Does supplemental external beam radiation therapy impact urinary, bowel, and erectile function following permanent prostate brachytherapy?: results of two prospective randomized trials.

PURPOSE: To evaluate the impact of supplemental external beam radiation therapy (EBRT) prior to permanent prostate brachytherapy on long term urinary, bowel, and erectile function. MATERIAL AND METHODS: Patient administered urinary, bowel, and erectile quality of life (QoL) instrument were obtained prior to treatment and following brachytherapy. The study population was comprised of the 457 patients who were alive as of June 2016, had been randomized to two markedly different supplemental EBRT dose regimens and a third arm without supplemental EBRT, and had completed the June 2016 QoL survey. The need for urinary or bowel surgical intervention was prospectively recorded during routine follow-up. Multiple parameters were evaluated for effect on outcomes. RESULTS: The urinary catheter was removed on day 0 in 92.1% of patients and 0.4% required a post-implant transurethral prostatic resection (TURP). On average, the International Prostate Symptom Score (IPSS) normalized at week 14. The 10-year rate of urethral strictures was 5.3%. No significant differences were discerned between baseline and post-implant rectal function assessment score (RFAS), and no patient developed a rectal ulcer or fistula. The 10-year potency preservation rate was 50.3%. Supplemental EBRT did not affect urinary, bowel, or erectile function. Urethral strictures were most closely related to bulbomembranous urethral brachytherapy doses, post-implant rectal function to pre-implant hemorroidal bleeding, and RFAS and erectile function to pre-brachytherapy international index of erectile function and age. CONCLUSIONS: Supplemental EBRT did not significantly effect catheter dependency, IPSS resolution, urethral stricture rate, the need for post-implant TURP, bowel, or erectile function. Careful attention to brachytherapy dose distributions appears to be most important in minimizing post-brachytherapy morbidity.

Is supplemental external beam radiation therapy essential to maximize brachytherapy outcomes in patients with unfavorable intermediate-risk disease?

PURPOSE: To evaluate whether supplemental external beam radiotherapy (EBRT) is essential to maximize Pd-103 brachytherapy outcomes in patients with unfavorable intermediate-risk (IR) disease. METHODS AND MATERIALS: A total of 630 patients were assessed from two prospective randomized brachytherapy trials evaluating the role of supplemental EBRT in patients with higher risk features. Patients were stratified into unfavorable IR (primary Gleason pattern 4, ≥50% positive biopsies, or ≥2 IR features), favorable IR, and high-risk (HR) cohorts. Median follow-up was 7.5 years. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a prostate-specific antigen >0.40 ng/mL after nadir. Patients with metastatic prostate cancer or nonmetastatic castrate-resistant disease who died of any cause were classified as dead of prostate cancer. Multiple parameters were evaluated for effect on outcomes. RESULTS: The 10-year BF for favorable IR, unfavorable IR, and HR was 1.7%, 6.6%, and 15.5% (p < 0.001). At 10 years, prostate cancer-specific mortality (PCSM) and overall mortality (OM) were 0% and 20.4%, 2.1% and 23.2%, and 4.3% and 42.4% for favorable IR, unfavorable IR, and HR. Although unfavorable IR patients had a greater incidence of BF, PCSM, and OM when compared with favorable IR, neither the addition nor dose of supplemental EBRT influenced outcome. CONCLUSIONS: Outcomes for favorable IR were superior to those with unfavorable IR. Within the confines of this study, neither the addition nor dose of supplemental EBRT influenced BF, PCSM, or OM in patients with IR disease.

Is supplemental external beam radiation therapy necessary for patients with higher risk prostate cancer treated with 103Pd? Results of two prospective randomized trials.

PURPOSE: To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 ((103)Pd) brachytherapy for high-risk prostate cancer patients. METHODS AND MATERIALS: Trial 44/20 randomized patients to 44 Gy plus 90 Gy (103)Pd vs. 20 Gy with 115 Gy (103)Pd, and the subsequent trial randomized patients to the 20 Gy arm vs. 125 Gy (103)Pd without EBRT (20/0 trial). Eligibility criteria included clinically organ-confined disease with Gleason scores 7-9 and/or a pretreatment prostate-specific antigen (PSA) 10-20 ng/mL. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a PSA >0.40 ng/mL after nadir. Median Day 0 minimum dose covering 90% of the prostate volume (D90) was >121.0% of the prescription dose. Multiple parameters were evaluated for effect on outcomes. RESULTS: In 44/20 trial, 13-year BF, prostate cancer-specific mortality (PCSM), and overall mortality (OM) were 8.2%, 4.0%, and 42.8% vs. 8.0%, 1.0%. and 40.3% for the 44 and 20 Gy arms. In 20/0 trial, 8-year BF, PCSM, and OM were 2.1%, 0%, and 14.4% vs. 3.6%, 0%, and 16.1% in the 20 vs. 0 Gy arms. When stratified by either pretreatment PSA or by Gleason score, supplemental EBRT dose did not impact BF, PCSM, or OM. In multivariate analysis, BF was most closely related to percent positive biopsies and prostate volume. In both trials, patients with biochemically controlled disease had a median PSA of <0.02 ng/mL. CONCLUSIONS: With high-quality brachytherapy dose distributions, supplemental EBRT did not influence BF or PCSM for patients with intermediate-risk disease. The number of patients with Gleason score 8-9 was too small to determine the role of supplemental EBRT in that cohort.

The case for hypofractionation of localized prostate cancer.

An optimal treatment regimen for localized prostate cancer (PCa) is yet to be determined. Increasing evidence reveals a lower α/ß ratio for PCa with hypofractionated radiation therapy (HFRT) regimens introduced to exploit this change in therapeutic ratio. HFRT also results in shortened overall treatment times of 4 to 5 weeks, thus reducing staffing and machine burden, and, more importantly, patient stress. This review evaluates pretreatment characteristics, outcomes, and toxicity for 15 HFRT studies on localized PCa. HFRT results in comparable or better biochemical relapse-free survival and toxicity and is a viable option for localized PCa.

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.

Gleason score 7 prostate cancer treated with interstitial brachytherapy with or without supplemental external beam radiation and androgen deprivation therapy: is the primary pattern on needle biopsy prognostic?

PURPOSE: To evaluate the effect of primary Gleason pattern on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) in Gleason 7 prostate cancer patients treated with low-dose-rate (LDR) interstitial brachytherapy with or without supplemental external beam radiation therapy and androgen deprivation therapy. METHODS AND MATERIALS: We retrospectively reviewed the medical records of 932 consecutive patients with biopsy-confirmed Gleason 7 prostate cancer who received LDR interstitial brachytherapy as a component of their definitive treatment regimen. Treatment outcomes were compared between patients with primary Gleason pattern 3 and 4. RESULTS: With a median followup of 7.4 years, the 10- and 14-year bPFS, CSS, and OS for the entire Gleason 7 study group were 95.7/95.7%, 98.6/98.6% and 77.2/64.3%, respectively. When biochemical control was evaluated as a function of primary Gleason pattern, the primary pattern 3 had a statistically higher 10- and 14-year bPFS (97.8/97.8% vs. 93.1/93.1%, p=0.006). The Gleason pattern 3 patients also trended toward a higher 10- and 14-year CSS (99.3/99.3% vs. 96.9/96.9%, p=0.058). OS was not statistically different between the two Gleason 7 cohorts. CONCLUSIONS: Gleason 7 prostate cancer patients treated with LDR interstitial brachytherapy have an excellent long-term outcome. There was a small but statistically significant advantage in bPFS and a trend toward improved CSS in patients with a primary Gleason pattern of 3.

Time to failure after definitive therapy for prostate cancer: implications for importance of aggressive local treatment.

PURPOSE: To explore patterns of time to failure in men receiving high doses of permanent seed brachytherapy with or without external beam radiation therapy as a function of risk status. MATERIAL AND METHODS: Two thousand two hundred and thirty four patients were treated with prostate brachytherapy with median follow up of 8.0 years. The population was 35% low risk, 49% intermediate risk, and 16% high risk (NCCN). Median day 0 implant D90 was 119% and V100 was 98%. Treatment failure was defined as PSA > 0.40 ng/mL after nadir. Rates of biochemical failure, distant metastases, and prostate cancer death were determined with non-prostate death as a competing risk. RESULTS: For all patients, the 10-year biochemical failure, distant metastases, and cause-specific mortality were 4.4%, 1.4%, and 1.3%, respectively. The biochemical failure rates were 1.3%, 4.8%, and 10.0% for men with low, intermediate, and high risk disease, respectively. Median time to failure was 2.8 years. In men who died from prostate cancer, the median time from treatment failure to death was 4.2 years. Overall, 83% of biochemical failures and 97% of metastases occurred within the first 4 years after treatment. CONCLUSIONS: With the dose escalation achieved by high quality brachytherapy dosimetry, even high-risk prostate cancer patients have excellent long term biochemical outcomes. Treatment failures occur early, and one third become metastatic and progress rapidly to prostate cancer death. The low frequency and pattern of failures suggest the presence of micrometastatic disease prior to treatment is rare, even in high risk patients.

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 small prostate size in men receiving definitive prostate brachytherapy.

PURPOSE: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. METHODS AND MATERIALS: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size (≤ 20 cm(3)) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Median prostate size for the entire cohort was 32.7 cm(3). For the 167 men with small prostates, median prostate size was 17.4 cm(3). There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. CONCLUSION: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.

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.

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.

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.

20 Gy versus 44 Gy of supplemental external beam radiotherapy with palladium-103 for patients with greater risk disease: results of a prospective randomized trial.

PURPOSE: The necessity of external beam radiotherapy (EBRT) as a supplement to prostate brachytherapy remains unknown. We report brachytherapy outcomes for patients with higher risk features randomized to substantially different supplemental EBRT regimens. METHODS AND MATERIALS: Between December 1999 and June 2004, 247 patients were randomized to 20 Gy vs. 44 Gy EBRT followed by a palladium-103 boost (115 Gy vs. 90 Gy). The eligibility criteria included clinically organ-confined disease with Gleason score 7-10 and/or pretreatment prostate-specific antigen (PSA) level 10-20 ng/mL. The median follow-up period was 9.0 years. Biochemical progression-free survival (bPFS) was defined as a PSA level of ≤0.40 ng/mL after nadir. The median day 0 prescribed dose covering 90% of the target volume was 125.7%; 80 men received androgen deprivation therapy (median, 4 months). Multiple parameters were evaluated for their effect on bPFS. RESULTS: For the entire cohort, the cause-specific survival, bPFS, and overall survival rates were 97.7%, 93.2%, and 80.8% at 8 years and 96.9%, 93.2%, and 75.4% at 10 years, respectively. The bPFS rate was 93.1% and 93.4% for the 20-Gy and 44-Gy arms, respectively (p = .994). However, no statistically significant differences were found in cause-specific survival or overall survival were identified. When stratified by PSA level of ≤10 ng/mL vs. >10 ng/mL, Gleason score, or androgen deprivation therapy, no statistically significant differences in bPFS were discerned between the two EBRT regimens. On multivariate analysis, bPFS was most closely related to the preimplant PSA and clinical stage. For patients with biochemically controlled disease, the median PSA level was <0.02 ng/mL. CONCLUSION: The results of the present trial strongly suggest that two markedly different supplemental EBRT regimens result in equivalent cause-specific survival, bPFS, and overall survival. It is probable that the lack of benefit for a higher supplemental EBRT dose is the result of the high-quality brachytherapy dose distributions.

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.

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.

Higher percentage of positive biopsy cores and Gleason score are associated with a greater degree of prostate gland shrinkage after neoadjuvant cytoreductive therapy.

PURPOSE: To determine whether adverse pathologic features, including tumor grade and percent positive biopsy (PPB) cores, predict for prostate size reduction after neoadjuvant cytoreductive therapy. METHODS AND MATERIALS: Eighty-two consecutive patients who were diagnosed with prostate cancer by transperineal template-guided mapping biopsy (TTMB) received neoadjuvant cytoreductive therapy. The median number of biopsy cores was 59. Thirty patients received a leutinizing hormone-releasing hormone agonist and bicalutamide, whereas 52 patients received bicalutamide (50mg daily) and dutasteride (0.5mg daily). A transrectal ultrasound volumetric study of the prostate gland and ellipsoid volume determinations of the prostate gland and transition zone (TZ) were obtained immediately before TTMB and at 90 days (±7 days) after the initiation of neoadjuvant medical therapy. Univariate and multivariate regression analyses were performed to identify predictors of prostate gland and TZ volume reduction. RESULTS: At TTMB, the mean prostate volumetric and ellipsoid volumes were 55.4 cm(3) and 49.0 cm(3), respectively. After neoadjuvant medical therapy, the mean volumetric and ellipsoid prostate volumes were 30.8 cm(3) and 28.5 cm(3), respectively. On average, the prostate volume decreased by 43.9% and 41.0% on volumetric and ellipsoid measurements, respectively. The TZ volume decreased from 19.8 cm(3) to 10.1 cm(3) (mean volume reduction of 47.7%). In multivariate analysis, prostate volume cytoreduction was most closely associated with PPB (p=0.014), TTMB prostate volume (p=0.01), and drug regimen (p=0.001). CONCLUSIONS: The degree of prostate volume cytoreduction was positively associated with higher Gleason score and PPBs. Greater reductions in prostate volume may be an indicator of more aggressive 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.

The correlation between annular treatment margins and biochemical failure in prostate brachytherapy patients with optimized intraprostatic dosimetry.

PURPOSE: To determine whether periprostatic treatment margins correlate with biochemical control in prostate brachytherapy patients with optimized intraprostatic dosimetry. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSION: 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.

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.