in biochemical progression-free survival (p=0.30) or cause-specific survival (p=0.72) at 10 years for smokers compared with nonsmokers. On univariate and multivariate analysis, tobacco use was an adverse risk factor for overall survival (p<0.001). There was no association between smoking and any prostate cancer-specific outcome. CONCLUSIONS: Smokers treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men who are nonsmokers.

Long-term outcome for very high-risk prostate cancer treated primarily with a triple modality approach to include permanent interstitial brachytherapy.

PURPOSE: To evaluate outcome in the most unfavorable subset of high-risk prostate cancer patients treated with a combination of supplemental external beam radiation therapy (EBRT) and brachytherapy. METHODS AND MATERIALS: Very high-risk prostate cancer was defined as follows: any Gleason score 10, Gleason score 8-9 with >50% of the biopsy cores positive for malignancy, Gleason score 8-9 with a prostate-specific antigen (PSA) >20ng/mL, any clinical stage T3, or any PSA >40ng/mL. One hundred thirty-one patients were identified who met the aforementioned criteria. The median followup was 6.6 years. One hundred twenty (91.6%) patients received supplemental EBRT and 100 (76.4%) received androgen deprivation therapy (median duration, 19.5 months; range, 4-36 months). The median postimplant day 0 D(90) (i.e., the minimum percentage of the prescription dose that covers the planning target volume) was 121.9% of prescription dose. Multiple clinical treatment and dosimetric parameters were evaluated for impact on the evaluated survival parameters. RESULTS: The median pretreatment PSA and Gleason score were 11.0ng/mL and 8. One hundred ten (84%) patients had a Gleason score ≥8. At 9 and 12 years, the cause-specific survival, biochemical progression-free survival, and overall survival were 91.0% and 86.5%, 87.3% and 87.3%, and 70.5% and 60.5%, respectively. The most common cause of death was heart disease (22.2%) with deaths from nonprostate cancer (12.7%) and prostate cancer (8.3%) being less likely. CONCLUSIONS: Permanent interstitial brachytherapy usually with supplemental EBRT and androgen deprivation therapy results in excellent biochemical control and cause-specific survival in the most unfavorable subset of high-risk prostate cancer patients. Death from diseases of the heart was more than twice as likely as death from prostate cancer.

Serum testosterone kinetics after brachytherapy for clinically localized prostate cancer.

PURPOSE: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSION: 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.

Distant metastases following permanent interstitial brachytherapy for patients with clinically localized prostate cancer.

PURPOSE: Recent publications have suggested high-risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival (CSS) than patients receiving definitive external beam radiation therapy (XRT). To date, none of these studies has compared distant metastases and CSS in brachytherapy patients. In this study, we evaluate such parameters in a consecutive cohort of brachytherapy patients. METHODS AND MATERIALS: From April 1995 to June 2007, 1,840 consecutive patients with clinically localized prostate cancer were treated with brachytherapy. Risk groups were stratified according to National Comprehensive Cancer Network (www.nccn.org) guidelines. Subgroups of 658, 893, and 289 patients were assigned to low, intermediate, and high-risk categories. Median follow-up was 7.2 years. Along with brachytherapy implantation, 901 (49.0%) patients received supplemental XRT, and 670 (36.4%) patients received androgen deprivation therapy (median duration, 4 months). The mode of failure (biochemical, local, or distant) was determined for each patient for whom therapy failed. Cause of death was determined for each deceased patient. Multiple parameters were evaluated for impact on outcome. RESULTS: For the entire cohort, metastases-free survival (MFS) and CSS at 12 years were 98.1% and 98.2%, respectively. When rates were stratified by low, intermediate, and high-risk groups, the 12-year MFS was 99.8%, 98.1%, and 93.8% (p < 0.001), respectively. CSS rates were 99.8%, 98.0%, and 95.3% (p < 0.001) for low, intermediate, and high-risk groups, respectively. Biochemical progression-free survival was 98.7%, 95.9% and 90.4% for low, intermediate, and high-risk patients, respectively (p < 0.001). In multivariate Cox-regression analysis, MFS was mostly closely related to Gleason score and year of treatment, whereas CSS was most closely associated with Gleason score. CONCLUSIONS: Excellent CSS and MFS rates are achievable with high-quality brachytherapy for low, intermediate, and high-risk patients. These results compare favorably to alternative treatment modalities. In particular, our MFS and CSS rates for high-risk patients appear superior to those of published radical prostatectomy series.

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy.

OBJECTIVE: To evaluate the relationship between pre-treatment erectile function and all-cause mortality in patients with prostate cancer treated with brachytherapy. PATIENTS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

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.

The effect of pro-qura case volume on post-implant prostate dosimetry.

PURPOSE: To evaluate the effect of prostate brachytherapy case volume on postimplant dosimetric quality in Pro-Qura proctored programs. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prostate cancer death is unlikely in high-risk patients following quality permanent interstitial brachytherapy.

OBJECTIVE: To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in high-risk prostate cancer brachytherapy patients. PATIENTS AND METHODS: From April 1995 to June 2005, 284 patients with high-risk prostate cancer (Gleason score ≥ 8 or prostate-specific antigen > 20 ng/mL or clinical stage ≥ T2 c) underwent brachytherapy. Supplemental external beam radiation therapy was given to 257 (90.5%) patients and 179 (63.0%) received androgen deprivation therapy (ADT). Median follow up was 7.8 years. The median post-implant day 0 D90 was 118.9% of prescription dose. Patients with metastatic prostate cancer or castrate-resistant disease without obvious metastases who died of any cause were classified as dead from prostate cancer. Multiple parameters were evaluated for impact on survival. RESULTS: Twelve-year CSS, bPFS and OS were 94.2%, 89.0% and 69.7%. On multivariate analysis, bPFS was best predicted by percent positive biopsies and ADT. The analysis failed to identify any predictors for CSS, while OS was highly correlated with patient age, percent positive biopsies and diabetes. Fourteen percent of patients died from diseases of the heart, while 8%, 8% and 6% of patients died from non-prostate cancer, other causes and prostate cancer, respectively. When OS was stratified by patients with 0-3 vs ≥ 4 comorbidities, the 12-year OS was 73.0% and 52.7% (P = 0.036). CONCLUSIONS: High-quality brachytherapy results in favourable bPFS and CSS for high-risk patients. Death from diseases of the heart is more than twice as likely as death from prostate cancer. Strategies to improve cardiovascular health may positively impact OS.

Long-term outcome for clinically localized prostate cancer treated with permanent interstitial brachytherapy.

PURPOSE: To present the largest series of prostate cancer brachytherapy patients treated with modern brachytherapy techniques and postimplant day 0 dosimetric evaluation. METHODS AND MATERIALS: Between April 1995 and July 2006, 1,656 consecutive patients were treated with permanent interstitial brachytherapy. Risk group stratification was carried out according to the Mt. Sinai guidelines. Median follow-up was 7.0 years. The median day 0 minimum dose covering at least 90% of the target volume was 118.8% of the prescription dose. 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 12 years, biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) for the entire cohort was 95.6%, 98.2%, and 72.6%, respectively. For low-, intermediate-, and high-risk patients, bPFS was 98.6%, 96.5%, and 90.5%; CSS was 99.8%, 99.3%, and 95.2%; and OS was 77.5%, 71.1%, and 69.2%, respectively. For biochemically controlled patients, the median posttreatment prostate-specific antigen (PSA) concentration was 0.02 ng/ml. bPFS was most closely related to percent positive biopsy specimens and risk group, while Gleason score was the strongest predictor of CSS. OS was best predicted by patient age, hypertension, diabetes, and tobacco use. At 12 years, biochemical failure and cause-specific mortality were 1.8% and 0.2%, 5.1% and 2.1%, and 10.4% and 7.1% for Gleason scores 5 to 6 and 7 and ≥8, respectively. CONCLUSIONS: Excellent long-term outcomes are achievable with high-quality brachytherapy for low-, intermediate-, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy.

Relationship between prostate cancer mortality and number of unfavourable risk factors in men treated with definitive brachytherapy.

OBJECTIVE: To explore whether the number of unfavourable pretreatment risk factors predicts cause-specific mortality in men treated with prostate brachytherapy. PATIENTS AND METHODS: Between April 1995 and March 2006, 739 patients were treated who had at least one of the following adverse risk factors: pretreatment prostate-specific antigen (PSA) level of >10 ng/mL, a Gleason score of > or =7, clinical stage > or =T2b, or a PSA velocity (PSAV) of >2 ng/mL/year. Supplemental external beam radiotherapy (EBRT) was delivered to 464 (62.8%) men and 301 (40.7%) received androgen deprivation therapy (ADT). Of men with more than two risk factors, 87% received EBRT and 62% received ADT. RESULTS: The biochemical progression-free survival (bPFS), cause-specific survival (CSS) and overall survival for all patients were 95.0%, 97.9% and 70.0% at 12 years. Men with three or four risk factors had a prostate cancer-specific mortality (PCSM) at 12 years of 5.3%, vs 1.7% for men with one or two risk factors (P= 0.006). When 'percentage of positive biopsy cores >50%' replaced PSAV as a risk factor, men with two or more risk factors had a PCSM of 8.9%, vs 1.0% for men with one or two risk factors (P= 0.001). There was no difference in all-cause mortality between the groups in either analysis. CONCLUSION: Multimodal brachytherapy results in high rates of bPFS and CSS, even for men with several unfavourable risk factors. Men with two or more unfavourable risk factors had a slightly greater risk of PCSM and no difference in all-cause mortality. The presence of three or four unfavourable intermediate-risk factors does not appear to clearly identify a group that requires further treatment intensification, although the percentage of positive cores might be more predictive than PSAV.

Erectile function durability following permanent prostate brachytherapy.

PURPOSE: To evaluate long-term changes in erectile function following prostate brachytherapy. METHODS AND MATERIALS: This study included 226 patients with prostate cancer and preimplant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) who underwent brachytherapy in two prospective randomized trials between February 2001 and January 2003. Median follow-up was 6.4 years. Pre- and postbrachytherapy potency was defined as IIEF-6 > or = 13 without pharmacologic or mechanical support. The relationship among clinical, treatment, and dosimetric parameters and erectile function was examined. RESULTS: The 7-year actuarial rate of potency preservation was 55.6% with median postimplant IIEF of 22 in potent patients. Potent patients were statistically younger (p = 0.014), had a higher preimplant IIEF (p < 0.001), were less likely to be diabetic (p = 0.002), and were more likely to report nocturnal erections (p = 0.008). Potency preservation in men with baseline IIEF scores of 29-30, 24-28, 18-23, and 13-17 were 75.5% vs. 73.6%, 51.7% vs. 44.8%, 48.0% vs. 40.0%, and 23.5% vs. 23.5% in 2004 vs. 2008. In multivariate Cox regression analysis, preimplant IIEF, hypertension, diabetes, prostate size, and brachytherapy dose to proximal penis strongly predicted for potency preservation. Impact of proximal penile dose was most pronounced for men with IIEF of 18-23 and aged 60-69. A significant minority of men who developed postimplant impotence ultimately regained erectile function. CONCLUSION: Potency preservation and median IIEF scores following brachytherapy are durable. Thoughtful dose sparing of proximal penile structures and early penile rehabilitation may further improve these results.

Pretreatment serum testosterone and androgen deprivation: effect on disease recurrence and overall survival in prostate cancer patients treated with brachytherapy.

PURPOSE: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. METHODS AND MATERIALS: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined for each deceased patient. RESULTS: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). CONCLUSIONS: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.

Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange.

BACKGROUND: In this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy. METHODS AND MATERIAL: From May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen (PSA)< or =0.40ng/mL after nadir. Patients with metastatic prostate cancer or hormone refractory disease without obvious metastases who died of any cause were classified as died of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple parameters were evaluated for impact on survival. RESULTS: At 9 years, Agent Orange-exposed men were least likely to remain biochemically controlled (89.5%, 100%, and 97.2% in Agent Orange-exposed, nonexposed veterans, and nonveterans, respectively, p=0.012). No significant differences in cause-specific (CSS) (p=0.832) or overall survival (OS) (p=0.363) were discerned. In multivariate analysis, CSS was best predicted by Gleason Score and day 0 D(90), whereas Gleason Score, % positive biopsies, and D(90) predicted for bPFS. None of the evaluated parameters predicted for OS, however, a trend was identified for better OS in younger patients and those with a higher D(90). In addition, Agent Orange exposure did not predict for any of the survival parameters. To date, 22 patients have died (metastatic prostate cancer two, second malignancies nine, cardiovascular disease eight, trauma two, and pulmonary one). CONCLUSIONS: In this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis.

Biochemical and functional outcomes following brachytherapy with or without supplemental therapies in men < or = 50 years of age with clinically organ-confined prostate cancer.

OBJECTIVES: Despite favorable long-term prostate brachytherapy outcomes, there remains a bias to recommend radical prostatectomy for young patients. Herein, we report cause-specific survival, biochemical progression-free survival (bPFS), overall survival and functional outcomes in men < or =50 years of age who underwent brachytherapy with or without supplemental therapies. METHODS: From October 1995 to November 2004, 42 consecutive patients < or =50 years of age underwent permanent interstitial brachytherapy. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The mean and median follow-up was 5.6 and 5.1 year. bPFS was defined as a prostate-specific antigen < or =0.40 ng/mL after nadir. Functional outcome determinations included urinary, bowel and erectile function evaluations. Multiple clinical, treatment and dosimetric parameters were evaluated for impact on survival. RESULTS: Cause-specific survival, bPFS, and overall survival for the entire cohort were 100%, 97.7%, and 100%, respectively. To date, only one patient has failed biochemically. Median time to International Prostate Symptom Score resolution was 3 months. No patient required a postimplant transurethral resection of the prostate or developed urinary incontinence. Two patients developed bulbomembtranous urethral strictures. The overall potency preservation rate was 75.6% (International Index of Erectile Function-6 >13 without mechanical or pharmacologic support). Bowel habits were reported to be the same or better than prior to treatment in 92.5% patients. No severe rectal complications requiring therapeutic intervention occurred. CONCLUSIONS: Men < or =50 years of age have favorable biochemical and functional outcomes following brachytherapy. Depending on risk group assignment, brachytherapy with or without supplemental therapies should be considered a viable option for all healthy men regardless of age.

The impact of acute urinary morbidity on late urinary function after permanent prostate brachytherapy.

PURPOSE: Acute prostate brachytherapy-related morbidity is dominated by urinary symptomatology. In this study, we evaluated the effect of severe early brachytherapy-related urinary morbidity on late urinary function. METHODS AND MATERIALS: From January 1998 to September 2003, 1029 patients were implanted for clinical stage T1b-T3a (2002 American Joint Committee on Cancer [AJCC] criteria) prostate cancer. Five hundred sixteen (50.1%) received supplemental external beam radiation therapy and 440 (42.8%) received androgen deprivation therapy. Severe acute urinary morbidity (SAUM) was defined as a dysuria frequency score of at least 4 (of 5), a dysuria severity score of at least 8 (of 10), an internation prostate symptom score (IPSS) elevated to at least 30 or 15 above preimplant value for 4 weeks, and/or requirement of a urinary catheter for at least 5 days. Dysuria severity and frequency resolution were defined as a return to within one point of baseline. IPSS resolution was defined as a return to within two points of baseline. RESULTS: Of the 1029 patients, 175 met at least one of the criteria for inclusion. Dysuria frequency resolved in 5.0 vs. 1.3 weeks and dysuria severity in 5.7 vs. 1.4 weeks, for patients with and without SAUM. The mean time for IPSS resolution was 13.8 vs. 6.6 weeks, for patients with and without SAUM. The incidence of transurethral resection (2.3% [4/173] vs. 1.5% [13/841]) and bulbomembranous urethral strictures (2.2% [4/175] vs. 1.8% [15/854]) were comparable among patients with and without SAUM. CONCLUSIONS: Patients experiencing brachytherapy-related SAUM have long-term urinary function and complications comparable to patients who did not develop SAUM.